Nifedipine

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Identification

Summary

Nifedipine is a dihydropyridine calcium channel blocker indicated for the management of several subtypes of angina pectoris, and hypertension.

Brand Names

Adalat, Afeditab CR, Nifediac, Nifedical, Procardia

Generic Name

Nifedipine

DrugBank Accession Number

DB01115

Background

Nifedipine, or BAY a 1040, is a first generation dihydropyridine L-type calcium channel blocker, similar to nicardipine.^3,10,11,13 Nifedipine was developed by Bayer and first described in the literature, along with other dihydropyridines, in 1972.^11,12 Since nifedipine's development, second and third generation dihydropyridines have been developed with slower onsets and longer durations of action.¹⁰ The most popular of the third generation dihydropyridines is amlodipine.¹⁰

Nifedipine was granted FDA approval on 31 December 1981.¹³

Type

Small Molecule

Groups

Approved

Structure

Similar Structures

Weight: Average: 346.3346
Monoisotopic: 346.116486318
Chemical Formula: C₁₇H₁₈N₂O₆

Synonyms

4-(2'-Nitrophenyl)-2,6-dimethyl-1,4-dihydropyridin-3,5-dicarbonsäuredimethylester
Nifedipine
Nifedipino
Nifedipinum

External IDs

BAY A 1040

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Pharmacology

Indication

Nifedipine capsules are indicated to treat vasospastic angina and chronic stable angina.¹³ Extended release tablets are indicated to treat vasospastic angina, chronic stable angina, and hypertension.^14,15

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Patient Characteristics	Dose Form
Treatment of	Achalasia		••• •••••
Used in combination to treat	Anal fissures	Combination Product in combination with: Lidocaine (DB00281)	••• •••		•••••
Management of	Chronic stable angina pectoris		••••••••••••	•••••• •••••••••••• •••••••	••••••• •••••••• •••••••
Management of	Hypertension		••••••••••••		••••••• •••••••• •••••••
Treatment of	Hypertensive emergency		••• •••••

Contraindications & Blackbox Warnings

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Pharmacodynamics

Nifedipine is an inhibitor of L-type voltage gated calcium channels that reduces blood pressure and increases oxygen supply to the heart.¹ Immediate release nifedipine's duration of action requires dosing 3 times daily.¹³ Nifedipine dosing is generally 10-120mg daily.¹³ Patients should be counselled regarding the risk of excessive hypotension, angina, and myocardial infarction.¹³

Mechanism of action

Nifedipine blocks voltage gated L-type calcium channels in vascular smooth muscle and myocardial cells.¹ This blockage prevents the entry of calcium ions into cells during depolarization, reducing peripheral arterial vascular resistance and dilating coronary arteries.¹ These actions reduce blood pressure and increase the supply of oxygen to the heart, alleviating angina.¹

Target	Actions	Organism
AVoltage-dependent L-type calcium channel subunit alpha-1C	inhibitor	Humans
AVoltage-dependent L-type calcium channel subunit alpha-1D	inhibitor	Humans
AVoltage-dependent L-type calcium channel subunit beta-2	inhibitor	Humans
UNuclear receptor subfamily 1 group I member 2	agonist	Humans
UVoltage-dependent L-type calcium channel subunit alpha-1S	inhibitor	Humans
UA-type voltage-gated potassium channel KCND3	inhibitor	Humans
UVoltage-dependent T-type calcium channel	inhibitor	Humans
UCalmodulin	inhibitor	Humans

Absorption

Sublingual dosing leads to a C_max of 10ng/mL, with a T_max of 50min, and an AUC of 25ng*h/mL.⁹ Oral dosing leads to a C_max of 82ng/mL, with a T_max of 28min, and an AUC of 152ng*h/mL.⁹

Nifedipine is a Biopharmaceutics Classification System Class II drug, meaning it has low solubility and high intestinal permeability.⁸ It is almost completely absorbed in the gastrointestinal tract but has a bioavilability of 45-68%, partly due to first pass metabolism.^3,8

Volume of distribution

The steady state volume of distribution of nifedipine is 0.62-0.77L/kg and the volume of distribution of the central compartment is 0.25-0.29L/kg.³

Protein binding

Nifedipine is 92-98% protein bound in serum.¹³ Nifedipine is 97±12% bound in a 40g/L solution of pure albumin.² Nifedipine is 51.4±5.9% protein bound in a 50mg/100mL solution of alpha-1-acid glycoprotein, and 75.5±3.5% protein bound in a 150mg/mL solution.²

Metabolism

Nifedipine is predominantly metabolized by CYP3A4.^1,8,13,14,15 Nifedipine is predominantly metabolized to 2,6-dimethyl-4-(2-nitrophenyl)-5-methoxycarbonyl-pyridine-3-carboxylic acid, and then further metabolized to 2-hydroxymethyl-pyridine carboxylic acid.⁶ Nifedipine is also minorly metabolized to dehydronifedipine.⁷

Hover over products below to view reaction partners

Nifedipine
- dehydronifedipine
- 2,6-dimethyl-4-(2-nitrophenyl)-5-methoxycarbonyl-pyridine-3-carboxylic acid
  - 2-hydroxymethyl-pyridine carboxylic acid

Route of elimination

Nifedipine is 60-80% recovered in the urine as inactive water soluble metabolites, and the rest is eliminated in the feces as metabolites.¹⁴

Half-life

The terminal elimination half life of nifedipine is approximately 2 hours.^3,8

Clearance

The total body clearance of nifedipine is 450-700mL/min.³

Adverse Effects

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Toxicity

The oral LD₅₀ in rats is 1022mg/kg and in mice is 202mg/kg.¹⁶

Patients experiencing an overdose may present with hypotension, sinus node dysfunction, atrioventricular node dysfunction, and reflex tachycardia.^4,5 Overdose may be managed by monitoring cardiovascular and respiratory function; elevating extremities; and administering vasopressors, fluids, and calcium infusions.¹³

Pathways

Pathway	Category
Nifedipine Action Pathway	Drug action

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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Abacavir	Abacavir may decrease the excretion rate of Nifedipine which could result in a higher serum level.
Abaloparatide	The risk or severity of adverse effects can be increased when Nifedipine is combined with Abaloparatide.
Abametapir	The serum concentration of Nifedipine can be increased when it is combined with Abametapir.
Abatacept	The metabolism of Nifedipine can be increased when combined with Abatacept.
Abiraterone	The serum concentration of Nifedipine can be increased when it is combined with Abiraterone.

Food Interactions

Avoid excessive or chronic alcohol consumption.
Avoid grapefruit products. Grapefruit down-regulates post-translational expression of CYP3A4, the major metabolizing enzyme of nifedipine. Grapefruit, in all forms (e.g. whole fruit, juice and rind), can significantly increase serum levels of nifedipine and may cause toxicity. Avoid grapefruit products while on this medication.
Avoid natural licorice.
Take with or without food.

Products

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Product Images

International/Other Brands

Adapine / Afeditab / Coracten / Nifecard / Nifecor / Nifedical / NifedicalXL / Nifedipres

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Adalat	Capsule	5 mg	Oral	Bayer Ag	1997-01-07	2005-07-27
Adalat - Cap 10mg	Capsule	10 mg	Oral	Bayer Ag	1982-12-31	2005-07-27
Adalat Cap 10mg	Capsule	10 mg	Oral	Miles Inc. Pharmaceutical Division	1982-12-31	2000-08-01
Adalat Cap 5mg	Capsule	5 mg	Oral	Miles Inc. Pharmaceutical Division	1986-12-31	2000-08-01
Adalat CC	Tablet, film coated	60 mg/1	Oral	Almatica Pharma LLC	2017-02-01	2020-04-01

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Afeditab CR	Tablet, film coated, extended release	30 mg/1	Oral	Carilion Materials Management	2002-11-01	Not applicable
Afeditab CR	Tablet, film coated, extended release	60 mg/1	Oral	Aphena Pharma Solutions - Tennessee, LLC	2002-11-01	Not applicable
Afeditab CR	Tablet, film coated, extended release	30 mg/1	Oral	Actavis Pharma, Inc.	2002-11-01	2019-01-31
Afeditab CR	Tablet, film coated, extended release	60 mg/1	Oral	bryant ranch prepack	2002-11-01	2010-05-01
Afeditab CR	Tablet, film coated, extended release	60 mg/1	Oral	Actavis Pharma, Inc.	2002-11-01	2018-11-30

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Adalat XL Plus	Nifedipine (60 mg) + Acetylsalicylic acid (81 mg)	Kit; Tablet, delayed release; Tablet, extended release	Oral	Bayer Ag	2008-07-24	2014-07-18
Adalat XL Plus	Nifedipine (30 mg) + Acetylsalicylic acid (81 mg)	Kit; Tablet, delayed release; Tablet, extended release	Oral	Bayer Ag	2008-07-24	2014-07-18
Adalat XL Plus	Nifedipine (20 mg) + Acetylsalicylic acid (81 mg)	Kit; Tablet, delayed release; Tablet, extended release	Oral	Bayer Ag	2008-07-24	2014-07-18
BELNIF	Nifedipine (15 mg/1) + Metoprolol tartrate (50 mg/1)	Capsule, extended release	Oral		2018-10-01	2021-09-15
BETA - NICARDIA CAPSULE	Nifedipine (20 mg) + Atenolol (50 mg)	Capsule	Oral	SINGAPORE PHARMACEUTICAL PRIVATE LIMITED	2003-08-14	Not applicable

Chemical Identifiers

UNII: I9ZF7L6G2L
CAS number: 21829-25-4
InChI Key: HYIMSNHJOBLJNT-UHFFFAOYSA-N
InChI: InChI=1S/C17H18N2O6/c1-9-13(16(20)24-3)15(14(10(2)18-9)17(21)25-4)11-7-5-6-8-12(11)19(22)23/h5-8,15,18H,1-4H3
IUPAC Name: 3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
SMILES: COC(=O)C1=C(C)NC(C)=C(C1C1=CC=CC=C1[N+]([O-])=O)C(=O)OC

References

Synthesis Reference

Hiroitsu Kawata, Tadayoshi Ohmura, Katsuhiko Yano, Mikio Matsumura, Saburo Higuchi, Yoshiaki Soeishi, "Nifedipine-containing solid preparation composition." U.S. Patent US4412986, issued November, 1976.

US4412986

General References

Khan KM, Patel J, Schaefer TJ: Nifedipine . [Article]
Otto J, Lesko LJ: Protein binding of nifedipine. J Pharm Pharmacol. 1986 May;38(5):399-400. doi: 10.1111/j.2042-7158.1986.tb04598.x. [Article]
Chung M, Reitberg DP, Gaffney M, Singleton W: Clinical pharmacokinetics of nifedipine gastrointestinal therapeutic system. A controlled-release formulation of nifedipine. Am J Med. 1987 Dec 21;83(6B):10-4. doi: 10.1016/0002-9343(87)90630-9. [Article]
Herrington DM, Insley BM, Weinmann GG: Nifedipine overdose. Am J Med. 1986 Aug;81(2):344-6. doi: 10.1016/0002-9343(86)90276-7. [Article]
Whitebloom D, Fitzharris J: Nifedipine overdose. Clin Cardiol. 1988 Jul;11(7):505-6. doi: 10.1002/clc.4960110714. [Article]
Raemsch KD, Sommer J: Pharmacokinetics and metabolism of nifedipine. Hypertension. 1983 Jul-Aug;5(4 Pt 2):II18-24. doi: 10.1161/01.hyp.5.4_pt_2.ii18. [Article]
Waller DG, Renwick AG, Gruchy BS, George CF: The first pass metabolism of nifedipine in man. Br J Clin Pharmacol. 1984 Dec;18(6):951-4. doi: 10.1111/j.1365-2125.1984.tb02569.x. [Article]
Nader AM, Quinney SK, Fadda HM, Foster DR: Effect of Gastric Fluid Volume on the In Vitro Dissolution and In Vivo Absorption of BCS Class II Drugs: a Case Study with Nifedipine. AAPS J. 2016 Jul;18(4):981-8. doi: 10.1208/s12248-016-9918-x. Epub 2016 Apr 22. [Article]
van Harten J, Burggraaf K, Danhof M, van Brummelen P, Breimer DD: Negligible sublingual absorption of nifedipine. Lancet. 1987 Dec 12;2(8572):1363-5. doi: 10.1016/s0140-6736(87)91258-x. [Article]
Wang AL, Iadecola C, Wang G: New generations of dihydropyridines for treatment of hypertension. J Geriatr Cardiol. 2017 Jan;14(1):67-72. doi: 10.11909/j.issn.1671-5411.2017.01.006. [Article]
Godfraind T: Discovery and Development of Calcium Channel Blockers. Front Pharmacol. 2017 May 29;8:286. doi: 10.3389/fphar.2017.00286. eCollection 2017. [Article]
Vater W, Kroneberg G, Hoffmeister F, Saller H, Meng K, Oberdorf A, Puls W, Schlossmann K, Stoepel K: [Pharmacology of 4-(2'-nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid dimethyl ester (Nifedipine, BAY a 1040)]. Arzneimittelforschung. 1972 Jan;22(1):1-14. [Article]
FDA Approved Drug Products: Procardia Nifedipine Oral Capsules [Link]
FDA Approved Drug Products: Procardia XL Nifedipine Oral Extended Release Tablets [Link]
FDA Approved Drug Products: Adalat CC Nifedipine Oral Extended Release Tablets [Link]
Cayman Chemical: Nifedipine MSDS [Link]

External Links

Human Metabolome Database: HMDB0015247
KEGG Drug: D00437
KEGG Compound: C07266
PubChem Compound: 4485
PubChem Substance: 46505103
ChemSpider: 4330
BindingDB: 50101817
RxNav: 7417
ChEBI: 7565
ChEMBL: CHEMBL193
ZINC: ZINC000085205448
Therapeutic Targets Database: DAP000529
PharmGKB: PA450631
Guide to Pharmacology: GtP Drug Page
PDBe Ligand: C5U
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Nifedipine

PDB Entries

6jp5

FDA label

Download (206 KB)

MSDS

Download (74.7 KB)

Clinical Trials

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Phase	Status	Purpose	Conditions	Count	Start Date	Why Stopped	100+ additional columns
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Not Available	Completed	Not Available	Adenovirus / Anesthesia therapy / Anxiety / Anxiolysis / Arrhythmia / Autism Disorder / Bacterial Septicemia / Benzodiazepines / Bipolar Disorder (BD) / Bone and Joint Infections / Bradycardia / Cardiac Arrest / Central Nervous System Infections / Chronic Kidney Disease (CKD) / Convulsions / Cytomegalovirus Retinitis / Early-onset Schizophrenia Spectrum Disorders / Endocarditis / Epilepsy / Fibrinolytic Bleeding / General Anesthesia / Gram-Negative Bacterial Infections / Gynecological Infection / Headache / Heart Failure / Hemophilia / Herpes Simplex Virus / Hospital-Acquired Pneumonia / Hyperaldosteronism / Hypertension / Hypokalemia / Infantile Hemangiomas / Infection / Infection caused by staphylococci / Inflammation / Inflammatory Conditions / Insomnia / Intraabdominal Infections / Lower Respiratory Tract Infection (LRTI) / Meningitis, Bacterial / Menstrual Bleeding, Heavy / Methicillin Resistant Staphylococcus Aureus (MRSA) / Migraine / Neuromuscular Blockade / Neutropenia / Pain / Pneumonia / Pulmonary Arterial Hypertension (PAH) / Schizophrenia / Sedation / Seizures / Sepsis / Skeletal Muscle Spasms / Skin and skin structure infections / Treatment Resistant Schizophrenia / Urinary Tract Infection / Withdrawal syndrome	1	somestatus	stop reason	just information to hide
Not Available	Completed	Not Available	Coronavirus Disease 2019 (COVID‑19) / COVID / Hypertension	1	somestatus	stop reason	just information to hide
Not Available	Completed	Not Available	Hypertension	3	somestatus	stop reason	just information to hide
Not Available	Completed	Not Available	Preeclampsia With Severe Features	1	somestatus	stop reason	just information to hide
Not Available	Completed	Not Available	Premature Labour	1	somestatus	stop reason	just information to hide

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Actavis Group
Amerisource Health Services Corp.
Apotheca Inc.
A-S Medication Solutions LLC
Atlantic Biologicals Corporation
Bayer Healthcare
Biovail Pharmaceuticals
Bryant Ranch Prepack
Cardinal Health
Caremark LLC
Catalent Pharma Solutions
Comprehensive Consultant Services Inc.
Coupler Enterprises Inc.
Dept Health Central Pharmacy
DHHS Program Support Center Supply Service Center
Direct Dispensing Inc.
Dispensing Solutions
Diversified Healthcare Services Inc.
Elan Pharmaceuticals Inc.
Eurand Pharmaceuticals Inc.
Gavis Pharmaceuticals LLC
Giant Food Inc.
Goldline Laboratories Inc.
Greenstone LLC
H.E. Butt Grocery Co.
H.J. Harkins Co. Inc.
Heartland Repack Services LLC
International Laboratories Inc.
Ivax Pharmaceuticals
IVC Industries Inc.
Kaiser Foundation Hospital
LeaderPharma
Liberty Pharmaceuticals
Major Pharmaceuticals
Mason Distributors
Mckesson Corp.
Medisca Inc.
Murfreesboro Pharmaceutical Nursing Supply
Mylan
Neuman Distributors Inc.
Novopharm Ltd.
Nucare Pharmaceuticals Inc.
Palmetto Pharmaceuticals Inc.
PD-Rx Pharmaceuticals Inc.
Pfizer Inc.
Pharmaceutical Utilization Management Program VA Inc.
Pharmacy Service Center
Pharmedix
Physicians Total Care Inc.
Prasco Labs
Pratt Pharmaceuticals
Preferred Pharmaceuticals Inc.
Prepackage Specialists
Prepak Systems Inc.
Qualitest
Rebel Distributors Corp.
Redpharm Drug
Remedy Repack
Resource Optimization and Innovation LLC
RP Scherer Canada Inc.
Sandhills Packaging Inc.
Schering Corp.
Schwarz Pharma Inc.
Southwood Pharmaceuticals
Talbert Medical Management Corp.
Teva Pharmaceutical Industries Ltd.
Tya Pharmaceuticals
UDL Laboratories
United Research Laboratories Inc.
Va Cmop Dallas
Vangard Labs Inc.
Warrick Pharmaceuticals Corp.
Watson Pharmaceuticals

Dosage Forms

Form	Route	Strength
Capsule	Oral
Tablet, coated	Oral
Tablet, delayed release	Oral	60 mg
Capsule, coated	Oral	10 mg
Tablet, film coated	Oral	30 mg/1
Tablet, film coated	Oral	60 mg/1
Tablet, film coated	Oral	90 mg/1
Tablet, extended release	Oral	30 mg
Tablet, extended release	Oral	60 mg
Tablet	Oral	30 MG
Tablet	Oral	60 MG
Tablet, film coated	Oral	60 mg
Tablet, extended release	Oral
Tablet, coated	Oral	20 mg
Tablet	Oral	10 mg
Tablet, film coated	Oral
Kit; tablet, delayed release; tablet, extended release	Oral
Tablet	Oral	25.000 mg
Tablet	Oral
Cream	Rectal
Capsule, extended release	Oral	30 mg
Spray	Sublingual	5 mg/spray
Capsule, coated	Oral	20 mg
Tablet, film coated	Oral	40 mg
Capsule	Oral	10.0000 mg
Capsule, extended release	Oral
Capsule	Oral	50 mg
Solution	Oral	20 MG/ML
Tablet, film coated	Oral	30 mg
Tablet, film coated, extended release	Oral	90 mg/1
Capsule	Oral	20 MG
Solution / drops	Oral	20 MG/ML
Tablet, film coated	Oral	20 mg
Tablet, extended release	Oral	40 MG
Tablet	Oral	20 mg
Capsule, liquid filled	Oral	10 mg
Tablet, coated	Oral	30 MG
Tablet, coated	Oral	60 MG
Capsule, extended release	Oral
Capsule	Oral	10 mg/1
Capsule	Oral	20 mg/1
Capsule, liquid filled	Oral	10 mg/1
Capsule, liquid filled	Oral	20 mg/1
Powder	Not applicable	1 g/1g
Tablet	Oral	30 mg/1
Tablet, extended release	Oral	30 mg/1
Tablet, extended release	Oral	60 mg/1
Tablet, extended release	Oral	90 mg/1
Tablet, film coated, extended release	Oral	30 mg/1
Tablet, film coated, extended release	Oral	60 mg/1
Tablet, extended release	Oral	10 mg / srt
Tablet, extended release	Oral	20 mg / srt
Capsule, coated	Oral	100 mg
Capsule, liquid filled	Oral	20 mg
Capsule, extended release	Oral	3000000 mg
Tablet, coated	Oral	10 mg
Tablet, extended release	Oral	20 mg
Tablet, film coated	Oral	10 mg
Capsule	Oral	10.000 mg
Capsule	Oral
Tablet	Oral	30.00 mg
Capsule	Oral	5 mg / cap
Tablet, extended release	Oral	10 mg
Spray	Sublingual	5 mg
Capsule	Oral	20 mg/1mL
Capsule	Oral	10 mg / cap
Capsule, extended release	Oral	60 mg
Capsule	Oral	5 mg
Capsule	Oral	10 mg
Capsule, extended release	Oral	20 mg

Prices

Unit description	Cost	Unit
Nifedipine powder	15.3USD	g
Procardia XL 90 mg 24 Hour tablet	4.77USD	tablet
Procardia xl 90 mg tablet	4.58USD	tablet
Procardia xl 60 mg tablet	4.43USD	tablet
Procardia XL 60 mg 24 Hour tablet	4.13USD	tablet
Adalat CC 90 mg 24 Hour tablet	3.5USD	tablet
Adalat cc 90 mg tablet	3.37USD	tablet
Adalat CC 60 mg 24 Hour tablet	2.99USD	tablet
Adalat cc 60 mg tablet	2.87USD	tablet
NIFEdipine CR Osmotic 90 mg 24 Hour tablet	2.66USD	tablet
Nifediac cc 90 mg tablet	2.57USD	tablet
Nifedipine er 90 mg tablet	2.56USD	tablet
Procardia xl 30 mg tablet	2.56USD	tablet
Procardia XL 30 mg 24 Hour tablet	2.39USD	tablet
NIFEdipine CR Osmotic 60 mg 24 Hour tablet	2.38USD	tablet
Nifedipine er 60 mg tablet	2.29USD	tablet
Afeditab cr 60 mg tablet	2.24USD	tablet
Nifediac cc 60 mg tablet	2.17USD	tablet
Adalat CC 30 mg 24 Hour tablet	1.81USD	tablet
NIFEdipine 20 mg capsule	1.74USD	capsule
Adalat cc 30 mg tablet	1.61USD	tablet
Adalat Xl 60 mg Extended-Release Tablet	1.41USD	tablet
NIFEdipine CR Osmotic 30 mg 24 Hour tablet	1.35USD	tablet
Adalat Xl 20 mg Extended-Release Tablet	1.34USD	tablet
Adalat Xl 30 mg Extended-Release Tablet	1.34USD	tablet
Nifedipine er 30 mg tablet	1.32USD	tablet
Afeditab cr 30 mg tablet	1.26USD	tablet
Mylan-Nifedipine Extended Release 60 mg Extended-Release Tablet	1.18USD	tablet
Procardia 10 mg capsule	1.17USD	capsule
Nifediac cc 30 mg tablet	1.15USD	tablet
NIFEdipine 10 mg capsule	0.97USD	capsule
Apo-Nifed 10 mg Capsule	0.51USD	capsule
Apo-Nifed 5 mg Capsule	0.39USD	capsule
Coral calcium plus 1500 mg caplet	0.13USD	caplet
Coral calcium 1000 mg caplet	0.09USD	caplet

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
US5264446	No	1993-11-23	2010-11-23

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	172-174 °C	PhysProp
water solubility	Insoluble	FDA Label
logP	2.20	MASUMOTO,K ET AL. (1995)

Predicted Properties

Property	Value	Source
Water Solubility	0.0177 mg/mL	ALOGPS
logP	2.49	ALOGPS
logP	1.82	Chemaxon
logS	-4.3	ALOGPS
pKa (Strongest Acidic)	16.94	Chemaxon
pKa (Strongest Basic)	-6.6	Chemaxon
Physiological Charge	0	Chemaxon
Hydrogen Acceptor Count	5	Chemaxon
Hydrogen Donor Count	1	Chemaxon
Polar Surface Area	107.77 Å²	Chemaxon
Rotatable Bond Count	6	Chemaxon
Refractivity	91.16 m³·mol^-1	Chemaxon
Polarizability	33.89 Å³	Chemaxon
Number of Rings	2	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	Yes	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	0.9073
Blood Brain Barrier	-	0.9536
Caco-2 permeable	+	0.7853
P-glycoprotein substrate	Non-substrate	0.5089
P-glycoprotein inhibitor I	Inhibitor	0.8771
P-glycoprotein inhibitor II	Inhibitor	0.7902
Renal organic cation transporter	Non-inhibitor	0.9182
CYP450 2C9 substrate	Non-substrate	0.7776
CYP450 2D6 substrate	Non-substrate	0.5726
CYP450 3A4 substrate	Substrate	0.705
CYP450 1A2 substrate	Inhibitor	0.9106
CYP450 2C9 inhibitor	Non-inhibitor	0.6122
CYP450 2D6 inhibitor	Non-inhibitor	0.9231
CYP450 2C19 inhibitor	Non-inhibitor	0.6715
CYP450 3A4 inhibitor	Inhibitor	0.796
CYP450 inhibitory promiscuity	High CYP Inhibitory Promiscuity	0.9013
Ames test	Non AMES toxic	0.6973
Carcinogenicity	Non-carcinogens	0.5412
Biodegradation	Not ready biodegradable	0.9675
Rat acute toxicity	2.5425 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.863
hERG inhibition (predictor II)	Non-inhibitor	0.903

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	splash10-00n0-1195000000-7e4e6770da078dff666a
LC-MS/MS Spectrum - LC-ESI-qTof , Positive	LC-MS/MS	splash10-0v4i-1691000000-c4842fe2c3070d6e90dd
MS/MS Spectrum - , positive	LC-MS/MS	splash10-0v4i-1691000000-c4842fe2c3070d6e90dd
Predicted 1H NMR Spectrum	1D NMR	Not Applicable
Predicted 13C NMR Spectrum	1D NMR	Not Applicable

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å²)	Source type	Source
[M-H]-	187.5191675	predicted	DarkChem Lite v0.1.0
[M-H]-	185.8429675	predicted	DarkChem Lite v0.1.0
[M-H]-	180.0825	predicted	DeepCCS 1.0 (2019)
[M+H]+	187.5979675	predicted	DarkChem Lite v0.1.0
[M+H]+	186.0972675	predicted	DarkChem Lite v0.1.0
[M+H]+	184.09636	predicted	DeepCCS 1.0 (2019)
[M+Na]+	187.2331675	predicted	DarkChem Lite v0.1.0
[M+Na]+	185.8507675	predicted	DarkChem Lite v0.1.0
[M+Na]+	192.91142	predicted	DeepCCS 1.0 (2019)

Targets

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Property	Measurement	pH	Temperature (°C)	References
Kd (nM)	0.4	N/A	N/A	A29464
Ki (nM)	1	N/A	N/A	A29396

Details1. Voltage-dependent L-type calcium channel subunit alpha-1C

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Inhibitor

General Function: Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents (PubMed:11741969, PubMed:12176756, PubMed:12181424, PubMed:15454078, PubMed:15863612, PubMed:16299511, PubMed:17071743, PubMed:17224476, PubMed:20953164, PubMed:23677916, PubMed:24728418, PubMed:26253506, PubMed:27218670, PubMed:29078335, PubMed:29742403, PubMed:30023270, PubMed:30172029, PubMed:34163037, PubMed:7737988, PubMed:8099908, PubMed:8392192, PubMed:9013606, PubMed:9087614, PubMed:9607315). Mediates influx of calcium ions into the cytoplasm, and thereby triggers calcium release from the sarcoplasm (By similarity). Plays an important role in excitation-contraction coupling in the heart. Required for normal heart development and normal regulation of heart rhythm (PubMed:15454078, PubMed:15863612, PubMed:17224476, PubMed:24728418, PubMed:26253506). Required for normal contraction of smooth muscle cells in blood vessels and in the intestine. Essential for normal blood pressure regulation via its role in the contraction of arterial smooth muscle cells (PubMed:28119464). Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group (Probable)
Specific Function: alpha-actinin binding
Gene Name: CACNA1C
Uniprot ID: Q13936
Uniprot Name: Voltage-dependent L-type calcium channel subunit alpha-1C
Molecular Weight: 248974.1 Da

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Morel N, Buryi V, Feron O, Gomez JP, Christen MO, Godfraind T: The action of calcium channel blockers on recombinant L-type calcium channel alpha1-subunits. Br J Pharmacol. 1998 Nov;125(5):1005-12. [Article]
Sinnegger-Brauns MJ, Huber IG, Koschak A, Wild C, Obermair GJ, Einzinger U, Hoda JC, Sartori SB, Striessnig J: Expression and 1,4-dihydropyridine-binding properties of brain L-type calcium channel isoforms. Mol Pharmacol. 2009 Feb;75(2):407-14. doi: 10.1124/mol.108.049981. Epub 2008 Nov 24. [Article]
Striessnig, J. (2004). Ca 2+ channel blockers. In Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin: Springer. [ISBN:9783540298328]

Details2. Voltage-dependent L-type calcium channel subunit alpha-1D

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Inhibitor

General Function: Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, and by benzothiazepines
Specific Function: alpha-actinin binding
Gene Name: CACNA1D
Uniprot ID: Q01668
Uniprot Name: Voltage-dependent L-type calcium channel subunit alpha-1D
Molecular Weight: 245138.75 Da

References

Bell DC, Butcher AJ, Berrow NS, Page KM, Brust PF, Nesterova A, Stauderman KA, Seabrook GR, Nurnberg B, Dolphin AC: Biophysical properties, pharmacology, and modulation of human, neuronal L-type (alpha(1D), Ca(V)1.3) voltage-dependent calcium currents. J Neurophysiol. 2001 Feb;85(2):816-27. [Article]
Sinnegger-Brauns MJ, Huber IG, Koschak A, Wild C, Obermair GJ, Einzinger U, Hoda JC, Sartori SB, Striessnig J: Expression and 1,4-dihydropyridine-binding properties of brain L-type calcium channel isoforms. Mol Pharmacol. 2009 Feb;75(2):407-14. doi: 10.1124/mol.108.049981. Epub 2008 Nov 24. [Article]

Details3. Voltage-dependent L-type calcium channel subunit beta-2

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Inhibitor

General Function: Beta subunit of voltage-dependent calcium channels which contributes to the function of the calcium channel by increasing peak calcium current (By similarity). Plays a role in shifting voltage dependencies of activation and inactivation of the channel (By similarity). May modulate G protein inhibition (By similarity). May contribute to beta-adrenergic augmentation of Ca(2+) influx in cardiomyocytes, thereby regulating increases in heart rate and contractile force (PubMed:36424916). Involved in membrane targeting of the alpha-1 subunit CACNA1C (PubMed:17525370)
Specific Function: actin filament binding
Gene Name: CACNB2
Uniprot ID: Q08289
Uniprot Name: Voltage-dependent L-type calcium channel subunit beta-2
Molecular Weight: 73579.925 Da

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Striessnig J, Ortner NJ, Pinggera A: Pharmacology of L-type Calcium Channels: Novel Drugs for Old Targets? Curr Mol Pharmacol. 2015;8(2):110-22. [Article]
Striessnig, J. (2004). Ca 2+ channel blockers. In Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin: Springer. [ISBN:9783540298328]

Details4. Nuclear receptor subfamily 1 group I member 2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Agonist

General Function: Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes
Specific Function: DNA-binding transcription activator activity, RNA polymerase II-specific
Gene Name: NR1I2
Uniprot ID: O75469
Uniprot Name: Nuclear receptor subfamily 1 group I member 2
Molecular Weight: 49761.245 Da

References

Krasowski MD, Ai N, Hagey LR, Kollitz EM, Kullman SW, Reschly EJ, Ekins S: The evolution of farnesoid X, vitamin D, and pregnane X receptors: insights from the green-spotted pufferfish (Tetraodon nigriviridis) and other non-mammalian species. BMC Biochem. 2011 Feb 3;12:5. doi: 10.1186/1471-2091-12-5. [Article]

Details5. Voltage-dependent L-type calcium channel subunit alpha-1S

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Pore-forming, alpha-1S subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle. Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle via their interaction with RYR1, which triggers Ca(2+) release from the sarcoplasmic reticulum and ultimately results in muscle contraction. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group
Specific Function: calmodulin binding
Gene Name: CACNA1S
Uniprot ID: Q13698
Uniprot Name: Voltage-dependent L-type calcium channel subunit alpha-1S
Molecular Weight: 212348.1 Da

References

Peterson BZ, Catterall WA: Allosteric interactions required for high-affinity binding of dihydropyridine antagonists to Ca(V)1.1 Channels are modulated by calcium in the pore. Mol Pharmacol. 2006 Aug;70(2):667-75. Epub 2006 May 4. [Article]

Details6. A-type voltage-gated potassium channel KCND3

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Pore-forming (alpha) subunit of voltage-gated A-type potassium channels that mediates transmembrane potassium transport in excitable membranes, in brain and heart (PubMed:10200233, PubMed:17187064, PubMed:21349352, PubMed:22457051, PubMed:23280837, PubMed:23280838, PubMed:34997220, PubMed:9843794). In cardiomyocytes, may generate the transient outward potassium current I(To) (By similarity). In neurons, may conduct the transient subthreshold somatodendritic A-type potassium current (ISA) (By similarity). Kinetics properties are characterized by fast activation at subthreshold membrane potentials, rapid inactivation, and quick recovery from inactivation (PubMed:10200233, PubMed:17187064, PubMed:21349352, PubMed:22457051, PubMed:23280837, PubMed:23280838, PubMed:34997220, PubMed:9843794). Channel properties are modulated by interactions with regulatory subunits (PubMed:17187064, PubMed:34997220). Interaction with the regulatory subunits KCNIP1 or KCNIP2 modulates the channel gating kinetics namely channel activation and inactivation kinetics and rate of recovery from inactivation (PubMed:17187064, PubMed:34997220). Likewise, interaction with DPP6 modulates the channel gating kinetics namely channel activation and inactivation kinetics (PubMed:34997220)
Specific Function: A-type (transient outward) potassium channel activity
Gene Name: KCND3
Uniprot ID: Q9UK17
Uniprot Name: A-type voltage-gated potassium channel KCND3
Molecular Weight: 73450.53 Da

References

Bett GC, Rasmusson RL: Modification of K+ channel-drug interactions by ancillary subunits. J Physiol. 2008 Feb 15;586(4):929-50. Epub 2007 Dec 20. [Article]

Details7. Voltage-dependent T-type calcium channel (Protein Group)

Kind: Protein group
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1G gives rise to T-type calcium currents. T-type calcium channels belong to the 'low-voltage activated (LVA)' group and are strongly blocked by mibefradil. A particularity of this type of channel is an opening at quite negative potentials and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes.
Specific Function: high voltage-gated calcium channel activity

Components:

Name	UniProt ID
Voltage-dependent T-type calcium channel subunit alpha-1G	O43497
Voltage-dependent T-type calcium channel subunit alpha-1H	O95180
Voltage-dependent T-type calcium channel subunit alpha-1I	Q9P0X4

References

Lee TS, Kaku T, Takebayashi S, Uchino T, Miyamoto S, Hadama T, Perez-Reyes E, Ono K: Actions of mibefradil, efonidipine and nifedipine block of recombinant T- and L-type Ca channels with distinct inhibitory mechanisms. Pharmacology. 2006;78(1):11-20. Epub 2006 Aug 7. [Article]
Godfraind T: Discovery and Development of Calcium Channel Blockers. Front Pharmacol. 2017 May 29;8:286. doi: 10.3389/fphar.2017.00286. eCollection 2017. [Article]

Details8. Calmodulin (Protein Group)

Kind: Protein group
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding (PubMed:16760425, PubMed:23893133, PubMed:26969752, PubMed:27165696, PubMed:28890335, PubMed:31454269, PubMed:35568036). Calcium-binding is required for the activation of calmodulin (PubMed:16760425, PubMed:23893133, PubMed:26969752, PubMed:27165696, PubMed:28890335, PubMed:31454269, PubMed:35568036). Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases, such as myosin light-chain kinases and calmodulin-dependent protein kinase type II (CaMK2), and phosphatases (PubMed:16760425, PubMed:23893133, PubMed:26969752, PubMed:27165696, PubMed:28890335, PubMed:31454269, PubMed:35568036). Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Is a regulator of voltage-dependent L-type calcium channels (PubMed:31454269). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696). Forms a potassium channel complex with KCNQ1 and regulates electrophysiological activity of the channel via calcium-binding (PubMed:25441029). Acts as a sensor to modulate the endoplasmic reticulum contacts with other organelles mediated by VMP1:ATP2A2 (PubMed:28890335)
Specific Function: adenylate cyclase activator activity

Components:

Name	UniProt ID
Calmodulin-1	P0DP23
Calmodulin-2	P0DP24
Calmodulin-3	P0DP25

References

Lamers JM, Cysouw KJ, Verdouw PD: Slow calcium channel blockers and calmodulin. Effect of felodipine, nifedipine, prenylamine and bepridil on cardiac sarcolemmal calcium pumping ATPase. Biochem Pharmacol. 1985 Nov 1;34(21):3837-43. [Article]

Enzymes

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	10000	N/A	N/A	A28687
IC 50 (nM)	4.70E+04	N/A	N/A	A27395
IC 50 (nM)	11000	N/A	N/A	A28806

Details1. Cytochrome P450 3A4

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inhibitor
Inducer

General Function: A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
Specific Function: 1,8-cineole 2-exo-monooxygenase activity
Gene Name: CYP3A4
Uniprot ID: P08684
Uniprot Name: Cytochrome P450 3A4
Molecular Weight: 57342.67 Da

References

Foti RS, Rock DA, Wienkers LC, Wahlstrom JL: Selection of alternative CYP3A4 probe substrates for clinical drug interaction studies using in vitro data and in vivo simulation. Drug Metab Dispos. 2010 Jun;38(6):981-7. doi: 10.1124/dmd.110.032094. Epub 2010 Mar 4. [Article]
Pelkonen O, Maenpaa J, Taavitsainen P, Rautio A, Raunio H: Inhibition and induction of human cytochrome P450 (CYP) enzymes. Xenobiotica. 1998 Dec;28(12):1203-53. [Article]
Galetin A, Clarke SE, Houston JB: Quinidine and haloperidol as modifiers of CYP3A4 activity: multisite kinetic model approach. Drug Metab Dispos. 2002 Dec;30(12):1512-22. [Article]
Ramachandran SD, Vivares A, Klieber S, Hewitt NJ, Muenst B, Heinz S, Walles H, Braspenning J: Applicability of second-generation upcyte(R) human hepatocytes for use in CYP inhibition and induction studies. Pharmacol Res Perspect. 2015 Oct;3(5):e00161. doi: 10.1002/prp2.161. Epub 2015 Aug 10. [Article]
Wrighton SA, Ring BJ: Inhibition of human CYP3A catalyzed 1'-hydroxy midazolam formation by ketoconazole, nifedipine, erythromycin, cimetidine, and nizatidine. Pharm Res. 1994 Jun;11(6):921-4. doi: 10.1023/a:1018906614320. [Article]
Flockhart Table of Drug Interactions [Link]
FDA Approved Drug Products: Procardia XL Nifedipine Oral Extended Release Tablets [Link]

Details2. Cytochrome P450 2D6

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
Specific Function: anandamide 11,12 epoxidase activity
Gene Name: CYP2D6
Uniprot ID: P10635
Uniprot Name: Cytochrome P450 2D6
Molecular Weight: 55768.94 Da

References

Ma B, Prueksaritanont T, Lin JH: Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30. [Article]

Details3. Cytochrome P450 1A2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inhibitor

General Function: A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
Specific Function: aromatase activity
Gene Name: CYP1A2
Uniprot ID: P05177
Uniprot Name: Cytochrome P450 1A2
Molecular Weight: 58406.915 Da

References

Katoh M, Nakajima M, Shimada N, Yamazaki H, Yokoi T: Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol. 2000 Feb-Mar;55(11-12):843-52. [Article]
Tassaneeyakul W, Birkett DJ, Veronese ME, McManus ME, Tukey RH, Quattrochi LC, Gelboin HV, Miners JO: Specificity of substrate and inhibitor probes for human cytochromes P450 1A1 and 1A2. J Pharmacol Exp Ther. 1993 Apr;265(1):401-7. [Article]
ADALAT® XL® (Nifedipine extended-release tablets) Product Monograph [Link]

Details4. Cytochrome P450 2A6

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity
Specific Function: arachidonic acid epoxygenase activity
Gene Name: CYP2A6
Uniprot ID: P11509
Uniprot Name: Cytochrome P450 2A6
Molecular Weight: 56517.005 Da

References

ADALAT® XL® (Nifedipine extended-release tablets) Product Monograph [Link]

Details5. Cytochrome P450 2C8

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
Specific Function: arachidonic acid epoxygenase activity
Gene Name: CYP2C8
Uniprot ID: P10632
Uniprot Name: Cytochrome P450 2C8
Molecular Weight: 55824.275 Da

References

Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. [Article]

Details6. Cytochrome P450 1A1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C15-alpha and C16-alpha positions (PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15805301). Displays different regioselectivities for polyunsaturated fatty acids (PUFA) hydroxylation (PubMed:15041462, PubMed:18577768). Catalyzes the epoxidation of double bonds of certain PUFA (PubMed:15041462, PubMed:19965576, PubMed:20972997). Converts arachidonic acid toward epoxyeicosatrienoic acid (EET) regioisomers, 8,9-, 11,12-, and 14,15-EET, that function as lipid mediators in the vascular system (PubMed:20972997). Displays an absolute stereoselectivity in the epoxidation of eicosapentaenoic acid (EPA) producing the 17(R),18(S) enantiomer (PubMed:15041462). May play an important role in all-trans retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195)
Specific Function: arachidonic acid monooxygenase activity
Gene Name: CYP1A1
Uniprot ID: P04798
Uniprot Name: Cytochrome P450 1A1
Molecular Weight: 58164.815 Da

References

Tassaneeyakul W, Birkett DJ, Veronese ME, McManus ME, Tukey RH, Quattrochi LC, Gelboin HV, Miners JO: Specificity of substrate and inhibitor probes for human cytochromes P450 1A1 and 1A2. J Pharmacol Exp Ther. 1993 Apr;265(1):401-7. [Article]

Details7. Cytochrome P450 2B6

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inducer
Curator comments: One in vitro study indicates that nifedipine induces CYP2B6 while another indicates that it does not demonstrate any induction of this enzyme. Clinical correlation of this enzyme action is known.

General Function: A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids (PubMed:12865317, PubMed:21289075). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the epoxidation of double bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:21289075). Hydroxylates steroid hormones, including testosterone at C-16 and estrogens at C-2 (PubMed:12865317, PubMed:21289075). Plays a role in the oxidative metabolism of xenobiotics, including plant lipids and drugs (PubMed:11695850, PubMed:22909231). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850)
Specific Function: anandamide 11,12 epoxidase activity
Gene Name: CYP2B6
Uniprot ID: P20813
Uniprot Name: Cytochrome P450 2B6
Molecular Weight: 56277.81 Da

References

Drocourt L, Pascussi JM, Assenat E, Fabre JM, Maurel P, Vilarem MJ: Calcium channel modulators of the dihydropyridine family are human pregnane X receptor activators and inducers of CYP3A, CYP2B, and CYP2C in human hepatocytes. Drug Metab Dispos. 2001 Oct;29(10):1325-31. [Article]
Ramachandran SD, Vivares A, Klieber S, Hewitt NJ, Muenst B, Heinz S, Walles H, Braspenning J: Applicability of second-generation upcyte(R) human hepatocytes for use in CYP inhibition and induction studies. Pharmacol Res Perspect. 2015 Oct;3(5):e00161. doi: 10.1002/prp2.161. Epub 2015 Aug 10. [Article]

Details8. Cytochrome P450 2E1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable)
Specific Function: 4-nitrophenol 2-monooxygenase activity
Gene Name: CYP2E1
Uniprot ID: P05181
Uniprot Name: Cytochrome P450 2E1
Molecular Weight: 56848.42 Da

References

Katoh M, Nakajima M, Shimada N, Yamazaki H, Yokoi T: Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol. 2000 Feb-Mar;55(11-12):843-52. [Article]

Details9. Cytochrome P450 2C9

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor
Inducer

General Function: A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
Specific Function: (R)-limonene 6-monooxygenase activity
Gene Name: CYP2C9
Uniprot ID: P11712
Uniprot Name: Cytochrome P450 2C9
Molecular Weight: 55627.365 Da

References

Ma B, Prueksaritanont T, Lin JH: Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30. [Article]
Drocourt L, Pascussi JM, Assenat E, Fabre JM, Maurel P, Vilarem MJ: Calcium channel modulators of the dihydropyridine family are human pregnane X receptor activators and inducers of CYP3A, CYP2B, and CYP2C in human hepatocytes. Drug Metab Dispos. 2001 Oct;29(10):1325-31. [Article]

Details10. Cytochrome P450 3A5

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
Specific Function: aromatase activity
Gene Name: CYP3A5
Uniprot ID: P20815
Uniprot Name: Cytochrome P450 3A5
Molecular Weight: 57108.065 Da

References

Patki KC, Von Moltke LL, Greenblatt DJ: In vitro metabolism of midazolam, triazolam, nifedipine, and testosterone by human liver microsomes and recombinant cytochromes p450: role of cyp3a4 and cyp3a5. Drug Metab Dispos. 2003 Jul;31(7):938-44. [Article]

Carriers

Details1. Albumin

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Binder

General Function: Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
Specific Function: antioxidant activity
Gene Name: ALB
Uniprot ID: P02768
Uniprot Name: Albumin
Molecular Weight: 69365.94 Da

References

Otto J, Lesko LJ: Protein binding of nifedipine. J Pharm Pharmacol. 1986 May;38(5):399-400. doi: 10.1111/j.2042-7158.1986.tb04598.x. [Article]

Details2. alpha1-acid glycoprotein (Protein Group)

Kind: Protein group
Organism: Humans
Pharmacological action: Unknown
Actions: Binder

General Function: Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction
Specific Function: Not Available

Components:

Name	UniProt ID
Alpha-1-acid glycoprotein 1	P02763
Alpha-1-acid glycoprotein 2	P19652

References

Otto J, Lesko LJ: Protein binding of nifedipine. J Pharm Pharmacol. 1986 May;38(5):399-400. doi: 10.1111/j.2042-7158.1986.tb04598.x. [Article]

Transporters

Details1. ATP-binding cassette sub-family C member 3

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inducer

General Function: ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes (PubMed:10359813, PubMed:11581266, PubMed:15083066). Transports glucuronide conjugates such as bilirubin diglucuronide, estradiol-17-beta-o-glucuronide and GSH conjugates such as leukotriene C4 (LTC4) (PubMed:11581266, PubMed:15083066). Transports also various bile salts (taurocholate, glycocholate, taurochenodeoxycholate-3-sulfate, taurolithocholate- 3-sulfate) (By similarity). Does not contribute substantially to bile salt physiology but provides an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes (By similarity). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can confer resistance to various anticancer drugs, methotrexate, tenoposide and etoposide, by decreasing accumulation of these drugs in cells (PubMed:10359813, PubMed:11581266)
Specific Function: ABC-type bile acid transporter activity
Gene Name: ABCC3
Uniprot ID: O15438
Uniprot Name: ATP-binding cassette sub-family C member 3
Molecular Weight: 169341.14 Da

References

Teng S, Jekerle V, Piquette-Miller M: Induction of ABCC3 (MRP3) by pregnane X receptor activators. Drug Metab Dispos. 2003 Nov;31(11):1296-9. [Article]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	113000	N/A	N/A	A15871

Details2. ATP-dependent translocase ABCB1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inducer

General Function: Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
Specific Function: ABC-type xenobiotic transporter activity
Gene Name: ABCB1
Uniprot ID: P08183
Uniprot Name: ATP-dependent translocase ABCB1
Molecular Weight: 141477.255 Da

References

Takara K, Sakaeda T, Tanigawara Y, Nishiguchi K, Ohmoto N, Horinouchi M, Komada F, Ohnishi N, Yokoyama T, Okumura K: Effects of 12 Ca2+ antagonists on multidrug resistance, MDR1-mediated transport and MDR1 mRNA expression. Eur J Pharm Sci. 2002 Aug;16(3):159-65. [Article]
Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. [Article]

Details3. ATP-binding cassette sub-family C member 2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inducer

General Function: ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes. Transports a wide variety of conjugated organic anions such as sulfate-, glucuronide- and glutathione (GSH)-conjugates of endo- and xenobiotics substrates (PubMed:10220572, PubMed:10421658, PubMed:11500505, PubMed:16332456). Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification (PubMed:10421658). Mediates also hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4 (PubMed:11500505). Transports sulfated bile salt such as taurolithocholate sulfate (PubMed:16332456). Transports various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors (PubMed:10220572, PubMed:11500505, PubMed:12441801). Confers resistance to several anti-cancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine (PubMed:10220572, PubMed:11500505)
Specific Function: ABC-type glutathione S-conjugate transporter activity
Gene Name: ABCC2
Uniprot ID: Q92887
Uniprot Name: ATP-binding cassette sub-family C member 2
Molecular Weight: 174205.64 Da

References

Payen L, Sparfel L, Courtois A, Vernhet L, Guillouzo A, Fardel O: The drug efflux pump MRP2: regulation of expression in physiopathological situations and by endogenous and exogenous compounds. Cell Biol Toxicol. 2002;18(4):221-33. [Article]

Details4. Solute carrier organic anion transporter family member 1B1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) (PubMed:10358072, PubMed:10601278, PubMed:10873595, PubMed:11159893, PubMed:12196548, PubMed:12568656, PubMed:15159445, PubMed:15970799, PubMed:16627748, PubMed:17412826, PubMed:19129463, PubMed:26979622). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Involved in the clearance of endogenous and exogenous substrates from the liver (PubMed:10358072, PubMed:10601278). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:10601278, PubMed:15159445, PubMed:15970799). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748). Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463)
Specific Function: bile acid transmembrane transporter activity
Gene Name: SLCO1B1
Uniprot ID: Q9Y6L6
Uniprot Name: Solute carrier organic anion transporter family member 1B1
Molecular Weight: 76447.99 Da

References

Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [Article]

Details5. Bile salt export pump

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Inhibitor

General Function: Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner (PubMed:15791618, PubMed:16332456, PubMed:18985798, PubMed:19228692, PubMed:20010382, PubMed:20398791, PubMed:22262466, PubMed:24711118, PubMed:29507376, PubMed:32203132). Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts (PubMed:16332456). Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion (PubMed:15901796, PubMed:18245269)
Specific Function: ABC-type bile acid transporter activity
Gene Name: ABCB11
Uniprot ID: O95342
Uniprot Name: Bile salt export pump
Molecular Weight: 146405.83 Da

References

Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [Article]
Stieger B: Role of the bile salt export pump, BSEP, in acquired forms of cholestasis. Drug Metab Rev. 2010 Aug;42(3):437-45. doi: 10.3109/03602530903492004. [Article]

Drug created at June 13, 2005 13:24 / Updated at October 21, 2024 12:39

Nifedipine

Identification

Structure for Nifedipine (DB01115)

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Clinical Trial & Rare Diseases Add-on Data Package

Pharmacoeconomics

Properties

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Collision Cross Sections (CCS)

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