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Identification
- Summary
Grazoprevir is an antiviral and NS3/4A protease inhibitor used to treat hepatitis C infections.
- Brand Names
- Zepatier
- Generic Name
- Grazoprevir
- DrugBank Accession Number
- DB11575
- Background
Grazoprevir is a direct acting antiviral medication used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients 6. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as Grazoprevir. Grazoprevir is an inhibitor of NS3/4A, a serine protease enzyme, encoded by HCV genotypes 1 and 4 Synthesis. These enzymes are essential for viral replication and serve to cleave the virally encoded polyprotein into mature proteins like NS3, NS4A, NS4B, NS5A and NS5B Label. The barrier for develoment of resistance to NS3/4A inhibitors is lower than that of NS5B inhibitors, another class of DAAs 4. Subtitutions at amino acid positions 155, 156, or 168 are known to confer resistance. The substitutions of the enzyme's catalytic triad consisting of H58, D82, and S139 are also likely to alter the affinity of the drug for NS3/4A or the activity of the enzyme itself. Despite this disadvantage Grazoprevir is still effective against HCV particularly when paired with Elbasvir.
In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommend Grazoprevir as first line therapy in combination with Elbasvir for genotypes 1a, 1b, and 4 of Hepatitis C 4. Grazoprevir and Elbasvir are used with or without Ribavirin with the intent to cure, or achieve a sustained virologic response (SVR), after 12 weeks of daily therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality 5.
Grazoprevir is available as a fixed dose combination product with Elbasvir (tradename Zepatier) used for the treatment of chronic Hepatitis C. Approved in January 2016 by the FDA, Zepatier is indicated for the treatment of HCV genotypes 1 and 4 with or without Ribavirin depending on the the presence of resistance associated amino acid substitutions in the NS5A protein and previous treatment failure with Ribavirin, Peginterferon alfa-2a, Peginterferon alfa-2b, or other NS3/4A inhibitors like Boceprevir, Simeprevir, or Telaprevir Label. When combined together, Grazoprevir and Elbasvir as the combination product Zepatier have been shown to achieve a SVR between 94% and 97% for genotype 1 and 97% and 100% for genotype 4 after 12 weeks of treatment 6. It can be used in patients with compensated cirrhosis, human immunodeficiency virus co-infection, or severe kidney disease.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Grazoprevir (DB11575)
- Weight
- Average: 766.903
Monoisotopic: 766.335997918 - Chemical Formula
- C38H50N6O9S
- Synonyms
- Grazoprevir
- Grazoprevir anhydrous
- External IDs
- MK 5172
- MK-5172
- MK5172
Pharmacology
- Indication
Grazoprevir is indicated in combination with Elbasvir (as the fixed dose combination product Zepatier) with or without Ribavirin for treatment of chronic HCV genotypes 1a, 1b, or 4 infection in adults.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Chronic hepatitis c genotype 1 Combination Product in combination with: Elbasvir (DB11574) •••••••••••• ••••••••••• ••••• •••• •••••• •• •• ••••• •• •• •••••• Used in combination to treat Chronic hepatitis c genotype 1a Combination Product in combination with: Elbasvir (DB11574), Ribavirin (DB00811) •••••••••••• ••••••••••• ••••• •••• •••••• •• •• ••••• •• •• •••••• Used in combination to treat Genotype 4 chronic hepatitis c Combination Product in combination with: Ribavirin (DB00811), Elbasvir (DB11574) •••••••••••• ••••••••••• ••••• •••• •••••• •• •• ••••• •• ••• •••••••••••••• ••••••••• ••••••••••• •••••• Used in combination to treat Genotype 4 chronic hepatitis c Combination Product in combination with: Elbasvir (DB11574) •••••••••••• ••••••••••• ••••• •••• •••••• •• •• ••••• •• •• •••••• - Contraindications & Blackbox Warnings
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Grazoprevir is classified as a direct-acting antiviral (DAA) and prevents viral replication in HCV genotypes 1a, 1b, and 4 Label.
- Mechanism of action
Grazoprevir is a second generation NS3/4a protease inhibitor used to inhibit viral HCV replication. NS3/4a protease is an integral part of viral replication and mediates the cleavage the virally encoded polyprotein to mature proteins (NS3, NS4A, NS4B, NS5A and NS5B) Label. Grazoprevir inhibits the NS3/4protease enzymes of HCV genotype 1a, 1B, and 4 with IC50 values of 7pM, 4pM, and 62pM, respectively.
Target Actions Organism AGenome polyprotein antagonistHepatitis C Virus - Absorption
Grazoprevir reaches peak plasma concentration 0.5-3 hours after administration Label. Grazoprevir has an absolute bioavailability of 27%. When taken with food the peak concentration of Grazoprevir increases 2.8 fold but this increase in exposure has not been deemed clinically relevant.
- Volume of distribution
Grazoprevir has an estimated apparent volume of distribution of 1250 liters Label. It is thought to distribute primarily to the liver with its uptake facilitated by organic anion transporting polypeptide 1B1/3.
- Protein binding
Grazoprevir is more than 98.8% bound to plasma proteins Label. It binds both human serum albumin and α1-acid glycoprotein.
- Metabolism
Grazoprevir is partially eliminated by oxidative metabolism meditated by CYP3A Label. No circulating metabolites of have been detected in human plasma.
- Route of elimination
Grazoprevir is mainly eliminated in the feces (90%) with very little eliminated in the urine (<1%) Label.
- Half-life
The geometric mean apparent terminal half-life for Grazoprevir is 31 hours in HCV-infected subjects Label.
- Clearance
The clearance of Grazoprevir has not been determined Label.
- Adverse Effects
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The most commonly reported adverse reactions of all intensity (greater than or equal to 5% in placebo-controlled trials) were fatigue, headache, and nausea Label.
- Pathways
- Not Available
- 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 Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Grazoprevir can be increased when it is combined with Abametapir. Abemaciclib Grazoprevir may decrease the excretion rate of Abemaciclib which could result in a higher serum level. Abrocitinib The serum concentration of Grazoprevir can be increased when it is combined with Abrocitinib. Acetylcysteine The excretion of Grazoprevir can be decreased when combined with Acetylcysteine. Adagrasib The serum concentration of Grazoprevir can be increased when it is combined with Adagrasib. - Food Interactions
- Take with or without food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Grazoprevir monohydrate 4O2AB118LA 1350462-55-3 RXSARIJMSJWJLZ-CIAYNJNFSA-N - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image ZEPATIER Grazoprevir (100 MG) + Elbasvir (50 MG) Tablet, film coated Oral Merck Sharp & Dohme B.V. 2016-11-10 Not applicable Italy 
ZEPATIER Grazoprevir (100 MG) + Elbasvir (50 MG) Tablet, film coated Oral บริษัท เอ็มเอสดี (ประเทศไทย) จำกัด 2017-06-09 2020-08-13 Thailand 
Zepatier Grazoprevir (100 mg) + Elbasvir (50 mg) Tablet, film coated Oral Merck Sharp & Dohme B.V. 2016-09-08 Not applicable EU 
Zepatier Grazoprevir (100 mg) + Elbasvir (50 mg) Tablet Oral Merck Ltd. 2016-01-25 2022-08-16 Canada 
Zepatier Grazoprevir (100 mg/1) + Elbasvir (50 mg/1) Tablet, film coated Oral Merck Sharp & Dohme LLC 2016-01-28 Not applicable US 
Categories
- ATC Codes
- J05AP11 — Grazoprevir
- J05AP — Antivirals for treatment of HCV infections
- J05A — DIRECT ACTING ANTIVIRALS
- J05 — ANTIVIRALS FOR SYSTEMIC USE
- J — ANTIINFECTIVES FOR SYSTEMIC USE
- Drug Categories
- Acids, Acyclic
- Amides
- Anti-Infective Agents
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- Antivirals for treatment of HCV infections
- BCRP/ABCG2 Inhibitors
- Cycloparaffins
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (weak)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Direct Acting Antivirals
- HCV NS3/4A Protease Inhibitors
- Heterocyclic Compounds, Fused-Ring
- Lactams
- NS3/4A Protease Inhibitors
- OATP1B1/SLCO1B1 Substrates
- OATP1B3 substrates
- P-glycoprotein substrates
- Sulfones
- Sulfur Compounds
- Treatments for Hepatitis C
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as cyclic peptides. These are compounds containing a cyclic moiety bearing a peptide backbone.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Cyclic peptides
- Alternative Parents
- Macrolactams / N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / Quinoxalines / Pyrrolidinecarboxamides / Anisoles / Alkyl aryl ethers / Cyclopropanecarboxylic acids and derivatives / Pyrazines / Heteroaromatic compounds show 14 more
- Substituents
- Alkyl aryl ether / Alpha-amino acid amide / Alpha-amino acid or derivatives / Aminosulfonyl compound / Anisole / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carbamic acid ester / Carbonic acid derivative show 30 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Hepatitis C Virus
Chemical Identifiers
- UNII
- 8YE81R1X1J
- CAS number
- 1350514-68-9
- InChI Key
- OBMNJSNZOWALQB-NCQNOWPTSA-N
- InChI
- InChI=1S/C38H50N6O9S/c1-6-22-19-38(22,35(47)43-54(49,50)25-13-14-25)42-32(45)29-18-24-20-44(29)34(46)31(37(2,3)4)41-36(48)53-30-16-21(30)10-8-7-9-11-27-33(52-24)40-28-17-23(51-5)12-15-26(28)39-27/h6,12,15,17,21-22,24-25,29-31H,1,7-11,13-14,16,18-20H2,2-5H3,(H,41,48)(H,42,45)(H,43,47)/t21-,22-,24-,29+,30-,31-,38-/m1/s1
- IUPAC Name
- (1R,18R,20R,24S,27S)-24-tert-butyl-N-[(1R,2S)-1-[(cyclopropanesulfonyl)carbamoyl]-2-ethenylcyclopropyl]-7-methoxy-22,25-dioxo-2,21-dioxa-4,11,23,26-tetraazapentacyclo[24.2.1.0^{3,12}.0^{5,10}.0^{18,20}]nonacosa-3(12),4,6,8,10-pentaene-27-carboxamide
- SMILES
- COC1=CC2=NC3=C(CCCCC[C@@H]4C[C@H]4OC(=O)N[C@H](C(=O)N4C[C@@H](C[C@H]4C(=O)N[C@@]4(C[C@H]4C=C)C(=O)NS(=O)(=O)C4CC4)O3)C(C)(C)C)N=C2C=C1
References
- Synthesis Reference
Harper S, McCauley JA, Rudd MT, Ferrara M, DiFilippo M, Crescenzi B, Koch U, Petrocchi A, Holloway MK, Butcher JW, Romano JJ, Bush KJ, Gilbert KF, McIntyre CJ, Nguyen KT, Nizi E, Carroll SS, Ludmerer SW, Burlein C, DiMuzio JM, Graham DJ, McHale CM, Stahlhut MW, Olsen DB, Monteagudo E, Cianetti S, Giuliano C, Pucci V, Trainor N, Fandozzi CM, Rowley M, Coleman PJ, Vacca JP, Summa V, Liverton NJ: Discovery of MK-5172, a Macrocyclic Hepatitis C Virus NS3/4a Protease Inhibitor. ACS Med Chem Lett. 2012 Mar 2;3(4):332-6. doi: 10.1021/ml300017p. eCollection 2012 Apr 12.
- General References
- Gentile I, Buonomo AR, Borgia F, Zappulo E, Castaldo G, Borgia G: MK-5172 : a second-generation protease inhibitor for the treatment of hepatitis C virus infection. Expert Opin Investig Drugs. 2014 May;23(5):719-28. doi: 10.1517/13543784.2014.902049. Epub 2014 Mar 26. [Article]
- Harper S, McCauley JA, Rudd MT, Ferrara M, DiFilippo M, Crescenzi B, Koch U, Petrocchi A, Holloway MK, Butcher JW, Romano JJ, Bush KJ, Gilbert KF, McIntyre CJ, Nguyen KT, Nizi E, Carroll SS, Ludmerer SW, Burlein C, DiMuzio JM, Graham DJ, McHale CM, Stahlhut MW, Olsen DB, Monteagudo E, Cianetti S, Giuliano C, Pucci V, Trainor N, Fandozzi CM, Rowley M, Coleman PJ, Vacca JP, Summa V, Liverton NJ: Discovery of MK-5172, a Macrocyclic Hepatitis C Virus NS3/4a Protease Inhibitor. ACS Med Chem Lett. 2012 Mar 2;3(4):332-6. doi: 10.1021/ml300017p. eCollection 2012 Apr 12. [Article]
- Summa V, Ludmerer SW, McCauley JA, Fandozzi C, Burlein C, Claudio G, Coleman PJ, Dimuzio JM, Ferrara M, Di Filippo M, Gates AT, Graham DJ, Harper S, Hazuda DJ, Huang Q, McHale C, Monteagudo E, Pucci V, Rowley M, Rudd MT, Soriano A, Stahlhut MW, Vacca JP, Olsen DB, Liverton NJ, Carroll SS: MK-5172, a selective inhibitor of hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants. Antimicrob Agents Chemother. 2012 Aug;56(8):4161-7. doi: 10.1128/AAC.00324-12. Epub 2012 May 21. [Article]
- Bagaglio S, Uberti-Foppa C, Morsica G: Resistance Mechanisms in Hepatitis C Virus: implications for Direct-Acting Antiviral Use. Drugs. 2017 May 12. doi: 10.1007/s40265-017-0753-x. [Article]
- Myers RP, Shah H, Burak KW, Cooper C, Feld JJ: An update on the management of chronic hepatitis C: 2015 Consensus guidelines from the Canadian Association for the Study of the Liver. Can J Gastroenterol Hepatol. 2015 Jan-Feb;29(1):19-34. Epub 2015 Jan 13. [Article]
- American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance. http://hcvguidelines.org. Accessed June 12, 2017. [Link]
- FDA Approved Drug Products: ZEPATIER (elbasvir and grazoprevir) tablets, for oral use [Link]
- External Links
- KEGG Drug
- D10639
- PubChem Compound
- 44603531
- PubChem Substance
- 347827989
- ChemSpider
- 28506694
- BindingDB
- 50485492
- 1734630
- ChEBI
- 132975
- ChEMBL
- CHEMBL2063090
- ZINC
- ZINC000095551509
- PharmGKB
- PA166163437
- PDBe Ligand
- SUE
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Grazoprevir
- PDB Entries
- 3sud / 3sue / 3suf / 3sug / 6c2m / 6p6q
- FDA label
- Download (441 KB)
- MSDS
- Download (175 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data4 Completed Basic Science Cardiovascular Disease (CVD) / Hepatitis C Virus (HCV) Infection / Human Immunodeficiency Virus (HIV) Infections 1 somestatus stop reason just information to hide 4 Completed Prevention Kidney Failure 1 somestatus stop reason just information to hide 4 Completed Treatment Chronic Hepatitis C Virus (HCV) Infection 2 somestatus stop reason just information to hide 4 Completed Treatment Chronic Kidney Disease, Stage 3 (Moderate) / Hepatitis C Virus (HCV) Infection 1 somestatus stop reason just information to hide 4 Completed Treatment Disorder of Transplanted Kidney / Hepatitis C Virus (HCV) Infection / Renal Insufficiency,Chronic 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral Tablet, film coated Oral Tablet, coated Oral Tablet, film coated Oral 50.00 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8871759 No 2014-10-28 2031-05-04 US US7973040 No 2011-07-05 2029-07-24 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0108 mg/mL ALOGPS logP 3.26 ALOGPS logP 3.35 Chemaxon logS -4.8 ALOGPS pKa (Strongest Acidic) 3.77 Chemaxon pKa (Strongest Basic) 1.79 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 10 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 195.22 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 193.61 m3·mol-1 Chemaxon Polarizability 79.37 Å3 Chemaxon Number of Rings 7 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 232.52275 predictedDeepCCS 1.0 (2019) [M+H]+ 234.24648 predictedDeepCCS 1.0 (2019) [M+Na]+ 240.48851 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Hepatitis C Virus
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Serine-type peptidase activity
- Specific Function
- Not Available
- Gene Name
- NS3/4A
- Uniprot ID
- B0B3C9
- Uniprot Name
- Genome polyprotein
- Molecular Weight
- 72789.28 Da
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- 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
- Zepatier FDA label [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- 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
- Gene Name
- ORM1
- Uniprot ID
- P02763
- Uniprot Name
- Alpha-1-acid glycoprotein 1
- Molecular Weight
- 23539.43 Da
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10779507, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) (PubMed:10779507, PubMed:11159893, PubMed:12568656, PubMed:15159445, PubMed:17412826, PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463). Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate 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). Involved in the clearance of bile acids and organic anions from the liver (PubMed:22232210). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). 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 pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:15159445). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel (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)
- Specific Function
- Bile acid transmembrane transporter activity
- Gene Name
- SLCO1B3
- Uniprot ID
- Q9NPD5
- Uniprot Name
- Solute carrier organic anion transporter family member 1B3
- Molecular Weight
- 77402.175 Da
Drug created at April 07, 2016 16:40 / Updated at March 24, 2022 01:23