Ertugliflozin
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Identification
- Summary
Ertugliflozin is an SGLT2 inhibitor used to treat type 2 diabetes mellitus alone or in combination with other antidiabetic drugs.
- Brand Names
- Segluromet, Steglatro, Steglujan
- Generic Name
- Ertugliflozin
- DrugBank Accession Number
- DB11827
- Background
Ertugliflozin is a sodium-dependent glucose cotransporter-2 (SGLT2) inhibitor used to treat type II diabetes mellitus. It works to block glucose reabsorption from the glomerulus.1
Ertugliflozin was first approved by the FDA in December 2017.5,6 It was also approved by the European Commission in March 2018.12
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 436.89
Monoisotopic: 436.1288808 - Chemical Formula
- C22H25ClO7
- Synonyms
- (1S,2S,3S,4R,5S)-5-(4-Chloro-3-(4-ethoxybenzyl)phenyl)-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol
- 1,6-Anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-5-C-(hydroxymethyl)-β-L-idopyranose
- Ertugliflozin
- β-L-Idopyranose, 1,6-anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-5-C-(hydroxymethyl)-
- External IDs
- MK-8835
- Pf 04971729
- PF-04971729
- PF-04971729-00
- PF04971729
Pharmacology
- Indication
Ertugliflozin is indicated as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus (T2DM).10 It is also available in combination with either metformin or sitagliptin.7,8
Ertugliflozin is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus.10
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used as adjunct in combination to manage Type 2 diabetes mellitus Combination Product in combination with: Metformin (DB00331) •••••••••••• ••••• •••••• Used as adjunct in combination to manage Type 2 diabetes mellitus Combination Product in combination with: Sitagliptin (DB01261) •••••••••••• ••••• •••••• Adjunct therapy in management of Type ii diabetes mellitus •••••••••••• ••••• ••••••••••••• ••••••••• ••••••• •••••• Adjunct therapy in management of Type ii diabetes mellitus •••••••••••• ••••• •••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Ertugliflozin causes a dose-dependent increase in urinary glucose excretion and an increase in urinary volume in patients with T2DM.3,10
- Mechanism of action
Kidneys play an integral role in glucose homeostasis. After being filtered into urine within the nephron, most of the plasma glucose is reabsorbed through two types of sodium-dependent glucose cotransporters (SGLTs), SGLT1 and SGLT2, expressed in proximal renal tubules.4 More specifically, SGLT2 is responsible for 80–90% of renal glucose reabsorption while SGLT1 is responsible for the remaining 10-20%.4 Under physiological conditions, less than one percent of glucose is excreted in urine.1,4 In the case of hyperglycemia, SGLTs become saturated and the renal threshold for urinary glucose excretion is increased. Kidneys respond to an elevated threshold for glycosuria by elevating glucose reabsorption and increasing maximum glucose reabsorptive capacity.4
Ertugliflozin is an inhibitor of SGLT2 that reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, thereby increasing urinary glucose excretion.10
Target Actions Organism ASodium/glucose cotransporter 2 inhibitorHumans - Absorption
After administering single doses of 5 mg and 15 mg ertugliflozin under fasted conditions, the median Tmax was one hour. Plasma Cmax and AUC of ertugliflozin increase dose-proportionally.10 Following administration of a 15 mg dose, the Cmax was 268 ng/mL and the AUC was 1193 ng h/mL.9 The absolute oral bioavailability of ertugliflozin following administration of a 15 mg dose was approximately 100%,10 though it is reported to range from 70% to 90%.2
Administration of ertugliflozin with a high-fat and high-calorie meal decreases ertugliflozin Cmax by 29%. It prolongs Tmax by one hour but does not alter AUC compared to the fasted state. The observed effect of food on ertugliflozin pharmacokinetics is not considered clinically relevant, and ertugliflozin may be administered with or without food.10
- Volume of distribution
The volume of distribution following oral administration was 215.3 L.9 The mean steady-state volume of distribution of ertugliflozin following an intravenous dose is 85.5 L.10
- Protein binding
Ertugliflozin is 93.6% bound to plasma proteins. Plasma protein binding is independent of ertugliflozin plasma concentrations and is not meaningfully altered in patients with renal or hepatic impairment. The blood-to-plasma concentration ratio of ertugliflozin is 0.66.10
- Metabolism
Ertugliflozin mainly undergoes O-glucuronidation mediated by UGT1A9 and UGT2B7 to form two pharmacologically inactive glucuronides. About 12% of the drug undergoes CYP-mediated oxidative metabolism.10 Several metabolites have been found in plasma, feces, and urine. In plasma, the unchanged form of ertugliflozin was found to be the major component of the administered dose.2
Hover over products below to view reaction partners
- Route of elimination
Following administration of an oral [14C]-ertugliflozin solution to healthy subjects, approximately 40.9% and 50.2% of the drug-related radioactivity was eliminated in feces and urine, respectively. Only 1.5% of the administered dose was excreted as unchanged ertugliflozin in urine and 33.8% as unchanged ertugliflozin in feces, which is likely due to biliary excretion of glucuronide metabolites and subsequent hydrolysis to form the parent compound.10
- Half-life
The terminal elimination half-life of ertugliflozin ranges from 11 to 17 hours.2 The mean elimination half-life in T2DM patients with normal renal function was estimated to be 16.6 hours based on the population pharmacokinetic analysis.10
- Clearance
In one clinical involving healthy males, the apparent total plasma clearance rate after oral administration of ertugliflozin was 178.7 mL/min and the systemic total plasma clearance after intravenous administration was 187.2 ml/min.9 In another study, the mean systemic plasma clearance following an intravenous 100 µg dose was 11.2 L/hr.10
- Adverse Effects
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- Toxicity
The oral LD50 is 500 mg/kg in rats.11 There are limited clinical experiences of ertugliflozin overdose. It is recommended to initiate supportive measures in the event of drug overdosage. Removal of ertugliflozin by hemodialysis has not been studied.10
- 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 softwareAcarbose Ertugliflozin may increase the hypoglycemic activities of Acarbose. Acebutolol The therapeutic efficacy of Ertugliflozin can be increased when used in combination with Acebutolol. Acetazolamide The therapeutic efficacy of Ertugliflozin can be increased when used in combination with Acetazolamide. Acetohexamide Ertugliflozin may increase the hypoglycemic activities of Acetohexamide. Acetyl sulfisoxazole The therapeutic efficacy of Ertugliflozin can be increased when used in combination with Acetyl sulfisoxazole. - Food Interactions
- Avoid excessive or chronic alcohol consumption. Alcohol abuse may increase the risk of ketoacidosis.
- Take with or without food. Food does not significantly affect drug pharmacokinetics. Take the drug the morning.
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 Ertugliflozin pidolate MLU731K321 1210344-83-4 YHIUPZFKHZTLSH-LXYIGGQGSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Steglatro Tablet, film coated 15 mg Oral Merck Sharp & Dohme B.V. 2020-12-16 Not applicable EU Steglatro Tablet, film coated 5 mg Oral Merck Sharp & Dohme B.V. 2020-12-16 Not applicable EU Steglatro Tablet, film coated 15 mg Oral Merck Sharp & Dohme B.V. 2020-12-16 Not applicable EU Steglatro Tablet, film coated 5 mg Oral Merck Sharp & Dohme B.V. 2020-12-16 Not applicable EU Steglatro Tablet, film coated 15 mg Oral Merck Sharp & Dohme B.V. 2020-12-16 Not applicable EU - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image SEGLUROMET Ertugliflozin (2.5 MG) + Metformin hydrochloride (1000 MG) Tablet, film coated Oral Merck Sharp & Dohme B.V. 2018-08-07 Not applicable Italy Segluromet Ertugliflozin pidolate (2.5 mg) + Metformin hydrochloride (850 mg) Tablet, film coated Oral Merck Sharp & Dohme B.V. 2020-12-16 Not applicable EU SEGLUROMET Ertugliflozin (7.5 MG) + Metformin hydrochloride (1000 MG) Tablet, film coated Oral Merck Sharp & Dohme B.V. 2018-08-07 Not applicable Italy Segluromet Ertugliflozin pidolate (7.5 mg) + Metformin hydrochloride (850 mg) Tablet, film coated Oral Merck Sharp & Dohme B.V. 2020-12-16 Not applicable EU SEGLUROMET Ertugliflozin (2.5 MG) + Metformin hydrochloride (1000 MG) Tablet, film coated Oral Merck Sharp & Dohme B.V. 2018-08-07 Not applicable Italy
Categories
- ATC Codes
- A10BD23 — Metformin and ertugliflozin
- A10BD — Combinations of oral blood glucose lowering drugs
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- A10BK — Sodium-glucose co-transporter 2 (SGLT2) inhibitors
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- Drug Categories
- Alimentary Tract and Metabolism
- BCRP/ABCG2 Substrates
- Blood Glucose Lowering Agents
- Diuretics
- Drugs Used in Diabetes
- P-glycoprotein substrates
- Sodium-glucose Cotransporter 2 (SGLT2) Inhibitors
- Sodium-Glucose Transporter 2 Inhibitors
- UGT1A1 Inhibitors
- UGT1A4 Inhibitors
- UGT1A9 Substrates
- UGT2B7 substrates
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Diphenylmethanes
- Direct Parent
- Diphenylmethanes
- Alternative Parents
- Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Oxepanes / Chlorobenzenes / Ketals / Oxanes / Aryl chlorides / Monosaccharides / 1,3-dioxolanes show 6 more
- Substituents
- Acetal / Alcohol / Alkyl aryl ether / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Chlorobenzene / Diphenylmethane / Ether / Halobenzene show 17 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 6C282481IP
- CAS number
- 1210344-57-2
- InChI Key
- MCIACXAZCBVDEE-CUUWFGFTSA-N
- InChI
- InChI=1S/C22H25ClO7/c1-2-28-16-6-3-13(4-7-16)9-14-10-15(5-8-17(14)23)22-20(27)18(25)19(26)21(11-24,30-22)12-29-22/h3-8,10,18-20,24-27H,2,9,11-12H2,1H3/t18-,19-,20+,21-,22-/m0/s1
- IUPAC Name
- (1S,2S,3S,4R,5S)-5-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol
- SMILES
- CCOC1=CC=C(CC2=CC(=CC=C2Cl)[C@]23OC[C@](CO)(O2)[C@@H](O)[C@H](O)[C@H]3O)C=C1
References
- General References
- Miao Z, Nucci G, Amin N, Sharma R, Mascitti V, Tugnait M, Vaz AD, Callegari E, Kalgutkar AS: Pharmacokinetics, metabolism, and excretion of the antidiabetic agent ertugliflozin (PF-04971729) in healthy male subjects. Drug Metab Dispos. 2013 Feb;41(2):445-56. doi: 10.1124/dmd.112.049551. Epub 2012 Nov 20. [Article]
- Abdul-Ghani MA, DeFronzo RA: Inhibition of renal glucose reabsorption: a novel strategy for achieving glucose control in type 2 diabetes mellitus. Endocr Pract. 2008 Sep;14(6):782-90. doi: 10.4158/EP.14.6.782. [Article]
- Kalgutkar AS, Tugnait M, Zhu T, Kimoto E, Miao Z, Mascitti V, Yang X, Tan B, Walsky RL, Chupka J, Feng B, Robinson RP: Preclinical species and human disposition of PF-04971729, a selective inhibitor of the sodium-dependent glucose cotransporter 2 and clinical candidate for the treatment of type 2 diabetes mellitus. Drug Metab Dispos. 2011 Sep;39(9):1609-19. doi: 10.1124/dmd.111.040675. Epub 2011 Jun 20. [Article]
- Cinti F, Moffa S, Impronta F, Cefalo CM, Sun VA, Sorice GP, Mezza T, Giaccari A: Spotlight on ertugliflozin and its potential in the treatment of type 2 diabetes: evidence to date. Drug Des Devel Ther. 2017 Oct 3;11:2905-2919. doi: 10.2147/DDDT.S114932. eCollection 2017. [Article]
- Markham A: Ertugliflozin: First Global Approval. Drugs. 2018 Mar;78(4):513-519. doi: 10.1007/s40265-018-0878-6. [Article]
- Pfizer: FDA Approves SGLT2 Inhibitor STEGLATRO™ (ertugliflozin) and Fixed-Dose Combination STEGLUJAN™ (ertugliflozin and sitagliptin) for Adults with Type 2 Diabetes [Link]
- FDA Approved Drug Products: Segluromet (ertugliflozin and metformin hydrochloride) tablets for oral use [Link]
- FDA Approved Drug Products: Steglujan (ertugliflozin and sitagliptin) tablets for oral use [Link]
- ClinicalTrials.gov: A Phase 1 Study of Ertugliflozin in Healthy Male Participants (MK-8835-020) [Link]
- FDA Approved Drug Products: STEGLATRO (ertugliflozin) tablets, for oral use (September 2023) [Link]
- MSD: Ertugliflozin MSDS [Link]
- EMA Approved Drug Products: STEGLATRO (ertugliflozin) Oral Tablets [Link]
- External Links
- PubChem Compound
- 44814423
- PubChem Substance
- 347828173
- ChemSpider
- 26340533
- BindingDB
- 50342885
- 1992672
- ChEBI
- 188719
- ChEMBL
- CHEMBL1770248
- ZINC
- ZINC000068197809
- PharmGKB
- PA166269521
- Wikipedia
- Ertugliflozin
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 dataNot Available Recruiting Not Available Myocardial Infarction / Type 2 Diabetes Mellitus 1 somestatus stop reason just information to hide Not Available Unknown Status Not Available Cardiovascular Events / Kidney Diseases / Type 2 Diabetes Mellitus 1 somestatus stop reason just information to hide Not Available Unknown Status Not Available Type 2 Diabetes Mellitus 1 somestatus stop reason just information to hide 4 Active Not Recruiting Treatment Coronavirus Disease 2019 (COVID‑19) 1 somestatus stop reason just information to hide 4 Completed Prevention Diabetic Kidney Disease (DKD) / Diabetic Nephropathy / Ertugliflozin / Kidney Hypoxia / Renoprotection / SGLT 2 Inhibitors / Type 2 Diabetes Mellitus 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral Tablet Oral 15 mg Tablet Oral 5 mg Tablet, film coated Oral 15 mg/1 Tablet, film coated Oral 5 mg/1 Tablet, film coated Oral Tablet, film coated Oral 15 mg Tablet, film coated Oral 5 mg Tablet, coated Oral Tablet, coated Oral 15 mg Tablet, coated Oral 5 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7326708 Yes 2008-02-05 2027-05-24 US US6699871 Yes 2004-03-02 2023-01-26 US US6890898 No 2005-05-10 2019-02-02 US US7078381 No 2006-07-18 2019-02-02 US US7459428 No 2008-12-02 2019-02-02 US US8080580 No 2011-12-20 2030-07-13 US US9439902 No 2016-09-13 2030-10-21 US US9439901 No 2016-09-13 2030-10-21 US US9308204 No 2016-04-12 2030-10-21 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.119 mg/mL ALOGPS logP 2.21 ALOGPS logP 2.32 Chemaxon logS -3.6 ALOGPS pKa (Strongest Acidic) 11.98 Chemaxon pKa (Strongest Basic) -3.1 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 108.61 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 109.07 m3·mol-1 Chemaxon Polarizability 44.95 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-000i-0001900000-ccc7b58f2866e09aa7ad Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-000i-0003900000-f23d448b27a3f152b544 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-000i-0104900000-a1d955d403bfa69c3a96 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0569-6009500000-dcf6ba56b71e5eac538d Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-00ks-1248900000-c65926e042a352ba73c1 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0a5l-9037700000-09725bd7e490ac2a6061 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]- 195.2837 predictedDeepCCS 1.0 (2019) [M+H]+ 197.67929 predictedDeepCCS 1.0 (2019) [M+Na]+ 204.20786 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose at the plasma membrane, with a Na(+) to sugar coupling ratio of 1:1. Transporter activity is driven by a transmembrane Na(+) electrochemical gradient set by the Na(+)/K(+) pump (PubMed:20980548, PubMed:28592437, PubMed:34880493). Has a primary role in D-glucose reabsorption from glomerular filtrate across the brush border of the early proximal tubules of the kidney (By similarity)
- Specific Function
- alpha-glucoside transmembrane transporter activity
- Gene Name
- SLC5A2
- Uniprot ID
- P31639
- Uniprot Name
- Sodium/glucose cotransporter 2
- Molecular Weight
- 72895.995 Da
References
- Miao Z, Nucci G, Amin N, Sharma R, Mascitti V, Tugnait M, Vaz AD, Callegari E, Kalgutkar AS: Pharmacokinetics, metabolism, and excretion of the antidiabetic agent ertugliflozin (PF-04971729) in healthy male subjects. Drug Metab Dispos. 2013 Feb;41(2):445-56. doi: 10.1124/dmd.112.049551. Epub 2012 Nov 20. [Article]
- FDA Approved Drug Products: STEGLATRO (ertugliflozin) tablets, for oral use (September 2023) [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15470161, PubMed:15472229, PubMed:18004212, PubMed:18052087, PubMed:18674515, PubMed:19545173). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol and estrone (PubMed:15472229). Also catalyzes the glucuronidation of the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist caderastan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:20610558). Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161, PubMed:18004212)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A9
- Uniprot ID
- O60656
- Uniprot Name
- UDP-glucuronosyltransferase 1A9
- Molecular Weight
- 59940.495 Da
References
- Sahasrabudhe V, Terra SG, Hickman A, Saur D, Shi H, O'Gorman M, Zhou Z, Cutler DL: The Effect of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of Ertugliflozin in Subjects With Type 2 Diabetes Mellitus. J Clin Pharmacol. 2017 Nov;57(11):1432-1443. doi: 10.1002/jcph.955. Epub 2017 Jul 13. [Article]
- FDA Approved Drug Products: STEGLATRO (ertugliflozin) tablets, for oral use (September 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:10702251, PubMed:15470161, PubMed:15472229, PubMed:17442341, PubMed:18674515, PubMed:18719240, PubMed:19022937, PubMed:23288867, PubMed:23756265, PubMed:26220143). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:15470161, PubMed:18674515, PubMed:23756265). Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (epitestosterone, androsterone) and estrogens (estradiol, epiestradiol, estriol, catechol estrogens) (PubMed:15472229, PubMed:17442341, PubMed:18719240, PubMed:19022937, PubMed:2159463, PubMed:23288867, PubMed:26220143). Also regulates the levels of retinoic acid, a major metabolite of vitamin A involved in apoptosis, cellular growth and differentiation, and embryonic development (PubMed:10702251). Contributes to bile acid (BA) detoxification by catalyzing the glucuronidation of BA substrates, which are natural detergents for dietary lipids absorption (PubMed:23756265). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, caderastan and zolarsatan, drugs which can inhibit the effect of angiotensin II (PubMed:18674515). Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161)
- Specific Function
- glucuronosyltransferase activity
- Gene Name
- UGT2B7
- Uniprot ID
- P16662
- Uniprot Name
- UDP-glucuronosyltransferase 2B7
- Molecular Weight
- 60720.15 Da
References
- Sahasrabudhe V, Terra SG, Hickman A, Saur D, Shi H, O'Gorman M, Zhou Z, Cutler DL: The Effect of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of Ertugliflozin in Subjects With Type 2 Diabetes Mellitus. J Clin Pharmacol. 2017 Nov;57(11):1432-1443. doi: 10.1002/jcph.955. Epub 2017 Jul 13. [Article]
- FDA Approved Drug Products: STEGLATRO (ertugliflozin) tablets, for oral use (September 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- Curator comments
- Ertugliflozin is a weak inhibitor of this enzyme in vitro, with an IC50 of >39 µM.
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15472229, PubMed:18004206, PubMed:18004212, PubMed:18719240, PubMed:19830808, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004206, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (PubMed:15472229, PubMed:18719240, PubMed:23288867). Involved in the glucuronidation of bilirubin, a degradation product occurring in the normal catabolic pathway that breaks down heme in vertebrates (PubMed:17187418, PubMed:18004206, PubMed:19830808, PubMed:24525562). Also catalyzes the glucuronidation the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:18004212, PubMed:20610558)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A1
- Uniprot ID
- P22309
- Uniprot Name
- UDP-glucuronosyltransferase 1A1
- Molecular Weight
- 59590.91 Da
References
- FDA Approved Drug Products: STEGLATRO (ertugliflozin) tablets, for oral use (September 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- Curator comments
- Ertugliflozin is a weak inhibitor of this enzyme in vitro, with an IC50 of >39 µM.
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:18177842, PubMed:24641623). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:18177842). Involved in the glucuronidation of calcidiol, which is the major circulating form of vitamin D3 essential for the regulation of calcium and phosphate homeostasis (PubMed:24641623). Also glucuronidates the biologically active form of vitamin D3, calcitriol, probably leading to its biliary transport and intestinal reabsorption (PubMed:18177842)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A4
- Uniprot ID
- P22310
- Uniprot Name
- UDP-glucuronosyltransferase 1A4
- Molecular Weight
- 60024.535 Da
References
- FDA Approved Drug Products: STEGLATRO (ertugliflozin) tablets, for oral use (September 2023) [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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
- Cinti F, Moffa S, Impronta F, Cefalo CM, Sun VA, Sorice GP, Mezza T, Giaccari A: Spotlight on ertugliflozin and its potential in the treatment of type 2 diabetes: evidence to date. Drug Des Devel Ther. 2017 Oct 3;11:2905-2919. doi: 10.2147/DDDT.S114932. eCollection 2017. [Article]
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
References
- FDA Approved Drug Products: STEGLATRO (ertugliflozin) tablets, for oral use (September 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
References
- FDA Approved Drug Products: STEGLATRO (ertugliflozin) tablets, for oral use (September 2023) [Link]
Drug created at October 20, 2016 20:51 / Updated at November 03, 2024 19:35