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Identification
- Summary
Bempedoic acid is a drug used in conjunction with lifestyle modification and/or other agents for the treatment of refractory hypercholesterolemia.
- Brand Names
- Nexletol, Nexlizet
- Generic Name
- Bempedoic acid
- DrugBank Accession Number
- DB11936
- Background
High levels of LDL cholesterol (LDL-C) are a major risk factor for cardiovascular events. Caused by genetic mutations or lifestyle factors, hypercholesterolemia can significantly reduce quality of life and increase the risk of mortality from cardiovascular disease.9 About 1 in 4 patients, or 15 million Americans with elevated LDL-C, are insufficiently managed with maximally tolerated statin therapy alone, requiring additional treatment for hypercholesterolemia.12
Bempedoic acid is first-in-class adenosine triphosphate-citrate lyase (ACL) inhibitor used once a day for reducing LDL cholesterol levels in statin-refractory patients.6,7 It was developed by Esperion Therapeutics Inc. and approved by the FDA on February 21, 2020. A combination product of bempedoic acid and ezetimibe was approved on February 26, 2020 for increased control of LDL cholesterol levels in patients experiencing refractory elevations despite previous statin treatment.6,8
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Bempedoic acid (DB11936)
- Weight
- Average: 344.492
Monoisotopic: 344.256274259 - Chemical Formula
- C19H36O5
- Synonyms
- Bempedoic acid
- External IDs
- ESP 55016
- ESP-55016
- ETC 1002
- ETC-1002
- ETC1002
Pharmacology
- Indication
Bempedoic acid is indicated to reduce the risk of myocardial infarction and coronary revascularization in adults who are unable to take recommended statin therapy and have established cardiovascular disease or are at high risk of a cardiovascular event.13
It is also indicated as an adjunct to diet, with or without other LDL-C lowering therapies, to reduce LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH).13 Bempedoic acid in combination with ezetimibe is also indicated for the same.14
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 Heterozygous familial hypercholesterolemia (hefh) Combination Product in combination with: Ezetimibe (DB00973) •••••••••••• ••••• •••••• Used as adjunct in combination to manage Heterozygous familial hypercholesterolemia (hefh) Combination Product in combination with: Ezetimibe (DB00973) •••••••••••• ••••• •••••• Adjunct therapy in management of Heterozygous familial hypercholesterolemia (hefh) •••••••••••• ••••• •••••• Adjunct therapy in management of Heterozygous familial hypercholesterolemia (hefh) •••••••••••• ••••• •••••• Prevention of Myocardial infarction •••••••••••• ••••• •••••••• •• ••••••••• •• • •••••••••••••• ••••• •••••• - 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
Bempedoic acid inhibits the synthesis of cholesterol in the liver, reducing LDL-C levels. This reduces the development of atherosclerotic plaques that may increase the risk of cardiovascular events.1,4 Earlier clinical trials studying the effects of bempedoic acid showed a dose‐dependent reduction of LDL‐C levels in addition to decreased LDL particle number, and reduced levels of apolipoprotein B, non–HDL cholesterol, and high‐sensitivity C‐reactive protein.2
Due to its unique mechanism of action, bempedoic acid is not associated with myositis, an adverse effect that frequently accompanies statin therapy.2
More recent trials have supported that this drug significantly decreases LDL-C levels after 12 weeks of therapy and provides additional lowering of LDL-C when combined with ezetimibe and statin therapy.5,2 The effects of bempedoic acid on mortality are currently unknown.4,6
- Mechanism of action
Normally, LDL cholesterol is produced in the liver and circulates in the blood. When the blood becomes saturated, excess LDL deposits in blood vessels including the coronary arteries, increasing the risk of cardiovascular events.9,11
Bempedoic acid is a prodrug that requires activation in the liver. The very-long-chain acyl-CoA synthetase-1 (ACSVL1) enzyme is responsible for its activation to ETC-1002-CoA, the pharmacologically active metabolite. ATP lyase (also known as ATP synthase) plays an important part of cholesterol synthesis. BETC-1002-CoA directly inhibits this enzyme after the parent drug is activated in the liver by coenzyme A (CoA).5,6
This inhibition leads to upregulation of the LDL cholesterol receptor, reducing serum LDL-C via increased uptake and LDL clearance in the liver. By the above mechanisms, bempedoic acid causes a total decrease of circulating LDL-C that normally damages blood vessels and leads to atherosclerosis.1,3,6 Lastly, ETC-1002 activates AMP-activated protein kinase (AMPK) in rodents, which inhibits the synthesis of cholesterol via the inhibition of HMG-CoA reductase. The relevance of this to humans is unknown.2
Target Actions Organism AATP-citrate synthase inhibitorHumans - Absorption
Bempedoic acid is rapidly absorbed in the small intestine.1,2 The Tmax of the 180mg tablet is estimated at 3.5 hours.6
- Volume of distribution
The apparent volume of distribution of bempedoic acid is about 18L.6
- Protein binding
The plasma protein binding of bempedoic acid and its metabolites is about 99%.6
- Metabolism
The two main metabolites of bempedoic metabolism are ETC-1002-CoA3 and ESP15228. Bempedoic acid is primarily eliminated via the metabolism of its acyl glucuronide. This drug is reversibly converted to an active metabolite (ESP15228) based on observations during in vitro studies. Both compounds resulting from the metabolism of bempedoic acid are metabolized to become inactive glucuronide conjugates by the enzyme UGT2B7.6
Hover over products below to view reaction partners
- Route of elimination
Bempedoic acid's conjugates are primarily eliminated via the urine (70%) and the feces (30%). A total of 5% of the unchanged drug is excreted in the urine and feces, combined.6
- Half-life
The half-life of bempedoic acid ranges between 15 and 24 hours.1 Prescribing information indicates a clearance of 21 hours +/- 11 hours.6
- Clearance
The clearance (CL/F) of bempedoic acid at steady state was estimated at 11.2 mL/min during clinical trials.6
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
LD50 information for bempedoic acid is not readily available in the literature. In the case of an overdose with bempedoic acid, contact the local poison control center. To this date, there is no experience with bempedoic acid overdoses. Employ general supportive measures.6
- 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 softwareAmbrisentan The excretion of Ambrisentan can be decreased when combined with Bempedoic acid. Asunaprevir The excretion of Asunaprevir can be decreased when combined with Bempedoic acid. Ataluren The excretion of Bempedoic acid can be decreased when combined with Ataluren. Atazanavir The excretion of Bempedoic acid can be decreased when combined with Atazanavir. Atogepant The serum concentration of Atogepant can be increased when it is combined with Bempedoic acid. - 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.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Nexletol Tablet, film coated 180 mg/1 Oral Esperion Therapeutics, Inc. 2020-03-06 Not applicable US 
Nilemdo Tablet, film coated 180 mg Oral Daiichi Sankyo Europe, Gmb H 2021-02-10 Not applicable EU 
Nilemdo Tablet, film coated 180 mg Oral Daiichi Sankyo Europe, Gmb H 2021-02-10 Not applicable EU Nilemdo Tablet, film coated 180 mg Oral Daiichi Sankyo Europe, Gmb H 2021-02-10 Not applicable EU Nilemdo Tablet, film coated 180 mg Oral Daiichi Sankyo Europe, Gmb H 2021-02-10 Not applicable EU - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Nexlizet Bempedoic acid (180 mg/1) + Ezetimibe (10 mg/1) Tablet, film coated Oral Esperion Therapeutics, Inc. 2020-03-09 Not applicable US NUSTENDI Bempedoic acid (180 MG) + Ezetimibe (10 MG) Tablet, film coated Oral Daiichi Sankyo Europe Gmbh 2020-07-14 Not applicable Italy 
Nustendi Bempedoic acid (180 mg) + Ezetimibe (10 mg) Tablet, film coated Oral Daiichi Sankyo Europe, Gmb H 2021-02-10 Not applicable EU Nustendi Bempedoic acid (180 mg) + Ezetimibe (10 mg) Tablet, film coated Oral Daiichi Sankyo Europe, Gmb H 2021-02-10 Not applicable EU NUSTENDI Bempedoic acid (180 MG) + Ezetimibe (10 MG) Tablet, film coated Oral Daiichi Sankyo Europe Gmbh 2020-07-14 Not applicable Italy
Categories
- ATC Codes
- C10AX15 — Bempedoic acid
- C10AX — Other lipid modifying agents
- C10A — LIPID MODIFYING AGENTS, PLAIN
- C10 — LIPID MODIFYING AGENTS
- C — CARDIOVASCULAR SYSTEM
- Drug Categories
- Acids, Acyclic
- Adenosine Triphosphate-Citrate Lyase Inhibitor
- Adenosine Triphosphate-Citrate Lyase Inhibitors
- Enzyme Inhibitors
- Hypolipidemic Agents
- Hypolipidemic Agents Indicated for Hyperlipidemia
- Lipid Modifying Agents
- Lipid Modifying Agents, Plain
- Lipid Regulating Agents
- Non-statin Hypolipidemic Agents Indicated for Hyperlipidemia
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B3 inhibitors
- OATP1B3 substrates
- UGT2B7 substrates
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as long-chain fatty acids. These are fatty acids with an aliphatic tail that contains between 13 and 21 carbon atoms.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- Fatty Acyls
- Sub Class
- Fatty acids and conjugates
- Direct Parent
- Long-chain fatty acids
- Alternative Parents
- Methyl-branched fatty acids / Hydroxy fatty acids / Dicarboxylic acids and derivatives / Secondary alcohols / Carboxylic acids / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- Alcohol / Aliphatic acyclic compound / Branched fatty acid / Carbonyl group / Carboxylic acid / Carboxylic acid derivative / Dicarboxylic acid or derivatives / Hydrocarbon derivative / Hydroxy fatty acid / Long-chain fatty acid
- Molecular Framework
- Aliphatic acyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 1EJ6Z6Q368
- CAS number
- 738606-46-7
- InChI Key
- HYHMLYSLQUKXKP-UHFFFAOYSA-N
- InChI
- InChI=1S/C19H36O5/c1-18(2,16(21)22)13-9-5-7-11-15(20)12-8-6-10-14-19(3,4)17(23)24/h15,20H,5-14H2,1-4H3,(H,21,22)(H,23,24)
- IUPAC Name
- 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
- SMILES
- CC(C)(CCCCCC(O)CCCCCC(C)(C)C(O)=O)C(O)=O
References
- Synthesis Reference
David M Paton. Bempedoic Acid: ATP-citrate lyase inhibitor.(2017). Drugs of the Future. 42(4):201-208
- General References
- Saeed A, Ballantyne CM: Bempedoic Acid (ETC-1002): A Current Review. Cardiol Clin. 2018 May;36(2):257-264. doi: 10.1016/j.ccl.2017.12.007. Epub 2018 Feb 21. [Article]
- Bilen O, Ballantyne CM: Bempedoic Acid (ETC-1002): an Investigational Inhibitor of ATP Citrate Lyase. Curr Atheroscler Rep. 2016 Oct;18(10):61. doi: 10.1007/s11883-016-0611-4. [Article]
- Zagelbaum NK, Yandrapalli S, Nabors C, Frishman WH: Bempedoic Acid (ETC-1002): ATP Citrate Lyase Inhibitor: Review of a First-in-Class Medication with Potential Benefit in Statin-Refractory Cases. Cardiol Rev. 2019 Jan/Feb;27(1):49-56. doi: 10.1097/CRD.0000000000000218. [Article]
- Jia X, Virani SS: CLEAR Serenity Trial: More Clarity for the Future of Bempedoic Acid in Patients Unable to Take Statins? J Am Heart Assoc. 2019 Apr 2;8(7):e012352. doi: 10.1161/JAHA.119.012352. [Article]
- Ray KK, Bays HE, Catapano AL, Lalwani ND, Bloedon LT, Sterling LR, Robinson PL, Ballantyne CM: Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol. N Engl J Med. 2019 Mar 14;380(11):1022-1032. doi: 10.1056/NEJMoa1803917. [Article]
- FDA Approved Products: Nexletol (bempedoic acid) oral tablets [Link]
- Bempedoic acid: A novel agent (Esperion) [Link]
- FDA Approved Products: Nexlizet (bempedoic acid and ezetimibe) oral tablets [Link]
- NIH StatPearls: Cholesterol levels [Link]
- Biovision: Bempedoic acid MSDS [Link]
- The Role of Lipids and Lipoproteins in Atherosclerosis [Link]
- Global News Wire: Esperion-Announces FDA Approval of NEXLETOL bempedoic acid Tablet an Oral Once Daily Non Statin LDL Cholesterol Lowering Medicine [Link]
- FDA Approved Drug Products: Nexletol (bempedoic acid) tablets for oral use (March 2024) [Link]
- FDA Approved Drug Products: Nexlizet (bempedoic acid and ezetimibe) tablets for oral use (March 2024) [Link]
- External Links
- Human Metabolome Database
- HMDB0251991
- PubChem Compound
- 10472693
- PubChem Substance
- 347828263
- ChemSpider
- 8648104
- 2282403
- ChEBI
- 149601
- ChEMBL
- CHEMBL3545313
- ZINC
- ZINC000003948738
- Wikipedia
- Bempedoic_acid
- FDA label
- Download (576 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 dataNot Available Recruiting Not Available High Cholesterol / Mixed Dyslipidemias 1 somestatus stop reason just information to hide 4 Completed Basic Science Healthy Lactating Women 1 somestatus stop reason just information to hide 4 Not Yet Recruiting Prevention Cardiovascular Disease (CVD) / Dyslipidemia / Metabolism Disorder, Lipid / Statin Adverse Reaction 1 somestatus stop reason just information to hide 4 Not Yet Recruiting Prevention Cardiovascular Disease (CVD) / Non ST Segment Elevation Myocardial Infarction (NSTEMI) / ST Segment Elevation Myocardial Infarction (STEMI) 1 somestatus stop reason just information to hide 4 Recruiting Treatment Atherosclerosis / Coronary Artery Disease (CAD) / Myocardial Infarction 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Oral 180 mg/1 Tablet, film coated Oral Tablet, film coated Oral 180 MG - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7335799 No 2008-02-26 2025-12-03 US US9624152 No 2017-04-18 2023-12-23 US US8497301 No 2013-07-30 2023-12-23 US US9000041 No 2015-04-07 2023-12-23 US US10118881 No 2018-11-06 2023-12-23 US US10941095 No 2021-03-09 2023-12-23 US US10912751 No 2021-02-09 2036-03-14 US US11613511 No 2020-06-19 2040-06-19 US US11744816 No 2016-03-14 2036-03-14 US US11760714 No 2020-06-19 2040-06-19 US US11926584 No 2020-06-19 2040-06-19 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 87-92 https://www.trc-canada.com/product-detail/?CatNum=B119700 - Predicted Properties
Property Value Source Water Solubility 0.0211 mg/mL ALOGPS logP 3.65 ALOGPS logP 5.3 Chemaxon logS -4.2 ALOGPS pKa (Strongest Acidic) 4.44 Chemaxon pKa (Strongest Basic) -1.3 Chemaxon Physiological Charge -2 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 94.83 Å2 Chemaxon Rotatable Bond Count 14 Chemaxon Refractivity 93.97 m3·mol-1 Chemaxon Polarizability 41.08 Å3 Chemaxon Number of Rings 0 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-002p-3982000000-078ef1febabf6869a2a7 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-002b-1497000000-2c0405011fb6bf5f5b77 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-0009000000-617f766f69c4f0db2eb8 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-000f-1479000000-610c67f8916cf44dc82c Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-002s-3970000000-91b7e74016b480caba5d Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0zfu-2690000000-3ab68c5b7b6d3cb02916 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-03ej-9640000000-2b809d6914ec35579a81 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]- 185.3574 predictedDeepCCS 1.0 (2019) [M+H]+ 187.7154 predictedDeepCCS 1.0 (2019) [M+Na]+ 194.00414 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Catalyzes the cleavage of citrate into oxaloacetate and acetyl-CoA, the latter serving as common substrate for de novo cholesterol and fatty acid synthesis
- Specific Function
- Atp binding
- Gene Name
- ACLY
- Uniprot ID
- P53396
- Uniprot Name
- ATP-citrate synthase
- Molecular Weight
- 120838.27 Da
References
- Saeed A, Ballantyne CM: Bempedoic Acid (ETC-1002): A Current Review. Cardiol Clin. 2018 May;36(2):257-264. doi: 10.1016/j.ccl.2017.12.007. Epub 2018 Feb 21. [Article]
- Bilen O, Ballantyne CM: Bempedoic Acid (ETC-1002): an Investigational Inhibitor of ATP Citrate Lyase. Curr Atheroscler Rep. 2016 Oct;18(10):61. doi: 10.1007/s11883-016-0611-4. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- FDA Approved Products: Nexletol (bempedoic acid) oral tablets [Link]
- Bempedoic acid: A novel agent (Esperion) [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Substrate
- Curator comments
- Bempedoic acid and its active metabolite, ESP15228, require coenzyme A (CoA) activation by very long-chain acyl-CoA synthetase 1 (ACSVL1) to ETC-1002-CoA and ESP15228-CoA, respectively.
- General Function
- Mediates the import of long-chain fatty acids (LCFA) into the cell by facilitating their transport across cell membranes, playing an important role in hepatic fatty acid uptake (PubMed:10198260, PubMed:10749848, PubMed:11980911, PubMed:20530735, PubMed:22022213, PubMed:24269233). Also functions as an acyl-CoA ligase catalyzing the ATP-dependent formation of fatty acyl-CoA using LCFA and very-long-chain fatty acids (VLCFA) as substrates, which prevents fatty acid efflux from cells and might drive more fatty acid uptake (PubMed:10198260, PubMed:10749848, PubMed:11980911, PubMed:20530735, PubMed:22022213, PubMed:24269233). Plays a pivotal role in regulating available LCFA substrates from exogenous sources in tissues undergoing high levels of beta-oxidation or triglyceride synthesis (PubMed:20530735). Can also activate branched-chain fatty acids such as phytanic acid and pristanic acid (PubMed:10198260). May contribute to the synthesis of sphingosine-1-phosphate (PubMed:24269233). Does not activate C24 bile acids, cholate and chenodeoxycholate (PubMed:11980911). In vitro, activates 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanate (THCA), the C27 precursor of cholic acid deriving from the de novo synthesis from cholesterol (PubMed:11980911). However, it is not critical for THCA activation and bile synthesis in vivo (PubMed:20530735)
- Specific Function
- Arachidonate-coa ligase activity
- Gene Name
- SLC27A2
- Uniprot ID
- O14975
- Uniprot Name
- Long-chain fatty acid transport protein 2
- Molecular Weight
- 70311.685 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- FDA Approved Products: Nexletol (bempedoic acid) oral tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Activator
- Curator comments
- This enzyme inhibition occurs in rats. Relevance to humans is unknown.
- General Function
- Stress-activated kinase involved in tolerance to glucose starvation. Induces cell-cell detachment by increasing F-actin conversion to G-actin. Expression is induced by CD95 or TNF-alpha, via NF-kappa-B. Protects cells from CD95-mediated apoptosis and is required for the increased motility and invasiveness of CD95-activated tumor cells. Phosphorylates LATS1 and LATS2. Plays a key role in neural tube closure during embryonic development through LATS2 phosphorylation and regulation of the nuclear localization of YAP1 a critical downstream regulatory target in the Hippo signaling pathway (PubMed:32845958)
- Specific Function
- Atp binding
- Gene Name
- NUAK2
- Uniprot ID
- Q9H093
- Uniprot Name
- NUAK family SNF1-like kinase 2
- Molecular Weight
- 69611.485 Da
References
- Bilen O, Ballantyne CM: Bempedoic Acid (ETC-1002): an Investigational Inhibitor of ATP Citrate Lyase. Curr Atheroscler Rep. 2016 Oct;18(10):61. doi: 10.1007/s11883-016-0611-4. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Weak inhibition.
- 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
- FDA Approved Products: Nexletol (bempedoic acid) oral tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Weak inhibition.
- 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
- FDA Approved Products: Nexletol (bempedoic acid) oral tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- Curator comments
- Weak inhibition.
- 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
References
- FDA Approved Products: Nexletol (bempedoic acid) oral tablets [Link]
Drug created at October 20, 2016 21:02 / Updated at July 26, 2024 04:51