Osilodrostat
Identification
- Summary
Osilodrostat is an oral inhibitor of cortisol synthesis used to treat Cushing's disease by normalizing hypercortisolism.
- Brand Names
- Isturisa
- Generic Name
- Osilodrostat
- DrugBank Accession Number
- DB11837
- Background
Osilodrostat is an inhibitor of 11β-hydroxylase (also referred to as CYP11B1), the enzyme that catalyzes the final step in the biosynthesis of endogenous cortisol.6 It is used to lower circulating cortisol levels in the treatment of Cushing's disease, a disorder in which cortisol levels are chronically and supraphysiologically elevated. Cushing's disease is often the result of ACTH hypersecretion secondary to a pituitary tumor, and surgical resection of the tumour is generally the treatment of choice.5 As an orally bioavailable drug therapy, osilodrostat provides a novel treatment option for patients in whom removal of the causative tumor is not an option or for whom previous pituitary surgery has not been curative.
Osilodrostat is manufactured by Novartis under the brand name Isturisa.6 It has undergone phase II clinical trials for the treatment of solid tumours, hypertension, and heart failure, but development for these indications was discontinued by Novartis in January 2013.4 Osilodrostat was approved for use in the EU in January 2020 for the treatment of endogenous Cushing's syndrome (i.e. Cushing's disease),4 and was granted FDA approval and Orphan Drug designation in the US in March 2020 for the same indication.9
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 227.242
Monoisotopic: 227.085875497 - Chemical Formula
- C13H10FN3
- Synonyms
- Osilodrostat
- External IDs
- LCI 699
- LCI-699-NX
- LCI699
- LCI699-NX
Pharmacology
- Indication
Osilodrostat is indicated for the treatment of adult patients with Cushing's disease for whom pituitary surgery is not an option or has not been curative.6,4
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Cushings disease •••••••••••• ••••• ••••••••• ••••••• •• ••• •• •••••• •• ••• ••• •••• •••••••• •••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
Osilodrostat lowers endogenous cortisol levels by inhibiting the enzyme that catalyzes the final step in cortisol synthesis.6 As endogenous cortisol levels function as a surrogate marker for drug effect, 24-hour urine free cortisol levels should be assessed 1-2x weekly during the initial titration stage and every 1-2 months thereafter to ensure cortisol levels remain physiologically appropriate.6 Osilodrostat is highly metabolized and requires dose adjustments in patient with hepatic dysfunction.6
Osilodrostat can cause a dose-dependent prolongation of the QTc interval and should be used with caution in patients with a higher baseline risk (e.g. concomitant QTc-prolonging medications, electrolyte abnormalities). Prior to beginning therapy, patients should have a baseline ECG and any electrolyte abnormalities (especially hypokalemia and/or hypomagnesemia) should be remedied.6
As osilodrostat halts cortisol synthesis at its final stage, its use can result in the accumulation of cortisol precursors, aldosterone precursors, and androgens. The accumulation of the cortisol precursor 11-deoxycorticosterone can activate mineralocorticoid receptors which may lead to hypokalemia, edema, or hypertension.6 Patients should be monitored for these symptoms as they are evidence of elevated 11-deoxycorticosterone levels, and for symptoms such as hirustism, acne, and hypertrichosis which may be suggestive of excessive circulating androgen levels.6
- Mechanism of action
Cushing’s syndrome is an endocrine disorder resulting from chronic and excessive exposure to glucocorticoids, the symptoms of which may include thinning of the skin and hair, weight gain, muscle weakness, and osteoporosis, as well a constellation of psychiatric, cardiovascular, and immunological deficiencies.5 Cushing’s syndrome is most commonly precipitated by exogenous treatment with supraphysiological doses of glucocorticoids such as those found in nasal sprays, skin creams, and inhalers. Cushing’s disease - another less common cause of Cushing’s syndrome - is generally the result of increased endogenous cortisol exposure due to excessive secretion of adrenocroticotrophic hormone (ACTH) from a pituitary adenoma.5
Osilodrostat is an inhibitor of 11β-hydroxylase (CYP11B1) and, to a lesser extent, aldosterone synthase (CYP11B2).6 The CYP11B1 enzyme is responsible for catalyzing the final step of cortisol synthesis - by inhibiting this enzyme, osilodrostat helps to normalize endogenous cortisol levels and alleviate symptoms of Cushing’s disease.6
Target Actions Organism ACytochrome P450 11B1, mitochondrial inhibitorHumans NCytochrome P450 11B2, mitochondrial inhibitorHumans - Absorption
The oral absorption of osilodrostat is rapid, with a Tmax of approximately 1 hour,6 and assumed to be essentially complete.7 Exposure (i.e. AUC and Cmax) increases slightly more than dose-proportionately over the standard dosing range.7
Coadministration of osilodrostat with food does not affect its pharmacokinetics to a clinically significant extent.6 Age and gender do not affect pharmacokinetics, but bioavailability and total exposure is higher (though not clinically significant) in patients of Asian descent.6 Exposure to osilodrostat is greater in patients with moderate-severe hepatic impairment - prescribing information recommends a starting dose of 1mg twice daily in patients with moderate hepatic impairment (Child-Pugh B) and a starting dose of 1mg each evening in patients with severe hepatic impairment (Child-Pugh C).6
- Volume of distribution
The median apparent volume of distribution of osilodrostat is 100 L.6
- Protein binding
Both osilodrostat and its M34.5 metabolite are minimally protein-bound in plasma at less than 40%.6,7 The extent of protein-binding is independent of drug concentration.7 The specific plasma proteins to which osilodrostat binds have not been elucidated.
- Metabolism
Osilodrostat is extensively metabolized - approximately 80% of an orally administered dose is excreted as metabolites, and this is the predominant means of drug clearance.7 The most abundant metabolites in plasma are M35.4 (di-oxygenated osilodrostat), M16.5, and M24.9 at 51%, 9%, and 7% of the administered dose, respectively.7 The M34.5 and M24.9 metabolites have longer half-lives than the parent drug which may lead to accumulation with twice-daily dosing. Of the thirteen metabolites observed in the urine, the most abundant are M16.5 (osilodrostat glucuronide), M22 (a glucuronide conjugate of M34.5), and M24.9 at 17%, 13%, and 11% of the administered dose, respectively.7 The M34.5 metabolite accounts for less than 1% of the dose excreted in urine, but its glucuronide conjugate (M22) accounts for approximately 13%.7
The biotransformation of osilodrostat is mediated by multiple cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes, though no single enzyme appears to contribute >25% to the total clearance.6 Of the total clearance, approximately 26% is CYP-mediated, 19% is UGT-mediated, and 50% is mediated by other enzymes.7 The formation of M34.5, the major metabolite of osilodrostat, is likely non-CYP-mediated. The formation of osilodrostat glucuronide (M16.5), its major urinary metabolite, is catalyzed by UGT1A4, UGT2B7, and UGT2B10.7
In vitro data suggest that none of the metabolites contribute to the therapeutic efficacy of osilodrostat, but the M34.5 metabolite has been implicated in the inhibition and/or induction of multiple enzymes and transporters.6,7
- Route of elimination
Following oral administration of radiolabeled osilodrostat, 90.6% of the radioactivity was eliminated in the urine with only 1.58% in the feces.6 Only 5.2% of the administered dose was eliminated in the urine as unchanged parent drug, suggesting that metabolism followed by urinary elimination is osildrostat's primary means of clearance.6
- Half-life
The elimination half-life of osilodrostat is approximately 4 hours.6,4
- Clearance
Data regarding the oral clearance of osilodrostat are not currently available.
- Adverse Effects
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- Toxicity
As an inhibitor of cortisol synthesis, overdose with osilodrostat may result in severe hypocortisolism.6 Symptoms may include nausea, vomiting, fatigue, hypotension, abdominal pain, loss of appetite, dizziness, and syncope. Treatment of overdose should include assessment of cortisol levels and supplementation with exogenous corticosteroids as necessary, as well as careful monitoring of the patient's heart rhythm, blood glucose, electrolytes, and blood pressure.6
Toxicity related to its osilodrostat's mechanism of action is difficult to observe in animal test subjects as human receptor profiles and densities for osilodrostat targets differ in humans as compared to these animals - for this reason, toxicological data gleaned from animal trials is of uncertain clinical relevance in humans.8
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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 Osilodrostat can be increased when it is combined with Abametapir. Abatacept The metabolism of Osilodrostat can be increased when combined with Abatacept. Abemaciclib The metabolism of Abemaciclib can be decreased when combined with Osilodrostat. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Osilodrostat. Acalabrutinib The metabolism of Acalabrutinib can be decreased when combined with Osilodrostat. - Food Interactions
- Take with or without food. Administration with food slightly alters absorption, but not to a clinically significant extent.
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 Osilodrostat phosphate Y6581YAW9V 1315449-72-9 FMCPYRDGUZBOJZ-BTQNPOSSSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Isturisa Tablet, film coated 1 mg Oral Recordati Rare Diseases 2020-12-16 Not applicable EU Isturisa Tablet, coated 1 mg/1 Oral RECORDATI RARE DISEASES, INC. 2020-03-31 Not applicable US Isturisa Tablet, film coated 10 mg Oral Recordati Rare Diseases 2020-12-16 Not applicable EU Isturisa Tablet, coated 10 mg/1 Oral RECORDATI RARE DISEASES, INC. 2020-03-31 2023-04-03 US Isturisa Tablet, film coated 5 mg Oral Recordati Rare Diseases 2020-12-16 Not applicable EU
Categories
- ATC Codes
- H02CA02 — Osilodrostat
- Drug Categories
- Antiadrenal Preparations
- Anticorticosteroids
- Cortisol Synthesis Inhibitors
- Cytochrome P-450 CYP11B2, antagonists & inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (moderate)
- Cytochrome P-450 CYP2B6 Substrates
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 Inhibitors (weak)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (weak)
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP2E1 Inhibitors
- Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)
- 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 CYP3A5 Inhibitors
- Cytochrome P-450 CYP3A5 Inhibitors (weak)
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Cytochrome P450 11B1 Inhibitors
- MATE 1 Inhibitors
- MATE inhibitors
- OAT1/SLC22A6 inhibitors
- OAT3/SLC22A8 Inhibitors
- OATP1B1/SLCO1B1 Inhibitors
- OCT1 inhibitors
- OCT2 Inhibitors
- Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins
- UGT1A4 substrates
- UGT2B7 substrates
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as benzonitriles. These are organic compounds containing a benzene bearing a nitrile substituent.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Benzonitriles
- Direct Parent
- Benzonitriles
- Alternative Parents
- Fluorobenzenes / N-substituted imidazoles / Aryl fluorides / Heteroaromatic compounds / Nitriles / Azacyclic compounds / Organofluorides / Hydrocarbon derivatives
- Substituents
- Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle / Azole / Benzonitrile / Carbonitrile / Cyanide / Fluorobenzene / Halobenzene
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 5YL4IQ1078
- CAS number
- 928134-65-0
- InChI Key
- USUZGMWDZDXMDG-CYBMUJFWSA-N
- InChI
- InChI=1S/C13H10FN3/c14-12-5-9(6-15)1-3-11(12)13-4-2-10-7-16-8-17(10)13/h1,3,5,7-8,13H,2,4H2/t13-/m1/s1
- IUPAC Name
- 3-fluoro-4-[(5R)-5H,6H,7H-pyrrolo[1,2-c]imidazol-5-yl]benzonitrile
- SMILES
- FC1=C(C=CC(=C1)C#N)[C@H]1CCC2=CN=CN12
References
- General References
- Armani S, Ting L, Sauter N, Darstein C, Tripathi AP, Wang L, Zhu B, Gu H, Chun DY, Einolf HJ, Kulkarni S: Drug Interaction Potential of Osilodrostat (LCI699) Based on Its Effect on the Pharmacokinetics of Probe Drugs of Cytochrome P450 Enzymes in Healthy Adults. Clin Drug Investig. 2017 May;37(5):465-472. doi: 10.1007/s40261-017-0497-0. [Article]
- Papillon JP, Adams CM, Hu QY, Lou C, Singh AK, Zhang C, Carvalho J, Rajan S, Amaral A, Beil ME, Fu F, Gangl E, Hu CW, Jeng AY, LaSala D, Liang G, Logman M, Maniara WM, Rigel DF, Smith SA, Ksander GM: Structure-Activity Relationships, Pharmacokinetics, and in Vivo Activity of CYP11B2 and CYP11B1 Inhibitors. J Med Chem. 2015 Jun 11;58(11):4749-70. doi: 10.1021/acs.jmedchem.5b00407. Epub 2015 May 21. [Article]
- Weldon SM, Cerny MA, Gueneva-Boucheva K, Cogan D, Guo X, Moss N, Parmentier JH, Richman JR, Reinhart GA, Brown NF: Selectivity of BI 689648, a Novel, Highly Selective Aldosterone Synthase Inhibitor: Comparison with FAD286 and LCI699 in Nonhuman Primates. J Pharmacol Exp Ther. 2016 Oct;359(1):142-50. doi: 10.1124/jpet.116.236463. Epub 2016 Aug 1. [Article]
- Duggan S: Osilodrostat: First Approval. Drugs. 2020 Mar 5. pii: 10.1007/s40265-020-01277-0. doi: 10.1007/s40265-020-01277-0. [Article]
- Prague JK, May S, Whitelaw BC: Cushing's syndrome. BMJ. 2013 Mar 27;346:f945. doi: 10.1136/bmj.f945. [Article]
- FDA Approved Drug Products: Isturisa (osilodrostat) oral tablets [Link]
- EMA Summary of Product Characteristics: Isturisa (osilodrostat) oral tablets [Link]
- EMA Assessment Report: Isturisa (osilodrostat) oral tablets [Link]
- FDA News Release: Osilodrostat Approval [Link]
- External Links
- PubChem Compound
- 44139752
- PubChem Substance
- 347828182
- ChemSpider
- 29340911
- BindingDB
- 50444549
- 2286252
- ChEMBL
- CHEMBL3099695
- ZINC
- ZINC000072318114
- PDBe Ligand
- YSY
- Wikipedia
- Osilodrostat
- PDB Entries
- 7m8v
- FDA label
- Download (456 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Completed Treatment Cushing's Disease 2 2 Active Not Recruiting Treatment Cushing's Syndrome 1 2 Completed Treatment Adrenal Adenoma / Adrenal Carcinoma / AIMAH / Cushing's Syndrome / Ectopic Corticotropin Syndrome / PPNAD 1 2 Completed Treatment Cushing's Disease 1 2 Completed Treatment Hypertension 2
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, coated Oral 1 mg/1 Tablet, coated Oral 10 mg/1 Tablet, coated Oral 5 mg/1 Tablet, film coated Oral 1 MG Tablet, film coated Oral 10 MG Tablet, film coated Oral 5 MG - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8609862 No 2013-12-17 2031-01-13 US US8835646 No 2014-09-16 2026-08-23 US US8314097 No 2012-11-20 2029-03-27 US US10143680 No 2018-12-04 2035-07-06 US US9434754 No 2016-09-06 2031-01-13 US US10709691 No 2020-07-14 2035-10-12 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.356 mg/mL ALOGPS logP 2.18 ALOGPS logP 2.11 Chemaxon logS -2.8 ALOGPS pKa (Strongest Basic) 7.15 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 41.61 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 62.07 m3·mol-1 Chemaxon Polarizability 22.53 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0f8a-3950000000-4431758f2deeb32e5959 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-0290000000-fdefd08476f428b8aa9b Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-0390000000-1d006989b149d7fecaf8 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0a6r-0790000000-ae502d10f6141c5b9244 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-0090000000-4039e092691e674e3f34 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-001i-2910000000-22ee732e9a23233da28d Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0a59-2930000000-7590b4dc22c00dbb40de 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]- 150.64629 predictedDeepCCS 1.0 (2019) [M+H]+ 153.04187 predictedDeepCCS 1.0 (2019) [M+Na]+ 159.08003 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Steroid 11-beta-monooxygenase activity
- Specific Function
- Has steroid 11-beta-hydroxylase activity. In addition to this activity, the 18 or 19-hydroxylation of steroids and the aromatization of androstendione to estrone have also been ascribed to cytochro...
- Gene Name
- CYP11B1
- Uniprot ID
- P15538
- Uniprot Name
- Cytochrome P450 11B1, mitochondrial
- Molecular Weight
- 57572.44 Da
References
- FDA Approved Drug Products: Isturisa (osilodrostat) oral tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Steroid 11-beta-monooxygenase activity
- Specific Function
- Preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone.
- Gene Name
- CYP11B2
- Uniprot ID
- P19099
- Uniprot Name
- Cytochrome P450 11B2, mitochondrial
- Molecular Weight
- 57559.62 Da
References
- Weldon SM, Cerny MA, Gueneva-Boucheva K, Cogan D, Guo X, Moss N, Parmentier JH, Richman JR, Reinhart GA, Brown NF: Selectivity of BI 689648, a Novel, Highly Selective Aldosterone Synthase Inhibitor: Comparison with FAD286 and LCI699 in Nonhuman Primates. J Pharmacol Exp Ther. 2016 Oct;359(1):142-50. doi: 10.1124/jpet.116.236463. Epub 2016 Aug 1. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Protein homodimerization activity
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
- Gene Name
- UGT1A4
- Uniprot ID
- P22310
- Uniprot Name
- UDP-glucuronosyltransferase 1-4
- Molecular Weight
- 60024.535 Da
References
- EMA Summary of Product Characteristics: Isturisa (osilodrostat) oral tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Glucuronosyltransferase activity
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
- Gene Name
- UGT2B7
- Uniprot ID
- P16662
- Uniprot Name
- UDP-glucuronosyltransferase 2B7
- Molecular Weight
- 60694.12 Da
References
- EMA Summary of Product Characteristics: Isturisa (osilodrostat) oral tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
- Specific Function
- Glucuronosyltransferase activity
- Gene Name
- UGT2B10
- Uniprot ID
- P36537
- Uniprot Name
- UDP-glucuronosyltransferase 2B10
- Molecular Weight
- 60773.485 Da
References
- EMA Summary of Product Characteristics: Isturisa (osilodrostat) oral tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
- Gene Name
- CYP2E1
- Uniprot ID
- P05181
- Uniprot Name
- Cytochrome P450 2E1
- Molecular Weight
- 56848.42 Da
References
- EMA Summary of Product Characteristics: Isturisa (osilodrostat) oral tablets [Link]
References
- EMA Summary of Product Characteristics: Isturisa (osilodrostat) oral tablets [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Secondary active organic cation transmembrane transporter activity
- Specific Function
- Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
- Gene Name
- SLC22A1
- Uniprot ID
- O15245
- Uniprot Name
- Solute carrier family 22 member 1
- Molecular Weight
- 61153.345 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Quaternary ammonium group transmembrane transporter activity
- Specific Function
- Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
- Gene Name
- SLC22A2
- Uniprot ID
- O15244
- Uniprot Name
- Solute carrier family 22 member 2
- Molecular Weight
- 62579.99 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
- Gene Name
- SLC22A6
- Uniprot ID
- Q4U2R8
- Uniprot Name
- Solute carrier family 22 member 6
- Molecular Weight
- 61815.78 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
- Gene Name
- SLC22A8
- Uniprot ID
- Q8TCC7
- Uniprot Name
- Solute carrier family 22 member 8
- Molecular Weight
- 59855.585 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Monovalent cation:proton antiporter activity
- Specific Function
- Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
- Gene Name
- SLC47A1
- Uniprot ID
- Q96FL8
- Uniprot Name
- Multidrug and toxin extrusion protein 1
- Molecular Weight
- 61921.585 Da
References
Drug created at October 20, 2016 20:52 / Updated at December 01, 2022 11:27