Identification

Name
Osilodrostat
Accession Number
DB11837
Description

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
Thumb
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

Associated Conditions
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 endocrinological 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

TargetActionsOrganism
ACytochrome P450 11B1, mitochondrial
inhibitor
Humans
NCytochrome P450 11B2, mitochondrial
inhibitor
Humans
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
Learn about our commercial Adverse Effects data.
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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

Affected organisms
  • Humans and other mammals
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.
DrugInteraction
AbametapirThe serum concentration of Osilodrostat can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Osilodrostat can be increased when combined with Abatacept.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Osilodrostat.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with Osilodrostat.
AcebutololThe metabolism of Acebutolol can be decreased when combined with Osilodrostat.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Osilodrostat.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Osilodrostat.
AcyclovirThe metabolism of Acyclovir can be decreased when combined with Osilodrostat.
AdalimumabThe metabolism of Osilodrostat can be increased when combined with Adalimumab.
AgomelatineThe serum concentration of Agomelatine can be increased when it is combined with Osilodrostat.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Take with or without food. Administration with food slightly alters absorption, but not to a clinically significant extent.

Products

Product Ingredients
IngredientUNIICASInChI Key
Osilodrostat phosphateY6581YAW9V1315449-72-9FMCPYRDGUZBOJZ-BTQNPOSSSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
IsturisaTablet, coated1 mg/1OralRECORDATI RARE DISEASES, INC.2020-03-31Not applicableUS flag
IsturisaTablet, coated10 mg/1OralRECORDATI RARE DISEASES, INC.2020-03-31Not applicableUS flag
IsturisaTablet, coated5 mg/1OralRECORDATI RARE DISEASES, INC.2020-03-31Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
H02CA02 — Osilodrostat
Drug Categories
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

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)[[email protected]]1CCC2=CN=CN12

References

General References
  1. 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. [PubMed:28155129]
  2. 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. [PubMed:25953419]
  3. 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. [PubMed:27481775]
  4. Duggan S: Osilodrostat: First Approval. Drugs. 2020 Mar 5. pii: 10.1007/s40265-020-01277-0. doi: 10.1007/s40265-020-01277-0. [PubMed:32141023]
  5. Prague JK, May S, Whitelaw BC: Cushing's syndrome. BMJ. 2013 Mar 27;346:f945. doi: 10.1136/bmj.f945. [PubMed:23535464]
  6. FDA Approved Drug Products: Isturisa (osilodrostat) oral tablets [Link]
  7. EMA Summary of Product Characteristics: Isturisa (osilodrostat) oral tablets [Link]
  8. EMA Assessment Report: Isturisa (osilodrostat) oral tablets [Link]
  9. FDA News Release: Osilodrostat Approval [Link]
PubChem Compound
44139752
PubChem Substance
347828182
ChemSpider
29340911
BindingDB
50444549
RxNav
2286252
ChEMBL
CHEMBL3099695
ZINC
ZINC000072318114
Wikipedia
Osilodrostat
FDA label
Download (456 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentCushing's Disease1
3CompletedTreatmentCushing's Disease1
2CompletedTreatmentAdrenal Adenoma / Adrenocortical Carcinoma / AIMAH / Cushing's Syndrome / Ectopic Corticotropin Syndrome / PPNAD1
2CompletedTreatmentCushing's Disease1
2CompletedTreatmentHigh Blood Pressure (Hypertension)2
2CompletedTreatmentHypertension,Essential1
2CompletedTreatmentPrimary Hyperaldosteronism1
2RecruitingTreatmentCushing's Disease1
2RecruitingTreatmentCushing's Syndrome1
1CompletedTreatmentHepatic Impairment1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet, coatedOral1 mg/1
Tablet, coatedOral10 mg/1
Tablet, coatedOral5 mg/1
Tablet, film coatedOral1 MG
Tablet, film coatedOral10 MG
Tablet, film coatedOral5 MG
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US8609862No2011-01-132031-01-13US flag
US8835646No2006-08-232026-08-23US flag
US8314097No2009-03-272029-03-27US flag
US10143680No2015-07-062035-07-06US flag
US9434754No2011-01-132031-01-13US flag
US10709691No2015-10-122035-10-12US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.356 mg/mLALOGPS
logP2.18ALOGPS
logP2.11ChemAxon
logS-2.8ALOGPS
pKa (Strongest Basic)7.15ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area41.61 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity62.07 m3·mol-1ChemAxon
Polarizability22.53 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

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
  1. 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
  1. 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. [PubMed:27481775]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
  1. Duggan S: Osilodrostat: First Approval. Drugs. 2020 Mar 5. pii: 10.1007/s40265-020-01277-0. doi: 10.1007/s40265-020-01277-0. [PubMed:32141023]
  2. FDA Approved Drug Products: Isturisa (osilodrostat) oral tablets [Link]
  3. EMA Summary of Product Characteristics: Isturisa (osilodrostat) oral tablets [Link]
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
  1. FDA Approved Drug Products: Isturisa (osilodrostat) oral tablets [Link]
  2. EMA Summary of Product Characteristics: Isturisa (osilodrostat) oral tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
  1. Duggan S: Osilodrostat: First Approval. Drugs. 2020 Mar 5. pii: 10.1007/s40265-020-01277-0. doi: 10.1007/s40265-020-01277-0. [PubMed:32141023]
  2. FDA Approved Drug Products: Isturisa (osilodrostat) oral tablets [Link]
  3. EMA Summary of Product Characteristics: Isturisa (osilodrostat) oral tablets [Link]
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
  1. 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
  1. 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
  1. 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
  1. Duggan S: Osilodrostat: First Approval. Drugs. 2020 Mar 5. pii: 10.1007/s40265-020-01277-0. doi: 10.1007/s40265-020-01277-0. [PubMed:32141023]
  2. EMA Summary of Product Characteristics: Isturisa (osilodrostat) oral tablets [Link]
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
  1. Duggan S: Osilodrostat: First Approval. Drugs. 2020 Mar 5. pii: 10.1007/s40265-020-01277-0. doi: 10.1007/s40265-020-01277-0. [PubMed:32141023]
  2. FDA Approved Drug Products: Isturisa (osilodrostat) oral tablets [Link]
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
  1. Duggan S: Osilodrostat: First Approval. Drugs. 2020 Mar 5. pii: 10.1007/s40265-020-01277-0. doi: 10.1007/s40265-020-01277-0. [PubMed:32141023]
  2. FDA Approved Drug Products: Isturisa (osilodrostat) oral tablets [Link]
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
  1. EMA Summary of Product Characteristics: Isturisa (osilodrostat) oral tablets [Link]
11. UDP-glucuronosyltransferase 1A1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
References
  1. 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
  1. Duggan S: Osilodrostat: First Approval. Drugs. 2020 Mar 5. pii: 10.1007/s40265-020-01277-0. doi: 10.1007/s40265-020-01277-0. [PubMed:32141023]
  2. EMA Summary of Product Characteristics: Isturisa (osilodrostat) oral tablets [Link]
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
  1. Duggan S: Osilodrostat: First Approval. Drugs. 2020 Mar 5. pii: 10.1007/s40265-020-01277-0. doi: 10.1007/s40265-020-01277-0. [PubMed:32141023]
  2. EMA Summary of Product Characteristics: Isturisa (osilodrostat) oral tablets [Link]
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
  1. Duggan S: Osilodrostat: First Approval. Drugs. 2020 Mar 5. pii: 10.1007/s40265-020-01277-0. doi: 10.1007/s40265-020-01277-0. [PubMed:32141023]
  2. EMA Summary of Product Characteristics: Isturisa (osilodrostat) oral tablets [Link]
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
  1. Duggan S: Osilodrostat: First Approval. Drugs. 2020 Mar 5. pii: 10.1007/s40265-020-01277-0. doi: 10.1007/s40265-020-01277-0. [PubMed:32141023]
  2. EMA Summary of Product Characteristics: Isturisa (osilodrostat) oral tablets [Link]
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
  1. Duggan S: Osilodrostat: First Approval. Drugs. 2020 Mar 5. pii: 10.1007/s40265-020-01277-0. doi: 10.1007/s40265-020-01277-0. [PubMed:32141023]
  2. FDA Approved Drug Products: Isturisa (osilodrostat) oral tablets [Link]
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
  1. Duggan S: Osilodrostat: First Approval. Drugs. 2020 Mar 5. pii: 10.1007/s40265-020-01277-0. doi: 10.1007/s40265-020-01277-0. [PubMed:32141023]
  2. EMA Summary of Product Characteristics: Isturisa (osilodrostat) oral tablets [Link]

Drug created on October 20, 2016 14:52 / Updated on June 12, 2020 10:53

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