Identification
- Generic Name
- Trilostane
- DrugBank Accession Number
- DB01108
- Background
Trilostane is an inhibitor of 3 beta-hydroxysteroid dehydrogenase used in the treatment of Cushing's syndrome. It was withdrawn from the United States market in April 1994.
- Type
- Small Molecule
- Groups
- Approved, Investigational, Vet approved, Withdrawn
- Structure
Structure for Trilostane (DB01108)
- Weight
- Average: 329.4333
Monoisotopic: 329.199093735 - Chemical Formula
- C20H27NO3
- Synonyms
- Trilostane
- Trilostano
- Trilostanum
- External IDs
- WIN 24,540
- WIN-24540
Pharmacology
- Indication
Used in the treatment of Cushing's syndrome. It is normally used in short-term treatment until permanent therapy is possible.
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.- 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
Trilostane blocks an enzyme involved in the production of several steroids including cortisol. Inhibiting this enzyme inhibits the production of cortisol. In Cushing's syndrome, the adrenal gland overproduces steroids. Although steroids are important for various functions of the body, too much can cause problems. Trilostane reduces the amount of steroids produced by the adrenal gland. This product was withdrawn from the U.S. market in April 1994.
- Mechanism of action
Trilostane produces suppression of the adrenal cortex by inhibiting enzymatic conversion of steroids by 3-beta-hydroxysteroid dehydrogenase/delta 5,4 ketosteroid isomerase, thus blocking synthesis of adrenal steroids.
Target Actions Organism A3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 inhibitorHumans A3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 inhibitorHumans AEstrogen receptor alpha allosteric modulatorHumans AEstrogen receptor beta allosteric modulatorHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Hepatic.
- Route of elimination
Not Available
- Half-life
8 hours.
- Clearance
Not Available
- 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
Symptoms of overdose include darkening of skin, drowsiness or tiredness, loss of appetite, mental depression, skin rash, and/or vomiting.
- 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 softwareAbatacept The risk or severity of adverse effects can be increased when Trilostane is combined with Abatacept. Acarbose The risk or severity of hyperglycemia can be increased when Trilostane is combined with Acarbose. Aceclofenac The risk or severity of gastrointestinal irritation can be increased when Trilostane is combined with Aceclofenac. Acemetacin The risk or severity of gastrointestinal irritation can be increased when Trilostane is combined with Acemetacin. Acenocoumarol Trilostane may increase the anticoagulant activities of Acenocoumarol. - Food Interactions
- No interactions found.
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.- International/Other Brands
- Desopan / Modrastane / Modrenal
Categories
- ATC Codes
- H02CA01 — Trilostane
- Drug Categories
- Abortifacient Agents
- Abortifacient Agents, Steroidal
- Adrenal Cortex Hormones
- Androstanes
- Androstanols
- Antiadrenal Preparations
- Anticorticosteroids
- Antineoplastic Agents
- Corticosteroids
- Corticosteroids for Systemic Use
- Enzyme Inhibitors
- Fused-Ring Compounds
- Gonadal Hormones
- Gonadal Steroid Hormones
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Immunosuppressive Agents
- Narrow Therapeutic Index Drugs
- Oxidative Phosphorylation Coupling Factors
- Reproductive Control Agents
- Steroids
- Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins
- Testosterone Congeners
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as estrane steroids. These are steroids with a structure based on the estrane skeleton.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- Steroids and steroid derivatives
- Sub Class
- Estrane steroids
- Direct Parent
- Estrane steroids
- Alternative Parents
- Secondary alcohols / Cyclic alcohols and derivatives / Oxacyclic compounds / Nitriles / Epoxides / Enols / Dialkyl ethers / Organopnictogen compounds / Hydrocarbon derivatives
- Substituents
- Alcohol / Aliphatic heteropolycyclic compound / Carbonitrile / Cyclic alcohol / Dialkyl ether / Enol / Estrane-skeleton / Ether / Hydrocarbon derivative / Nitrile
- Molecular Framework
- Aliphatic heteropolycyclic compounds
- External Descriptors
- 17beta-hydroxy steroid, androstanoid, 3-hydroxy steroid (CHEBI:32260)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- L0FPV48Q5R
- CAS number
- 13647-35-3
- InChI Key
- KVJXBPDAXMEYOA-CXANFOAXSA-N
- InChI
- InChI=1S/C20H27NO3/c1-18-7-6-14-12(13(18)3-4-15(18)22)5-8-20-17(24-20)16(23)11(10-21)9-19(14,20)2/h12-15,17,22-23H,3-9H2,1-2H3/t12-,13-,14-,15-,17+,18-,19+,20+/m0/s1
- IUPAC Name
- (1S,2R,6R,8S,11S,12S,15S,16S)-5,15-dihydroxy-2,16-dimethyl-7-oxapentacyclo[9.7.0.0^{2,8}.0^{6,8}.0^{12,16}]octadec-4-ene-4-carbonitrile
- SMILES
- [H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC[C@@]23O[C@@H]2C(O)=C(C[C@]13C)C#N
References
- Synthesis Reference
Walter Elger, Sybille Beier, Beate Kosub, Marianne Faehnrich, Krzysztof Chwalisz, Syed Hamiduddin Hasan, Gordon Oliver Potts, "Combined use of an antigestagen and a progesterone synthesis inhibitor of the trilostane and epostane type." U.S. Patent US5795881, issued June, 1987.
US5795881- General References
- Komanicky P, Spark RF, Melby JC: Treatment of Cushing's syndrome with trilostane (WIN 24,540), an inhibitor of adrenal steroid biosynthesis. J Clin Endocrinol Metab. 1978 Nov;47(5):1042-51. [Article]
- External Links
- Human Metabolome Database
- HMDB0015240
- KEGG Drug
- D01180
- KEGG Compound
- C12580
- PubChem Compound
- 656583
- PubChem Substance
- 46507062
- ChemSpider
- 570949
- 38668
- ChEBI
- 32260
- ChEMBL
- CHEMBL1200907
- ZINC
- ZINC000100038546
- Therapeutic Targets Database
- DAP000148
- PharmGKB
- PA164748507
- Wikipedia
- Trilostane
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 2 Completed Treatment Adenocarcinoma of Prostate / Prostate Cancer 1 2 Terminated Treatment Medical Abortion, Complete or Unspecified, Without Complication 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 264 dec °C PhysProp logP 3 Not Available - Predicted Properties
Property Value Source Water Solubility 0.0592 mg/mL ALOGPS logP 2.41 ALOGPS logP 2.3 Chemaxon logS -3.8 ALOGPS pKa (Strongest Acidic) 5.23 Chemaxon pKa (Strongest Basic) -0.88 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 76.78 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 90.17 m3·mol-1 Chemaxon Polarizability 36.81 Å3 Chemaxon Number of Rings 5 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
Property Value Probability Human Intestinal Absorption + 0.9935 Blood Brain Barrier + 0.8356 Caco-2 permeable + 0.5851 P-glycoprotein substrate Substrate 0.7338 P-glycoprotein inhibitor I Non-inhibitor 0.5276 P-glycoprotein inhibitor II Non-inhibitor 0.9432 Renal organic cation transporter Non-inhibitor 0.8024 CYP450 2C9 substrate Non-substrate 0.7859 CYP450 2D6 substrate Non-substrate 0.846 CYP450 3A4 substrate Substrate 0.6846 CYP450 1A2 substrate Non-inhibitor 0.5204 CYP450 2C9 inhibitor Non-inhibitor 0.6766 CYP450 2D6 inhibitor Non-inhibitor 0.9217 CYP450 2C19 inhibitor Non-inhibitor 0.6442 CYP450 3A4 inhibitor Non-inhibitor 0.7319 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7769 Ames test Non AMES toxic 0.506 Carcinogenicity Non-carcinogens 0.9434 Biodegradation Not ready biodegradable 0.9918 Rat acute toxicity 1.3725 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9531 hERG inhibition (predictor II) Non-inhibitor 0.7363
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0ik9-3697000000-af2f49f13d139eac8699 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-01q9-0009000000-c6be551cc5c453bff235 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-0009000000-51245c1c24f1f5e80598 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-01t9-0009000000-f79804e1291033b8c795 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-003r-5943000000-019cd21a945cb3daef06 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-01t9-0049000000-306ae2281a5edcdfc7d1 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0zgi-5491000000-9a9935cf4c61c275af9c 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]- 188.0340374 predictedDarkChem Lite v0.1.0 [M-H]- 188.5073374 predictedDarkChem Lite v0.1.0 [M-H]- 188.2523374 predictedDarkChem Lite v0.1.0 [M-H]- 176.40294 predictedDeepCCS 1.0 (2019) [M+H]+ 188.2048374 predictedDarkChem Lite v0.1.0 [M+H]+ 189.3648374 predictedDarkChem Lite v0.1.0 [M+H]+ 189.2915374 predictedDarkChem Lite v0.1.0 [M+H]+ 178.29832 predictedDeepCCS 1.0 (2019) [M+Na]+ 188.0876374 predictedDarkChem Lite v0.1.0 [M+Na]+ 188.6165374 predictedDarkChem Lite v0.1.0 [M+Na]+ 184.07626 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Steroid delta-isomerase activity
- Specific Function
- 3-beta-HSD is a bifunctional enzyme, that catalyzes the oxidative conversion of Delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. The 3-beta-HSD enzymatic system pl...
- Gene Name
- HSD3B1
- Uniprot ID
- P14060
- Uniprot Name
- 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1
- Molecular Weight
- 42251.25 Da
References
- Naville D, Keeney DS, Jenkin G, Murry BA, Head JR, Mason JI: Regulation of expression of male-specific rat liver microsomal 3 beta-hydroxysteroid dehydrogenase. Mol Endocrinol. 1991 Aug;5(8):1090-100. [Article]
- Takahashi M, Luu-The V, Labrie F: Inhibitory effect of synthetic progestins, 4-MA and cyanoketone on human placental 3 beta-hydroxysteroid dehydrogenase/5----4-ene-isomerase activity. J Steroid Biochem Mol Biol. 1990 Oct;37(2):231-6. [Article]
- Suzuki S, Endo Y, Tanaka S, Iizuka R: Indirect immunofluorescence studies on the steroid-producing activity of hamster ova. Am J Obstet Gynecol. 1984 Jan 1;148(1):76-85. [Article]
- Duffy DM, Hess DL, Stouffer RL: Acute administration of a 3 beta-hydroxysteroid dehydrogenase inhibitor to rhesus monkeys at the midluteal phase of the menstrual cycle: evidence for possible autocrine regulation of the primate corpus luteum by progesterone. J Clin Endocrinol Metab. 1994 Dec;79(6):1587-94. [Article]
- Mensah-Nyagan AG, Feuilloley M, Dupont E, Do-Rego JL, Leboulenger F, Pelletier G, Vaudry H: Immunocytochemical localization and biological activity of 3 beta-hydroxysteroid dehydrogenase in the central nervous system of the frog. J Neurosci. 1994 Dec;14(12):7306-18. [Article]
- Cooke GM: Differential effects of trilostane and cyanoketone on the 3 beta-hydroxysteroid dehydrogenase-isomerase reactions in androgen and 16-androstene biosynthetic pathways in the pig testis. J Steroid Biochem Mol Biol. 1996 Apr;58(1):95-101. [Article]
- Igaz P, Tombol Z, Szabo PM, Liko I, Racz K: Steroid biosynthesis inhibitors in the therapy of hypercortisolism: theory and practice. Curr Med Chem. 2008;15(26):2734-47. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Steroid delta-isomerase activity
- Specific Function
- 3-beta-HSD is a bifunctional enzyme, that catalyzes the oxidative conversion of Delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. The 3-beta-HSD enzymatic system pl...
- Gene Name
- HSD3B2
- Uniprot ID
- P26439
- Uniprot Name
- 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2
- Molecular Weight
- 42051.845 Da
References
- Naville D, Keeney DS, Jenkin G, Murry BA, Head JR, Mason JI: Regulation of expression of male-specific rat liver microsomal 3 beta-hydroxysteroid dehydrogenase. Mol Endocrinol. 1991 Aug;5(8):1090-100. [Article]
- Cooke GM: Differential effects of trilostane and cyanoketone on the 3 beta-hydroxysteroid dehydrogenase-isomerase reactions in androgen and 16-androstene biosynthetic pathways in the pig testis. J Steroid Biochem Mol Biol. 1996 Apr;58(1):95-101. [Article]
- Takahashi M, Luu-The V, Labrie F: Inhibitory effect of synthetic progestins, 4-MA and cyanoketone on human placental 3 beta-hydroxysteroid dehydrogenase/5----4-ene-isomerase activity. J Steroid Biochem Mol Biol. 1990 Oct;37(2):231-6. [Article]
- Suzuki S, Endo Y, Tanaka S, Iizuka R: Indirect immunofluorescence studies on the steroid-producing activity of hamster ova. Am J Obstet Gynecol. 1984 Jan 1;148(1):76-85. [Article]
- Duffy DM, Hess DL, Stouffer RL: Acute administration of a 3 beta-hydroxysteroid dehydrogenase inhibitor to rhesus monkeys at the midluteal phase of the menstrual cycle: evidence for possible autocrine regulation of the primate corpus luteum by progesterone. J Clin Endocrinol Metab. 1994 Dec;79(6):1587-94. [Article]
- Mensah-Nyagan AG, Feuilloley M, Dupont E, Do-Rego JL, Leboulenger F, Pelletier G, Vaudry H: Immunocytochemical localization and biological activity of 3 beta-hydroxysteroid dehydrogenase in the central nervous system of the frog. J Neurosci. 1994 Dec;14(12):7306-18. [Article]
- Igaz P, Tombol Z, Szabo PM, Liko I, Racz K: Steroid biosynthesis inhibitors in the therapy of hypercortisolism: theory and practice. Curr Med Chem. 2008;15(26):2734-47. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Allosteric modulator
- General Function
- Zinc ion binding
- Specific Function
- Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissu...
- Gene Name
- ESR1
- Uniprot ID
- P03372
- Uniprot Name
- Estrogen receptor
- Molecular Weight
- 66215.45 Da
References
- Puddefoot JR, Barker S, Vinson GP: Trilostane in advanced breast cancer. Expert Opin Pharmacother. 2006 Dec;7(17):2413-9. [Article]
- Puddefoot JR, Barker S, Glover HR, Malouitre SD, Vinson GP: Non-competitive steroid inhibition of oestrogen receptor functions. Int J Cancer. 2002 Sep 1;101(1):17-22. [Article]
- Barker S, Malouitre SD, Glover HR, Puddefoot JR, Vinson GP: Comparison of effects of 4-hydroxy tamoxifen and trilostane on oestrogen-regulated gene expression in MCF-7 cells: up-regulation of oestrogen receptor beta. J Steroid Biochem Mol Biol. 2006 Aug;100(4-5):141-51. Epub 2006 Jun 27. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Allosteric modulator
- General Function
- Zinc ion binding
- Specific Function
- Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent m...
- Gene Name
- ESR2
- Uniprot ID
- Q92731
- Uniprot Name
- Estrogen receptor beta
- Molecular Weight
- 59215.765 Da
References
- Puddefoot JR, Barker S, Vinson GP: Trilostane in advanced breast cancer. Expert Opin Pharmacother. 2006 Dec;7(17):2413-9. [Article]
- Puddefoot JR, Barker S, Glover HR, Malouitre SD, Vinson GP: Non-competitive steroid inhibition of oestrogen receptor functions. Int J Cancer. 2002 Sep 1;101(1):17-22. [Article]
- Barker S, Malouitre SD, Glover HR, Puddefoot JR, Vinson GP: Comparison of effects of 4-hydroxy tamoxifen and trilostane on oestrogen-regulated gene expression in MCF-7 cells: up-regulation of oestrogen receptor beta. J Steroid Biochem Mol Biol. 2006 Aug;100(4-5):141-51. Epub 2006 Jun 27. [Article]
Drug created at June 13, 2005 13:24 / Updated at May 07, 2021 21:23