WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 203020
Description: Trilostane is an inhibitor of 3β-hydroxysteroid dehydrogenase used in the treatment of Cushing's syndrome. It was withdrawn from the United States market in April 1994. However, it was recently approved in 2008 for the treatment of Cushing's disease (hyperandrenocorticism) in dogs. It is also the first drug approved to treat both pituitary- and adrenal-dependent Cushing's in dogs. This prescription drug works by stopping the production of cortisol in the adrenal glands.
MedKoo Cat#: 203020
Chemical Formula: C20H27NO3
Exact Mass: 329.19909
Molecular Weight: 329.43
Elemental Analysis: C, 72.92; H, 8.26; N, 4.25; O, 14.57
Synonym: WIN24540; WIN-24540; WIN 24540; Trilostane; DB01108; D-01180; D 01180; Modrastane. Desopan; Modrenal.
IUPAC/Chemical Name: (1aR,4aR,4bS,6aS,7S,9aS,9bS,11aS)-2,7-dihydroxy-4a,6a-dimethyl-1a,4,4a,4b,5,6,6a,7,8,9,9a,9b,10,11-tetradecahydrocyclopenta[7,8]phenanthro[1,10a-b]oxirene-3-carbonitrile.
InChi Key: KVJXBPDAXMEYOA-CXANFOAXSA-N
InChi Code: 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
SMILES Code: N#CC1=C(O)[C@@]2([H])O[C@@]23[C@]([C@@]4([H])CC[C@@]5(C)[C@](CC[C@@H]5O)([H])[C@]4([H])CC3)(C)C1
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
|Biological target:||Trilostane (Win 24540; Modrastane) is an inhibitor of 3 β-hydroxysteroid dehydrogenase.|
|In vitro activity:||The influence of trilostane on steroid hormone metabolism in dogs was investigated by means of an in vitro model. Canine adrenal glands from freshly euthanized dogs and corpora lutea (CL) were incubated with increasing doses of trilostane. Tritiated P5 or DHEA were used as substrates. The resulting radioactive metabolites were extracted, separated by thin layer chromatography and visualized by autoradiography. A wide variety of radioactive metabolites were formed in the adrenal glands and in the CL, indicating high metabolic activity in both tissues. In the adrenal cortex, trilostane influences the P5 metabolism in a dose- and time-dependent manner, while DHEA metabolism and metabolism of both hormones in the CL were unaffected. The results indicate for the first time that there might be more than one enzyme of 3β-HSD present in dogs and that trilostane selectively inhibits P5 conversion to P4 only in the adrenal gland. Reference: Vet Res Commun. 2012 Mar;36(1):35-40. https://link.springer.com/article/10.1007%2Fs11259-011-9509-3|
|In vivo activity:||The immunomodulatory effects of trilostane were examined in a contact hypersensitivity model induced by DNFB (2,4-dinitrofluorobenzene). The animals were sensitized to DNFB and then challenged on the right ear 5 days later. Ear thickness increase was used as an end point. After the initial sensitization, there was no increase in the ear thickness. On challenge 5 days later, the DNFB-challenged animals that were treated with vehicle control experienced an increase in ear thickness of 76% to 0.34 mm. The trilostane-treated animals exhibited less swelling, with a maximum thickness of 0.27 mm at 48 hours. This finding constitutes a statistically significant 19% reduction (P < 0.05) compared with the vehicle-treated group. Reference: Curr Ther Res Clin Exp. 2013 Dec;75:71-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898193/|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
|DMF:PBS (pH 7.2) (1:1)||0.5||1.52|
The following data is based on the product molecular weight 329.43 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
|Formulation protocol:||1. Ouschan C, Lepschy M, Zeugswetter F, Möstl E. The influence of trilostane on steroid hormone metabolism in canine adrenal glands and corpora lutea-an in vitro study. Vet Res Commun. 2012 Mar;36(1):35-40. doi: 10.1007/s11259-011-9509-3. Epub 2011 Nov 25. PMID: 22113849. 2. Tung D, Ciallella J, Hain H, Cheung PH, Saha S. Possible therapeutic effect of trilostane in rodent models of inflammation and nociception. Curr Ther Res Clin Exp. 2013 Dec;75:71-6. doi: 10.1016/j.curtheres.2013.09.004. PMID: 24465047; PMCID: PMC3898193.|
|In vitro protocol:||1. Ouschan C, Lepschy M, Zeugswetter F, Möstl E. The influence of trilostane on steroid hormone metabolism in canine adrenal glands and corpora lutea-an in vitro study. Vet Res Commun. 2012 Mar;36(1):35-40. doi: 10.1007/s11259-011-9509-3. Epub 2011 Nov 25. PMID: 22113849.|
|In vivo protocol:||1. Tung D, Ciallella J, Hain H, Cheung PH, Saha S. Possible therapeutic effect of trilostane in rodent models of inflammation and nociception. Curr Ther Res Clin Exp. 2013 Dec;75:71-6. doi: 10.1016/j.curtheres.2013.09.004. PMID: 24465047; PMCID: PMC3898193.|
1: Midence JN, Drobatz KJ, Hess RS. Cortisol Concentrations in Well-Regulated Dogs with Hyperadrenocorticism Treated with Trilostane. J Vet Intern Med. 2015 Nov;29(6):1529-33. doi: 10.1111/jvim.13615. Epub 2015 Sep 16. PubMed PMID: 26374943.
2: Fracassi F, Corradini S, Floriano D, Boari A, Aste G, Pietra M, Bergamini PF, Dondi F. Prognostic factors for survival in dogs with pituitary-dependent hypercortisolism treated with trilostane. Vet Rec. 2015 Jan 10;176(2):49. doi: 10.1136/vr.102546. Epub 2014 Aug 28. PubMed PMID: 25170036.
3: Bonadio CM, Feldman EC, Cohen TA, Kass PH. Comparison of adrenocorticotropic hormone stimulation test results started 2 versus 4 hours after trilostane administration in dogs with naturally occurring hyperadrenocorticism. J Vet Intern Med. 2014 Jul-Aug;28(4):1239-43. doi: 10.1111/jvim.12357. Epub 2014 May 26. PubMed PMID: 24863172.
4: Sun L, Jin R, Peng Z, Zhou Q, Qian H, Fu Z. Effects of trilostane and fipronil on the reproductive axis in an early life stage of the Japanese medaka (Oryzias latipes). Ecotoxicology. 2014 Aug;23(6):1044-54. doi: 10.1007/s10646-014-1248-0. Epub 2014 Apr 29. PubMed PMID: 24777665.
5: Teshima T, Matsumoto H, Kumagai T, Kurano M, Koyama H. Expression of 11β-hydroxysteroid dehydrogenase isoforms in canine adrenal glands treated with trilostane. Vet J. 2014 Jun;200(3):452-5. doi: 10.1016/j.tvjl.2014.03.022. Epub 2014 Mar 26. PubMed PMID: 24745768.
6: Arenas C, Melián C, Pérez-Alenza MD. Long-term survival of dogs with adrenal-dependent hyperadrenocorticism: a comparison between mitotane and twice daily trilostane treatment. J Vet Intern Med. 2014 Mar-Apr;28(2):473-80. doi: 10.1111/jvim.12303. Epub 2014 Feb 3. PubMed PMID: 24495125.
7: Tung D, Ciallella J, Hain H, Cheung PH, Saha S. Possible therapeutic effect of trilostane in rodent models of inflammation and nociception. Curr Ther Res Clin Exp. 2013 Dec;75:71-6. doi: 10.1016/j.curtheres.2013.09.004. PubMed PMID: 24465047; PubMed Central PMCID: PMC3898193.
8: Reid LE, Behrend EN, Martin LG, Kemppainen RJ, Ward CR, Lurye JC, Donovan TC, Lee HP. Effect of trilostane and mitotane on aldosterone secretory reserve in dogs with pituitary-dependent hyperadrenocorticism. J Vet Intern Med. 2014 Mar-Apr;28(2):443-50. doi: 10.1111/jvim.12276. Epub 2014 Jan 8. PubMed PMID: 24400747.
9: Griebsch C, Lehnert C, Williams GJ, Failing K, Neiger R. Effect of trilostane on hormone and serum electrolyte concentrations in dogs with pituitary-dependent hyperadrenocorticism. J Vet Intern Med. 2014 Jan-Feb;28(1):160-5. doi: 10.1111/jvim.12268. Epub 2013 Dec 16. PubMed PMID: 24341822.
10: Arenas C, Melián C, Pérez-Alenza MD. Evaluation of 2 trilostane protocols for the treatment of canine pituitary-dependent hyperadrenocorticism: twice daily versus once daily. J Vet Intern Med. 2013 Nov-Dec;27(6):1478-85. doi: 10.1111/jvim.12207. Epub 2013 Sep 30. PubMed PMID: 24118316.
11: Braun C, Boretti FS, Reusch CE, Sieber-Ruckstuhl NS. Comparison of two treatment regimens with trilostane in dogs with pituitary-dependent hyperadrenocorticism. Schweiz Arch Tierheilkd. 2013 Oct;155(10):551-8. doi: 10.1024/0036-7281/a000511. PubMed PMID: 24091230.
12: Mellett Keith AM, Bruyette D, Stanley S. Trilostane therapy for treatment of spontaneous hyperadrenocorticism in cats: 15 cases (2004-2012). J Vet Intern Med. 2013 Nov-Dec;27(6):1471-7. doi: 10.1111/jvim.12178. Epub 2013 Sep 6. PubMed PMID: 24011349.
13: Burkhardt WA, Boretti FS, Reusch CE, Sieber-Ruckstuhl NS. Evaluation of baseline cortisol, endogenous ACTH, and cortisol/ACTH ratio to monitor trilostane treatment in dogs with pituitary-dependent hypercortisolism. J Vet Intern Med. 2013 Jul-Aug;27(4):919-23. doi: 10.1111/jvim.12111. Epub 2013 May 23. PubMed PMID: 23701195.
14: Augusto M, Burden A, Neiger R, Ramsey I. A comparison of once and twice daily administration of trilostane to dogs with hyperadrenocorticism. Tierarztl Prax Ausg K Kleintiere Heimtiere. 2012;40(6):415-24. PubMed PMID: 23242222.
15: Cho KD, Kang JH, Chang D, Na KJ, Yang MP. Efficacy of low- and high-dose trilostane treatment in dogs (< 5 kg) with pituitary-dependent hyperadrenocorticism. J Vet Intern Med. 2013 Jan-Feb;27(1):91-8. doi: 10.1111/jvim.12007. Epub 2012 Nov 20. PubMed PMID: 23167780.
16: Reine NJ. Medical management of pituitary-dependent hyperadrenocorticism: mitotane versus trilostane. Top Companion Anim Med. 2012 Feb;27(1):25-30. doi: 10.1053/j.tcam.2012.06.002. PubMed PMID: 22958794.
17: Feldman EC, Kass PH. Trilostane dose versus body weight in the treatment of naturally occurring pituitary-dependent hyperadrenocorticism in dogs. J Vet Intern Med. 2012 Jul-Aug;26(4):1078-80. doi: 10.1111/j.1939-1676.2012.00956.x. Epub 2012 Jun 18. PubMed PMID: 22708554.
18: Cook AK, Nieuwoudt CD, Longhofer SL. Pharmaceutical evaluation of compounded trilostane products. J Am Anim Hosp Assoc. 2012 Jul-Aug;48(4):228-33. doi: 10.5326/JAAHA-MS-5763. Epub 2012 May 18. PubMed PMID: 22611212.
19: Griffies JD. Old or new? A comparison of mitotane and trilostane for the management of hyperadrenocorticism. Compend Contin Educ Vet. 2013 May;35(5):E3. PubMed PMID: 23677783.
20: Ouschan C, Lepschy M, Zeugswetter F, Möstl E. The influence of trilostane on steroid hormone metabolism in canine adrenal glands and corpora lutea-an in vitro study. Vet Res Commun. 2012 Mar;36(1):35-40. doi: 10.1007/s11259-011-9509-3. Epub 2011 Nov 25. PubMed PMID: 22113849.