Trilostane

Names

[ Name ]:
Trilostane

[Synonym ]:
MODRASTANE
(4a,5a,17b)-4,5-Epoxy-3,17-dihydroxyandrost-2-ene-2-carbonitrile
2a-Cyano-4a,5a-epoxyandrostan-17b-ol-3-one
Desopan
Trilostane
MFCD00199295
Modrenal
(4α,5α,17β)-3,17-Dihydroxy-4,5-epoxyandrost-2-ene-2-carbonitrile
Androst-2-ene-2-carbonitrile, 4,5-epoxy-3,17-dihydroxy-, (4α,5α,17β)-
Modrefen
Vetoryl
EINECS 237-133-0
4α,5-Epoxy-3,17β-dihydroxy-5α-androst-2-ene-2-carbonitrile
Trilostane(Win 24540; Modrastane)

Biological Activity

[Description]:

Trilostane(Win 24540; Modrastane) is an inhibitor of 3 β-hydroxysteroid dehydrogenase used in the treatment of Cushing's syndrome.IC50 value:Target: 3 β-HSDTrilostane is an inhibitor of 3 β-hydroxysteroid dehydrogenase (3-β-HSD or delta 5-delta 4-isomerase), an essential enzyme for the biosynthesis of all classes of hormonal steroids. It has been used in the treatment of Cushing′s syndrome for stopping the production of cortisol, and is currently approved for dogs in the US, but is still a human drug in the UK and other countries. It is being investigated as a possible treatment for both breast cancer and prostate cancer to prevent the synthesis of estrogens and androgens from endogenous precursors. It has also been used to inhibit endogenous production of progesterone in research studies.

[Related Catalog]:

Signaling Pathways >> Others >> Others

Research Areas >> Endocrinology

[References]

[1]. Helm JR, et al. A comparison of factors that influence survival in dogs with adrenal-dependent hyperadrenocorticism treated with mitotane or trilostane. J Vet Intern Med. 2011 Mar-Apr;25(2):251-60.

[2]. Feldman EC, et al. 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.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
497.8±45.0 °C at 760 mmHg

[ Melting Point ]:
264ºC

[ Molecular Formula ]:
C₂₀H₂₇NO₃

[ Molecular Weight ]:
329.433

[ Flash Point ]:
254.8±28.7 °C

[ Exact Mass ]:
329.199097

[ PSA ]:
76.78000

[ LogP ]:
3.61

[ Vapour Pressure ]:
0.0±2.9 mmHg at 25°C

[ Index of Refraction ]:
1.610

[ Storage condition ]:
-20°C Freezer

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: BV8044200

CHEMICAL NAME :: 5-alpha-Androstane-2-alpha-carbonitrile, 4-alpha,5-epoxy-17-beta-hydroxy-3-oxo-

CAS REGISTRY NUMBER :: 13647-35-3

LAST UPDATED :: 199603

DATA ITEMS CITED :: 12

MOLECULAR FORMULA :: C20-H27-N-O3

MOLECULAR WEIGHT :: 329.48

WISWESSER LINE NOTATION :: T E5 D6663 1A R AX PV RO QHTTTT&J HQ I1 M1 OCN

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >15 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,752,1990

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1055 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 37,1637,1986

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 7050 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 17,365,1986

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 102 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 17,365,1986

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >15 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,752,1990

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1205 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 37,1637,1986

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >15 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,752,1990

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 109 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 17,365,1986 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 54750 mg/kg/1Y-I

TOXIC EFFECTS :: Cardiac - pulse rate Lungs, Thorax, or Respiration - respiratory depression Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :: YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 37,1637,1986 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 48 mg/kg

SEX/DURATION :: male 14 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - other effects on male

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 33,754,1983

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1050 mg/kg

SEX/DURATION :: male 7 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - other effects on male

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 33,754,1983

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 5 mg/kg

SEX/DURATION :: female 25-29 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - abortion

REFERENCE :: FESTAS Fertility and Sterility. (American Fertility Soc., 608 13th Ave. S, Birmingham, AL 35282) V.1- 1950- Volume(issue)/page/year: 32,464,1979

Safety Information

[ Symbol ]:

GHS07, GHS08

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H315-H319-H361

[ Precautionary Statements ]:
P281-P305 + P351 + P338

[ Hazard Codes ]:
Xi

[ Risk Phrases ]:
36/37/38-62

[ Safety Phrases ]:
26-36/37

[ RIDADR ]:
NONH for all modes of transport

[ HS Code ]:
2937290090

Customs

[ HS Code ]: 2937290090

Articles

Disturbances in production of progesterone and their implications in plant studies.

Steroids 96 , 153-63, (2015)

Progesterone is a mammalian hormone that has also been discovered in plants but its physiological function in plants is not explained. Experiments using inhibitors of progesterone synthesis and bindin...

Guanosine triphosphate can directly regulate cortisol production by activating Ca(2+)-messenger systems in bovine adrenal fasciculata cells.

Endocr. J. 63 , 77-85, (2016)

Adenosine triphosphate (ATP) is known to stimulate cortisol production in vitro, however, the effect of guanosine triphosphate (GTP) on cortisol production is not known. We studied the effect of GTP o...

Trilostane dose versus body weight in the treatment of naturally occurring pituitary-dependent hyperadrenocorticism in dogs.

J. Vet. Intern. Med. 26(4) , 1078-80, (2012)

Trilostane is commonly used in the treatment of dogs with naturally occurring pituitary-dependent hyperadrenocorticism (PDH). Dose recommendations have varied from the manufacturer and the literature....