Fadrozole hydrochloride

Fadrozole hydrochloride is a potent, selective and nonsteroidal inhibitor of aromatase with an IC50 of 6.4 nM.

Signaling Pathways >> Others >> Aromatase

Research Areas >> Cancer

IC50: 6.4 nM (aromatase)[1]

Fadrozole hydrochloride is a potent, selective and nonsteroidal inhibitor of aromatase with an IC50 of 6.4 nM. In hamster ovarian slices, Fadrozole hydrochloride inhibits the production of estrogen with an IC50 of 0.03 μM. The production of progesterone is inhibited with an IC50 of 120 μM. Synthesis of other cytochrome P-450 dependent steroids can be suppressed to various degrees with higher doses of Fadrozole hydrochloride[1].

Fadrozole hydrochloride is able to inhibit the aromatase-mediated androstenedione-induced uterine hypertrophy in immature female rats with an ED50 of 0.03 mg/kg when given orally. In the same model, aminoglutethimide elicits the same effect with an ED50 of 30 mg/kg when given orally[1]. Fadrozole hydrochloride prevents the development of both benign and malignant spontaneus mammary neoplasns in female Sprague-Dawley rats. It also slows the spontaneous development of ptuitary pars distalis adenomas in female rats, and reduces the incidence of spontaneous hepatocellular tumours in male and female rats[2]. Administration of Fadrozole hydrochloride in male and female mice suppresses the production of 17b-estradiol, accompanied with a 70% reduction in parasite burden. This protective effect is associated in male mice with a recovery of the specific cellular immune response. Interleukin-6 (IL-6) serum levels, and its production by splenocytes, is augmented by 80%, together with a 10-fold increase in its expression in testes of infected male mice. Fadrozole hydrochloride treatment returns these levels to baseline values[3].

Rats: Rats are treated with daily dosing with Fadrozole hydrochloride in purified water by gavage for 2 years. There are 60 rats in each of four groups given 0, 0.05, 0.25 or 1.25 mg/kg daily. Control rats receive only water. Clinical signs are recorded weekly and the animals are examined for palpable masses every 4 weeks for the first 9 months, then every 2 weeks for the remainder of the study[2]. Mice: Fadrozole hydrochloride is administered in the form of sub-dermal long-term release pellets (20 mg/wt kg, in three-week-release pellets), starting 1 week prior to the infection, using a 10-gauge needle. Three pellets are administrated during the study. Placebo pellets are administered to another group of infected mice, in the same fashion as the inhibitor. After 1 week, mice are infected and killed 8 weeks later[3].

[1]. Browne LJ, et al. Fadrozole hydrochloride: a potent, selective, nonsteroidal inhibitor of aromatase for the treatment of estrogen-dependent disease. J Med Chem. 1991 Feb;34(2):725-36.

[2]. Gunson DE, et al. Prevention of spontaneous tumours in female rats by fadrozole hydrochloride, an aromatase inhibitor. Br J Cancer. 1995 Jul;72(1):72-5.

[3]. Morales-Montor J, et al. Inhibition of p-450 aromatase prevents feminisation and induces protection during cysticercosis. Int J Parasitol. 2002 Oct;32(11):1379-87.

Fadrozole | Exemestane | Endoxifen

MOLECULAR FORMULA :

C14-H13-N3.Cl-H

MOLECULAR WEIGHT :

259.76

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 :

200 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: 26,740,1995

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

47200 ug/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: 26,740,1995

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

163 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: 26,740,1995

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

63600 ug/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: 26,740,1995

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

5 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: 26,740,1995

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

2 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: 26,740,1995 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

2500 ug/kg

SEX/DURATION :

female 16-20 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - other effects to embryo

REFERENCE :

NISFAY Nippon Sanka Fujinka Gakkai Zasshi. Journal of the Japan Society of Obstetrics and Gynecology. (Nippon Sanka Fujinka Gakkai Zasshi, Hoken Kaikan Bekkan, 1-1 Sadohara-cho, Ichigaya, Shijuku-ku, Tokyo 162, Japan) V.1- 1949- Volume(issue)/page/year: 46,227,1994