LY191704

LY191704, as a benzoquinolinone, is a potent, nonsteroidal, noncompetitive and selective human type I 5α-reductase inhibitor. LY191704 is a racemic mixture of the compounds LY300502 and LY300503. LY191704 may be useful in the research of human endocrine disorders associated with overproduction of dihydrotestosterone (DHT) by 5α-reductase type 1[1][2].

Research Areas >> Endocrinology

Signaling Pathways >> Metabolic Enzyme/Protease >> 5 alpha Reductase

Human Type I 5α-Reductase[1][2]

LY191704 (0.001-100 uM) inhibits the conversion of testosterone to DHT with an IC50 of 10 nM in Hs68 cells. LY191704 inhibits the enzyme expressed by the human cells with an IC50 of 12 nM but is virtually inactive against the 5α-reductase expressed by rat prostate cells. LY191704 is a potent and specific inhibitor of human 5α-reductase type 1 but had little or no activity against human 5α-reductase type 2 or rat 5α-reductase type 1. A Ki value of 17.1 μM is determined for the human type 2 enzyme, indicating that LY191704 demonstrates an 5000-fold selectivity for the human type 1 isozyme[2].

LY191704 (10, 30, or 100 mg/kg; p.o.; 1 month) increases plasma concentrations[1]. Animal Model: Rats[1] Dosage: 10, 30, or 100 mg/kg Administration: P.o.; 1 month Result: Increased plasma concentrations.

[1]. Farid NA, et al. Stereoselective disposition of the enantiomers of the benzoquinolinone LY191704, a human type I 5 alpha-reductase inhibitor. Differences between rats and dogs. Drug Metab Dispos. 1996;24(10):1162-1165.

[2]. Hirsch KS, et al. LY191704: a selective, nonsteroidal inhibitor of human steroid 5 alpha-reductase type 1. Proc Natl Acad Sci U S A. 1993;90(11):5277-5281.