Thyroid receptor agonists for the treatment of androgenetic alopecia.
A thyroid hormone receptor beta subtype-selective thyromimetic 5 was found to be efficacious in both mouse and monkey hair growth models after topical applications. It penetrates the skin according to the test in human cadaver skin mounted onto Franz diffusion chambers. The serum drug level of 5 is below the limit of quantification during tests in the bald stump-tailed macaques (Macaca arctoides). It is tested negative in the 3T3 neutral red uptake (NRU) phototoxicity test, indicating a low risk for causing photo-irritation. It is also rapidly metabolized according to the PK data, thus the systemic exposure is limited.
Li
Jie Jack
JJ
Department of Chemistry, Michigan Laboratories, Pfizer Global Research & Development, 2800 Plymouth Road, Ann Arbor, MI 48105, United States. jack.li@bms.com
Mitchell
Lorna H
LH
Dow
Robert L
RL
D000287:Administration, Topical; D000505:Alopecia / Q000188:drug therapy*; D000818:Animals; D041702:BALB 3T3 Cells; D006197:Hair / Q000254:growth & development; D006801:Humans; D008251:Macaca; D051379:Mice; D009499:Neutral Red / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000819:agonists* / Q000378:metabolism; D012869:Skin Absorption; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
C549136:PF 00277343; D011988:Receptors, Thyroid Hormone; D014227:Triazines; D009499:Neutral Red