Definition
ChEBI: A carboxamide that is 1,8-diaminooctane in which a hydrogen attached to each of the amino groups has been replaced by a dichloroacetyl group. Inhibitor of aldehyde dehydrogenase 1a2 (ALDH1a2). Inhibits the biosynthesis of retinoic acid from retinol in neon
tal and adult murine testis. It down-regulates sex related genes in zebrafish.
Biological Activity
win 18446 is a bis-(dichloroacetyl)-diamine which inhibits aldehyde dehydrogenase 1a2 (aldh1a2), with ic50 value of 300 nm [1].aldh1a2, expressed almost exclusively in the testes, localizes to developing germ cells within the seminiferous tubules and strongly binds retinol, but does not recognize acetaldehyde as a substrate, suggesting that aldh1a2 functions in testicular retinoic acid biosynthesis [1].in whole testes or germ cells isolated from mice at 2 days postpartum, win 18,446 alone (1 μm) or in combination with retinol significantly reduced the expression of stra8, a marker for retinoic acid activity [2].in male rabbits, oral administration of win 18446 at 200 mg/kg for 16 weeks substantially reduced intratesticular concentrations of retinoic acid, significantly impaired spermatogenesis, and resulted in infertility. reduced concentrations of intratesticular retinoic acid became obvious after only 4 weeks of treatment and preceded the decrease in sperm counts and the loss of mature germ cells in tissue samples. sperm counts and fertility recovered after treatment was discontinued [1].[1]. amory j k, muller c h, shimshoni j a, et al. suppression of spermatogenesis by bisdichloroacetyldiamines is mediated by inhibition of testicular retinoic acid biosynthesis. journal of andrology, 2011, 32(1): 111-119.[2]. hogarth c a, evanoff r, snyder e, et al. suppression of stra8 expression in the mouse gonad by win 18,446. biology of reproduction, 2011, 84(5): 957-965.
