The aldo-keto reductase (AKR) enzymes constitute a family of related NADP-dependent oxidoreductases. The 1C subfamily (AKR1C) includes four human hydroxysteroid dehydrogenases (HSD), with AKR1C1 being a 20α-HSD and the other three being 3α-HSDs. AKR1C1 metabolizes progesterone to an inactive progestin, 20α-hydroxy progesterone. In addition, AKR1C1 actions have been implicated in cancer and in the processing of neuroactive steroids involved in brain function. 5-bromo-3-phenyl Salicyclic acid selectively inhibits AKR1C1 (Ki = 140 nM) over AKR1C2 (K1 = 1.97 μM) and AKR1C3 (Ki = 21 μM). It does not inhibit AKR1C4 at 100 μM.
