Vosilasarm

Vosilasarm (RAD140) is a potent, orally active, nonsteroidal selective androgen receptor modulator (SARM) with a K_i of 7 nM. Vosilasarm shows good selectivity over other steroid hormone nuclear receptors^[1]. IC50 & Target:Ki: 7 nM (Androgen receptor)^[1] In Vitro: Vosilasarm (0-300 nM; pretreated for 1 hour) increases neuron viability against Aβ in a concentration-dependent manner^[2].
Vosilasarm (100 nM; 1 hour) protects cultured neurons against apoptotic insults. Vosilasarm shows protective profiles of significantly protecting against neuronal death induced by Aβ and AAII, but not H₂O₂^[2].
Vosilasarm (100 nM; 15 minutes) induces a significant increase in levels of phosphorylated but not total ERK in neuronal cultures^[2]. In Vivo: The stability of Vosilasarm is high (t_1/2 > 2 h) in incubations with rat, monkey, and human microsomes, and Vosilasarm also has good bioavailability in rats (F = 27-63%) and monkeys (65-75%)^[1].
In castrated immature rats, Vosilasarm (0.03-0.3 mg/kg; for 11 days) stimulates the levator ani bulbocavernosus muscle weight and prostate weight^[1].
A high dose of Vosilasarm (10 mg/kg, p.o.) actually antagonizes the effect of testosterone propionate (TP) at 1 mg/kg on the seminal vesicles but adds to the effect of TP on the levator ani muscle. The effective dose for achieving antagonism by Vosilasarm is 0.3-1 mg/kg (p.o.) for 1 mg/kg TP (s.c.). In the young castrate male rat model, Vosilasarm appears to be a potent and complete androgen agonist on the levator ani, but a weaker, partial antagonist on the seminal vesicle and possibly the prostate^[1].
Vosilasarm is neuroprotective in vivo using the rat kainate lesion model. In experiments with gonadectomized, adult male rats, Vosilasarm is shown to exhibit peripheral tissue-specific androgen action that largely spared prostate, neural efficacy as demonstrated by activation of androgenic gene regulation effects, and neuroprotection of hippocampal neurons against cell death caused by systemic administration of the excitotoxin kainate^[2].