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Acetothiolutamide is a selective androgen receptor modulator (SARM) derived from the nonsteroidal antiandrogen bicalutamide that was described in 2002 and was one of the first SARMs to be discovered and developed.[1][2][3][4] It is a high-affinity, selective ligand of the androgen receptor (AR) (Ki = 2.1–4.9 nM), where it acts as a full agonist in vitro, and has in vitro potency comparable to that of testosterone.[2][4][5] However, in vivo, acetothiolutamide displayed overall negligible androgenic effects, though significant (albeit very low) anabolic effects were observed at high doses.[2] In addition, notable antiandrogen effects were observed in castrated male rats treated with testosterone propionate.[2] The discrepancy between the in vitro and in vivo actions of acetothiolutamide was determined to be related to rapid plasma clearance and extensive hepatic metabolism into a variety of metabolites with differing pharmacological activity, including AR partial agonism and antagonism.[2][4][6] In accordance with its poor metabolic stability, acetothiolutamide is not orally bioavailable, and shows activity only via injected routes such as subcutaneous and intravenous.[2]

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