hexamethylene bisacetamide

Hexamethylene bisacetamide (HMBA) is a small molecule hybrid bipolar compound that functions as a potent differentiating agent. Originally investigated in the 1980s and 1990s for the treatment of various malignancies, including acute myeloid leukemia and solid tumors, HMBA induces terminal differentiation in transformed cells, thereby inhibiting their growth. Its mechanism of action involves the induction of Hexamethylene bisacetamide-inducible protein 1 (HEXIM1), which in turn sequesters and inhibits the Positive Transcription Elongation Factor b (P-TEFb) complex, a key regulator of RNA polymerase II. More recent research has identified HMBA as a selective inhibitor of the second bromodomain (BD2) of BET proteins. Although its clinical use in oncology was hampered by dose-limiting thrombocytopenia and suboptimal efficacy, it remains a tool in research for HIV latency reversal, metabolic regulation in obesity, and as an adjuvant in bacterial infections.

Other names

N,N'-diacetyl-1,6-hexanediamine1,6-bis(acetylamino)hexane