Hexamethylene bisacetamide (HMBA) (HMBA)

Hexamethylene bisacetamide (HMBA) is a polar-planar small molecule that serves as a potent inducer of terminal differentiation in various neoplastic cell lines (PubChem, CID 3604). Although it has been investigated in numerous clinical trials for the treatment of cancers such as leukemia and solid tumors, HMBA is a pharmacological agent rather than a biological target itself (NIH, National Cancer Institute). Its therapeutic effects are primarily attributed to the induction of the Hexamethylene bis-acetamide inducible 1 (HEXIM1) protein, which subsequently inhibits the Positive Transcription Elongation Factor b (P-TEFb) complex (He et al., 2008, Molecular Cell). This inhibition leads to a decrease in the transcription of genes required for cell cycle progression, thereby promoting differentiation and apoptosis in cancer cells (PubMed, PMID 18249148). HMBA is considered the prototype for a class of compounds that led to the development of histone deacetylase (HDAC) inhibitors, though its own direct molecular target remains unconfirmed (Marks et al., 2000, Journal of the National Cancer Institute). Clinical development was largely halted due to the high plasma concentrations required for efficacy and the occurrence of dose-limiting toxicities such as thrombocytopenia (ClinicalTrials.gov).

Other names

HMBANSC 955801,6-Bis(acetylamino)hexaneHexamethylenebisacetamide

Induces terminal differentiation of transformed cells by increasing the expression of HEXIM1, which inhibits the P-TEFb complex and arrests transcriptional elongation of growth-related genes.