LMK-235

LMK-235 is a synthetic, highly potent and selective small molecule inhibitor of class IIa histone deacetylases (HDAC4 and HDAC5). It exhibits inhibitory activity in the low nanomolar range for HDAC4 (IC50 = 11.9 nM) and HDAC5 (IC50 = 4.2 nM), with substantially lower potency against other HDAC isoforms. LMK-235 induces apoptosis in multiple myeloma and leukemic cell lines and has shown synergy with the BCL-2 inhibitor venetoclax in preclinical studies. Proposed mechanisms of action include downregulation of heme oxygenase-1 (HO-1), effects on JNK phosphorylation, and upregulation of VMAT2 expression, potentially providing neuroprotection. It is being investigated in vitro and in animal models for various indications including hematological malignancies, fibrosis, and neurodegenerative and inflammatory conditions.

Other names

N-[6-(hydroxyamino)-6-oxohexoxy]-3,5-dimethylbenzamide