Imofinostat

Imofinostat (ABT-301; MPT0E028) is an orally active and selective HDAC inhibitor with IC₅₀s of 53.0 nM, 106.2 nM, 29.5 nM for HDAC1, HDAC2 and HDAC6, respectively. Imofinostat has a weak inhibitory effect on HDAC8 (IC₅₀ of 2.5 ​​μM), but no inhibitory effect on HDAC4 (IC₅₀>10 μM). Imofinostat reduces the viability of B-cell lymphomas by inducing apoptosis and possesses potent direct Akt targeting ability and reduces Akt phosphorylation in B-cell lymphoma. Imofinostat has a broad-spectrum antitumor activity, including colorectal cancer, B-cell lymphoma, non-small cell lung carcinoma (NSCLC), and pancreatic cancer, while also showing therapeutic potential in non-tumor diseases like emphysema and pulmonary fibrosis^{[1][2][3][14][5][6]}. In Vitro: Imofinostat (MPT0E028) (0-10 μM; 48 h) significantly inhibits cell proliferation and induces apoptosis in HCT116 cells^[1].
Imofinostat (0-10 μM; 24 h) inhibits cell growth in a concentration-dependent manner. Imofinostat increases the number of cells in the sub-G1 phase of the cell cycle. Imofinostat induces caspase 3 and PARP activation in a concentrationdependent manner, and this apoptosis^[1].
Imofinostat (0.3-100 μM; 24 h) induces significant concentration-dependent growth inhibition in Ramos and BJAB cells. Imofinostat increases the subG1 phase population in a time- and concentration-dependent manner. Imofinostat induces caspase-3, -6, -7, -8, -9 activation and PARP cleavage^[2].
Imofinostat (0.01-1 μM) pretreated human lung fibroblasts (WI-38) for 30 minutes and then treated with stimulants, which inhibits the expression of CTGF induced by TGF-β, thrombin, and ET-1^[5].
In Vivo: Imofinostat (MPT0E028) (50-200 mg/kg; oral gavage; once a day for 15 days) delays and inhibits tumor growth in a dose-dependent manner in nude mice xenografted with human colorectal cancer HCT116 cells, with complete tumor regression observed in 3 mice at 200 mg/kg, without significant body weight changes or other adverse effects^[1].
Imofinostat (100 mg/kg; oral gavage; once daily;) significantly prolongs survival in NOD/SCID mice bearing human B-cell lymphoma Ramos cells^[2].
Imofinostat (50-200 mg/kg; oral gavage; once daily; 31 days) inhibits tumor growth in a dose-dependent manner, activates caspase 3 and PARP, and increases acetylation levels of histone H3 and α-tubulin in nude mice xenografted with BJAB cells, without significant body weight changes^[2].
Imofinostat (25-100 mg/kg; oral gavage; once daily; 20 days) reduces pulmonary fibrosis in a dose-dependent manner, decreases expression of CTGF, fibronectin, α-SMA, and collagen, and inhibits phosphorylation of ERK, JNK, and p38 in Bleomycin (HY-17565A)-induced C57BL/6 mouse model^[5].
Imofinostat (25 mg/kg; oral gavage; once daily; continuous administration) significantly reduces tumor volume, increases cleaved caspase-3 levels, downregulates EGFR expression, and causes no weight loss or adverse effects in AsPC-1 pancreatic cancer xenograft nude mice^[6].