MS-275

Orally available Class I HDAC inhibitor inducing histone hyperacetylation and gene reactivation, leading to anti-tumor, pro-apoptotic, and immunomodulatory outcomes.


MS-275 (Entinostat), a long-acting, orally bioavailable, cell-permeable, brain-region selective Class I HDACs (HDAC1 IC50 ~0.18-0.51 μM; HDAC3 IC50 ~0.74-1.7 μM) inhibitor via reversible active site zinc binding. This inhibition induces histone hyperacetylation, promoting euchromatin formation and DNA accessibility to transcription factors, which reactivates silenced tumor suppressor and cancer-associated genes, mediating anti-proliferative, pro-apoptotic, and differentiation-inducing effects, ultimately inhibiting cancer cell growth and survival (IC50 ~0.0415-1.92 μM in human tumor cell lines). Furthermore, MS-275 demonstrates significant in vivo antitumor activity (e.g., 5 mg/kg), exhibits immunomodulation including Treg suppression, sensitizes cancer cells to other therapies, and modulates the tumor microenvironment.