4SC-202 is an inhibitor of the class I histone deacetylases (HDACs) HDAC1-3 and the histone demethylase KDM1A. It reduces cell viability in a panel of colorectal cancer (CRC) cell lines when used at concentrations ranging from 1 to 10 μM and in patient-derived CRC cell lines when used at a concentration of 5 μM. 4SC-202 (5 μM) induces cell cycle arrest at the G2/M phase in HT-29 cells and primary human CRC cells and increases apoptosis in HT-29 cells in a concentration-dependent manner, an effect that is enhanced by the Akt inhibitors perifosine and MK-2206 . 4SC-202 (100 mg/kg, p.o., every other day) reduces tumor growth in an HT-29 mouse xenograft model when administered alone and to an enhanced degree when co-administered with oxaliplatin (Item No. 13106).
Domatinostat tosylate (4SC-202) is a selective class I HDAC inhibitor with IC50 of 1.20 μM, 1.12 μM, and 0.57 μM for HDAC1, HDAC2, and HDAC3, respectively. It also displays inhibitory activity against Lysine specific demethylase 1 (LSD1).
studies, 4sc-202 has shown a good tolerability and dose-dependent effect on anti-tumour activity compared with other inhibitors in the a549nsclc xenograft model and the rko27 colon carcinoma model [1].
HDAC-3: 0.57 μM (IC50); HDAC-2: 1.12 μM (IC50); HDAC-1: 1.2 μM (IC50); HDAC-11: 9.7 μM (IC50); HDAC-5: 11.3 μM (IC50); HDAC-10: 21 μM (IC50); HDAC-9: 50 μM (IC50)
[1] henning s w, doblhofer r, kohlhof h, et al. 178 preclinical characterization of 4sc-202, a novel isotype specific hdac inhibitor[j]. european journal of cancer supplements, 2010, 8(7): 61.
