tcsc0491 Droxinostat

Droxinostat(NS41080) is a selective inhibitor of HDAC3, HDAC6, and HDAC8 with IC50 of 16.9, 2.47 and 1.46 μM, respectively; > 8-fold selective against HDAC3 and no inhibition to HDAC1, 2, 4, 5, 7, 9, and 10.

IC50 Value: 16.9 μM(HDAC3); 2.47 μM(HDAC6); 1.46 μM(HDAC8)

Target: HDAC3/6/8

in vitro: Droxinostat is originally identified as a sensitizer of PPC-1 cells to FAS and TRAIL by downregulating the expression of c-Fas-associated death domain-like interleukin-1-converting enzyme-like inhibitory protein (c-FLIP). the direct targets of Droxinostat remains enigma until recently. It is revealed that in histone deacetylases (HDAC) isoform 1-10, Droxinostat selective inhibits HDAC3, 6, and 8, with IC50 values of 16.9 μM, 2.47 μM, and 1.46 μM, respectively, without inhibiting other HDAC members (IC50 > 20 μM). In MCF-7 breast cancer cells, Droxinostat (10 μM–100 μM) sensitizes cells to apoptosis by decreasing c-FLIPL and c-FLIPS expression, reducing cell survival, and inducing apoptosis.

in vivo: In SCID mice models, Droxinostat (30 μM)-treated PPC-1 cells results in decreased distant tumor formation than untreated cells.