Resminostat

"目录号: HY-14718

Resminostat(RAS2410; 4SC-201)是HDAC1/3/6抑制剂，IC50为43到72 nM，而对HDAC8的IC50为877 nM。

生物活性

Description

Resminostat(RAS2410; 4SC-201) is a potent inhibitor of HDAC1/3/6(IC50=43-72 nM); less potent to HDAC8 with IC50 of 877 nM.IC50 Value: 43-72 nM (HDAC1/3/6) [1]Target: HDAC1/3/6in vitro: Resminostat strongly induced apoptosis (IC50=2.5-3 micromol/l in 3 out of 4 MM cell lines) in MM cell lines as well as primary MM cells. At 1micromol/l, resminostat inhibited proliferation and induced G0/G1 cell cycle arrest in 3 out of 4 MM cell lines accompanied with decreased levels of cyclin D1, cdc25a, Cdk4 and pRb as well as upregulation of p21. Resminostat decreased phosphorylation of 4E-BP1 and p70S6k indicating an interference with Akt pathway signalling. Treatment with resminostat resulted in increased protein levels of Bim and Bax and decreased levels of Bcl-xL. Caspases 3, 8 and 9 were activated by resminostat [1].in vivo: Oral resminostat at 600 mg QD continuously d1?5 in a 14 day cycle is well-tolerated. Resminostat shows a favourable PK profile, with high bioavailability and low inter-pt variability. The apparent t 1/2 of oral resminostat ranged from 2.7 to 4.4 hours. The modulation of plasma biomarkers further indicates drug activity [2].Clinical trial: SAPHIRE: Resminostat (4SC-201) in Relapsed or Refractory Hodgkin's Lymphoma. Phase 2

Clinical Trial

NCT01037478

4SC AG

Hodgkin's Lymphoma

December 2009

Phase 2

NCT00943449

4SC AG

Hepatocellular Carcinoma

July 2009

Phase 2

NCT01277406