"目录号: HY-14718A
Cell Cycle/DNA DamageEpigenetics-
Resminostat(RAS2410; 4SC-201)盐酸盐是HDAC1/3/6抑制剂，IC50为43到72 nM，而对HDAC8的IC50为877 nM。
HDAC
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生物活性
Description
Resminostat Hcl(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
4SC AG
Advanced Colorectal Carcinoma
January 2011
Phase 1-Phase 2
NCT01037478
4SC AG
Hodgkin's Lymphoma
December 2009
Phase 2
NCT00943449
4SC AG
Hepatocellular Carcinoma
July 2009
Phase 2
NCT01277406
4SC AG
Advanced Colorectal Carcinoma
January 2011
Phase 1-Phase 2
NCT01037478
4SC AG
Hodgkin's Lymphoma
December 2009
Phase 2
NCT00943449
4SC AG
Hepatocellular Carcinoma
July 2009
Phase 2
NCT01277406
4SC AG
Advanced Colorectal Carcinoma
January 2011
Phase 1-Phase 2
NCT02953301
4SC AG
Mycosis Fungoides-Sezary Syndrome-Lymphoma, T-Cell, Cutaneous
November 2016
Phase 2
NCT02400788
Yakult Honsha Co., LTD
Hepatocellular Carcinoma
April 2013
Phase 1-Phase 2
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References
[1].Mandl-Weber S, Meinel FG, Jankowsky R, The novel inhibitor of histone deacetylase resminostat (RAS2410) inhibits proliferation and induces apoptosis in multiple myeloma (MM) cells. Br J Haematol. 2010 May;149(4):518-28.
[2].J.E. Ang, B. Hauns, A. Mais. 393 POSTER First-in-man Phase I trial of BYK408740, an oral histone deacetylase inhibitor, in patients with advanced malignancies. EJC Supplements, 2008, 6(12), 123-124.