| Description: |
Resminostat [HCl] is acting as a potent inhibitor of recombinant HDAC 1, 3 and 6 isoenzymes with a substrate competitive binding mode. It can induce hyperacetylation of histone H4 in MM cells. Low micromolar concentrations of resminostat abrogates cell growth and strongly induces apoptosis in MM cell lines (OPM-2, NCI-H929, U266 ) as well as primary MM cells. At 1 μM, resminostat inhibits proliferation and induces G0/G1 cell cycle arrest in OPM-2, NCI-H929, U266 MM cell lines accompanied with decreased levels of cyclin D1, cdc25a, Cdk4 and pRb as well as upregulation of p21. Resminostat decreases phosphorylation of 4E-BP1 and p70S6k indicating an interference with Akt pathway signalling. Treatment with resminostat results in increased protein levels of Bim and Bax and decreases levels of Bcl-xL. Caspases 3, 8 and 9 are activated by resminostat. Furthermore, synergistic effects are observed For combinations of resminostat with melphalan and the proteasome inhibitors bortezomib and S-2209. 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. For the detailed information of Resminostat, the solubility of Resminostat in water, the solubility of Resminostat in DMSO, the solubility of Resminostat in PBS buffer, the animal experiment (test) of Resminostat, the cell expriment (test) of Resminostat, the in vivo, in vitro and clinical trial test of Resminostat, the EC50, IC50,and Affinity of Resminostat, Please contact DC Chemicals. |
