Citarinostat

Description

ACY-241 is an inhibitor of histone deacetylase 6 (HDAC6; IC₅₀ = 2.6 nM). It is selective for HDAC6 over HDAC1-3, HDAC7, and HDAC9 (IC₅₀s = 35, 45, 46, 7,300, and 137 nM, respectively), as well as HDAC4, HDAC5, and HDAC9 (IC₅₀ = >20,000 nM for all). It reduces proliferation of A2780, TOV-21G, and MDA-MB-231 cells when used at a concentration of 3 μM and completely inhibits it and induces apoptosis at a concentration of 10 μM. ACY-241, when used in combination with paclitaxel , inhibits proliferation in MiaPaCa-2, TOV-21G, and T47D cells. It also reduces tumor growth in a MiaPaCa-2 mouse xenograft model when administered at a dose of 50 mg/kg in combination with paclitaxel. ACY-241, in combination with the somatostatin receptor agonist pasireotide , reduces hepatorenal cystogenesis in a rat model of polycystic liver disease.

Uses

Citarinostat is a HDAC inhibitor.

References

[1]. quayle sn, almeciga-pinto i, tamang d, et al. selective hdac inhibition by ricolinostat (acy-1215) or acy-241 synergizes with imid® immunomodulatory drugs in multiple myeloma (mm) and mantle cell lymphoma (mcl) cells. in: proceedings of the 106th annual meeting of the american association for cancer research, 2015, philadelphia, pa. philadelphia (pa): aacr; cancer res 2015;75(15 suppl):abstract nr 5380.
[2]. huang p, almeciga-pinto i, jordan m, et al. selective hdac inhibition by acy-241 enhances the activity of paclitaxel in solid tumor models. in: proceedings of the 2015 aacr-nci-eortc international conference on molecular targets and cancer therapeutics; 2015 nov 5-9; boston, massachusetts. philadelphia (pa): aacr