Selective and orally active HDAC6 inhibitor
CAS：1316215-12-9
分子式：C24H26ClN5O3
分子量：467.95
纯度：98%
存储：Store at -20°C

Background:

ACY-241 is a new, selective and orally available inhibitor of HDAC6 [1][2].

Histone deacetylase 6 (HDAC6) is an enzyme that removes acetyl groups from an ε-N-acetyl lysine on a histone, allowing the histones to wrap the DNA more tightly. HDAC6 plays an important role in transcriptional regulation and cell cycle progression.

ACY-241 is a new, selective and orally available HDAC6 inhibitor. In MM and MCL cells, the addition of ACY-241 to either lenalidomide (len) or pomalidomide (pom) resulted in synergistic increases in apoptosis and further reduced the expression of transcription factors MYC and IRF4 [1]. In multiple solid tumor cell lines, combination treatment with ACY-241 and paclitaxel resulted in enhanced inhibition of cell proliferation and increased cell death, compared with either single agent alone [2].

In MM xenograft model, combination treatment with ACY-241 and pomalidomide was well tolerated with no overt toxicity and significantly extended survival [1]. In xenograft models of pancreatic and ovarian cancer, combination treatment with ACY-241 and paclitaxel significantly increased mitotic cells with multipolar spindles. ACY-241 dose-dependently increased α-tubulin hyperacetylation [2].

参考文献:
[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