CHDI-390576，一种有效的细胞渗透性和中枢神经系统渗透性的 IIa 类组织乙酰酶 (HDAC) 抑制剂，IIa 类 HDAC 4、HDAC 5、HDAC 7、HDAC 9 的 IC50 值分别为 54 nM、60 nM、31 nM、50 nM，选择性高于 I 类 HDAC (1, 2, 3) 500 倍，高于 HDAC8 和 IIb 类 HDAC6 亚型约 150 倍。
货号:ajcx38602
CAS:1629729-98-1
分子式:C19H13F4N3O2
分子量：391.32
溶解度:DMSO : 250 mg/mL (638.86 mM; Need ultrasonic)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

CHDI-390576, a potent, cell permeable and CNS penetrant class IIa histone deacetylase (HDAC) inhibitor with IC50s of 54 nM, 60 nM, 31 nM, 50 nM for class IIa HDAC4, HDAC5, HDAC7, HDAC9, respectively, shows >500-fold selectivity over class I HDACs (1, 2, 3) and ~150-fold selectivity over HDAC8 and the class IIb HDAC6 isoform[1].

The affinity (Kd) of CHDI-390576 to the catalytic domain of immobilized HDAC4 is 80 nM[1].CHDI-390576 inhibits class I HDACs (1, 3, 8) and class IIb HDAC6 isoforms with IC50s of 39.7μM, 25.8 μM, 9.1 μM, 6.2 μM, respectively[1].

[1]. Luckhurst CA, et al. Development and characterization of a CNS-penetrant benzhydryl hydroxamic acid class IIa histone deacetylase inhibitor. Bioorg Med Chem Lett. 2019 Jan 1;29(1):83-88.

Protocol:

HDAC4 54nM(IC50)

HDAC5 60nM(IC50)

HDAC7 31nM(IC50)

hHDAC9 50nM(IC50)

HDAC1 39.7μM(IC50)

HDAC3 25.8μM(IC50)

HDAC8 9.1μM(IC50)

hHDAC6 6.2μM(IC50)