AES-135 是一种基于羟肟酸的泛 HDAC 抑制剂，可延长胰腺癌原位小鼠模型的存活时间。AES-135 抑制 HDAC3、HDAC6、HDAC8 和 HDAC11，IC50 范围为190-1100 nM。
货号:ajcx39370
CAS:2361659-61-0
分子式:C33H29F6N3O5S
分子量：693.66
溶解度:DMSO : 100 mg/mL (144.16 mM; Need ultrasonic)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

AES-135, a hydroxamic acid-based pan-HDAC inhibitor, prolongs survival in an orthotopic mouse model of pancreatic cancer. AES-135 inhibits HDAC3, HDAC6, HDAC8, and HDAC11 with IC50s ranging from 190-1100 nM[1].

AES-135 inhibits cancer cells growth with IC50 values of 2.3 µM, 1.4 µM, 0.27 µM, 0.94 µM, 1.9 µM, 2.72 µM, 2.1 µM, 15.0 µM, 1.6 µM and 19.2 µM for BT143, BT189, D425, D458, MV4-11, MOLM-13, MDA-MB-231, K562, PC-3 and MRC-9 cells, respectively[1].

AES-135 (50 mg/kg; intraperitoneal injection; 5 days a week; for 1 month) treatment significantly increases survival of C57Bl/6 mice implanted with KPC2 cells[1].NSG mice are dosed with a single 20 mg/kg intraperitoneal (IP) injection, and blood is taken at 0.5 h, 1 h, 2 h, 4 h, 8 h, and 24 h. AES-135 achieved μM concentrations in the blood, reaching Cmax 7452 ng/mL (10.74 μM) within 30 min, which is sustained for 8 h. The blood concentration of AES-135 is dose dependent, achieving an average of 323 ng/mL (0.47 μM) with 10 mg/kg dosing and 1829 ng/mL (2.64 μM) with 40 mg/kg. AES-135 shows an impressive pharmacokinetic profile in mice with an in vivo half-life of 5.0 h[1].

[1]. Shouksmith AE, et al. Identification and Characterization of AES-135, a Hydroxamic Acid-Based HDAC Inhibitor That Prolongs Survival in an Orthotopic Mouse Model of Pancreatic Cancer. J Med Chem. 2019 Mar 14;62(5):2651-2665.

Protocol:

HDAC6 190nM(IC50)

HDAC11 636nM(IC50)

HDAC3 654nM(IC50)

HDAC8 1100nM(IC50)