INY-03-041 是一种有效且高度选择性的基于 PROTAC 的泛-AKT 降解物，由与来那度胺 (Cereblon 配体) 偶联的 ATP 竞争性 AKT 抑制剂 GDC-0068 组成。 INY-03-041 抑制 AKT1，AKT2 和 AKT3，IC50 分别为 2.0 nM，6.8 nM 和 3.5 nM。
货号:ajcx39818
CAS:2503017-97-6
分子式:C44H56ClN7O5
分子量：798.41
溶解度:DMSO : 115 mg/mL (144.04 mM; ultrasonic and warming and heat to 80°C)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

INY-03-041 is a potent, highly selective and PROTAC-based pan-AKT degrader consisting of the ATP-competitive AKT inhibitor GDC-0068 conjugated to Lenalidomide (Cereblon ligand). INY-03-041 inhibits AKT1, AKT2 and AKT3 with IC50s of 2.0 nM, 6.8 nM and 3.5 nM, respectively[1].

INY-03-041 (10-1000 nM; 2-24 hours; MDA-MB-468 cells) treatment induces potent degradation of all three AKT isoforms in a dose-dependent manner after a 12-h treatment, with maximal degradation observed between 100 and 250 nM. At concentrations of 500 nM and greater, AKT degradation is diminished. Treatment with 250 nM of INY-03-041 over time reveals partial degradation of all AKT isoforms within 4 h and progressive loss of AKT abundance out to 24 h[1].INY-03-041 exhibits potent in vitro inhibition of S6K1 (IC50 =37.3 nM) and PKG1 (IC50 = 33.2 nM)[1].INY-03-041 displays enhanced anti-proliferative effects compared with GDC-0068 in MDA-MB-468 and HCC1937 cells[1].

[1]. You I, et al. Discovery of an AKT Degrader with Prolonged Inhibition of Downstream Signaling. Cell Chem Biol. 2020 Jan 16;27(1):66-73.e7.

Protocol:

Akt1 2.0nM(IC50)

Akt2 6.8nM(IC50)

Akt3 3.5nM(IC50)

Cereblon