Akt3 degrader 1

Akt3 degrader 1 (compound 12l) is a selective Akt3 degrader that overcomes Osimertinib (HY-15772)-induced resistance in H1975OR NSCLC cells. Akt3 degrader 1 also has anti-proliferative activity and significantly inhibits tumour growth in mice. Akt3 degrader 1 can be used in the study of drug-resistant non-small cell lung cancer[1].

Research Areas >> Cancer

Signaling Pathways >> PI3K/Akt/mTOR >> Akt

Akt3[1].

Akt3 degrader 1 (0.001-100 µM; 24 h) shows antiproliferative effects on H1975OR cells with an IC50 of 0.972 µM[1]. Akt3 degrader 1 (1.6, 8, 40, 200, 1000 nM; 24 h) induces degradation of Akt3 through the ubiquitin proteasome-mediated proteolysis process in NSCLC cell lines[1]. Akt3 degrader 1 (10, 100 nM) selectively and dose-dependently degrades exogenous PH domain-only Akt3 protein but not the Akt3 del PH mutant in H1975OR cells[1]. Akt3 degrader 1 overcomes osimertinib-induced resistance in H1975OR NSCLC cells via disrupting the noncatalytic functions of Akt3[1]. Cell Proliferation Assay[1] Cell Line: H1975OR cells Concentration: 0.001-100 µM Incubation Time: 24 h Result: Inhibited growth of H1975OR cells with an IC50 of 0.972 µM. Western Blot Analysis[1] Cell Line: A549, HCC827, H1975, H1975OR, PC9, H1299, and H460 cells Concentration: 1.6, 8, 40, 200, 1000 nM Incubation Time: 24 h Result: Selectively induced Akt3 degradation in all of these cell lines in a dose-dependent manner, whereas had minimal influence on Akt1 and Akt2 protein levels.

Akt3 degrader 1 (10, 20 mg/kg; i.p.; every 3 days for 5 weeks) induces significant tumor growth inhibition (TGI) with an approximately TGI value of 75% in mice[1]. Animal Model: NOD-SCID-IL2Rg-/-(NSI) mice (H1975OR xenograft model)[1]. Dosage: 10, 20 mg/kg Administration: Intraperitoneal administration; every 3 days for 5 weeks Result: Inhibited tumor growth without causing obvious body weight loss or other signs of toxicity.