JR-AB2-011 is a selective mTORC2 inhibitor with an IC50 value of 0.36 μM. It inhibits mTORC2 activity by blocking Rictor-mTOR association (Ki: 0.19 μM) and exhibits cytotoxicity in glioblastoma [1].

mTORC2:0.36 μM

JR-AB2-011 (1 μM; 24 hours) shows good anti-GBM properties, blocks mTORC2 signaling and Rictor association with mTOR [1]. JR-AB2-011 (0.5-2 μM; 48 hours) displays the least toxicity to normal neurons with no significant cytotoxic effects for concentrations up to 10 mM compared to CID613034 [1]. Apoptosis Analysis [1] Cell Line: U87 GBM cells; LN229 GBM cells Concentration: 1 μM Incubation Time: 24 hours Result: Had good anti-GBM properties and blocked mTORC2 signaling and Rictor association with mTOR. Cell Cytotoxicity Assay [1] Cell Line: Normal mature human neurons Concentration: 0.5, 1, 2 μM Incubation Time: 48 hours Result: Displayed the least toxicity to normal neurons with no significant cytotoxic effects for concentrations up to 10 mM.

Mice administered JR-AB2-011 through intraperitoneal injection at doses of 4 mg/kg or 20 mg/kg daily for 10 days exhibited significant suppression of tumor growth compared to those treated with a vehicle control. Specifically, the lower dose achieved a 74% reduction in tumor growth rate with a 10-day delay in tumor progression, while the higher dose resulted in an 80% reduction and a 12-day delay. This study utilized female C.B.-17-scid mice implanted with LN229 cells, demonstrating that JR-AB2-011 is potent in inhibiting tumor growth at both tested concentrations.