JR-AB2-011 is a selective mTORC2 inhibitor with an IC 50 value of 0.36 μM. JR-AB2-011 inhibits mTORC2 activity by blocking Rictor-mTOR association ( K i : 0.19 μM). JR-AB2-011 has anti-glioblastoma multiforme (GBM) properties
In Vitro
JR-AB2-011 (1 μM; 24 hours) has good anti-GBM properties, blocks mTORC2 signaling and Rictor association with mTOR. ?\nJR-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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Apoptosis AnalysisCell 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 AssayCell 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.
In Vivo
Mice receiving JR-AB2-011 (4 mg/kg; daily i.p. for 10 days; 20 mg/kg; daily i.p. for 10 days) at either dosing regimen display marked inhibition of tumor growth rate (JR-AB2-011 at 4 mg/kg/d; 74% inhibition at end of dosing period; tumor growth delay 10.0 days; JR-AB2-011 at 20 mg/kg/d; 80% inhibition at end of dosing period; tumor growth delay 12.0 days) as compared to mice receiving vehicle alone . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: LN229 cells in female C.B.-17-scid (Taconic) mice Dosage: 4 mg/kg; 20 mg/kg Administration: Daily i.p.; 10 days Result: Either dosing regimen displayed marked inhibition of tumor growth rate as compared to mice receiving vehicle alone.
