3-Thiazolidinecarboxamide, N-(3,4-dichlorophenyl)-2-[(4-fluorophenyl)imino]-5-methyl-

Biological Activity

JR-AB2-011 is a selective mTORC2 inhibitor th at blocks the interaction of Rictor and mTOR (IC50 = 0.31 μM) without affecing mTORC1 activity or assembly. JR-AB2-011 exhibits anti-glioblastoma (GBM) activity in vitro (proliferation IC50 = 0.31 μM post 72h treatment, 36.3% apoptosis post 48h 1 μM treatment in LN229 cultures) and in vivo (4 or 20 mg/kg/d i.p. to LN229 xenografted mice).

in vivo

Mice were subcutaneously implanted with tumor cells and when tumors were palpable (~200 mm3), mice were randomized into treatment groups receiving vehicle, JR-AB2-011 (4 mg/kg/d) and JR-AB2-011 (20 mg/kg/d). As shown in Fig 6A, mice receiving JR-AB2-011 at either dosing regimen displayed 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. Consistent with the effects on xenograft growth, overall survival of mice at either JR-AB2-011 dosing regimen was significantly extended relative to vehicle treated mice. _x000D_ _x000D_ Reference: PLoS One. 2017 Apr 28;12(4):e0176599. https://pubmed.ncbi.nlm.nih.gov/28453552/

target

JR-AB2-011 is a selective mTORC2 inhibitor with an IC50 value of 0.36 μM. JR-AB2-011 inhibits mTORC2 activity by blocking Rictor-mTOR association (Ki: 0.19 μM).