2411853-34-2

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)[1].JR-AB2-011 decreases the phosphorylation level of Akt, decreases MMP2 activity, thereby reducing the ability of tumor cells to migrate and invade. JR-AB2-011 also induces non-apoptotic cell death[2].

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 treatment36.3% apoptosis post 48h 1 μM treatment in LN229 cultures) and in vivo (4 or 20 mg/kg/d i.p. to LN229 xenografted mice).

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/

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).

mTORC2: 0.36 μM (IC₅₀)

[1] Zhang A, et al. CCL17 exerts neuroprotection through activation of CCR4/mTORC2 axis in microglia after subarachnoid haemorrhage in rats. Stroke Vasc Neurol. 2022 Jul 26;8(1):4–16. DOI:10.1136/svn-2022-001659
[2] Guenzle J, et al. Pharmacological Inhibition of mTORC2 Reduces Migration and Metastasis in Melanoma. Int J Mol Sci. 2020 Dec 22;22(1):30
[3] Wu M, et al Dioscin ameliorates murine ulcerative colitis by regulating macrophage polarization. Pharmacol Res. 2021 Oct ; 172:105796 DOI:10.1016/j.phrs.2021.105796