Rheb inhibitor NR1 (C09-1167-849)

Rheb inhibitor NR1 is a Rheb inhibitor with an IC 50 of 2.1 µM in the Rheb-IVK assay. Rheb inhibitor NR1 can directly bind Rheb in the switch II domain and selectively inhibit the activation of mechanistic target of rapamycin complex 1 (mTORC1) . Rheb inhibitor NR1 inhibits the phosphorylation of mTORC1 driven T389 pS6K1 and increases the phosphorylation of S473 pAKT in a dose-dependent manner. Rheb inhibitor NR1 does not influence mTORC2 activity (Rheb-IVK: Rheb-dependent mTORC1 kinase activity)In VitroNR1 (1-10 μM; 48 h) reduces the size of Jurkat cells. NR1 (0.37-30 μM; 90 min for MCF-7 and TRI102; 24 h for PC3) inhibits the phosphorylation of T389 pS6K1 and increases the phosphorylation of S473 pAKT in MCF-7, TRI102 and PC3 cells. NR1 (1-30 μM; 2.5 h) reduced protein synthesis in MCF-7. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: Jurkat cells Concentration: 1, 3 and 10 μM Incubation Time: 48 h Result: Effectively reduced the size of Jurkat cells in a dose-dependent manner. Western Blot AnalysisCell Line: MCF-7, TRI102 and PC3 cells Concentration: 0.37, 1.1, 3.3, 10 and 30 μM Incubation Time: 90 min for MCF-7 and TRI102; 24 h for PC3 Result: Inhibited the phosphorylation of T389 pS6K1 and increased the phosphorylation of S473 pAKT in a dose-dependent manner. Western Blot AnalysisCell Line: MCF-7 Concentration: 1, 3, 10 and 30 μM Incubation Time: 2.5 h (then labeled the cells with an 35 S-Met labeling mix for 30 min) Result: Dose-dependently reduced protein synthesis.In VivoNR1 (30 mg/kg; IP; single dosage) significantly reduces mTORC1 activity in both kidney and skeletal muscle, and exhibited a clear band shift for T37/46 4E-BP1 in skeletal muscle . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male C57BL/6 mice (6-7 weeks; fast for 16 hours) Dosage: 30 mg/kg Administration: IP; single dosage Result: Sustained over 5 µM for 2 h. Significantly reduced mTORC1 activity in both kidney and skeletal muscle, and exhibited a clear band shift for T37/46 4E-BP1 in skeletal muscle.Form:SolidIC50& Target:Rheb, mTORC1. Specification: 0.99 Molecular Formula: C25H19BrCl2N2O3S Molecular Weight: 578.3 PubChem CID: 132281917 Isomeric SMILES: CN(C)C(=O)C1=CC=C(C=C1)CN2C(=CC3=C2C=C(C=C3Br)SC4=CC(=C(C=C4)Cl)Cl)C(=O)O