Rheb inhibitor NR1

• CAT Number: I017622
• CAS Number: 2216763-38-9
• Molecular Formula: C25H19BrCl2N2O3S
• Molecular Weight: 578.30
• Purity: ≥95%
• Synonyms: 4-bromo-6-(3,4-dichlorophenyl)sulfanyl-1-[[4-(dimethylcarbamoyl)phenyl]methyl]indole-2-carboxylic acid
• InChI: InChI=1S/C25H19BrCl2N2O3S/c1-29(2)24(31)15-5-3-14(4-6-15)13-30-22-11-17(34-16-7-8-20(27)21(28)10-16)9-19(26)18(22)12-23(30)25(32)33/h3-12H,13H2,1-2H3,(H,32,33)
• InChIKey: MJYFVDNMTKLGTH-UHFFFAOYSA-N
• 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

Rheb inhibitor NR1 is a Rheb inhibitor with an IC50 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 T389pS6K1 and increases the phosphorylation of S473pAKT in a dose-dependent manner. Rheb inhibitor NR1 does not influence mTORC2 activity[1].
(Rheb-IVK: Rheb-dependent mTORC1 kinase activity)
NR1 (1-10 μM; 48 h) reduces the size of Jurkat cells[1].
NR1 (0.37-30 μM; 90 min for MCF-7 and TRI102; 24 h for PC3) inhibits the phosphorylation of T389pS6K1 and increases the phosphorylation of S473pAKT in MCF-7, TRI102 and PC3 cells[1].
NR1 (1-30 μM; 2.5 h) reduced protein synthesis in MCF-7[1].
NR1 (30 mg/kg; IP; single dosage) significantly reduces mTORC1 activity in both kidney and skeletal muscle, and exhibited a clear band shift for T37/464E-BP1 in skeletal muscle[1].

Reference

[1]. Mahoney SJ, et al. A small molecule inhibitor of Rheb selectively targets mTORC1 signaling. Nat Commun. 2018 Feb 7;9(1):548.
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