CB-103 is an inhibitor of Notch signaling.1 It binds to the b-trefoil domain (BTD) of recombination signal binding protein for immunoglobulin kappa J region (RBPJ) and inhibits the assembly of the RBPJ-Notch intracellular domain (NICD) transcription complex. CB-103 inhibits ligand-induced Notch signaling in HeLa cells expressing mouse Notch1, -2, -3, or -4 (IC50s = 1.5, 0.9, 1.1, and 2.9 ?M, respectively). It reduces expression of the Notch target genes HES1, MYC, and DTX1 in RPMI-8402 T cell acute lymphoblastic leukemia (T-ALL) cells. In vivo, CB-103 (25 mg/kg) reduces tumor volume and increases survival in an HCC-1187 mouse xenograft model.
1.Lehal, R., Zaric, J., Vigolo, M., et al.Pharmacological disruption of the Notch transcription factor complexProc. Natl. Acad. Sci. USA117(28)16292-16301(2020)