SCR130

SCR130 is a SCR7-based DNA nonhomologous end-joining (NHEJ) inhibitor. SCR130 inhibits the end-joining of DNA in a Ligase IV-dependent manner. SCR130 is specific to Ligase IV, and shows minimal or no effect on Ligase III and Ligase I mediated joining. SCR130 induces cell apoptosis and has anticancer activity[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA/RNA Synthesis

SCR130 (7-21 μM; 48 hours) increase in the number of late and early apoptotic cells. SCR130 induces apoptosis by both intrinsic and extrinsic pathways. SCR130 increases the expression of p-p53, BCL2 and MCL1, and CYTOCHROME C, BAX, and BAK also increaseed. The activation of caspase 8, increase in expression of FAS and SMAC-DIABLO proteins are also observed[1]. SCR130 (48 hours) exhibits cytotoxicity in Reh, HeLa, CEM, Nalm6, and N114 cells with IC50 values of 14.1 μM, 5.9 μM, 6.5 μM, 2.2 μM, and 11 μM, respectively[1]. SCR130 can potentiate the effect of radiation (0.5 and 1 Gy) by inducing enhanced cell death upon coadministration in Reh and Nalm6 cell lines[1]. SCR130 blocks the endogenous NHEJ leading to accumulation of unrepaired DNA breaks. Treatment with SCR130 leads to inhibition of endogenous NHEJ, resulting in the accumulation of DNA double-strand breaks (DSBs) and cell death by activating apoptotic pathways[1]. Apoptosis Analysis[1] Cell Line: Reh cells Concentration: 7 μM, 14 μM, and 21 μM Incubation Time: 48 hours Result: Showed a concentration-dependent increase in the number of late and early apoptotic cells. Western Blot Analysis[1] Cell Line: Reh cells Concentration: 7 μM, 14 μM, and 21 μM Incubation Time: 48 hours Result: Revealed a concentration-dependent increase in levels of pATM and activation of p53 through phosphorylation.

[1]. Ujjayinee Ray, et al. Identification and characterization of novel SCR7-based small-molecule inhibitor of DNA end-joining, SCR130 and its relevance in cancer therapeutics. Mol Carcinog. 2020 Jun;59(6):618-628.