SC-13

SC-13 is an inhibitor of flap endonuclease 1 (FEN1; IC₅₀ = 4.2 nM) and an activator of stimulator of interferon genes (STING).^1,2 It increases the levels of γ histone H2AX (γH2AX) in MCF-7 and MDA-MB-231 breast cancer cells when used at a concentration of 40 µM.¹ SC13 (20 or 50 µM) induces chromosomal aberrations in MCF-7 cells. It potentiates the proliferation inhibition induced by cisplatin (Item No. 13119), 5-fluorouracil (Item No. 14416), or temozolomide (Item No. 14163) in MCF-7 cells when used at a concentration of 20 µM. SC-13 (20 µM) increases levels of cyclic GMP-AMP (cGAMP) synthase (cGAS), phosphorylated STING, chemokine (C-C motif) ligand 5 (CCL5), and CCL10 in HeLa cervical cancer and MCF-7 cells.² In vivo, SC-13 (5 mg/kg every other day), in combination with T cells expressing chimeric antigen receptors (CARs), reduces tumor volume and weight without affecting body weight, as well as increases the number of CD8⁺ T cell tumor infiltrates, in a HeLa mouse xenograft model.

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1. He, L., Zhang, Y., Sun, H., et al. Targeting DNA flap endonuclease 1 to impede breast cancer progression. EBioMedicine 14, 32-43 (2016).

2. Dong, Y., Wang, Y., Yin, X., et al. FEN1 inhibitor SC13 promotes CAR-T cells infiltration into solid tumours through cGAS-STING signalling pathway. Immunology 170(3), 388-400 (2023).