SN-38

SN-38 is an active metabolite of the Topoisomerase I inhibitor Irinotecan. SN-38 inhibits DNA and RNA synthesis with IC₅₀s of 0.077 and 1.3 μM, respectively. SN-38 is a payload of sacituzumab govitecan (HY -132254)^{[1][2][3][4][5]}. IC50 & Target:Topoisomerase I^[1] In Vitro:The IC₅₀ values for LoVo, HCT116, and HT29 cell lines is 20 nM, 50 nM, 130 nM, respectively. In all three SN-38 resistant cell lines Top1 activity is maintained in the presence of high concentrations of SN-38^[2]. In Vivo:SN-38, the active and toxic metabolite of the anticancer prodrug Irinotecan. At 30 minutes after administration, Irinotecan plasma concentrations in Slco1a/1b(-/-) mice are 1.9-fold higher than in the wild-type mice (1.89 vs. 1.01 μM, respectively), whereas SN-38 plasma concentrations of Slco1a/1b(-/-) mice are 8-fold higher compare with wild-type mice (0.4 μg/mL vs. 0.05 μg/mL, respectively). Overall plasma exposure [AUC_(5-240)] of Irinotecan is 1.7-fold higher in Oatp1a/1b knockout mice versus wild-type mice (209.8±6.7 vs. 120.9±4.4 μM/min; P<0.01), and 2.9-fold higher for SN-38 (50±2.9 vs. 12±2 μM/min; P<0.001)^[3].