PARP1/NAMPT-IN-1 is a potent and dual PARP1 and NAMPT inhibitor with IC50 values of 1.2 nM and 6.7 nM, respectively. PARP1/NAMPT-IN-1 can disrupt the homologous recombination repair (HRR) pathway, leading to the accumulation of DNA double-strand breaks (DSBs), inducing cell cycle arrest and apoptosis, and also has antimigratory effects. PARP1/NAMPT-IN-1 exhibits excellent antitumor effects in a breast cancer xenograft model. PARP1/NAMPT-IN-1 can be used for the study of triple-negative breast cancer (TNBC) [1].
In Vivo, PARP1/NAMPT-IN-1 (compound 10 n) (5-10 mg/kg; i.p.; once a day; for 14 days) has antitumor efficacy with a good safety profile in MDA-MB-231 xenograft models[1]. PARP1/NAMPT-IN-1 (5 mg/kg; i.p.; once a day; for 5 days) effectively inhibits in 4T1 mouse xenograft models[1]. PARP1/NAMPT-IN-1 (5 mg/kg; i.p.; once a day; for 14 days) activates the STING pathway to drive antitumor immunity in 4T1murine BRCA wild-Type TNBC model[1].
In Vitro, PARP1/NAMPT-IN-1 (compound 10 n) (24 h-7 days) shows selective antiproliferative activity against MDA-MB-231 cells (IC50 = 1.28 nM) and MDA-MB-468 cells (IC50 = 0.46 nM). PARP1/NAMPT-IN-1 shows the negligible cytotoxic effects (IC50 > 20 μM) against MCF-10A cells[1]. PARP1/NAMPT-IN-1 (0.3-1 μM; 48 h) induces cell cycle arrest and apoptosis in MDA-MB-231 cells[1]. PARP1/NAMPT-IN-1 (0.3-1 μM; 48 h) disrupts HRR pathway to induce synthetic lethality and rrigger DSBs in MDA-MB-231 cells[1]. PARP1/NAMPT-IN-1 (0.3-1 μM; 48 h) exhibits marked antimigratory effects in MDA-MB-231 cells[1]. PARP1/NAMPT-IN-1 (0.3-1 μM; 48 h) significantly increases cGAS level and phosphorylation of STING, TBK1, and IRF3 in 4T1 cells in vitro, suggesting its intratumoral activation of STING signaling pathway[1]. PARP1/NAMPT-IN-1 (0.3-1 μM; 48 h) enhances TBK1 and IRF3 phosphorylation in MDA-MB-231 cells[1].
References:
[1]. Wang K, et al. Dual PARP/NAMPT Inhibitors for BRCA Wild-Type Triple-Negative Breast Cancer: Disrupting Homologous Recombination Repair and Activating Antitumor Immunity. J Med Chem. 2026 Feb 12;69(3):2746-2772.
In Vivo, PARP1/NAMPT-IN-1 (compound 10 n) (5-10 mg/kg; i.p.; once a day; for 14 days) has antitumor efficacy with a good safety profile in MDA-MB-231 xenograft models[1]. PARP1/NAMPT-IN-1 (5 mg/kg; i.p.; once a day; for 5 days) effectively inhibits in 4T1 mouse xenograft models[1]. PARP1/NAMPT-IN-1 (5 mg/kg; i.p.; once a day; for 14 days) activates the STING pathway to drive antitumor immunity in 4T1murine BRCA wild-Type TNBC model[1].
In Vitro, PARP1/NAMPT-IN-1 (compound 10 n) (24 h-7 days) shows selective antiproliferative activity against MDA-MB-231 cells (IC50 = 1.28 nM) and MDA-MB-468 cells (IC50 = 0.46 nM). PARP1/NAMPT-IN-1 shows the negligible cytotoxic effects (IC50 > 20 μM) against MCF-10A cells[1]. PARP1/NAMPT-IN-1 (0.3-1 μM; 48 h) induces cell cycle arrest and apoptosis in MDA-MB-231 cells[1]. PARP1/NAMPT-IN-1 (0.3-1 μM; 48 h) disrupts HRR pathway to induce synthetic lethality and rrigger DSBs in MDA-MB-231 cells[1]. PARP1/NAMPT-IN-1 (0.3-1 μM; 48 h) exhibits marked antimigratory effects in MDA-MB-231 cells[1]. PARP1/NAMPT-IN-1 (0.3-1 μM; 48 h) significantly increases cGAS level and phosphorylation of STING, TBK1, and IRF3 in 4T1 cells in vitro, suggesting its intratumoral activation of STING signaling pathway[1]. PARP1/NAMPT-IN-1 (0.3-1 μM; 48 h) enhances TBK1 and IRF3 phosphorylation in MDA-MB-231 cells[1].
References:
[1]. Wang K, et al. Dual PARP/NAMPT Inhibitors for BRCA Wild-Type Triple-Negative Breast Cancer: Disrupting Homologous Recombination Repair and Activating Antitumor Immunity. J Med Chem. 2026 Feb 12;69(3):2746-2772.