PARP1/c-Met-IN-3 (Compound L19) is a selective c-Met and PARP1 inhibitor, with an IC50 of 5.4 nM against c-Met and an IC50 of 3.7 nM against PARP1. PARP1/c-Met-IN-3 inhibits PARP2 enzymatic activity with an IC50 of 4.52 nM, and shows no specificity for PARP1 and PARP2. PARP1/c-Met-IN-3 induces cell cycle arrest and apoptosis. PARP1/c-Met-IN-3 exhibits anti-tumor activity against triple-negative breast cancer [1].
In Vivo, PARP1/c-Met-IN-3 (10 mg/kg, i.p., once every other day for 30 consecutive days) exhibits antitumor activity in Balb/c nude mice bearing MDA-MB-231 xenografts[1]. PARP1/c-Met-IN-3 (10 mg/kg; i.p.; administered once every other day for 28 consecutive days) achieves a 56% tumor growth inhibition rate in NCG mice bearing MDA-MB-231 xenografts, with low observed toxicity[1].
In Vitro, PARP1/c-Met-IN-3 (L19) potently inhibits c-Met enzymatic activity with an IC50 of 5.4 ± 0.4 nM[1]. PARP1/c-Met-IN-3 (L19) potently inhibits the enzymatic activity of PARP1, with an IC50 of 3.7 ± 0.3 nM[1]. PARP1/c-Met-IN-3 (L19) inhibits the enzymatic activity of PARP2 with an IC50 of 4.52 ± 0.52 nM, and lacks specificity for PARP1 and PARP2[1]. PARP1/c-Met-IN-3 (L19) (72 h) potently inhibits the proliferation of BRCA wild-type triple-negative breast cancer cell lines (MDA-MB-231, MDA-MB-453, MDA-MB-468, BT-549), with IC50 values ranging from 0.19 ± 0.07 μM to 1.61 ± 0.02 μM; it shows weak activity against BRCA1-mutant HCC1937 cells (IC50 = 8.95 ± 0.85 μM)[1]. PARP1/c-Met-IN-3 (L19) (0.05-1 μM; 72 h) inhibits the invasion of MDA-MB-231 cells in a concentration-dependent manner[1]. PARP1/c-Met-IN-3 (L19) (0.1-4 μM; 72 h) induces apoptosis and activates apoptotic signaling pathways in MDA-MB-231 cells in a concentration-dependent manner in vitro[1]. PARP1/c-Met-IN-3 (L19) (0.5-4 μM; 72 h) arrests MDA-MB-231 cells at the S phase in a concentration-dependent manner[1].
References:
[1]. Liu F, et al. Design and synthesis of c-Met/PARP dual-target inhibitors for the treatment of BRCA wild-type TNBC. Eur J Med Chem. 2026;308:118722.
In Vivo, PARP1/c-Met-IN-3 (10 mg/kg, i.p., once every other day for 30 consecutive days) exhibits antitumor activity in Balb/c nude mice bearing MDA-MB-231 xenografts[1]. PARP1/c-Met-IN-3 (10 mg/kg; i.p.; administered once every other day for 28 consecutive days) achieves a 56% tumor growth inhibition rate in NCG mice bearing MDA-MB-231 xenografts, with low observed toxicity[1].
In Vitro, PARP1/c-Met-IN-3 (L19) potently inhibits c-Met enzymatic activity with an IC50 of 5.4 ± 0.4 nM[1]. PARP1/c-Met-IN-3 (L19) potently inhibits the enzymatic activity of PARP1, with an IC50 of 3.7 ± 0.3 nM[1]. PARP1/c-Met-IN-3 (L19) inhibits the enzymatic activity of PARP2 with an IC50 of 4.52 ± 0.52 nM, and lacks specificity for PARP1 and PARP2[1]. PARP1/c-Met-IN-3 (L19) (72 h) potently inhibits the proliferation of BRCA wild-type triple-negative breast cancer cell lines (MDA-MB-231, MDA-MB-453, MDA-MB-468, BT-549), with IC50 values ranging from 0.19 ± 0.07 μM to 1.61 ± 0.02 μM; it shows weak activity against BRCA1-mutant HCC1937 cells (IC50 = 8.95 ± 0.85 μM)[1]. PARP1/c-Met-IN-3 (L19) (0.05-1 μM; 72 h) inhibits the invasion of MDA-MB-231 cells in a concentration-dependent manner[1]. PARP1/c-Met-IN-3 (L19) (0.1-4 μM; 72 h) induces apoptosis and activates apoptotic signaling pathways in MDA-MB-231 cells in a concentration-dependent manner in vitro[1]. PARP1/c-Met-IN-3 (L19) (0.5-4 μM; 72 h) arrests MDA-MB-231 cells at the S phase in a concentration-dependent manner[1].
References:
[1]. Liu F, et al. Design and synthesis of c-Met/PARP dual-target inhibitors for the treatment of BRCA wild-type TNBC. Eur J Med Chem. 2026;308:118722.