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PARP1/c-Met-IN-1 (Compound 16) is a selective dual inhibitor for PARP1 and c-Met, with IC50s of 3.3 and 32.2 nM, respectively. PARP1/c-Met-IN-1 induces cell apoptosis and cell cycle arrest in G2/M phase in MDA-MB-231 cells. PARP1/c-Met-IN-1 exhibits antitumor activity in mice[1]. | [in vivo]
PARP1/c-Met-IN-1 (12.5-100 mg/kg, i.p. for 28 days) exhibits antitumor efficacy with tumor growth inhibition (TGI) values of 49-77 % and 62-70 % in MDA-MB-231 and HCT116OR xenograft nude mice, respectively[1].
Pharmacokinetic Analysis of PARP1/c-Met-IN-1 in BALB/c mice[1]
| route | Dose (mg/kg) | T1/2 (h) | Tmax (h) | Cmax (ng/mL) | AUC0-t (ng·h/mL) | AUC0-inf (ng·h/mL) | MRT0-t (h) | MRT0-inf (h) | CLblood (mL/h/kg) | | i.p. | 10 | 1.42 | 0.25 | 152.47 | 95.42 | 96.70 | 1.67 | 1.77 | 121232 |
| Animal Model: | MDA-MB-231 and HCT116OR xenograft BALB/c nude mice[1] | | Dosage: | 12.5-50 mg/kg for MDA-MB-231 xenograft mice, 20-100 mg/kg for HCT116OR xenograft mice | | Administration: | I.p., 21 days for HCT116OR xenograft mice, 28 days for MDA-MB-231 xenograft mice | | Result: | Inhibited tumor growth with TGI of 49-77% in MDA-MB-231 xenograft mice.
Inhibited tumor growth with TGI of 62-70% in HCT116OR xenograft mice. |
| [IC 50]
PARP1: 3.3 nM (IC50); c-Met: 32.2 nM (IC50) | [References]
[1] Sun Z, et al., Rational Design of PARP1/c-Met Dual Inhibitors for Overcoming PARP1 Inhibitor Resistance Induced by c-Met Overexpression. J Med Chem. 2024 Mar 28;67(6):4916-4935. DOI:10.1021/acs.jmedchem.4c00077 |
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