Polθ/PARP-IN-1 (compound 25d) is a potent dual DNA polymerase theta (Polθ) and PARP inhibitor with IC50 values of 45.6, 5.4 nM, respectively. Polθ/PARP-IN-1 shows antiproliferative activity. Polθ/PARP-IN-1 induces apoptosis and cell cycle arrest at G2/M phase, causes DNA damage. Polθ/PARP-IN-1 shows anti-tumor activity [1].
In Vivo, Polθ/PARP-IN-1 (20, 40 mg/kg; i.p.; daily for 21 consecutive days) inhibits tumor growth in MDA-MB-436 xenograft model[1].
In Vitro, Polθ/PARP-IN-1 (compound 25d) (0-80 µM; 3 days) shows antiproliferative activity with IC50s of 20.9, 2.7, 8.9, 2.9, 18.9, >80 µM for HCC1937, MDA-MB-436, HCT116, SW48, SKOV-3, MCF-10A cells, respectively[1]. Polθ/PARP-IN-1 (compound 25d) (2 µM; 3 days) induces apoptosis and cell cycle arrest at G2/M phase, causes DNA damage[1].
References:
[1]. Ma L, et al. Discovery and Proof of Concept of Potent Dual Polθ/PARP Inhibitors for Efficient Treatment of Homologous Recombination-Deficient Tumors. J Med Chem. 2024 Feb 20.
In Vivo, Polθ/PARP-IN-1 (20, 40 mg/kg; i.p.; daily for 21 consecutive days) inhibits tumor growth in MDA-MB-436 xenograft model[1].
In Vitro, Polθ/PARP-IN-1 (compound 25d) (0-80 µM; 3 days) shows antiproliferative activity with IC50s of 20.9, 2.7, 8.9, 2.9, 18.9, >80 µM for HCC1937, MDA-MB-436, HCT116, SW48, SKOV-3, MCF-10A cells, respectively[1]. Polθ/PARP-IN-1 (compound 25d) (2 µM; 3 days) induces apoptosis and cell cycle arrest at G2/M phase, causes DNA damage[1].
References:
[1]. Ma L, et al. Discovery and Proof of Concept of Potent Dual Polθ/PARP Inhibitors for Efficient Treatment of Homologous Recombination-Deficient Tumors. J Med Chem. 2024 Feb 20.