RP-6685是一种有效且具有选择性和口服活性的 DNA 聚合酶 θ (Polθ) 抑制剂，PicoGreen 实验表明其IC50值为5.8 nM。RP-6685 在小鼠肿瘤移植模型中显示出抗肿瘤功效。

RP-6685 is a potent, selective and orally active DNA polymerase theta (Polθ) inhibitor with an IC 50 value of 5.8 nM in PicoGreen assay. RP-6685 shows antitumor efficacy in mouse tumor xenograft model [1].

RP-6685 is extremely potent with an IC 50 of 550 pM against the pol activity of full-length Polθ whereas inactive on the ATPase activity [1]. RP-6685 inhibits Polθ in HEK293 LIG4 -/- cellswith an IC 50 of 0.94 μM [1].

RP-6685 (80 mg/kg; p.o.; BID for 21 days) shows potent antitumor efficacy in BRCA2-deficient HCT116 mice [1]. Animal Model: Female CD1 nude mice (HCT116 BRCA2 +/+ and BRCA2 -/- xenograft tumor models) [1] Dosage: 80 mg/kg Administration: p.o.; BID for 21 days Result: Showed tumor regression during the first 8 days of treatment in BRCA2 -/- HCT116 model, while did not inhibit tumor growth in BRCA2 +/+ HCT116 tumors mice. Animal Model: CD1 mice (20-30 g) [1] Dosage: 2.5 mg/kg Administration: i.v. or p.o.; single dosage Result: CL (mL/min/kg) V dss (L/kg) t 1/2 (h) F (%) 36.8 1.1 0.4 66

2832047-80-8

C22H14F7N5O

497.37

DMSO:112.5mg/mL (226.2mM),Need ultrasonic
Powder: -20°C for 3 years
In solvent: -80°C for 2 years