RP-6685 is a potent, selective and orally active DNA polymerase theta (Polθ) inhibitor with an IC50 value of 5.8 nM (PicoGreen assay). RP-6685 shows antitumor efficacy in mouse tumor xenograft model[1].
RP-6685 is extremely potent with an IC50 of 550 pM against the pol activity of full-length Polθ and inactive on the ATPase activity[1].
RP-6685 inhibits Polθ in HEK293 LIG4-/- cellswith an IC50 of 0.94 μM[1].
RP-6685 (80 mg/kg; p.o.; BID for 21 days) exhibits 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: |
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[1]. Bubenik M, et al. Identification of RP-6685, an Orally Bioavailable Compound that Inhibits the DNA Polymerase Activity of Polθ. J Med Chem. 2022 Sep 20.