RP-6685

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].

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA/RNA Synthesis

IC50: 5.8 nM (Polθ)[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: CL (mL/min/kg) Vdss (L/kg) t1/2 (h) F (%) 36.8 1.1 0.4 66