tcbc074297 RP-3500

RP-3500 (RP3500) is a novel potent, selective, orally bioavailable ATR inhibitor with IC50 of 1.0 and 0.33 nM in biochemical and cell-based assays, respectively.

RP-3500 displays 30-fold selectivity over mTOR and >2,000-fold selectivity over ATM, DNA-PK, and PI3Kα kinases.

RP-3500 inhibited phosphorylated checkpoint kinase 1 (pCHK1) (IC80=18.6 nM) and induction of phosphorylated H2A.X variant histone (γH2AX), phosphorylated DNA-PK catalytic subunit (pDNA-PKcs), and phosphorylated KRAB-associated protein 1 (pKAP1).

RP-3500 demonstrated potent single-agent efficacy and/or tumor regression in multiple xenograft models at minimum effective doses (MED) of 5 to 7 mg/kg once daily.

RP-3500 demonstrated superior efficacy when combined with PARP inhibitor olaparib or niraparib.