INX-315 (INX315) is a highly potent, selective CDK2 inhibitor with IC50 of 0.6 and 2.5 nM for CDK2/cyclin E1 and CDK2/cyclin A2 respectively, shows high selectivity over other CDK family members.
INX-315 shows greater potency against CDK2/cyclin E1 in the NanoBRET assay (2.3 nM) and a greater selectivity over CDK1 and 9 compared to PF-07104091 (Cat# PC-20283).
INX-315 displays selectivity for CDK2/cyclin A1/E1/O with IC50 values of 4 nM or less, also potently inhibits CSF1R with IC50 of 2.29 nM.
INX-315 has a cellular mean IC50 of 26 nM against a panel of ovarian cancer cell lines (including five HGSOC with CCNE1-amplification), induces cell cycle arrest.
INX-315 promotes retinoblastoma protein hypo-phosphorylation and therapy-induced senescence (TIS) in CCNE1-amplified tumors, leading to durable control of tumor growth.
INX-315 overcomes breast cancer resistance to CDK4/6i, restoring cell cycle control whilst re-instating the chromatin architecture of CDK4/6i-induced TIS.
INX-315 delays the onset of CDK4/6i resistance in breast cancer by driving deeper suppression of E2F targets