CH7057288 (CH-7057288) is a novel potent and selective pan-TRK inhibitor with IC50 of 1.1/7.8/5.1 nM for TRKA/TRKB/TRKC, respectively.
CH7057288 shows excellect selectivity, binds to only 6 kinases the KINOMEscan panel (403 non-mutant and 65 mutant kinases) at 100 nM.
CH7057288 suppresses TRK signaling and proliferation of TRK fusion-driven cancer cell (CUTO3, IC50= 9 nM), but not that of TRK-negative cell lines.
CH7057288 significantly induces tumor regression and improves event-free survival in an intracranial implantation model mimicking brain metastasis, maintaines similar levels of in vitro and in vivo activity against one of these resistant mutants as it did to wild‑type TRK.
