TNO155 is a potent selective and orally active allosteric inhibitor of wild-type SHP2 (IC50=0.011 µM). TNO155 has the potential for the study of RTK-dependent malignancies, especially advanced solid tumors[1].
Batoprotafib (TNO155) is a highly potent, selective, and orally active allosteric inhibitor of wild-type SHP2, with an IC50 of 0.011 µM. It holds promise for investigating RTK-dependent malignancies, particularly advanced solid tumors [1].
体内研究
The oral bioavailability in mouse, rat, and monkey is 78%, 86%, and 60%, respectively [1].
Batoprotafib (20 mg/kg; oral administration; twice daily for 40 days) suppresses tumor growth and exhibits enhanced efficacy when administered in combination with Dabrafenib plus Trametinib in nude mice harboring HT-29 xenografts [2].
Batoprotafib (7.5 mg/kg; pO.; b.iD. or qD. for 36 days) in combination with JDQ-443 (100 mg/kg; pO.; qD.) enhances the efficacy of JDQ443 alone in KRASG12C-mutated cell-derived (CDX) models in nude mice [3].
体外研究
Batoprotafib exhibits an IC50 of 0.008 μM in the KYSE520 pERK assay and a 0.100 μM IC50 in the KYSE520 5-day cell proliferation assay. Off-target IC50 values are 18 μM, 6.9 μM, and 11 μM for Cav1.2, VMAT, and SST3, respectively [1].
Batoprotafib (0-1000 nM; 6 days) demonstrates inhibition of NCI-H3255, HCC827, and PC9 cell viability with IC50 values below 1.5 μM. It exhibits efficacy in EGFR-mutant NSCLC cell lines [2].
Batoprotafib is effective in acquired resistance models of EGFR inhibitors and shows synergistic effects when combined with EGFR inhibitors [2].
Batoprotafib improves the effectiveness of KRASG12C inhibitors in treating KRASG12C lung and colorectal cancers [2].
Batoprotafib suppresses immune-suppressive macrophages and enhances the effects of PD1 blockade [2].
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