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Batoprotafib

CAS No. : 1801765-04-7

MCE 站：Batoprotafib

产品活性：Batoprotafib (TNO155) 是一种有效的，选择性的，和具有口服活性野生型 SHP2 的变构抑制剂 (IC₅₀= 0.011 μM)。Batoprotafib 有研究 RTK 依赖性恶性肿瘤的潜力，尤其是晚期实体瘤。

研究领域：Protein Tyrosine Kinase/RTK  |  Metabolic Enzyme/Protease

作用靶点：SHP2  |  Phosphatase

In Vitro: Batoprotafib shows an IC₅₀ of 0.008 μM in KYSE520 pERK assay ａnd shows an IC₅₀ of 0.100 μM in KYSE520 5-day cell proliferation assay. The off-target IC₅₀ values are 18 μM, 6.9 μM, ａnd 11 μM for Cav1.2, VMAT, ａnd SST3, respectively.
Batoprotafib (0-1000 nM; 6 days) inhibits the viability of NCI-H3255, HCC827, ａnd PC9 cells with IC₅₀ values lower than 1.5 μM. Batoprotafib is efficacious in EGFR-mutant NSCLC cell lines.
Batoprotafib is efficacious in acquired resistance models of EGFR inhibitors ａnd demonstrates combination benefit with EGFR inhibitors.
Batoprotafib enhances the efficacy of KRAS^G12C inhibitors against KRAS^G12C lung ａnd colorectal cancers.
Batoprotafib inhibits immune-suppressive macrophages ａnd synergizes with PD1 blockade.

In Vivo: The oral bioavailability in mouse, rat ａnd money are 78%, 86%, ａnd 60%, respectively.
Batoprotafib (20 mg/kg; p.o.; twice daily for 40 days) inhibits tumor growth ａnd is more effective when combined with Dabrafenib (HY-14660) plus Trametinib (HY-10999) in nude mice bearing HT-29 xenografts.
Batoprotafib (7.5 mg/kg; p.o.; b.i.d. or q.d. for 36 days) plus JDQ-443 (HY-139612) (100 mg/kg; p.o.; q.d.) improves the single-agent activity of JDQ443 in KRAS^G12C-mutated cell-derived (CDX) models in nude mice.

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