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AdipoGen AST-487 (1 mg)
Supplier: AdipoGen AGCR13745M001
Chemical. CAS: 630124-46-8. Formula: C26H30F3N7O2. MW: 529.6. AST487 is an inhibitor of RET (IC50 = 0.88µM), FLT3 (Ki = 0.52µM), KDR (IC50 = 0.17µM), c-Abl (IC50 = 0.02µM) and c-Kit (IC50 = 0.5µM). AST-487 has been shown to inhibit RET autophosphorylation and activation of downstream effectors and to prevent the growth of human thyroid cancer cell lines with activating mutations of RET but not of lines without RET mutations. In xenografts of NIH3T3 cells expressing oncogenic RET and of the MTC cell line TT in nude mice, AST-487 dose dependently inhibited tumor growth. AST-487, which selectively targets mutant FLT3 protein kinase activity, is also shown to override PKC412 resistance in vitro, and has significant antileukemic activity in an in vivo model of FLT3-ITD(+) leukemia. The combination of AST-487 with standard chemotherapeutic agents leads to enhanced inhibition of proliferation of mutant FLT3-expressing cells.
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