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amuvatinib + carboplatin + etoposide
- Development stage
- Discontinued
- Lead developer
- Astex Pharmaceuticals
- Modality
- Small Molecules
- Administration
- Oral, Intravenous
01
Overview
MP-470 + carboplatin + etoposide is a combination chemotherapy regimen consisting of the multi-targeted tyrosine kinase inhibitor amuvatinib (MP-470) and the standard-of-care cytotoxic agents carboplatin and etoposide. Amuvatinib, developed by Astex Pharmaceuticals, is a small molecule inhibitor of mutant forms of c-Kit and PDGFRα, and it uniquely suppresses the Rad51 protein, which is essential for homologous recombination DNA repair. By disrupting DNA repair mechanisms, amuvatinib was designed to act synergistically with DNA-damaging agents like carboplatin (a platinum-based alkylating agent) and etoposide (a topoisomerase II inhibitor). The combination was primarily investigated for the treatment of small cell lung cancer (SCLC) and other advanced solid tumors. Clinical development was discontinued in 2012 after the Phase 2 ESCAPE trial in platinum-refractory SCLC failed to meet its primary efficacy endpoints.
- Other names
- amuvatinib + carboplatin + etoposide
02
Targets
TOP2A (DNA topoisomerase II)MET (Mesenchymal-epithelial transition factor receptor)KIT (c-KIT proto-oncogene receptor tyrosine kinase)PDGFRA (Platelet-derived growth factor receptor alpha)RAD51 (RAD51 Recombinase)DNARET (Rearranged during transfection receptor tyrosine kinase)FLT3 (Fms related receptor tyrosine kinase 3)
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