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Tivantinib

HGF pathway inhibitor; Inhibits MET

STEMCELL Technologies Inc.

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Tivantinib is a staurosporine derivative which binds to inactive, dephosphorylated MET receptor tyrosine kinase, in a manner that is not competitive with ATP (Munshi et al.; Eathiraj et al.). It is selective for MET (Ki ≅ 355 nM) in a screen of 230 kinases (Munshi et al.). It also shows cytotoxic activity which is distinct from its inhibition of MET (Basilico et al.; Katayama et al.). It has also been shown to bind directly to the colchicine binding pocket of tubulin, thereby reducing tubulin polymerization (Aoyama et al.).

CANCER RESEARCH

  • Induces apoptosis of human myeloma CD138+ plasma cells in vitro, and demonstrates efficacy in a mouse xenograft model of myeloma (Zaman et al.).
  • Inhibits metastatic growth of breast cancer cells in bone and reduces tumor-induced osteolysis, in a mouse xenograft model (Previdi et al.).
  • Perturbs microtubule dynamics, induces G2/M arrest, and promotes apoptosis independently of c-MET inhibition in a variety of cancer cell lines (Basilico et al.).

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