Drug intelligence / Profile preview

ganetespib + crizotinib

Development stage: Unknown
Lead developer: Madrigal Pharmaceuticals
Modality: Small Molecules
Administration: Intravenous, Oral

Overview

A combination therapy that pairs ganetespib, a potent HSP90 inhibitor, with crizotinib, an ALK tyrosine kinase inhibitor. This combination has demonstrated synergistic inhibition of MET, its downstream signaling pathways, and tumor growth in both TKI-sensitive and TKI-resistant MET-driven tumor models. The combination works through complementary mechanisms: while crizotinib directly inhibits ALK kinase activity, ganetespib leads to the degradation of the ALK protein itself, allowing it to overcome crizotinib resistance in ALK-positive cancers.

Targets

ALK (Anaplastic lymphoma kinase receptor tyrosine kinase)MET (Mesenchymal-epithelial transition factor receptor)HSP90 (Heat shock protein 90 chaperone complex)

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