AT13387 + imatinib

AT13387 + imatinib is a combination of two small molecule drugs under investigation primarily for the treatment of gastrointestinal stromal tumors (GIST), including those resistant to standard therapies. AT13387 is a potent non-geldanamycin inhibitor of heat shock protein 90 (HSP90), a molecular chaperone essential for the stability and function of multiple oncogenic client proteins such as KIT and AKT. By inhibiting HSP90, AT13387 leads to degradation of these client proteins and ablation of their signaling pathways, resulting in antitumor activity across various cancer cell lines[3][6][8]. Imatinib is a BCR-ABL tyrosine kinase inhibitor that also targets other kinases such as KIT and PDGFR; it is approved for several cancers including chronic myeloid leukemia and GIST[1][4]. The combination has shown enhanced efficacy in preclinical models of both imatinib-sensitive and -resistant GIST by simultaneously targeting KIT signaling through different mechanisms—direct kinase inhibition by imatinib and destabilization via HSP90 inhibition by AT13387. This dual approach may overcome resistance seen with monotherapy. The combination has been well tolerated in animal studies[3].

Brand names

GleevecImkeldi

Other names

imatinib mesylate