Multi-kinase target profile (DDR2, TrkA, Eph2A, SAPK2, PTK5, Abl, CSF1R)

This target entry represents a multi-kinase profile consisting of several distinct proteins: Discoidin Domain Receptor 2 (DDR2), Tropomyosin Receptor Kinase A (TrkA), Ephrin Type-A Receptor 2 (EphA2), Stress-Activated Protein Kinase 2 (SAPK2/p38 alpha), Protein Tyrosine Kinase 5 (PTK5/FRK), Abelson Murine Leukemia Viral Oncogene Homolog 1 (Abl), and Colony Stimulating Factor 1 Receptor (CSF1R). These kinases are integral to various cellular processes, including collagen-mediated signaling (DDR2), neuronal survival (TrkA), cell migration (EphA2), stress response (SAPK2), and myeloid cell differentiation (CSF1R) (UniProt Q16832, P04629, P29317, Q16539, P42685, P00519, P07333). Many of these proteins are dysregulated in malignancies, such as the BCR-ABL fusion in chronic myeloid leukemia or NTRK fusions in various solid tumors. Multi-kinase inhibitors like Dasatinib are designed to target this broad spectrum of kinases to overcome resistance and inhibit multiple oncogenic pathways simultaneously (PubMed: 17259973). However, the broad inhibition of these diverse targets also contributes to a complex safety profile, including risks of myelosuppression and fluid retention (FDA Label: Sprycel).

Other names

Discoidin domain receptor 2 (DDR2)Tropomyosin receptor kinase A (TrkA/NTRK1)Ephrin type-A receptor 2 (EphA2)Stress-activated protein kinase 2 (SAPK2/p38 alpha/MAPK14)Protein tyrosine kinase 5 (PTK5/FRK)Abelson murine leukemia viral oncogene homolog 1 (Abl/ABL1)Colony stimulating factor 1 receptor (CSF1R)

Inhibition of the adenosine triphosphate (ATP) binding site within the kinase domain of multiple tyrosine and serine/threonine kinases, thereby preventing autophosphorylation and downstream signaling cascades essential for tumor growth and survival (DrugBank DB01254).