Identification of potent pan-ephrin receptor kinase inhibitors using DNA-encoded chemistry technology.

ABSTRACT: EPH receptors (EPHs), the largest family of tyrosine kinases, phosphorylate downstream substrates upon binding of ephrin cell surface-associated ligands. In a large cohort of endometriotic lesions from individuals with endometriosis, we found that EPHA2 and EPHA4 expressions are increased in endometriotic lesions relative to normal eutopic endometrium. Because signaling through EPHs is associated with increased cell migration and invasion, we hypothesized that chemical inhibition of EPHA2/4 could have therapeutic value. We screened DNA-encoded chemical libraries (DECL) to rapidly identify EPHA2/4 kinase inhibitors. Hit compound, CDD-2693, exhibited picomolar/nanomolar kinase activity against EPHA2 (K_i: 4.0 nM) and EPHA4 (K_i: 0.81 nM). Kinome profiling re

SUBMITTER: Madasu C 

PROVIDER: S-EPMC11087803 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature