6''-Amino-N-[2-(4-morpholinyl)oxazolo[4,5-b]pyridin-6-yl][2,3''-bipyridine]-6-carboxamide was a useful reagent in preparation of bicyclic heterocyclyl derivatives as IRAK4 inhibitors.
CA-4948 is a novel oral small-molecule inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK4). IRAK4 is part of the Myddosome signaling pathway, and is essential for signaling downstream of toll-like receptors (TLR) and the interleukin-1 receptor (IL-1R) family in immune cells including B lymphocytes. . Dysregulated signaling in these pathways is frequently observed in Non-Hodgkin Lymphomas (NHL), particularly in ABC-subtype of Diffuse Large B-cell lymphoma (DLBCL) and Waldenstr?m macroglobulinemia (WM). Furthermore, IRAK4 activation has recently been identified as a driver of an adaptive resistance mechanism of malignancies. CA-4948 is the first clinical candidate targeting IRAK4 to be evaluated in cancer patients[1].
[1] G. Nowakowski. “Safety, Pharmacokinetics and Activity of CA-4948, an IRAK4 Inhibitor, for Treatment of Patients with Relapsed or Refractory Hematologic Malignancies: Results from the Phase 1 Study.” Blood 136 1 (2020): 44–45.
