CA-4948 Chemical Properties

Melting point:

>294°C (dec.)

Density 

1.444±0.06 g/cm3(Predicted)

storage temp. 

-20°C Freezer, Under inert atmosphere

solubility 

DMSO (Slightly), Methanol (Slightly)

pka

10.41±0.43(Predicted)

form 

Solid

color 

Pale Yellow to Brown

InChI

InChI=1S/C21H19N7O3/c22-18-5-4-13(11-23-18)15-2-1-3-16(26-15)20(29)25-14-10-17-19(24-12-14)27-21(31-17)28-6-8-30-9-7-28/h1-5,10-12H,6-9H2,(H2,22,23)(H,25,29)

InChIKey

RWIMETUXCNDSLE-UHFFFAOYSA-N

SMILES

C1(C2=CC=C(N)N=C2)=NC(C(NC2=CN=C3N=C(N4CCOCC4)OC3=C2)=O)=CC=C1

CA-4948 Usage And Synthesis

Uses

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.

General Description

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].

References

[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.