WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 533013
Description: CA-4948 is a potent, and orally active interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor. CA-4948 exhibited the greatest efficacy in four of the five ABC-DLBCL PDX models tested as compared to GBC-DLBCL and ABC/GCB DLBCL PDX models. Furthermore, CA-4948 was efficacious in ABC-DLBCL PDX tumors containing activating mutations in both TLR/IL-1R and BCR signaling pathways (MYD88 and CD79B double mutants).
MedKoo Cat#: 533013
Chemical Formula: C21H19N7O3
Exact Mass: 417.1549
Molecular Weight: 417.43
Elemental Analysis: C, 60.42; H, 4.59; N, 23.49; O, 11.50
Synonym: CA-4948; CA 4948; CA4948.
IUPAC/Chemical Name: 6'-amino-N-(2-morpholinooxazolo[4,5-b]pyridin-6-yl)-[2,3'-bipyridine]-6-carboxamide
InChi Key: RWIMETUXCNDSLE-UHFFFAOYSA-N
InChi Code: 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)
SMILES Code: O=C(C1=CC=CC(C2=CC=C(N)N=C2)=N1)NC3=CN=C4C(OC(N5CCOCC5)=N4)=C3
IRAK4 kinase activity is required for toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling in a variety of myeloid and lymphoid cell types. Recruitment of IRAK4 to these receptors and its subsequent activation is facilitated by the MYD88 adaptor protein, which is mutated in ~22% of DLBCL cases. The MYD88 L265P activating mutation is found in ~30% of the activated B-cell (ABC) and ~6% of germinal center B-cell (GCB) subtypes of DLBCL and leads to constitutive activation of NF-κB signaling that is associated with worse prognosis. Thus, the development of small molecule inhibitors targeting IRAK4 is an attractive anticancer strategy for MYD88 mutation-containing cancers such as DLBCL.
1. Booher, R.N., Samson, M.E., Xu, G.-X., et al. Abstract 1168: Efficacy of the IRAK4 inhibitor CA-4948 in patient-derived xenograft models of diffuse large B cell lymphoma. Cancer Res. 77(13 Supp), 1168 (2017).