CA-4948

CA-4948 is a potent, selective and orally bioavailable IRAK4 kinase inhibitor with an IC50 of < 50 nM. CA-4948 can be used for the treatment of lymphoma[1].

Research Areas >> Cancer

Signaling Pathways >> Immunology/Inflammation >> IRAK

Research Areas >> Inflammation/Immunology

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> IRAK

IRAK4:50 nM (IC50)

CA-4948 is a selective and potent IRAK4 kinase inhibitor with in vivo activity in a TLR4-induced cytokine release model. CA-4948 exhibits favorable drug metabolism and pharmacokinetic (DMPK) properties, oral bioavailability, and is well tolerated in mice. Moreover, CA-4948 exhibits dose-dependent efficacy in activated B-cell (ABC)-DLBCL MYD88-L265P xenograft tumor models using cell lines OCI-LY3 and OCI-LY10. CA-4948 exhibits the greatest efficacy in four of the five ABC-DLBCL PDX models tested as compared to GBC-DLBCL and ABC/GCB DLBCL patient-derived DLBCL tumor xenograft (PDX) models. Furthermore, CA-4948 is efficacious in ABC-DLBCL PDX tumors containing activating mutations in both TLR/IL-1R and BCR signaling pathways (MYD88 and CD79B double mutants)[2].

[1]. McElroy WT. et al. Interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitors: an updated patent review (2016-2018). Expert Opin Ther Pat. 2019 Apr;29(4):243-259.

[2]. Robert N. Booher, et al. Abstract 1168: Efficacy of the IRAK4 inhibitor CA-4948 in patient-derived xenograft models of diffuse large B cell lymphoma. AACR Annual Meeting 2017; April 1-5, 2017.