JBI-589 is a non-covalent PAD4 isoform-selective inhibitor with oral bioavailability. JBI-589 reduces CXCR2 expression and blocks neutrophil chemotaxis. JBI-589 reduces primary tumor and metastases, and enhances the anti-tumor effect of checkpoint inhibitors. JBI-589 can be used in cancer research.
JBI-589 (1 μM, 2 h) significantly downregulates the expression of CXCR2 on neutrophils and reduces their migration induced by CXCL1 in vitro, with no effect on the suppressive activity of Ly6G cells generated from HPCs[1].
JBI-589 (50 mg/kg, p.o., twice a day for 24 days) significantly inhibits the growth of primary tumors in LL2 and B16F10 tumor C57BL/6 mouse models[1].
References:
[1]. Deng H, et al. A Novel Selective Inhibitor JBI-589 Targets PAD4-Mediated Neutrophil Migration to Suppress Tumor Progression. Cancer Res. 2022 Oct 4;82(19):3561-3572.
[2]. Gajendran C, et al. Alleviation of arthritis through prevention of neutrophil extracellular traps by an orally available inhibitor of protein arginine deiminase 4. Sci Rep. 2023 Feb 23;13(1):3189.