AZ10397767

AZ10397767 is an orally active, selective CXCR2 receptor antagonist with an IC₅₀ of 1 nM. AZ10397767 attenuates the Oxaliplatin (HY-17371)-induced NF-κB transcriptional activity and potentiates Oxaliplatin-induced apoptosis in androgen-independent prostate cancer (AIPC) cells. AZ10397767 significantly inhibits neutrophil recruitment into tumors which then adversely affects tumor growth in vitro and in vivo^[1][2][3][4]. In Vitro:AZ10397767 (20 nM; 48 h) abrogates the IL-8-induced (3 nM) increase in proliferation, reducing cell number to below basal levels^[2].
AZ10397767 (20 nM; 72 h) increases Oxaliplatin (HY-17371) cytotoxicity, and potentiates Oxaliplatin-induced apoptosis in AIPC cells. AZ10397767 by itself fails to induce apoptosis in either PC3 or DU145 cells^[3].
AZ10397767 (20 nM; 24 h) attenuates the Oxaliplatin-induced NF-κB transcriptional activity and the increases in mRNA transcript levels for each of the CXC-chemokines (CXCL8 and CXCL1) and antiapoptotic genes (Bcl-2 and survivin) in the PC3 and DU145 cells^[3].
In Vivo:AZ10397767 (100 mg/kg; Orally; twice daily; for 22 days) display reduced neutrophil infiltration accompanied with retardation in tumor growth in A549 xenograft tumors^[4].
AZ10397767 (compound 30a) has a CL of 4 ml/min/kg in rat^[1].