azd9056

Description: AZD9056 is a novel, potent, selective, orally bioavailable antagonist of P2X7 receptor which is an adenosine triphosphate (ATP)-gated cation channel expressed on a variety of cell types believed to play a role in inflammation. AZD9056 was an inhibitor of BCRP and weakly inhibited BCRP-mediated transport of methotrexate (IC(50)=92uM). Sulfasalazine inhibited methotrexate transport mediated by all transporters studied (IC(50)< 5uM). Subsequent assessment of the in vitro data using I/IC(50) ratios indicated that both AZD9056 and sulfasalazine were unlikely to cause a DDI with methotrexate in vivo. In conclusion, to support rheumatoid arthritis drug development it is proposed that regulatory in vitro studies for OAT1, OAT3 and BCRP inhibition be routinely conducted to assess the potential for a transporter-mediated DDI with methotrexate in vivo.

References: Eur J Pharm Sci. 2011 May 18; 43(1-2):41-9.; Int J Mol Med. 2016 Dec; 38(6):1922-1932.

Related CAS#:345303-91-5 (HCl)