生物活性

• 描述AZD4635 is an oral A2AR antagonist with Ki value of 1.7nM for affinity to human A2AR, > 30-fold selectivity over other adenosine receptors. AZD4635 inhibited cAMP production in CHO cells stably expressing human A2AR with IC50 values of 0.79, 10.0 and 142.9 nM in the presence of 0.1, 1 and 10 μM adenosine, respectively. AZD4635 reversed suppression and restored IFNγ secretion in cells incubated NECA, a stable analog of adenosine, in an ex vivo CD8+ T cell assay. AZD4635 led to a reduction in tumor growth alone and in combination with checkpoint inhibitors, and enhanced antitumor immunity as tumors harvested from the treated mice exhibited changes in infiltrating lymphocyte populations and increases in the functional activity of T cells.
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT03381274	Carcinoma, Non-Small-Cell Lung	Phase 1 Phase 2	Recruiting	December 29, 2021	United States, California ... more >> Research Site Recruiting La Jolla, California, United States, 92093 Research Site Recruiting San Francisco, California, United States, 94143 Research Site Withdrawn Santa Monica, California, United States, 90404 United States, Colorado Research Site Recruiting Aurora, Colorado, United States, 80045 United States, Connecticut Research Site Recruiting New Haven, Connecticut, United States, 06510 United States, Florida Research Site Not yet recruiting Gainesville, Florida, United States, 32608 United States, Georgia Research Site Recruiting Atlanta, Georgia, United States, 30322 United States, Illinois Research Site Not yet recruiting Chicago, Illinois, United States, 60611 United States, Maryland Research Site Recruiting Baltimore, Maryland, United States, 21224 United States, New York Research Site Recruiting New York, New York, United States, 10032 United States, Texas Research Site Recruiting Houston, Texas, United States, 77030 Korea, Republic of Research Site Recruiting Seoul, Korea, Republic of, 03080 Research Site Recruiting Seoul, Korea, Republic of, 06351 Research Site Recruiting Seoul, Korea, Republic of, 138-736 Taiwan Research Site Not yet recruiting Taichung, Taiwan, 40705 Research Site Not yet recruiting Taipei City, Taiwan, 10050 Collapse <<
  NCT03710434	Healthy Volunteers	Phase 1	Recruiting	April 4, 2019	United Kingdom ... more >> Research Site Recruiting Ruddington, United Kingdom, NG11 6JS Collapse <<
  NCT02740985	Advanced Solid Malignancies ... more >> Non-Small Cell Lung Cancer (NSCLC) Metastatic Castrate-Resistant Prostate Carcinoma (mCRPC) Colorectal Carcinoma (CRC) Collapse <<	Phase 1	Recruiting	May 13, 2020	United States, California ... more >> Research Site Recruiting Fresno, California, United States, 93720 United States, Colorado Research Site Recruiting Denver, Colorado, United States, 80218 United States, Connecticut Research Site Not yet recruiting New Haven, Connecticut, United States, 06519 United States, Florida Research Site Not yet recruiting Daytona Beach, Florida, United States, 32117 Research Site Not yet recruiting Lecanto, Florida, United States, 34461 Research Site Not yet recruiting North Port, Florida, United States, 34288 Research Site Recruiting Sarasota, Florida, United States, 34232 United States, Illinois Research Site Recruiting Decatur, Illinois, United States, 62526 United States, Massachusetts Research Site Not yet recruiting Boston, Massachusetts, United States, 02215 United States, Nebraska Research Site Not yet recruiting Omaha, Nebraska, United States, 68130 United States, Nevada Research Site Recruiting Las Vegas, Nevada, United States, 89119 United States, New York Research Site Recruiting New York, New York, United States, 10032 United States, North Carolina Research Site Recruiting Durham, North Carolina, United States, 27710 United States, Pennsylvania Research Site Recruiting Philadelphia, Pennsylvania, United States, 19107 United States, South Carolina Research Site Not yet recruiting Myrtle Beach, South Carolina, United States, 29572 United States, Tennessee Research Site Not yet recruiting Chattanooga, Tennessee, United States, 37404 Research Site Recruiting Nashville, Tennessee, United States, 37203 Collapse <<

• 参考文献

• [1] Preclinical pharmacodynamics and antitumor activity of AZD4635, a novel adenosine 2A receptor inhibitor that reverses adenosine mediated T cell suppression