Amide derivatives as chemokine receptor type 4 (CXCR4) modulators for the treatment of inflammation or prevention of cancer cell metastasis.
CXCR4 receptors play a crucial role in recruitment of inflammatory cells to inflammation sites at the beginning of the disease process. Overexpression of CXCR4 receptors is correlated with cancer metastasis and prognosis. Expression of CXCR4 is increased in many types of cancer such as breast, pancreatic, and colon among others. Modulating CXCR4 functions present a new avenue for effective anti-cancer and anti-inflammation strategies. Almost all drugs targeting CXCR4 receptors are currently in discovery or preclinical phase in a few selected preclinical animal models of inflammation.
Emory researchers have developed partial CXCR4 antagonists with potential in treating medical disorders such as inflammation and metastatic tumors. These novel amide-sulfamide derivatives were developed using virtual high-throughput screening method and show excellent efficacy against CXCR4 and blocking CXCL12. The compounds show increased CXCR4 inhibition for inflammation and reduced risk of serious side effects or cytotoxicity. These CXCR4 antagonists also have potential in cancer treatment as a combination therapy with other anticancer molecules. The compounds have been tested and selected through two animal models of basic inflammation.
Early pre-clinical development.
Publications
Bai, R. et al. (2017). European Journal of Medicinal Chemistry, 126, 464-475. Bai, R. et al. (2018) European Journal of Medicinal Chemistry. 150, 195-205.