Download MendeleyStructure-Based Design of Novel TLR7/8 Agonist Payloads Enabling an Immunomodulatory Conjugate Approach.
Poudel, Y.B., Lo, J.C., Norris, D.J., Cox, M., He, L., Johnson, W.L., A M Subbaiah, M., Mondal, S., Thangavel, S., Subramani, L., Reddy, M., Jain, S., Weiss, D.R., Sivaprakasam, P., Critton, D., Mulligan, D., Xie, C., Dhar, P., Li, Y., Sega, E., Yamazoe, S., Gavai, A.V., Mathur, A., Zapf, C.W., Chekler, E.P.(2025) ACS Med Chem Lett 16: 80-88
- PubMed: 39811121
- DOI: https://doi.org/10.1021/acsmedchemlett.4c00463
- Primary Citation of Related Structures:
9MHV, 9MHW, 9MHX, 9MHY - PubMed Abstract:
Dual activation of the TLR7 and TLR8 pathways leads to the production of type I interferon and proinflammatory cytokines, resulting in efficient antigen presentation by dendritic cells to promote T-cell priming and antitumor immunity. We developed a novel series of TLR7/8 dual agonists with varying ratios of TLR7 and TLR8 activity for use as payloads for an antibody-drug conjugate approach. The agonist-induced production of several cytokines in human whole blood confirmed their functional activity. Structure-activity relationship studies guided by structure-based drug design are described.
Organizational Affiliation:
Bristol Myers Squibb Research & Development, 700 Bay Road, Redwood City, California 94063, United States.
