9MHY

Human TLR8 ectodomain with small molecule agonist 1

This is a non-PDB format compatible entry.

Summary for 9MHY

• Entry DOI: 10.2210/pdb9mhy/pdb
• Descriptor: Toll-like receptor 8, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(2-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: toll-like receptor 8, agonist, immune system
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 194024.44

Authors

Critton, D.A. (deposition date: 2024-12-12, release date: 2025-03-05)

Primary citation

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.
Structure-Based Design of Novel TLR7/8 Agonist Payloads Enabling an Immunomodulatory Conjugate Approach.
Acs Med.Chem.Lett., 16:80-88, 2025

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.

PubMed: 39811121
DOI: 10.1021/acsmedchemlett.4c00463

Experimental method

X-RAY DIFFRACTION (1.66 Å)