References
- K. A. Fitzgerald and J. C. Kagan, Toll-like receptors and the control of immunity, Cell 180(6) (2020) 1044–1066; https://doi.org/10.1016/j.cell.2020.02.041
- C. A. Janeway and R. Medzhitov, Innate immune recognition, Annu. Rev. Immunol. 20 (2002) 197–216; https://doi.org/10.1146/annurev.immunol.20.083001.084359
- R. Medzhitov, Toll-like receptors and innate immunity, Nat. Rev. Immunol. 1 (2001) 135–145; https://doi.org/10.1038/35100529
- T. Kawai and S. Akira, Toll-like receptors and their crosstalk with other innate receptors in infection and immunity, Immunity 34(5) (2011) 637–650; https://doi.org/10.1016/j.immuni.2011.05.006
- F. J. Barrat and R. L. Coffman, Development of TLR inhibitors for the treatment of autoimmune diseases, Immunol. Rev. 223(1) (2008) 271–283; https://doi.org/10.1111/j.1600-065X.2008.00630.x
- I. Martínez-Espinoza and A. Guerrero-Plata, The relevance of TLR8 in viral infections, Pathogens 11(2) (2022) Article ID 134; https://doi.org/10.3390/pathogens11020134
- M. J. Braunstein, J. Kucharczyk and S. Adams, Targeting Toll-like receptors for cancer therapy, Targ. Oncol. 13 (2018) 583–598; https://doi.org/10.1007/s11523-018-0589-7
- J. A. Hamerman and G. M. Barton, The path ahead for understanding Toll-like receptor-driven systemic autoimmunity, Curr. Opin. Immunol. 91 (2024) Article ID 102482; https://doi.org/10.1016/j.coi.2024.102482
- J.-Q. Chen, P. Szodoray and M. Zeher, Toll-like receptor pathways in autoimmune diseases, Clinic Rev. Allerg. Immunol. 50 (2016) 1–17; https://doi.org/10.1007/s12016-015-8473-z
- C.-Y. Lai, Y.-W. Su, K.-I. Lin, L.-C. Hsu and T.-H. Chuang, Natural modulators of endosomal Toll-like receptor-mediated psoriatic skin inflammation, J. Immunol. Res. 2017 (2017) Article ID 7807313 (15 pages); https://doi.org/10.1155/2017/7807313
- T. Celhar and A.-M. Fairhurst, Toll-like receptors in systemic lupus erythematosus: Potential for personalized treatment, Front. Pharmacol. 5 (2014) Article ID 265 (8 pages); https://doi.org/10.3389/fphar.2014.00265
- D. -Y. Oh, S. Taube, O. Hamouda, C. Kücherer, G. Poggensee, H. Jessen, J. K. Eckert, K. Neumann, A. Storek, M. Pouliot, P. Borgeat, N. Oh, E. Schreier, A. Pruss, K. Hattermann and R. R. Schumann, A functional Toll-like receptor 8 variant is associated with HIV disease restriction, J. Infecty. Dis. 198(5) (2008) 701–709; https://doi.org/10.1086/590431
- H. Z. Meås, M. Haug, M. S. Beckwith, C. Louet, L. Ryan, Z. Hu, J. Landskron, S. A. Nordbø, K. Taskén, H. Yin, J. K. Damås and T. H. Flo, Sensing of HIV-1 by TLR8 activates human T cells and reverses latency, Nat. Commun. 11 (2020) Article ID 147 (16 pages); https://doi.org/10.1038/s41467-019-13837-4
- T. Knoepfel, P. Nimsgern, S. Jacquier, M. Bourrel, E. Vangrevelinghe, R. Glatthar, D. Behnke, P. B. Alper, P.-Y. Michellys, J. Deane, T. Junt, G. Zipfel, S. Limonta, S. Hawtin, C. Andre, T. Boulay, P. Loetscher, M. Faller, J. Blank, R. Feifel and C. Betschart, Target-based identification and optimization of 5-indazol-5-yl pyridones as Toll-like receptor 7 and 8 antagonists using a biochemical TLR8 antagonist competition assay, J. Med. Chem. 63(15) (2020) 8276–8295; https://doi.org/10.1021/acs.jmedchem.0c00130
- P. B. Alper, J. Deane, C. Betschart, D. Buffet, G. Collignon Zipfel, P. Gordon, J. Hampton, S. Hawtin, M. Ibanez, T. Jiang, T. Junt, T. Knoepfel, B. Liu, J. Maginnis, U. McKeever, P.-Y. Michellys, D. Mut-nick, B. Nayak, S. Niwa, W. Richmond and X. Zhu, Discovery of potent, orally bioavailable in vivo efficacious antagonists of the TLR7/8 pathway, Bioorg. Med. Chem. Lett. 30(17) (2020) Article ID 127366; https://doi.org/10.1016/j.bmcl.2020.127366
- C. P. Mussari, D. S. Dodd, R. K. Sreekantha, L. Pasunoori, H. Wan, S. L. Posy, D. Critton, S. Ruepp, M. Subramanian, A. Watson, P. Davies, G. L. Schieven, L. M. Salter-Cid, R. Srivastava, D. M. Tagore, S. Dudhgaonkar, M. A. Poss, P. H. Carter and A. J. Dickman, Discovery of potent and orally bioavailable small molecule antagonists of Toll-like receptors 7/8/9 (TLR7/8/9), ACS Med. Chem. Lett. 11(9) (2020) 1751–1758; https://doi.org/10.1021/acsmedchemlett.0c00264
- M. Grabowski, M. Bermudez, T. Rudolf, D. Šribar, P. Varga, M. S. Murgueitio, G. Wolber, J. Rade-mann and G. Weindl, Identification and validation of a novel dual small-molecule TLR2/8 anta- gonist, Biochem. Pharmacol. 177 (2020) Article ID 113957; https://doi.org/10.1016/j.bcp.2020.113957
- A. Dolšak, D. Šribar, A. Scheffler, M. Grabowski, U. Švajger, S. Gobec, J. Holze, G. Weindl, G. Wolber and M. Sova, Further hit optimization of 6-(trifluoromethyl)pyrimidin-2-amine based TLR8 modulators: Synthesis, biological evaluation and structure–activity relationships, Eur. J. Med. Chem. 225 (2021) Article ID 113809; https://doi.org/10.1016/j.ejmech.2021.113809
- D. Šribar, M. Grabowski, M. S. Murgueitio, M. Bermudez, G. Weindl and G. Wolber, Identification and characterization of a novel chemotype for human TLR8 inhibitors, Eur. J. Med. Chem. 179 (2019) 744–752; https://doi.org/10.1016/j.ejmech.2019.06.084
- J. J. Naleway, Y. Jiang and R. Link-Cole, Reagents and methods for direct labeling of nucleotides; Retrieved from https://patents.google.com/patent/US20130150254A1/en?oq=US20130150254
- N. Varga, I. Sutkeviciute, C. Guzzi, J. McGeagh, I. Petit-Haertlein, S. Gugliotta, J. Weiser, J. Angulo, F. Fieschi and A. Bernardi, Selective targeting of dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) with mannose-based glycomimetics: Synthesis and interaction studies of bis(benzylamide) derivatives of a pseudomannobioside, Chem. Eur. J. 19(15) (2013) 4786–4797; https://doi.org/10.1002/chem.201202764
- M. Grabowski, M. S. Murgueitio, M. Bermudez, J. Rademann, G. Wolber and G. Weindl, Identification of a pyrogallol derivative as a potent and selective human TLR2 antagonist by structure-based virtual screening, Biochem. Pharmacol. 154 (2018) 148–160; https://doi.org/10.1016/j.bcp.2018.04.018
- J. Holze, F. Lauber, S. Soler, E. Kostenis and G. Weindl, Label-free biosensor assay decodes the dynamics of Toll-like receptor signaling, Nat. Commun. 15 (2024) Article ID 9554 (18 pages); https://doi.org/10.1038/s41467-024-53770-9
- P. Labute, Protonate3D: Assignment of ionization states and hydrogen coordinates to macromolecular structures, Proteins 75(1) (2009) 187–205; https://doi.org/10.1002/prot.22234
- G. Jones, P. Willett, R. C. Glen, A. R. Leach and R. Taylor, Development and validation of a genetic algorithm for flexible docking, J. Mol. Biol. 267(3) (1997) 727–748; https://doi.org/10.1006/jmbi.1996.0897
- O. Korb, T. Stützle and T. E. Exner, Empirical scoring functions for advanced protein-ligand docking with PLANTS, J. Chem. Inf. Model. 49(1) (2009) 84–96; https://doi.org/10.1021/ci800298z
- T. A. Halgren, Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94, J. Comput. Chem. 17(5–6) (1996) 490–519; https://doi.org/10.1002/(SICI)1096-987X(199604)17:5/6<490::AID-JCC1>3.0.CO;2-P
- G. Wolber and T. Langer, LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters, J. Chem. Inf. Model. 45(1) (2005) 160–169; https://doi.org/10.1021/ci049885e
- P. Mark and L. Nilsson, Structure and dynamics of the TIP3P, SPC, and SPC/E water models at 298 K, J. Phys. Chem. A 105(43) (2001) 9954–9960; https://doi.org/10.1021/jp003020w
- E. Harder, W. Damm, J. Maple, C. Wu, M. Reboul, J. Y. Xiang, L. Wang, D. Lupyan, M. K. Dahlgren, J. L. Knight, J. W. Kaus, D. S. Cerutti, G. Krilov, W. L. Jorgensen, R. Abel and R. A. Friesner, OPLS3: A force field providing broad coverage of drug-like small molecules and proteins, J. Chem. Theory Comput. 12(1) (2016) 281–296; https://doi.org/10.1021/acs.jctc.5b00864
- S. Nosé, A molecular dynamics method for simulations in the canonical ensemble, Mol. Phys. 52(2) (1984) 255–268; https://doi.org/10.1080/00268978400101201
- W. G. Hoover, Canonical dynamics: Equilibrium phase-space distributions, Phys. Rev. A Gen. Phys. 31 (1985) 1695–1697; https://doi.org/10.1103/physreva.31.1695
- G. J. Martyna, M. E. Tuckerman, D. J. Tobias and M. L. Klein, Explicit reversible integrators for extended systems dynamics, Mol. Phys. 87(5) (1996) 1117–1157; https://doi.org/10.1080/00268979600100761
- W. Humphrey, A. Dalke and K. Schulten, VMD: Visual molecular dynamics, J. Mol. Graph. 14(1) (1996) 33–38; https://doi.org/10.1016/0263-7855(96)00018-5
- A. Bock, M. Bermudez, F. Krebs, C. Matera, B. Chirinda, D. Sydow, C. Dallanoce, U. Holzgrabe, M. De Amici, M. J. Lohse, G. Wolber and K. Mohr, Ligand binding ensembles determine graded agonist efficacies at a G protein-coupled receptor, J. Biol. Chem. 291(31) (2016) 16375–16389; https://doi.org/10.1074/jbc.M116.735431
- M. Janežič, K. Valjavec, K. B. Loboda, B. Herlah, I. Ogris, M. Kozorog, M. Podobnik, S. G. Grdadolnik, G. Wolber and A. Perdih, Dynophore-based approach in virtual screening: A case of human DNA topoisomerase IIα, Int. J. Mol. Sci. 22(24) (2021) Article ID 13474; https://doi.org/10.3390/ijms222413474
- N. Fuchs, L. Calvo-Barreiro, V. Talagayev, S. Pach, G. Wolber and M. T. Gabr, From virtual screens to cellular target engagement: New small molecule ligands for the immune checkpoint LAG-3, ACS Med. Chem. Lett. 15(11) (2024) 1884–1890; https://doi.org/10.1021/acsmedchemlett.4c00350
- H. Tanji, U. Ohto, T. Shibata, K. Miyake and T. Shimizu, Structural reorganization of the Toll-like receptor 8 dimer induced by agonistic ligands, Science 339(6126) (2013) 1426–1429; https://doi.org/10.1126/science.1229159
- S. Zhang, Z. Hu, H. Tanji, S. Jiang, N. Das, J. Li, K. Sakaniwa, J. Jin, Y. Bian, U. Ohto, T. Shimizu and H. Yin, Small-molecule inhibition of TLR8 through stabilization of its resting state, Nat. Chem. Biol. 14 (2018) 58–64; https://doi.org/10.1038/nchembio.2518
- T. Matziol, V. Talagayev, T. Slokan, N. Strašek Benedik, J. Holze, M. Sova, G. Wolber and G. Weindl, Discovery of novel isoxazole-based small-molecule Toll-like receptor 8 antagonists, J. Med. Chem. 68(4) (2025) 4888–4907; https://doi.org/10.1021/acs.jmedchem.4c03148
- Z. Hu, H. Tanji, S. Jiang, S. Zhang, K. Koo, J. Chan, K. Sakaniwa, U. Ohto, A. Candia, T. Shimizu and H. Yin, Small-molecule TLR8 antagonists via structure-based rational design, Cell. Chem. Biol. 25(10) (2018) 1286–1291; https://doi.org/10.1016/j.chembiol.2018.07.004