Design, Synthesis, and Biological Evaluation of Novel Cyclic Adenosine-Inosine Monophosphate (cAIMP) Analogs That Activate Stimulator of Interferon Genes (STING)

Journal of Medicinal Chemistry

Volumn 59, Issue 22, 2016, Pages 10253-10267

  Lioux, Thierry ^a   Mauny, Marc Antoine ^a   Lamoureux, Alain ^a   Bascoul, Nicolas ^a   Hays, Mathieu ^a   Vernejoul, Fabienne ^a   Baudru, Anne Sophie ^a   Boularan, Cédric ^a   Lopes Vicente, Justine ^a   Qushair, Gregory ^a   Tiraby, Gérard ^a  

^a Zone industrielle de Montaudran   (France)

Author keywords

[No Author keywords available]

Indexed keywords

2' FLUORO 2' DEOXYRIBOSE; ADAPTOR PROTEIN; CYCLIC ADENOSINE INOSINE MONOPHOSPHATE DERIVATIVE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INOSINE PHOSPHATE; INTERFERON; PHOSPHOROTHIOIC ACID; UNCLASSIFIED DRUG; ADENOSINE; CYCLIC IMP; CYTOKINE;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; DRUG DESIGN; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; EC50; ENZYME METABOLISM; ENZYME STABILITY; GENE ACTIVATION; HUMAN; HUMAN CELL; MACROPHAGE; MARKER GENE; NONHUMAN; STIMULATOR OF INTERFERON GENES; ANIMAL; CELL LINE; CHEMICAL STRUCTURE; CHEMISTRY; DOSE RESPONSE; METABOLISM; MOUSE; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

ADENOSINE; ANIMALS; CELL LINE; CYCLIC IMP; CYTOKINES; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; HUMANS; INTERFERON TYPE I; MICE; MOLECULAR STRUCTURE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84999633698     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.6b01300     Document Type: Article

References (30)

1. Gomelsky, M. cAMP, c-di-GMP, c-di-AMP and now cGMP: bacteria use them all! Mol. Microbiol. 2011, 79 (3) 562-565 10.1111/j.1365-2958.2010.07514.x
2. Ablasser, A.; Hornung, V. DNA sensing unchained Cell Res. 2013, 23 (5) 585-587 10.1038/cr.2013.28
3. Zhang, X.; Shi, H.; Wu, J.; Zhang, X.; Sun, L.; Chen, C.; Chen, Z. J. Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING Mol. Cell 2013, 51 (2) 226-235 10.1016/j.molcel.2013.05.022
4. Ishikawa, H.; Barber, G. N. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling Nature 2008, 455 (7213) 674-678 10.1038/nature07317
5. Barber, G. N. STING: infection, inflammation and cancer Nat. Rev. Immunol. 2015, 15 (12) 760-770 10.1038/nri3921
6. Corrales, L.; McWhirter, S. M.; Dubensky, T. W., Jr.; Gajewski, T. F. The host STING pathway at the interface of cancer and immunity J. Clin. Invest. 2016, 126 (7) 2404-2411 10.1172/JCI86892
7. Hyodo, M.; Sato, Y.; Hayakawa, Y. Synthesis of cyclic bis(3′-5′)diguanylic acid (c-di-GMP) analogs Tetrahedron 2006, 62 (13) 3089-3094 10.1016/j.tet.2006.01.025
8. Gaffney, B. L.; Jones, R. A. One-flask synthesis of cyclic diguanosine monophosphate (c-di-GMP). Current Protocols in Nucleic Acid Chemistry; John Wiley & Sons: Hoboken, NJ, U.S., 2012; Chapter 14, Unit 14.8, 1-7, DOI: 10.1002/0471142700.nc1408s48.
9. Rammler, D. H.; Lapidot, Y.; Khorana, H. G. Studies on Polynucleotides. XIX. The specific synthesis of C3″-C5″ inter-ribonucleotidic linkage. A new approach and its use in the synthesis of C3″-C5″-linked uridine oligonucleotides J. Am. Chem. Soc. 1963, 85 (13) 1989-1997 10.1021/ja00896a019
10. Shanahan, C. A.; Strobel, S. A. The bacterial second messenger c-di-GMP: probing interactions with protein and RNA binding partners using cyclic dinucleotide analogs Org. Biomol. Chem. 2012, 10 (46) 9113-9129 10.1039/c2ob26724a
11. Zhou, J.; Watt, S.; Wang, J.; Nakayama, S.; Sayre, D. A.; Lam, Y. F.; Lee, V. T.; Sintim, H. O. Potent suppression of c-di-GMP synthesis via I-site allosteric inhibition of diguanylate cyclases with 2′-F-c-di-GMP Bioorg. Med. Chem. 2013, 21 (14) 4396-4404 10.1016/j.bmc.2013.04.050
12. Ora, M.; Martikainen, K.; Lautkoski, K. Hydrolytic reactions of cyclic bis(3′-5′)diadenylic acid (c-di-AMP) J. Phys. Org. Chem. 2013, 26 (3) 218-225 10.1002/poc.3070
13. Tiwari, K. N.; Secrist, J. A., III; Montgomery, J. A. Synthesis and biological activity of 4′-thionucleosides of 2-chloroadenine Nucleosides Nucleotides 1994, 13 (8) 1819-1828 10.1080/15257779408009484
14. Gosselin, G.; Mathé, C.; Bergogne, M. C.; Aubertin, A. M.; Kirn, A.; Sommadossi, J.-P.; Schinazi, R.; Imbach, J. L. 2′-and/or 3Y-deoxy-β-L-pentofuranosyl nucleoside derivatives: stereospecific synthesis and antiviral activities Nucleosides, Nucleotides Nucleic Acids 1995, 14 (3-5) 611-617 10.1080/15257779508012437
15. Prantner, D.; Perkins, D. J.; Lai, W.; Williams, M. S.; Sharma, S.; Fitzgerald, K. A.; Vogel, S. N. 5,6-Dimethylxanthenone-4-acetic acid (DMXAA) activates stimulator of interferon gene (STING)-dependent innate immune pathways and is regulated by mitochondrial membrane potential J. Biol. Chem. 2012, 287 (47) 39776-39788 10.1074/jbc.M112.382986
16. Conlon, J.; Burdette, D. L.; Sharma, S.; Bhat, N.; Thompson, M.; Jiang, Z.; Rathinam, V. A.; Monks, B.; Jin, T.; Xiao, T. S.; Vogel, S. N.; Vance, R. E.; Fitzgerald, K. A. Mouse, but not human STING, binds and signals in response to the vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid J. Immunol. 2013, 190 (10) 5216-5225 10.4049/jimmunol.1300097
17. Shanahan, C. A.; Gaffney, B. L.; Jones, R. A.; Strobel, S. A. Identification of c-di-GMP derivatives resistant to an EAL domain phosphodiesterase Biochemistry 2013, 52 (2) 365-377 10.1021/bi301510v
18. Ablasser, A.; Goldeck, M.; Cavlar, T.; Deimling, T.; Witte, G.; Rohl, I.; Hopfner, K. P.; Ludwig, J.; Hornung, V. cGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING Nature 2013, 498 (7454) 380-384 10.1038/nature12306
19. Diner, E. J.; Burdette, D. L.; Wilson, S. C.; Monroe, K. M.; Kellenberger, C. A.; Hyodo, M.; Hayakawa, Y.; Hammond, M. C.; Vance, R. E. The innate immune DNA sensor cGAS produces a noncanonical cyclic dinucleotide that activates human STING Cell Rep. 2013, 3 (5) 1355-1361 10.1016/j.celrep.2013.05.009
20. Che, X.; Zhang, J.; Zhu, Y.; Yang, L.; Quan, H.; Gao, Y. Q. Structural flexibility and conformation features of cyclic dinucleotides in aqueous solutions J. Phys. Chem. B 2016, 120 (10) 2670-2680 10.1021/acs.jpcb.5b11531
21. Shi, H.; Wu, J.; Chen, Z. J.; Chen, C. Molecular basis for the specific recognition of the metazoan cyclic GMP-AMP by the innate immune adaptor protein STING Proc. Natl. Acad. Sci. U. S. A. 2015, 112 (29) 8947-8952 10.1073/pnas.1507317112
22. Danilchanka, O.; Mekalanos, J. J. Cyclic dinucleotides and the innate immune response Cell 2013, 154 (5) 962-970 10.1016/j.cell.2013.08.014
23. Gao, J.; Tao, J.; Liang, W.; Zhao, M.; Du, X.; Cui, S.; Duan, H.; Kan, B.; Su, X.; Jiang, Z. Identification and characterization of phosphodiesterases that specifically degrade 3′3′-cyclic GMP-AMP Cell Res. 2015, 25, 539-550 10.1038/cr.2015.40
24. Li, L.; Yin, Q.; Kuss, P.; Maliga, Z.; Millan, J. L.; Wu, H.; Mitchison, T. J. Hydrolysis of 2′3′-cGAMP by ENPP1 and design of nonhydrolyzable analogs Nat. Chem. Biol. 2014, 10 (12) 1043-1048 10.1038/nchembio.1661
25. Gillis, E. P.; Eastman, K. J.; Hill, M. D.; Donnelly, D. J.; Meanwell, N. A. Applications of fluorine in medicinal chemistry J. Med. Chem. 2015, 58 (21) 8315-8359 10.1021/acs.jmedchem.5b00258
26. Srinivasan, S. K.; Iversen, P. Review of in vivo pharmacokinetics and toxicology of phosphorothioate oligonucleotides J. Clin. Lab. Anal. 1995, 9 (2) 129-137 10.1002/jcla.1860090210
27. Corrales, L.; Glickman, L. H.; McWhirter, S. M.; Kanne, D. B.; Sivick, K. E.; Katibah, G. E.; Woo, S. R.; Lemmens, E.; Banda, T.; Leong, J. J.; Metchette, K.; Dubensky, T. W., Jr.; Gajewski, T. F. Direct activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity Cell Rep. 2015, 11 (7) 1018-1030 10.1016/j.celrep.2015.04.031
28. McWhirter, S. M.; Barbalat, R.; Monroe, K. M.; Fontana, M. F.; Hyodo, M.; Joncker, N. T.; Ishii, K. J.; Akira, S.; Colonna, M.; Chen, Z. J.; Fitzgerald, K. A.; Hayakawa, Y.; Vance, R. E. A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP J. Exp. Med. 2009, 206 (9) 1899-1911 10.1084/jem.20082874
29. Fu, J.; Kanne, D. B.; Leong, M.; Glickman, L. H.; McWhirter, S. M.; Lemmens, E.; Mechette, K.; Leong, J. J.; Lauer, P.; Liu, W.; Sivick, K. E.; Zeng, Q.; Soares, K. C.; Zheng, L.; Portnoy, D. A.; Woodward, J. J.; Pardoll, D. M.; Dubensky, T. W., Jr.; Kim, Y. STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade Sci. Transl. Med. 2015, 7 (283) 283ra52 10.1126/scitranslmed.aaa4306
30. Yi, G.; Brendel, V. P.; Shu, C.; Li, P.; Palanathan, S.; Cheng Kao, C. Single nucleotide polymorphisms of human STING can affect innate immune response to cyclic dinucleotides PLoS One 2013, 8 (10) e77846 10.1371/journal.pone.0077846