Network pharmacology of JAK inhibitors

Proceedings of the National Academy of Sciences of the United States of America

Volumn 113, Issue 35, 2016, Pages 9852-9857

  Moodley, Devapregasan ^a   Yoshida, Hideyuki ^a   Mostafavi, Sara ^b   Asinovski, Natasha ^a   Ortiz Lopez, Adriana ^a   Symanowicz, Peter ^c   Telliez, Jean Baptiste ^c   Hegen, Martin ^c   Clark, James D ^c   Mathis, Diane ^a   Benoist, Christophe ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^c PFIZER INC   (United States)

Author keywords

Jak inhibitor; Systems pharmacology; Tofacitinib

Indexed keywords

INTERFERON; JANUS KINASE INHIBITOR; CYTOKINE; JANUS KINASE; TRANSCRIPTOME;

ANIMAL CELL; ANIMAL EXPERIMENT; CONFERENCE PAPER; CONTROLLED STUDY; DRUG MECHANISM; GENE REPRESSION; HOMEOSTASIS; IMMUNOGENETICS; IMMUNOPHENOTYPING; MACROPHAGE; MALE; MOUSE; NATURAL KILLER CELL; NONHUMAN; PRIORITY JOURNAL; ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; DRUG EFFECTS; GENE REGULATORY NETWORK; GENETICS; IMMUNOLOGY; METABOLISM; SIGNAL TRANSDUCTION;

ANIMALS; CYTOKINES; GENE REGULATORY NETWORKS; IMMUNOGENETIC PHENOMENA; JANUS KINASE INHIBITORS; JANUS KINASES; KILLER CELLS, NATURAL; MACROPHAGES; MALE; MICE, INBRED C57BL; SIGNAL TRANSDUCTION; TRANSCRIPTOME;

EID: 84984679654     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1610253113     Document Type: Article

References (33)

1. Hopkins AL (2008) Network pharmacology: The next paradigm in drug discovery. Nat Chem Biol 4(11):682-690.
2. Clark JD, Flanagan ME, Telliez JB (2014) Discovery and development of Janus kinase (JAK) inhibitors for inflammatory diseases. J Med Chem 57(12):5023-5038.
3. Schwartz DM, Bonelli M, Gadina M, O'Shea JJ (2016) Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases. Nat Rev Rheumatol 12(1):25-36.
4. O'Shea JJ, Plenge R (2012) JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. Immunity 36(4):542-550.
5. Kontzias A, Kotlyar A, Laurence A, Changelian P, O'Shea JJ (2012) Jakinibs: A new class of kinase inhibitors in cancer and autoimmune disease. Curr Opin Pharmacol 12(4):464-470.
6. Tefferi A (2012) JAK inhibitors for myeloproliferative neoplasms: Clarifying facts from myths. Blood 119(12):2721-2730.
7. Van Rompaey L, et al. (2013) Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases. J Immunol 191(7):3568-3577.
8. Genovese MC, van Vollenhoven RF, Pacheco-Tena C, Zhang Y, Kinnman N (2016) VX-509(Decernotinib), an oral selective JAK-3 inhibitor, in combination with methotrexate in patients with rheumatoid arthritis. Arthritis Rheumatol 68(1):46-55.
9. Schönberg K, et al. (2015) JAK inhibition impairs NK cell function in myeloproliferative neoplasms. Cancer Res 75(11):2187-2199.
10. Valenzuela F, et al. (2015) Effects of tofacitinib on lymphocyte sub-populations, CMV and EBV viral load in patients with plaque psoriasis. BMC Dermatol 15:32.
11. Ferraro A, et al. (2014) Interindividual variation in human T regulatory cells. Proc Natl Acad Sci USA 111(12):E1111-E1120.
12. Bandyopadhyay S, et al. (2010) Rewiring of genetic networks in response to DNA damage. Science 330(6009):1385-1389.
13. Zhang B, et al. (2013) Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer's disease. Cell 153(3):707-720.
14. Woo JH, et al. (2015) Elucidating compound mechanism of action by network perturbation analysis. Cell 162(2):441-451.
15. Jojic V, et al.; Immunological Genome Project Consortium (2013) Identification of transcriptional regulators in the mouse immune system. Nat Immunol 14(6):633-643.
16. Arase H, Mocarski ES, Campbell AE, Hill AB, Lanier LL (2002) Direct recognition of cytomegalovirus by activating and inhibitory NK cell receptors. Science 296(5571):1323-1326.
17. Mostafavi S, et al.; Immunological Genome Project Consortium (2016) Parsing the interferon transcriptional network and its disease associations. Cell 164(3):564-578.
18. Buenrostro JD, Giresi PG, Zaba LC, Chang HY, Greenleaf WJ (2013) Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat Methods 10(12):1213-1218.
19. Stark GR, Darnell JE, Jr (2012) The JAK-STAT pathway at twenty. Immunity 36(4):503-514.
20. Villarino AV, Kanno Y, Ferdinand JR, O'Shea JJ (2015) Mechanisms of Jak/STAT signaling in immunity and disease. J Immunol 194(1):21-27.
21. Boyman O, Sprent J (2012) The role of interleukin-2 during homeostasis and activation of the immune system. Nat Rev Immunol 12(3):180-190.
22. Haan C, et al. (2011) Jak1 has a dominant role over Jak3 in signal transduction through ?c-containing cytokine receptors. Chem Biol 18(3):314-323.
23. Zhou YJ, et al. (2000) Hierarchy of protein tyrosine kinases in interleukin-2(IL-2) signaling: Activation of syk depends on Jak3; however, neither Syk nor Lck is required for IL-2-mediated STAT activation. Mol Cell Biol 20(12):4371-4380.
24. Kubota A, Lian RH, Lohwasser S, Salcedo M, Takei F (1999) IFN-gamma production and cytotoxicity of IL-2-activated murine NK cells are differentially regulated by MHC class I molecules. J Immunol 163(12):6488-6493.
25. Ghoreschi K, et al. (2011) Modulation of innate and adaptive immune responses by tofacitinib (CP-690, 550). J Immunol 186(7):4234-4243.
26. Boyle DL, et al. (2015) The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis. Ann Rheum Dis 74(6):1311-1316.
27. Roberts CA, Dickinson AK, Taams LS (2015) The interplay between monocytes/macrophages and CD4 (+) T cell subsets in rheumatoid arthritis. Front Immunol 6:32.
28. American College of Rheumatology (2014) 2014 ACR/ARHP Annual Meeting abstract supplement. Arthritis Rheumatol 66(Suppl 10):S1-S1402.
29. Fleischmann RM, et al. (2015) A randomized, double-blind, placebo-controlled, twelve-week, dose-ranging study of decernotinib, an oral selective JAK-3 inhibitor, as monotherapy in patients with active rheumatoid arthritis. Arthritis Rheumatol 67(2):334-343.
30. American College of Rheumatology (2015) 2015 ACR/ARHP Annual Meeting abstract supplement. Arthritis Rheumatol 67(Suppl 10):1-4046.
31. Abt MC, et al. (2012) Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity 37(1):158-170.
32. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: A practical and powerful approach to multiple testing. Roy Stat Soc B 57:32-300.
33. Zhang Y, et al. (2008) Model-based analysis of ChIP-Seq (MACS). Genome Biol 9(9):R137.