دورية أكاديمية
أعرض في EDS

Selective inhibitors of JAK1 targeting an isoform-restricted allosteric cysteine.

التفاصيل البيبلوغرافية
العنوان: Selective inhibitors of JAK1 targeting an isoform-restricted allosteric cysteine.
المؤلفون: Kavanagh ME; Department of Chemistry, Scripps Research, La Jolla, CA, USA., Horning BD; Vividion Therapeutics, San Diego, CA, USA., Khattri R; Vividion Therapeutics, San Diego, CA, USA., Roy N; Vividion Therapeutics, San Diego, CA, USA., Lu JP; Vividion Therapeutics, San Diego, CA, USA., Whitby LR; Vividion Therapeutics, San Diego, CA, USA., Ye E; Department of Chemistry, Scripps Research, La Jolla, CA, USA., Brannon JC; Vividion Therapeutics, San Diego, CA, USA., Parker A; Vividion Therapeutics, San Diego, CA, USA., Chick JM; Vividion Therapeutics, San Diego, CA, USA., Eissler CL; Vividion Therapeutics, San Diego, CA, USA., Wong AJ; Vividion Therapeutics, San Diego, CA, USA., Rodriguez JL; Vividion Therapeutics, San Diego, CA, USA., Rodiles S; Vividion Therapeutics, San Diego, CA, USA., Masuda K; Department of Chemistry, Scripps Research, La Jolla, CA, USA., Teijaro JR; Department of Immunology and Microbial Science, Scripps Research, La Jolla, CA, USA., Simon GM; Vividion Therapeutics, San Diego, CA, USA., Patricelli MP; Vividion Therapeutics, San Diego, CA, USA. mattp@vividion.com., Cravatt BF; Department of Chemistry, Scripps Research, La Jolla, CA, USA. cravatt@scripps.edu.
المصدر: Nature chemical biology [Nat Chem Biol] 2022 Dec; Vol. 18 (12), pp. 1388-1398. Date of Electronic Publication: 2022 Sep 12.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101231976 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-4469 (Electronic) Linking ISSN: 15524450 NLM ISO Abbreviation: Nat Chem Biol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Nature Pub. Group, [2005]-
مواضيع طبية MeSH: Cysteine* , Proteomics*, Signal Transduction ; Cytokines ; Protein Isoforms
مستخلص: The Janus tyrosine kinase (JAK) family of non-receptor tyrosine kinases includes four isoforms (JAK1, JAK2, JAK3, and TYK2) and is responsible for signal transduction downstream of diverse cytokine receptors. JAK inhibitors have emerged as important therapies for immun(onc)ological disorders, but their use is limited by undesirable side effects presumed to arise from poor isoform selectivity, a common challenge for inhibitors targeting the ATP-binding pocket of kinases. Here we describe the chemical proteomic discovery of a druggable allosteric cysteine present in the non-catalytic pseudokinase domain of JAK1 (C817) and TYK2 (C838), but absent from JAK2 or JAK3. Electrophilic compounds selectively engaging this site block JAK1-dependent trans-phosphorylation and cytokine signaling, while appearing to act largely as 'silent' ligands for TYK2. Importantly, the allosteric JAK1 inhibitors do not impair JAK2-dependent cytokine signaling and are inactive in cells expressing a C817A JAK1 mutant. Our findings thus reveal an allosteric approach for inhibiting JAK1 with unprecedented isoform selectivity.
(© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
التعليقات: Erratum in: Nat Chem Biol. 2022 Nov;18(11):1288. doi: 10.1038/s41589-022-01181-6. (PMID: 36180594)
References: J Immunol. 2007 Nov 15;179(10):6504-13. (PMID: 17982039)
Eur J Immunol. 2021 Jul;51(7):1615-1627. (PMID: 33930196)
ACS Chem Biol. 2016 Dec 16;11(12):3442-3451. (PMID: 27791347)
Immunity. 2000 Oct;13(4):549-60. (PMID: 11070173)
Drug Des Devel Ther. 2022 Feb 17;16:363-374. (PMID: 35210753)
Annu Rev Med. 2015;66:311-28. (PMID: 25587654)
Cell. 2003 Mar 21;112(6):859-71. (PMID: 12654251)
Front Immunol. 2019 Jan 08;9:3108. (PMID: 30671064)
Nat Chem Biol. 2006 Feb;2(2):95-102. (PMID: 16415863)
Eur J Pharmacol. 2020 Oct 15;885:173505. (PMID: 32861662)
J Dtsch Dermatol Ges. 2021 Oct;19(10):1409-1420. (PMID: 34580985)
Cancers (Basel). 2019 Dec 27;12(1):. (PMID: 31892268)
Immunity. 2020 Sep 15;53(3):672-684.e11. (PMID: 32750333)
Cell. 2020 Aug 20;182(4):1009-1026.e29. (PMID: 32730809)
Lancet. 2005 Mar 19-25;365(9464):1054-61. (PMID: 15781101)
Front Immunol. 2018 Jan 30;9:94. (PMID: 29441069)
J Med Chem. 2019 Oct 24;62(20):8973-8995. (PMID: 31318208)
Nat Rev Immunol. 2007 Jun;7(6):429-42. (PMID: 17525752)
Chem Biol. 2011 Mar 25;18(3):314-23. (PMID: 21439476)
J Med Chem. 2017 Mar 9;60(5):1971-1993. (PMID: 28139931)
Cancer Res. 2005 Apr 15;65(8):3447-53. (PMID: 15833880)
EMBO J. 1996 Feb 15;15(4):799-809. (PMID: 8631301)
Expert Rev Clin Immunol. 2022 Mar;18(3):185-187. (PMID: 34809510)
J Med Chem. 2018 Feb 8;61(3):1130-1152. (PMID: 29298069)
Cell Metab. 2022 Mar 1;34(3):487-501.e8. (PMID: 35235776)
Mol Endocrinol. 2007 Sep;21(9):2218-32. (PMID: 17550976)
Cell. 1998 May 1;93(3):373-83. (PMID: 9590172)
J Immunol. 2013 Oct 1;191(7):3568-77. (PMID: 24006460)
Eur J Biochem. 1999 Oct 1;265(1):251-7. (PMID: 10491180)
Immunity. 2000 Oct;13(4):561-71. (PMID: 11070174)
Nature. 2017 Mar 30;543(7647):733-737. (PMID: 28329763)
Nature. 2016 Jun 15;534(7608):570-4. (PMID: 27309814)
Cell Stem Cell. 2017 Oct 5;21(4):489-501.e7. (PMID: 28965767)
Nat Chem Biol. 2019 Aug;15(8):776-785. (PMID: 31285595)
Cell. 2017 Oct 19;171(3):696-709.e23. (PMID: 28965760)
Angew Chem Int Ed Engl. 2002 Jul 15;41(14):2596-9. (PMID: 12203546)
Mucosal Immunol. 2021 Sep;14(5):1172-1182. (PMID: 34226674)
Br J Haematol. 2015 Jun;169(6):824-33. (PMID: 25824483)
J Exp Med. 2007 Jan 22;204(1):65-71. (PMID: 17227909)
Science. 1994 Jun 3;264(5164):1415-21. (PMID: 8197455)
Future Med Chem. 2010 Jun;2(6):949-64. (PMID: 20640225)
Transgenic Res. 2014 Jun;23(3):519-29. (PMID: 24696087)
J Immunol. 2011 Apr 1;186(7):4234-43. (PMID: 21383241)
Nat Struct Mol Biol. 2014 Jul;21(7):579-84. (PMID: 24918548)
Nat Rev Drug Discov. 2021 Nov;20(11):839-861. (PMID: 34354255)
Cytokine. 2019 Jun;118:48-63. (PMID: 29685781)
Nat Rev Drug Discov. 2017 Dec;16(12):843-862. (PMID: 29104284)
BioDrugs. 2019 Feb;33(1):15-32. (PMID: 30701418)
Angew Chem Int Ed Engl. 2020 Aug 10;59(33):13764-13776. (PMID: 31889388)
معلومات مُعتمدة: United Kingdom WT_ Wellcome Trust; 210890 United Kingdom WT_ Wellcome Trust; R35 CA231991 United States CA NCI NIH HHS; 210890/Z/18/Z United Kingdom WT_ Wellcome Trust
المشرفين على المادة: K848JZ4886 (Cysteine)
0 (Cytokines)
0 (Protein Isoforms)
تواريخ الأحداث: Date Created: 20220913 Date Completed: 20221125 Latest Revision: 20240611
رمز التحديث: 20240611
مُعرف محوري في PubMed: PMC7614775
DOI: 10.1038/s41589-022-01098-0
PMID: 36097295
قاعدة البيانات: MEDLINE
الوصف
تدمد:1552-4469
DOI:10.1038/s41589-022-01098-0