دورية أكاديمية
أعرض في EDS

Linking ATP and allosteric sites to achieve superadditive binding with bivalent EGFR kinase inhibitors.

التفاصيل البيبلوغرافية
العنوان: Linking ATP and allosteric sites to achieve superadditive binding with bivalent EGFR kinase inhibitors.
المؤلفون: Wittlinger F; Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmaceutical Sciences, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, 72076, Tübingen, Germany., Ogboo BC; Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY, 14260, USA., Shevchenko E; Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmaceutical Sciences, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, 72076, Tübingen, Germany.; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies' Eberhard Karls Universität Tübingen, 72076, Tübingen, Germany.; Tübingen Center for Academic Drug Discovery & Development (TüCAD2), 72076, Tübingen, Germany., Damghani T; Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY, 14260, USA., Pham CD; Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY, 14260, USA., Schaeffner IK; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA., Oligny BT; Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY, 14260, USA., Chitnis SP; Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY, 14260, USA., Beyett TS; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.; Department of Pharmacology and Chemical Biology, Emory University School of Medicine, 5119 Rollins Research Center, 1510 Clifton Rd, Atlanta, GA, 30322, USA., Rasch A; Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmaceutical Sciences, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, 72076, Tübingen, Germany., Buckley B; Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14203, USA., Urul DA; AssayQuant Technologies, Inc., Marlboro, MA, 01752, USA., Shaurova T; Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14203, USA., May EW; AssayQuant Technologies, Inc., Marlboro, MA, 01752, USA., Schaefer EM; AssayQuant Technologies, Inc., Marlboro, MA, 01752, USA., Eck MJ; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA., Hershberger PA; Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14203, USA., Poso A; Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmaceutical Sciences, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, 72076, Tübingen, Germany.; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies' Eberhard Karls Universität Tübingen, 72076, Tübingen, Germany.; Tübingen Center for Academic Drug Discovery & Development (TüCAD2), 72076, Tübingen, Germany.; School of Pharmacy, University of Eastern Finland, 70210, Kuopio, Finland., Laufer SA; Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmaceutical Sciences, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, 72076, Tübingen, Germany. stefan.laufer@uni-tuebingen.de.; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies' Eberhard Karls Universität Tübingen, 72076, Tübingen, Germany. stefan.laufer@uni-tuebingen.de.; Tübingen Center for Academic Drug Discovery & Development (TüCAD2), 72076, Tübingen, Germany. stefan.laufer@uni-tuebingen.de., Heppner DE; Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY, 14260, USA. davidhep@buffalo.edu.; Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14203, USA. davidhep@buffalo.edu.; Department of Structural Biology, University at Buffalo, The State University of New York, Buffalo, NY, 14260, USA. davidhep@buffalo.edu.
المصدر: Communications chemistry [Commun Chem] 2024 Feb 20; Vol. 7 (1), pp. 38. Date of Electronic Publication: 2024 Feb 20.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer Nature Country of Publication: England NLM ID: 101725670 Publication Model: Electronic Cited Medium: Internet ISSN: 2399-3669 (Electronic) Linking ISSN: 23993669 NLM ISO Abbreviation: Commun Chem Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [London] : Springer Nature, [2018]-
مستخلص: Bivalent molecules consisting of groups connected through bridging linkers often exhibit strong target binding and unique biological effects. However, developing bivalent inhibitors with the desired activity is challenging due to the dual motif architecture of these molecules and the variability that can be introduced through differing linker structures and geometries. We report a set of alternatively linked bivalent EGFR inhibitors that simultaneously occupy the ATP substrate and allosteric pockets. Crystal structures show that initial and redesigned linkers bridging a trisubstituted imidazole ATP-site inhibitor and dibenzodiazepinone allosteric-site inhibitor proved successful in spanning these sites. The re-engineered linker yielded a compound that exhibited significantly higher potency (~60 pM) against the drug-resistant EGFR L858R/T790M and L858R/T790M/C797S, which was superadditive as compared with the parent molecules. The enhanced potency is attributed to factors stemming from the linker connection to the allosteric-site group and informs strategies to engineer linkers in bivalent agent design.
(© 2024. The Author(s).)
التعليقات: Update of: Res Sq. 2023 Sep 13;:. (PMID: 37790373)
References: J Med Chem. 2022 Jun 23;65(12):8091-8112. (PMID: 35686733)
Protein Sci. 2021 Aug;30(8):1535-1553. (PMID: 34008902)
Angew Chem Int Ed Engl. 2016 Aug 26;55(36):10890-4. (PMID: 27466205)
Nat Chem Biol. 2015 Nov;11(11):818-21. (PMID: 26485069)
Nature. 2023 Aug;620(7973):417-425. (PMID: 37495688)
Nature. 2005 Jun 2;435(7042):677-81. (PMID: 15902208)
Acc Chem Res. 2009 Jun 16;42(6):724-33. (PMID: 19317443)
Anal Biochem. 2009 Aug 1;391(1):31-8. (PMID: 19406097)
Nat Chem Biol. 2016 Dec;12(12):1089-1096. (PMID: 27775715)
ACS Med Chem Lett. 2023 Aug 14;14(9):1231-1236. (PMID: 37736196)
Pharmacol Ther. 2015 Dec;156:59-68. (PMID: 26478442)
Mol Biosyst. 2011 Feb;7(2):359-64. (PMID: 20922213)
J Comput Aided Mol Des. 2013 Mar;27(3):221-34. (PMID: 23579614)
Proc Natl Acad Sci U S A. 1981 Jul;78(7):4046-50. (PMID: 16593049)
Elife. 2021 Jul 28;10:. (PMID: 34319231)
Curr Opin Biotechnol. 2007 Dec;18(6):489-96. (PMID: 17959370)
Explor Target Antitumor Ther. 2020;1(5):273-312. (PMID: 36046485)
ACS Chem Biol. 2012 Mar 16;7(3):487-95. (PMID: 22148755)
Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):808-13. (PMID: 17204562)
Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8348-52. (PMID: 10411878)
J Am Chem Soc. 2023 Dec 6;145(48):26028-26037. (PMID: 37992275)
J Med Chem. 2006 Oct 19;49(21):6177-96. (PMID: 17034125)
Mol Inform. 2011 Apr 18;30(4):298-306. (PMID: 27466947)
J Med Chem. 2017 Jun 8;60(11):4636-4656. (PMID: 28482151)
Nat Chem Biol. 2022 Apr;18(4):412-421. (PMID: 35210618)
Cancer Discov. 2019 Jul;9(7):926-943. (PMID: 31092401)
J Chem Theory Comput. 2021 Jul 13;17(7):4291-4300. (PMID: 34096718)
Nat Commun. 2022 May 9;13(1):2530. (PMID: 35534503)
J Med Chem. 2017 Jul 13;60(13):5613-5637. (PMID: 28603991)
Chem Biol Drug Des. 2022 Oct;100(4):469-486. (PMID: 35854428)
Nature. 2009 Dec 24;462(7276):1070-4. (PMID: 20033049)
Nat Rev Drug Discov. 2019 Dec;18(12):949-963. (PMID: 31666732)
J Am Chem Soc. 2021 Oct 13;143(40):16700-16708. (PMID: 34592107)
Nat Commun. 2022 Nov 10;13(1):6791. (PMID: 36357385)
ACS Chem Biol. 2021 Dec 17;16(12):2808-2815. (PMID: 34780684)
Curr Opin Struct Biol. 2010 Aug;20(4):497-507. (PMID: 20471246)
Nat Chem Biol. 2018 Jul;14(7):706-714. (PMID: 29892083)
Drugs. 2016 Jun;76(9):979-87. (PMID: 27260335)
Bioorg Chem. 2022 Oct;127:105921. (PMID: 35709578)
J Med Chem. 2011 May 12;54(9):3283-97. (PMID: 21449619)
J Am Chem Soc. 2008 Mar 5;130(9):2817-31. (PMID: 18266362)
J Am Chem Soc. 2020 Aug 19;142(33):14052-14057. (PMID: 32787262)
ACS Med Chem Lett. 2019 Oct 22;10(11):1549-1553. (PMID: 31749909)
Front Chem. 2020 Feb 18;8:93. (PMID: 32133344)
Nat Cancer. 2022 Apr;3(4):402-417. (PMID: 35422503)
Cell. 2021 Jan 7;184(1):3-9. (PMID: 33417864)
Nat Chem Biol. 2009 Jun;5(6):407-13. (PMID: 19396178)
Nat Rev Cancer. 2009 Jan;9(1):28-39. (PMID: 19104514)
Curr Protoc. 2022 Dec;2(12):e611. (PMID: 36469581)
Science. 2004 Jun 4;304(5676):1497-500. (PMID: 15118125)
J Chem Theory Comput. 2021 Jan 12;17(1):450-462. (PMID: 33372778)
J Synchrotron Radiat. 2021 Mar 1;28(Pt 2):650-665. (PMID: 33650577)
ACS Chem Biol. 2008 Nov 21;3(11):677-692. (PMID: 19112665)
J Med Chem. 2006 Jan 26;49(2):656-63. (PMID: 16420051)
ACS Cent Sci. 2023 Jul 14;9(7):1269-1284. (PMID: 37521793)
J Am Chem Soc. 2007 Nov 14;129(45):13812-3. (PMID: 17944472)
ACS Med Chem Lett. 2019 May 22;10(6):869-873. (PMID: 31223440)
J Med Chem. 2022 Jan 27;65(2):1370-1383. (PMID: 34668706)
Nature. 2016 May 25;534(7605):129-32. (PMID: 27251290)
Nat Rev Drug Discov. 2021 Nov;20(11):839-861. (PMID: 34354255)
J Am Chem Soc. 2009 May 20;131(19):6686-8. (PMID: 19391594)
J Mol Biol. 2002 Jul 12;320(3):597-608. (PMID: 12096912)
ACS Med Chem Lett. 2020 Nov 05;11(12):2484-2490. (PMID: 33335671)
J Comput Chem. 2005 Dec;26(16):1752-80. (PMID: 16211539)
Bioorg Med Chem. 2017 Jul 1;25(13):3540-3546. (PMID: 28511909)
J Med Chem. 2021 Aug 12;64(15):10606-10620. (PMID: 34319094)
J Med Chem. 2020 Oct 22;63(20):11420-11435. (PMID: 32539387)
Nat Rev Drug Discov. 2016 Sep;15(9):605-619. (PMID: 27417849)
J Med Chem. 2020 Apr 23;63(8):4293-4305. (PMID: 32243152)
Nat Chem Biol. 2016 Dec;12(12):1097-1104. (PMID: 27775716)
Nat Rev Drug Discov. 2004 Aug;3(8):660-72. (PMID: 15286733)
Chem Rev. 2019 Feb 13;119(3):1626-1665. (PMID: 30698416)
J Comput Aided Mol Des. 2002 Oct;16(10):741-53. (PMID: 12650591)
Proteins. 2004 May 1;55(2):351-67. (PMID: 15048827)
Angew Chem Int Ed Engl. 2020 Aug 10;59(33):13764-13776. (PMID: 31889388)
معلومات مُعتمدة: R01 CA197967 United States CA NCI NIH HHS; P41 GM103403 United States GM NIGMS NIH HHS; P30 CA016056 United States CA NCI NIH HHS; UL1 TR001412 United States TR NCATS NIH HHS; R35 CA242461 United States CA NCI NIH HHS; R01 CA116020 United States CA NCI NIH HHS; F32 CA247198 United States CA NCI NIH HHS; R01 CA201049 United States CA NCI NIH HHS; P30 GM124165 United States GM NIGMS NIH HHS
تواريخ الأحداث: Date Created: 20240220 Latest Revision: 20240304
رمز التحديث: 20240304
مُعرف محوري في PubMed: PMC10879502
DOI: 10.1038/s42004-024-01108-3
PMID: 38378740
قاعدة البيانات: MEDLINE
الوصف
تدمد:2399-3669
DOI:10.1038/s42004-024-01108-3