دورية أكاديمية
أعرض في EDS

SuFEx-based chemical diversification for the systematic discovery of CRBN molecular glues.

التفاصيل البيبلوغرافية
العنوان: SuFEx-based chemical diversification for the systematic discovery of CRBN molecular glues.
المؤلفون: Carter TR; Department of Chemistry, The Scripps Research Institute, United States., Milosevich N; Department of Chemistry, The Scripps Research Institute, United States., Dada L; Department of Biochemistry, Albert Einstein College of Medicine, United States., Shaum JB; Department of Chemistry, The Scripps Research Institute, United States., Barry Sharpless K; Department of Chemistry, The Scripps Research Institute, United States., Kitamura S; Department of Chemistry, The Scripps Research Institute, United States; Department of Biochemistry, Albert Einstein College of Medicine, United States., Erb MA; Department of Chemistry, The Scripps Research Institute, United States.
المصدر: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2024 Apr 15; Vol. 104, pp. 117699. Date of Electronic Publication: 2024 Apr 04.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: England NLM ID: 9413298 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1464-3391 (Electronic) Linking ISSN: 09680896 NLM ISO Abbreviation: Bioorg Med Chem Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford : Elsevier Science
Original Publication: Oxford : New York : Pergamon Press, c1993-
مواضيع طبية MeSH: Ubiquitin-Protein Ligases*/metabolism, Proteolysis ; Lenalidomide
مستخلص: Molecular glues are small molecules that stabilize protein-protein interactions, enabling new molecular pharmacologies, such as targeted protein degradation. They offer advantages over proteolysis targeting chimeras (PROTACs), which present challenges associated with the size and properties of heterobifunctional constructions, but glues lack the rational design principles analogous to PROTACs. One notable exception is the ability to alter the structure of Cereblon (CRBN)-based molecular glues and redirect their activity toward new neo-substrate proteins. We took a focused approach toward modifying the CRBN ligand, 5'-amino lenalidomide, to alter its neo-substrate specificity using high-throughput chemical diversification by parallelized sulfur(VI)-fluoride exchange (SuFEx) transformations. We synthesized over 3,000 analogs of 5'-amino lenalidomide using this approach and screened the crude products using a phenotypic screen for cell viability, identifying dozens of analogs with differentiated activity. We characterized four compounds that degrade G-to-S phase transition 1 (GSPT1) protein, providing a proof-of-concept model for SuFEx-based discovery of CRBN molecular glues.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Michael Erb reports a relationship with Nexo Therapeutics that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
References: Cell Chem Biol. 2023 Mar 16;30(3):235-247.e12. (PMID: 36863346)
Mol Cell. 2017 Jul 6;67(1):5-18.e19. (PMID: 28673542)
ACS Cent Sci. 2021 May 26;7(5):815-830. (PMID: 34079898)
Nat Commun. 2023 Dec 19;14(1):8437. (PMID: 38114468)
Science. 2022 Nov 4;378(6619):549-553. (PMID: 36378961)
Nat Chem Biol. 2020 Jan;16(1):7-14. (PMID: 31686031)
Nat Commun. 2024 Jan 16;15(1):482. (PMID: 38228616)
Nat Chem Biol. 2020 Nov;16(11):1199-1207. (PMID: 32747809)
Nat Struct Mol Biol. 2020 Apr;27(4):319-322. (PMID: 32251415)
Cell Chem Biol. 2019 Feb 21;26(2):300-306.e9. (PMID: 30595531)
Nat Chem Biol. 2021 Jun;17(6):711-717. (PMID: 34035522)
Science. 2010 Mar 12;327(5971):1345-50. (PMID: 20223979)
Leukemia. 2012 Nov;26(11):2326-35. (PMID: 22552008)
Nat Chem Biol. 2017 Jun;13(6):675-680. (PMID: 28437394)
Science. 2017 Apr 28;356(6336):. (PMID: 28302793)
Science. 2014 Jan 17;343(6168):301-5. (PMID: 24292625)
ACS Chem Biol. 2018 Mar 16;13(3):553-560. (PMID: 29356495)
Nature. 2020 Sep;585(7824):293-297. (PMID: 32494016)
Cell Chem Biol. 2021 Jul 15;28(7):1032-1047. (PMID: 33930325)
Nature. 2016 Jun 22;535(7611):252-7. (PMID: 27338790)
Science. 2018 Mar 9;359(6380):. (PMID: 29590011)
Nat Methods. 2011 Oct 02;8(11):937-40. (PMID: 21963607)
Cell. 2021 Jan 7;184(1):3-9. (PMID: 33417864)
Eur J Med Chem. 2023 Oct 5;258:115567. (PMID: 37390512)
Elife. 2018 Aug 01;7:. (PMID: 30067223)
ACS Chem Biol. 2023 Dec 15;18(12):2464-2473. (PMID: 38098458)
Nature. 2015 Jul 9;523(7559):183-188. (PMID: 26131937)
Nat Chem Biol. 2020 Jan;16(1):15-23. (PMID: 31819272)
Nature. 2016 Apr 7;532(7597):127-30. (PMID: 26909574)
Angew Chem Int Ed Engl. 2019 Jun 11;58(24):8029-8033. (PMID: 30998840)
Cell. 2020 Apr 2;181(1):102-114. (PMID: 31955850)
Science. 2014 Jan 17;343(6168):305-9. (PMID: 24292623)
ACS Chem Biol. 2020 Oct 16;15(10):2722-2730. (PMID: 32865967)
J Med Chem. 2021 Jun 10;64(11):7296-7311. (PMID: 34042448)
Nat Chem Biol. 2018 Oct;14(10):981-987. (PMID: 30190590)
Science. 2018 Nov 2;362(6414):. (PMID: 30385546)
J Am Chem Soc. 2020 Jun 24;142(25):10899-10904. (PMID: 32479075)
معلومات مُعتمدة: P30 CA013330 United States CA NCI NIH HHS; DP5 OD026380 United States OD NIH HHS; K99 GM138758 United States GM NIGMS NIH HHS; S10 OD016305 United States OD NIH HHS; R00 GM138758 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: CRBN; Degradation; GSPT1; Lenalidomide; Molecular glue; SuFEx
المشرفين على المادة: EC 2.3.2.27 (Ubiquitin-Protein Ligases)
F0P408N6V4 (Lenalidomide)
تواريخ الأحداث: Date Created: 20240412 Date Completed: 20240422 Latest Revision: 20240625
رمز التحديث: 20240625
مُعرف محوري في PubMed: PMC11195152
DOI: 10.1016/j.bmc.2024.117699
PMID: 38608634
قاعدة البيانات: MEDLINE
الوصف
تدمد:1464-3391
DOI:10.1016/j.bmc.2024.117699