{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:56:38Z","timestamp":1792598198469,"version":"4.5.0"},"reference-count":50,"publisher":"American Chemical Society (ACS)","issue":"41","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Protein\u2013DNA interfaces are central to genome maintenance but remain challenging targets for small-molecule discovery because they are often broad, polar, solvent-exposed, and lack classical druggable pockets. Here, we establish a structure-guided strategy to chemically target such interfaces by combining the fragment-based identification of DNA-mimetic binders with the covalent capture of a proximal nucleophilic residue. Using the ssDNA-binding groove of RAD52 as a representative model system, an X-ray fragment screen identified carboxylate-containing fragments that recapitulate key phosphate backbone interactions of ssDNA within the conserved DNA-binding groove. Structural analysis revealed a recurrent 2:1 fragment-binding mode that enabled fragment linking and preorganization, yielding reversible inhibitors with nanomolar biochemical activity. Subsequent exploitation of C64, located adjacent to the bound ligand, converted this reversible scaffold into potent covalent inhibitors. Optimization led to the identification of FORX-864, a beyond-rule-of-5 covalent RAD52 chemical probe with low nanomolar ssDNA-displacement activity, efficient covalent target engagement, favorable in vitro properties, and submicromolar inhibition of RAD52-dependent single-strand annealing in cells. This work provides a chemical strategy for targeting DNA-binding proteins through DNA-mimetic fragment recognition, structure-guided preorganization, and covalent stabilization while delivering validated probes to interrogate RAD52 biology.<\/jats:p>","DOI":"10.1021\/jacs.6c16278","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:02:17Z","timestamp":1791482537000},"page":"45059-45070","source":"Crossref","is-referenced-by-count":0,"title":["Integrating Fragment\nScreening and Covalent Chemistry\nto Drug DNA-Binding Proteins: RAD52 as a Case Study"],"prefix":"10.1021","volume":"148","author":[{"given":"Nicolas","family":"Bocquet","sequence":"first","affiliation":[{"name":"FoRx Therapeutics AG , Lichtstrasse 35 , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Potenza","sequence":"additional","affiliation":[{"name":"FoRx Therapeutics AG , Lichtstrasse 35 , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Clochard","sequence":"additional","affiliation":[{"name":"FoRx Therapeutics AG , Lichtstrasse 35 , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anika","family":"Kuster","sequence":"additional","affiliation":[{"name":"FoRx Therapeutics AG , Lichtstrasse 35 , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5130-4757","authenticated-orcid":true,"given":"Hanna","family":"Kok","sequence":"additional","affiliation":[{"name":"FoRx Therapeutics AG , Lichtstrasse 35 , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Iacovino","sequence":"additional","affiliation":[{"name":"FoRx Therapeutics AG , Lichtstrasse 35 , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Jin","sequence":"additional","affiliation":[{"name":"WuXi AppTec (Wuhan) Co., Ltd. , No. 68 Middle Jiulong Road, Wuhan East Lake High-Tech Development Zone , , ,","place":["Wuhan, Hubei, China, 430075"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaixu","family":"Xu","sequence":"additional","affiliation":[{"name":"WuXi AppTec (Wuhan) Co., Ltd. , No. 68 Middle Jiulong Road, Wuhan East Lake High-Tech Development Zone , , ,","place":["Wuhan, Hubei, China, 430075"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ailsa J.","family":"Powell","sequence":"additional","affiliation":[{"name":"Diamond Light Source Ltd , Harwell Science and Innovation Campus , , ,","place":["Didcot, Oxfordshire, U.K., OX11 0DE"]},{"name":"Research Complex at Harwell , Harwell Science and Innovation Campus , , ,","place":["Didcot, Oxfordshire, U.K., OX11 0FA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel A.","family":"Barker","sequence":"additional","affiliation":[{"name":"Diamond Light Source Ltd , Harwell Science and Innovation Campus , , ,","place":["Didcot, Oxfordshire, U.K., OX11 0DE"]},{"name":"Research Complex at Harwell , Harwell Science and Innovation Campus , , ,","place":["Didcot, Oxfordshire, U.K., OX11 0FA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Rempel","sequence":"additional","affiliation":[{"name":"FoRx Therapeutics AG , Lichtstrasse 35 , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lia","family":"Mela","sequence":"additional","affiliation":[{"name":"FoRx Therapeutics AG , Lichtstrasse 35 , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo G.","family":"Rossetti","sequence":"additional","affiliation":[{"name":"University of Bern , , ,","place":["Bern, Switzerland, 3008"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4690-0568","authenticated-orcid":true,"given":"Sotirios K.","family":"Sotiriou","sequence":"additional","affiliation":[{"name":"FoRx Therapeutics AG , Lichtstrasse 35 , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanos D.","family":"Halazonetis","sequence":"additional","affiliation":[{"name":"University of Bern , , ,","place":["Bern, Switzerland, 3008"]},{"name":"Inselspital, Hospital of the University of Bern , , ,","place":["Bern, Switzerland, 3010"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irena","family":"Konstantinova","sequence":"additional","affiliation":[{"name":"FoRx Therapeutics AG , Lichtstrasse 35 , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Goutopoulos","sequence":"additional","affiliation":[{"name":"FoRx Therapeutics AG , Lichtstrasse 35 , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2567-3872","authenticated-orcid":true,"given":"James","family":"Mills","sequence":"additional","affiliation":[{"name":"Sandexis Medicinal Chemistry Ltd , Innovation House, Discovery Park, Ramsgate Road , ,","place":["Sandwich, U.K., CT13 9FF"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3626-5073","authenticated-orcid":true,"given":"Ronen","family":"Gabizon","sequence":"additional","affiliation":[{"name":"Department of Chemical and Structural Biology , , ,","place":["Rehovot, Israel, 76100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almog","family":"Nadir","sequence":"additional","affiliation":[{"name":"Department of Chemical and Structural Biology , , ,","place":["Rehovot, Israel, 76100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2687-0699","authenticated-orcid":true,"given":"Nir","family":"London","sequence":"additional","affiliation":[{"name":"Department of Chemical and Structural Biology , , ,","place":["Rehovot, Israel, 76100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarig","family":"Bashir","sequence":"additional","affiliation":[{"name":"FoRx Therapeutics AG , Lichtstrasse 35 , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank T.","family":"Zenke","sequence":"additional","affiliation":[{"name":"FoRx Therapeutics AG , Lichtstrasse 35 , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Querolle","sequence":"additional","affiliation":[{"name":"FoRx Therapeutics AG , Lichtstrasse 35 , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2466-5800","authenticated-orcid":true,"given":"Ulrich","family":"Lu\u0308cking","sequence":"additional","affiliation":[{"name":"FoRx Therapeutics AG , Lichtstrasse 35 , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"2026102111091780300_cit1","doi-asserted-by":"publisher","first-page":"3702","DOI":"10.1039\/D5CC06239J","article-title":"Protein-DNA Interactions in Disease and Drug Discovery","volume":"62","author":"Mishra","year":"2026","journal-title":"Chem. Commun."},{"issue":"11","key":"2026102111091780300_cit2","doi-asserted-by":"publisher","first-page":"2660","DOI":"10.1016\/j.drudis.2021.07.018","article-title":"Drugging the\n\u2018Undruggable\u2019. Therapeutic Targeting of Protein\u2013DNA\nInteractions with the Use of Computer-Aided Drug Discovery Methods","volume":"26","author":"Radaeva","year":"2021","journal-title":"Drug Discovery Today"},{"issue":"21","key":"2026102111091780300_cit3","doi-asserted-by":"publisher","first-page":"9305","DOI":"10.1128\/MCB.24.21.9305-9316.2004","article-title":"Genetic Steps\nof Mammalian Homologous Repair with Distinct Mutagenic Consequences","volume":"24","author":"Stark","year":"2004","journal-title":"Mol. Cell. Biol."},{"issue":"6","key":"2026102111091780300_cit4","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1016\/j.molcel.2016.10.038","article-title":"Mammalian RAD52 Functions in Break-Induced\nReplication Repair of Collapsed DNA Replication Forks","volume":"64","author":"Sotiriou","year":"2016","journal-title":"Mol. Cell"},{"issue":"6","key":"2026102111091780300_cit5","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1016\/j.molcel.2016.10.037","article-title":"RAD52 Facilitates Mitotic DNA Synthesis\nFollowing Replication Stress","volume":"64","author":"Bhowmick","year":"2016","journal-title":"Mol. Cell"},{"key":"2026102111091780300_cit6","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1038\/nature13682","article-title":"Transcript-RNA-Templated\nDNA Recombination and Repair","volume":"515","author":"Keskin","year":"2014","journal-title":"Nature"},{"issue":"4","key":"2026102111091780300_cit7","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1016\/j.celrep.2018.12.102","article-title":"Alternative\nLengthening of Telomeres through Two Distinct Break-Induced Replication\nPathways","volume":"26","author":"Zhang","year":"2019","journal-title":"Cell Rep."},{"issue":"12","key":"2026102111091780300_cit8","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.15252\/embr.201643169","article-title":"Alternative Lengthening\nof Human Telomeres Is a Conservative DNA\nReplication Process with Features of Break-induced Replication","volume":"17","author":"Roumelioti","year":"2016","journal-title":"EMBO Rep."},{"issue":"3\u20134","key":"2026102111091780300_cit9","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1101\/gad.319723.118","article-title":"RAD52 and\nSLX4 Act Nonepistatically to Ensure Telomere\nStability during Alternative Telomere Lengthening","volume":"33","author":"Verma","year":"2019","journal-title":"Genes Dev."},{"issue":"7316","key":"2026102111091780300_cit10","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1038\/nature09399","article-title":"Purified\nHuman BRCA2 Stimulates RAD51-Mediated\nRecombination","volume":"467","author":"Jensen","year":"2010","journal-title":"Nature"},{"issue":"11","key":"2026102111091780300_cit11","doi-asserted-by":"publisher","first-page":"6423","DOI":"10.1128\/MCB.18.11.6423","article-title":"Targeted Inactivation\nof Mouse RAD52 Reduces Homologous Recombination but Not Resistance\nto Ionizing Radiation","volume":"18","author":"Rijkers","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"2026102111091780300_cit12","doi-asserted-by":"publisher","first-page":"103421","DOI":"10.1016\/j.dnarep.2022.103421","article-title":"A Moving Target\nfor Drug Discovery:\nStructure Activity Relationship and Many Genome (de)Stabilizing Functions\nof the RAD52","volume":"120","author":"Bhat","year":"2022","journal-title":"DNA Repair (Amst)."},{"key":"2026102111091780300_cit13","doi-asserted-by":"publisher","first-page":"780293","DOI":"10.3389\/fgene.2021.780293","article-title":"RAD52: Paradigm\nof Synthetic Lethality and New Developments","volume":"12","author":"Rossi","year":"2021","journal-title":"Front. Genet."},{"issue":"2","key":"2026102111091780300_cit14","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1073\/pnas.1010959107","article-title":"Rad52 Inactivation Is Synthetically\nLethal with BRCA2 Deficiency","volume":"108","author":"Feng","year":"2011","journal-title":"Proc. Natl. Acad.\nSci. U. S. A."},{"issue":"30","key":"2026102111091780300_cit15","doi-asserted-by":"publisher","first-page":"3552","DOI":"10.1038\/onc.2012.391","article-title":"RAD52 Inactivation\nIs Synthetically Lethal with Deficiencies in BRCA1 and PALB2 in Addition\nto BRCA2 through RAD51-Mediated Homologous Recombination","volume":"32","author":"Lok","year":"2013","journal-title":"Oncogene"},{"issue":"2","key":"2026102111091780300_cit16","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1128\/MCB.00465-12","article-title":"Rad51 Paralog Complexes BCDX2 and\nCX3 Act at Different Stages in the BRCA1-BRCA2-Dependent Homologous\nRecombination Pathway","volume":"33","author":"Chun","year":"2013","journal-title":"Mol. Cell. Biol."},{"issue":"1","key":"2026102111091780300_cit17","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1186\/s13058-017-0912-8","article-title":"The Endonuclease EEPD1 Mediates Synthetic\nLethality in RAD52-Depleted BRCA1 Mutant Breast Cancer Cells","volume":"19","author":"Hromas","year":"2017","journal-title":"Breast Cancer Res."},{"issue":"17","key":"2026102111091780300_cit18","doi-asserted-by":"publisher","first-page":"9906","DOI":"10.1093\/nar\/gkab785","article-title":"XAB2 Promotes\nKu Eviction from Single-Ended DNA Double-Strand Breaks Independently\nof the ATM Kinase","volume":"49","author":"Sharma","year":"2021","journal-title":"Nucleic Acids Res."},{"issue":"4","key":"2026102111091780300_cit19","doi-asserted-by":"publisher","first-page":"114116","DOI":"10.1016\/j.celrep.2024.114116","article-title":"RAD52-Dependent Mitotic DNA Synthesis\nIs Required for Genome Stability in Cyclin E1-Overexpressing Cells","volume":"43","author":"Audrey","year":"2024","journal-title":"Cell Rep."},{"issue":"5","key":"2026102111091780300_cit20","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The CBio Cancer Genomics\nPortal: An Open Platform for\nExploring Multidimensional Cancer Genomics Data","volume":"2","author":"Cerami","year":"2012","journal-title":"Cancer Discovery"},{"issue":"269","key":"2026102111091780300_cit21","doi-asserted-by":"publisher","first-page":"pl1","DOI":"10.1126\/scisignal.2004088","article-title":"Integrative\nAnalysis of Complex Cancer Genomics and Clinical Profiles Using the\nCBioPortal","volume":"6","author":"Gao","year":"2013","journal-title":"Sci. Signal."},{"issue":"5","key":"2026102111091780300_cit22","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.3390\/ijms21051768","article-title":"Aberrant Expression\nof RAD52, Its Prognostic Impact in Rectal Cancer and Association with\nPoor Survival of Patients","volume":"21","author":"Ho","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"2026102111091780300_cit23","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1186\/s12935-019-0996-6","article-title":"Evaluating\nthe Role of RAD52 and Its Interactors as Novel Potential Molecular\nTargets for Hepatocellular Carcinoma","volume":"19","author":"Li","year":"2019","journal-title":"Cancer\nCell Int."},{"issue":"37","key":"2026102111091780300_cit24","doi-asserted-by":"publisher","first-page":"35201","DOI":"10.1074\/jbc.M104938200","article-title":"Homologous\nPairing Promoted by the Human Rad52 Protein","volume":"276","author":"Kagawa","year":"2001","journal-title":"J. Biol. Chem."},{"issue":"15","key":"2026102111091780300_cit25","doi-asserted-by":"publisher","first-page":"4175","DOI":"10.1093\/emboj\/19.15.4175","article-title":"Precise Binding\nof Single-Stranded DNA Termini by Human RAD52 Protein","volume":"19","author":"Parsons","year":"2000","journal-title":"Embo J."},{"key":"2026102111091780300_cit26","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.isci.2018.04.005","article-title":"Structural Basis of\nHomology-Directed DNA Repair Mediated by RAD52","volume":"3","author":"Saotome","year":"2018","journal-title":"iScience"},{"issue":"21","key":"2026102111091780300_cit27","doi-asserted-by":"publisher","first-page":"13492","DOI":"10.1073\/pnas.212449899","article-title":"Structure\nof the Single-Strand Annealing Domain of Human RAD52 Protein","volume":"99","author":"Singleton","year":"2002","journal-title":"PNAS"},{"key":"2026102111091780300_cit28","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1107\/S2053230X1601027X","article-title":"Structure of the Human DNA-Repair Protein RAD52 Containing\nSurface Mutations","volume":"72","author":"Saotome","year":"2016","journal-title":"Acta Crystallographica Section:\nF Structural Biol. Commun."},{"issue":"1","key":"2026102111091780300_cit29","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1038\/s42003-024-06644-1","article-title":"An Integrative Structural\nStudy of the Human Full-Length RAD52 at 2.2 \u00c5 Resolution","volume":"7","author":"Balboni","year":"2024","journal-title":"Commun. Biol."},{"issue":"3","key":"2026102111091780300_cit30","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1002\/2211-5463.13565","article-title":"The Cryo-EM Structure of Full-Length\nRAD52 Protein\nContains an Undecameric Ring","volume":"13","author":"Kinoshita","year":"2023","journal-title":"FEBS Open Bio"},{"issue":"6729","key":"2026102111091780300_cit31","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1038\/19560","article-title":"Binding of Double-Strand\nBreaks in DNA by Human Rad52 Protein","volume":"398","author":"Van Dyck","year":"1999","journal-title":"Nature"},{"issue":"48","key":"2026102111091780300_cit32","doi-asserted-by":"publisher","first-page":"46172","DOI":"10.1074\/jbc.M207262200","article-title":"Correlation\nof Biochemical Properties\nwith the Oligomeric State of Human Rad52 Protein","volume":"277","author":"Lloyd","year":"2002","journal-title":"J. Biol. Chem."},{"issue":"3","key":"2026102111091780300_cit33","doi-asserted-by":"publisher","first-page":"108115","DOI":"10.1016\/j.jsb.2024.108115","article-title":"A Glimpse\ninto the Hidden World of\nthe Flexible C-Terminal Protein Binding Domains of Human RAD52","volume":"216","author":"Struble","year":"2024","journal-title":"J. Struct Biol."},{"issue":"1","key":"2026102111091780300_cit34","doi-asserted-by":"publisher","first-page":"5589","DOI":"10.1038\/s41467-025-60664-x","article-title":"A Large C-Terminal Rad52 Segment Acts as a Chaperone\nto Form and Stabilize Rad51 Filaments","volume":"16","author":"Ma","year":"2025","journal-title":"Nat.\nCommun."},{"issue":"8","key":"2026102111091780300_cit35","doi-asserted-by":"publisher","first-page":"5377","DOI":"10.1021\/acs.jmedchem.3c00134","article-title":"Macrocycles in Drug\nDiscovery\u2500Learning from the Past for the Future","volume":"66","author":"Garcia Jimenez","year":"2023","journal-title":"J. Med. Chem."},{"issue":"3","key":"2026102111091780300_cit36","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1023\/a:1016212804288","article-title":"A Theoretical Basis\nfor a Biopharmaceutic Drug Classification: The Correlation of in Vitro\nDrug Product Dissolution and in Vivo Bioavailability","volume":"12","author":"Amidon","year":"1995","journal-title":"Pharm. Res."},{"key":"2026102111091780300_cit37","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1517\/17460441003605098","article-title":"Lipophilicity\nin Drug Discovery","volume":"5","author":"Waring","year":"2010","journal-title":"Expert Opin. Drug Discovery"},{"issue":"3","key":"2026102111091780300_cit38","doi-asserted-by":"publisher","first-page":"1802","DOI":"10.1529\/biophysj.105.060871","article-title":"Permeation of Aromatic Carboxylic\nAcids across Lipid Bilayers: The PH-Partition Hypothesis Revisited","volume":"89","author":"Thomae","year":"2005","journal-title":"Biophys. J."},{"issue":"7","key":"2026102111091780300_cit39","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1039\/D1MD00068C","article-title":"Recent Advances\nin the Development of Covalent Inhibitors","volume":"12","author":"Kim","year":"2021","journal-title":"RSC\nMed. Chem."},{"issue":"6","key":"2026102111091780300_cit40","doi-asserted-by":"publisher","first-page":"6298","DOI":"10.1021\/acs.jmedchem.5c01803","article-title":"Normalizing Covalent Potency for\nElectrophilicity with Ligand Reactivity Efficiency","volume":"69","author":"Horning","year":"2026","journal-title":"J. Med. Chem."},{"key":"2026102111091780300_cit41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/bph.70344","article-title":"Covalent Drug Discovery: Progress\nagainst Key Targets, Emerging Strategies and Lessons Learnt","author":"Brown","year":"2026","journal-title":"Br. J. Pharmacol."},{"issue":"36","key":"2026102111091780300_cit42","doi-asserted-by":"publisher","first-page":"9399","DOI":"10.1002\/anie.201302209","article-title":"Sulfoximines:\nA Neglected Opportunity in Medicinal Chemistry","volume":"52","author":"Lu\u0308cking","year":"2013","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026102111091780300_cit43","doi-asserted-by":"publisher","first-page":"112885","DOI":"10.1016\/j.ejmech.2020.112885","article-title":"Application\nof Sulfoximines in Medicinal Chemistry from 2013 to 2020","volume":"209","author":"Han","year":"2021","journal-title":"Eur. J. Med. Chem."},{"issue":"56","key":"2026102111091780300_cit44","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202201993","article-title":"New Opportunities\nfor the Utilization of the Sulfoximine Group in Medicinal Chemistry\nfrom the Drug Designer\u2019s Perspective","volume":"28","author":"Lu\u0308cking","year":"2022","journal-title":"Chem.\u2500Eur. J."},{"issue":"7","key":"2026102111091780300_cit45","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1002\/cmdc.201700044","article-title":"Novel Pieces for the Emerging Picture of Sulfoximines\nin Drug Discovery: Synthesis and Evaluation of Sulfoximine Analogues\nof Marketed Drugs and Advanced Clinical Candidates","volume":"12","author":"Sirvent","year":"2017","journal-title":"ChemMedchem"},{"issue":"2","key":"2026102111091780300_cit46","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1080\/17460441.2017.1264385","article-title":"Drug Discovery beyond the Rule of 5 - Opportunities\nand Challenges","volume":"12","author":"Doak","year":"2017","journal-title":"Expert Opin. Drug Discovery"},{"issue":"7","key":"2026102111091780300_cit47","doi-asserted-by":"publisher","first-page":"2851","DOI":"10.1002\/ange.201912075","article-title":"Isotopically Labeled Desthiobiotin\nAzide (IsoDTB) Tags Enable Global Profiling of the Bacterial Cysteinome","volume":"132","author":"Zanon","year":"2020","journal-title":"Angew. Chem."},{"key":"2026102111091780300_cit48","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1007\/978-1-61779-998-3_27","article-title":"I-SceI-Based Assays\nto Examine Distinct Repair Outcomes\nof Mammalian Chromosomal Double Strand Breaks","volume":"920","author":"Gunn","year":"2012","journal-title":"Methods Mol Biol."},{"issue":"6","key":"2026102111091780300_cit49","doi-asserted-by":"publisher","first-page":"e1000110","DOI":"10.1371\/journal.pgen.1000110","article-title":"Alternative-NHEJ\nIs a Mechanistically Distinct Pathway of Mammalian Chromosome Break\nRepair","volume":"4","author":"Bennardo","year":"2008","journal-title":"PLoS Genet."},{"key":"2026102111091780300_cit50","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1038\/s41580-019-0152-0","article-title":"DNA Double-Strand\nBreak Repair-Pathway Choice in Somatic Mammalian Cells","volume":"20","author":"Scully","year":"2019","journal-title":"Nat. Rev. Molecular Cell Biol."}],"container-title":["Journal of the American\nChemical Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/jacs.6c16278","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jacsat\/article-pdf\/doi\/10.1021\/jacs.6c16278\/68792257\/jacs.6c16278.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jacsat\/article-pdf\/doi\/10.1021\/jacs.6c16278\/68792257\/jacs.6c16278.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:31:30Z","timestamp":1792596690000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jacsat\/article\/148\/41\/45059\/5447275\/Integrating-Fragment-Screening-and-Covalent"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,8]]},"references-count":50,"journal-issue":{"issue":"41","published-online":{"date-parts":[[2026,10,8]]},"published-print":{"date-parts":[[2026,10,21]]}},"URL":"https:\/\/doi.org\/10.1021\/jacs.6c16278","relation":{"has-preprint":[{"id-type":"doi","id":"10.26434\/chemrxiv.15006471\/v1","asserted-by":"object"},{"id-type":"doi","id":"10.26434\/chemrxiv.15006471\/v2","asserted-by":"object"}]},"ISSN":["0002-7863","1520-5126"],"issn-type":[{"value":"0002-7863","type":"print"},{"value":"1520-5126","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,8]]}}}