{"id":"https://openalex.org/W4362658300","doi":"https://doi.org/10.1021/acs.jcim.3c00014","title":"Analysis of the ERK Pathway Cysteinome for Targeted Covalent Inhibition of RAF and MEK Kinases","display_name":"Analysis of the ERK Pathway Cysteinome for Targeted Covalent Inhibition of RAF and MEK Kinases","publication_year":2023,"publication_date":"2023-04-06","ids":{"openalex":"https://openalex.org/W4362658300","doi":"https://doi.org/10.1021/acs.jcim.3c00014","pmid":"https://pubmed.ncbi.nlm.nih.gov/37022803"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.3c00014","is_oa":false,"landing_page_url":"http://dx.doi.org/10.1021/acs.jcim.3c00014","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10214248/pdf/nihms-1896706.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5044346429","display_name":"Aarion Romany","orcid":"https://orcid.org/0000-0001-5439-8235"},"institutions":[{"id":"https://openalex.org/I126744593","display_name":"University of Maryland, Baltimore","ror":"https://ror.org/04rq5mt64","country_code":"US","type":"education","lineage":["https://openalex.org/I126744593"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Aarion Romany","raw_affiliation_strings":["Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland 21201, United States"],"raw_orcid":"https://orcid.org/0000-0001-5439-8235","affiliations":[{"raw_affiliation_string":"Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland 21201, United States","institution_ids":["https://openalex.org/I126744593"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5062355763","display_name":"Ruibin Liu","orcid":"https://orcid.org/0000-0001-8395-9353"},"institutions":[{"id":"https://openalex.org/I126744593","display_name":"University of Maryland, Baltimore","ror":"https://ror.org/04rq5mt64","country_code":"US","type":"education","lineage":["https://openalex.org/I126744593"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ruibin Liu","raw_affiliation_strings":["Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland 21201, United States"],"raw_orcid":"https://orcid.org/0000-0001-8395-9353","affiliations":[{"raw_affiliation_string":"Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland 21201, United States","institution_ids":["https://openalex.org/I126744593"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5066941541","display_name":"Shaoqi Zhan","orcid":"https://orcid.org/0000-0002-6383-1771"},"institutions":[{"id":"https://openalex.org/I126744593","display_name":"University of Maryland, Baltimore","ror":"https://ror.org/04rq5mt64","country_code":"US","type":"education","lineage":["https://openalex.org/I126744593"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Shaoqi Zhan","raw_affiliation_strings":["Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland 21201, United States"],"raw_orcid":"https://orcid.org/0000-0002-6383-1771","affiliations":[{"raw_affiliation_string":"Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland 21201, United States","institution_ids":["https://openalex.org/I126744593"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5031325613","display_name":"Joseph Clayton","orcid":"https://orcid.org/0000-0002-2652-5994"},"institutions":[{"id":"https://openalex.org/I126744593","display_name":"University of Maryland, Baltimore","ror":"https://ror.org/04rq5mt64","country_code":"US","type":"education","lineage":["https://openalex.org/I126744593"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Joseph Clayton","raw_affiliation_strings":["Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland 21201, United States"],"raw_orcid":"https://orcid.org/0000-0002-2652-5994","affiliations":[{"raw_affiliation_string":"Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland 21201, United States","institution_ids":["https://openalex.org/I126744593"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5084434392","display_name":"Jana Shen","orcid":"https://orcid.org/0000-0002-3234-0769"},"institutions":[{"id":"https://openalex.org/I126744593","display_name":"University of Maryland, Baltimore","ror":"https://ror.org/04rq5mt64","country_code":"US","type":"education","lineage":["https://openalex.org/I126744593"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Jana Shen","raw_affiliation_strings":["Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland 21201, United States"],"raw_orcid":"https://orcid.org/0000-0002-3234-0769","affiliations":[{"raw_affiliation_string":"Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland 21201, United States","institution_ids":["https://openalex.org/I126744593"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":5,"corresponding_author_ids":["https://openalex.org/A5084434392"],"corresponding_institution_ids":["https://openalex.org/I126744593"],"apc_list":null,"apc_paid":null,"fwci":1.0496,"has_fulltext":true,"cited_by_count":7,"citation_normalized_percentile":{"value":0.76619478,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":96,"max":98},"biblio":{"volume":"63","issue":"8","first_page":"2483","last_page":"2494"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11533","display_name":"Melanoma and MAPK Pathways","score":0.9998999834060669,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11533","display_name":"Melanoma and MAPK Pathways","score":0.9998999834060669,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10274","display_name":"Synthesis and biological activity","score":0.9988999962806702,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.9959999918937683,"subfield":{"id":"https://openalex.org/subfields/1703","display_name":"Computational Theory and Mathematics"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/cysteine","display_name":"Cysteine","score":0.7966398596763611},{"id":"https://openalex.org/keywords/kinase","display_name":"Kinase","score":0.7925639748573303},{"id":"https://openalex.org/keywords/mapk/erk-pathway","display_name":"MAPK/ERK pathway","score":0.7393428683280945},{"id":"https://openalex.org/keywords/covalent-bond","display_name":"Covalent bond","score":0.565437912940979},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.5066960453987122},{"id":"https://openalex.org/keywords/protein-serine-threonine-kinases","display_name":"Protein-Serine-Threonine Kinases","score":0.4485822021961212},{"id":"https://openalex.org/keywords/biochemistry","display_name":"Biochemistry","score":0.43509992957115173},{"id":"https://openalex.org/keywords/cysteine-metabolism","display_name":"Cysteine metabolism","score":0.4183931052684784},{"id":"https://openalex.org/keywords/enzyme","display_name":"Enzyme","score":0.3036190867424011},{"id":"https://openalex.org/keywords/protein-kinase-a","display_name":"Protein kinase A","score":0.2555506229400635}],"concepts":[{"id":"https://openalex.org/C2779201268","wikidata":"https://www.wikidata.org/wiki/Q186474","display_name":"Cysteine","level":3,"score":0.7966398596763611},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.7925639748573303},{"id":"https://openalex.org/C57074206","wikidata":"https://www.wikidata.org/wiki/Q14197552","display_name":"MAPK/ERK pathway","level":3,"score":0.7393428683280945},{"id":"https://openalex.org/C180577832","wikidata":"https://www.wikidata.org/wiki/Q127920","display_name":"Covalent bond","level":2,"score":0.565437912940979},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5066960453987122},{"id":"https://openalex.org/C2910050888","wikidata":"https://www.wikidata.org/wiki/Q4857068","display_name":"Protein-Serine-Threonine Kinases","level":4,"score":0.4485822021961212},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.43509992957115173},{"id":"https://openalex.org/C2781139505","wikidata":"https://www.wikidata.org/wiki/Q5201195","display_name":"Cysteine metabolism","level":4,"score":0.4183931052684784},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.3036190867424011},{"id":"https://openalex.org/C97029542","wikidata":"https://www.wikidata.org/wiki/Q281417","display_name":"Protein kinase A","level":3,"score":0.2555506229400635},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D003545","descriptor_name":"Cysteine","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D003545","descriptor_name":"Cysteine","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D003545","descriptor_name":"Cysteine","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015398","descriptor_name":"Signal Transduction","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015398","descriptor_name":"Signal Transduction","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015398","descriptor_name":"Signal Transduction","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020930","descriptor_name":"MAP Kinase Kinase Kinases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D020930","descriptor_name":"MAP Kinase Kinase Kinases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D020930","descriptor_name":"MAP Kinase Kinase Kinases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D020935","descriptor_name":"MAP Kinase Signaling System","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":true},{"descriptor_ui":"D020935","descriptor_name":"MAP Kinase Signaling System","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":true},{"descriptor_ui":"D020935","descriptor_name":"MAP Kinase Signaling System","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":true},{"descriptor_ui":"D048490","descriptor_name":"raf Kinases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D048490","descriptor_name":"raf Kinases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D048490","descriptor_name":"raf Kinases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D048493","descriptor_name":"Proto-Oncogene Proteins B-raf","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D048493","descriptor_name":"Proto-Oncogene Proteins B-raf","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D048493","descriptor_name":"Proto-Oncogene Proteins B-raf","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D048493","descriptor_name":"Proto-Oncogene Proteins B-raf","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D048493","descriptor_name":"Proto-Oncogene Proteins B-raf","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D048493","descriptor_name":"Proto-Oncogene Proteins B-raf","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false}],"locations_count":3,"locations":[{"id":"doi:10.1021/acs.jcim.3c00014","is_oa":false,"landing_page_url":"http://dx.doi.org/10.1021/acs.jcim.3c00014","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},{"id":"pmid:37022803","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/37022803","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of chemical information and modeling","raw_type":null},{"id":"pmh:oai:pubmedcentral.nih.gov:10214248","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10214248","pdf_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10214248/pdf/nihms-1896706.pdf","source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"J Chem Inf Model","raw_type":"Text"}],"best_oa_location":{"id":"pmh:oai:pubmedcentral.nih.gov:10214248","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10214248","pdf_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10214248/pdf/nihms-1896706.pdf","source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"J Chem Inf Model","raw_type":"Text"},"sustainable_development_goals":[{"score":0.7799999713897705,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"awards":[{"id":"https://openalex.org/G2054682893","display_name":null,"funder_award_id":"R01CA256557","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"},{"id":"https://openalex.org/G4636650593","display_name":null,"funder_award_id":"R01GM098818","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"},{"id":"https://openalex.org/G5224315540","display_name":null,"funder_award_id":"R01GM098818","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"},{"id":"https://openalex.org/G7809807058","display_name":null,"funder_award_id":"R01CA256557","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"}],"funders":[{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320337351","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81"},{"id":"https://openalex.org/F4320337354","display_name":"National Institute of General Medical Sciences","ror":"https://ror.org/04q48ey07"}],"has_content":{"pdf":true,"grobid_xml":false},"content_urls":{"pdf":"https://content.openalex.org/works/W4362658300.pdf"},"referenced_works_count":88,"referenced_works":["https://openalex.org/W18135420","https://openalex.org/W248383993","https://openalex.org/W1607931568","https://openalex.org/W1848470479","https://openalex.org/W1891334654","https://openalex.org/W1940641879","https://openalex.org/W1965133242","https://openalex.org/W1971947883","https://openalex.org/W1975436091","https://openalex.org/W1977565331","https://openalex.org/W1999966467","https://openalex.org/W2004295816","https://openalex.org/W2008708467","https://openalex.org/W2018339027","https://openalex.org/W2029079594","https://openalex.org/W2032187756","https://openalex.org/W2035024352","https://openalex.org/W2035032093","https://openalex.org/W2043058822","https://openalex.org/W2047514293","https://openalex.org/W2049701513","https://openalex.org/W2050422354","https://openalex.org/W2051165598","https://openalex.org/W2062175357","https://openalex.org/W2065208438","https://openalex.org/W2066314848","https://openalex.org/W2085094809","https://openalex.org/W2100738068","https://openalex.org/W2132262459","https://openalex.org/W2149662085","https://openalex.org/W2164088236","https://openalex.org/W2168240189","https://openalex.org/W2171613528","https://openalex.org/W2176608409","https://openalex.org/W2254024823","https://openalex.org/W2318603372","https://openalex.org/W2327581403","https://openalex.org/W2329540625","https://openalex.org/W2330799739","https://openalex.org/W2404280981","https://openalex.org/W2430132928","https://openalex.org/W2511955955","https://openalex.org/W2512442926","https://openalex.org/W2527718275","https://openalex.org/W2762490319","https://openalex.org/W2769901316","https://openalex.org/W2773258053","https://openalex.org/W2775590543","https://openalex.org/W2780194508","https://openalex.org/W2783904016","https://openalex.org/W2788806246","https://openalex.org/W2789715646","https://openalex.org/W2804822363","https://openalex.org/W2810398033","https://openalex.org/W2894347564","https://openalex.org/W2904506792","https://openalex.org/W2914461011","https://openalex.org/W2933867250","https://openalex.org/W2937076225","https://openalex.org/W2937281589","https://openalex.org/W2944700152","https://openalex.org/W2947282900","https://openalex.org/W2981777666","https://openalex.org/W2982700906","https://openalex.org/W2995798573","https://openalex.org/W3005196658","https://openalex.org/W3007811953","https://openalex.org/W3009349681","https://openalex.org/W3010907970","https://openalex.org/W3018223376","https://openalex.org/W3036759197","https://openalex.org/W3082514675","https://openalex.org/W3084762951","https://openalex.org/W3085029011","https://openalex.org/W3091345378","https://openalex.org/W3093634533","https://openalex.org/W3125039781","https://openalex.org/W3127613787","https://openalex.org/W3153375892","https://openalex.org/W3157426342","https://openalex.org/W3203077262","https://openalex.org/W3207110989","https://openalex.org/W3209724370","https://openalex.org/W3215650009","https://openalex.org/W4211196614","https://openalex.org/W4220931691","https://openalex.org/W4224113503","https://openalex.org/W4281627201"],"related_works":["https://openalex.org/W2077515371","https://openalex.org/W1865864547","https://openalex.org/W2158738251","https://openalex.org/W1553836831","https://openalex.org/W2080180300","https://openalex.org/W317506201","https://openalex.org/W1981625038","https://openalex.org/W1989071670","https://openalex.org/W2052056252","https://openalex.org/W2301304620"],"abstract_inverted_index":{"The":[0,172,212],"ERK":[1,26,72,209],"pathway":[2,27,73,210],"is":[3,50,215],"one":[4],"of":[5,19,37,66,70,176,207,225,228],"the":[6,25,32,35,67,71,98,115,131,152,156,166,177,183,208,222,229],"most":[7],"important":[8],"signaling":[9],"cascades":[10],"involved":[11],"in":[12,24,104,119,170,180,186],"tumorigenesis.":[13],"So":[14],"far,":[15],"eight":[16],"noncovalent":[17],"inhibitors":[18,134,149,206],"RAF":[20,105],"and":[21,83,91,112,114,121,125,136,174,182,188,217],"MEK":[22],"kinases":[23,74,107],"have":[28],"been":[29],"approved":[30],"by":[31],"FDA":[33],"for":[34,143,199],"treatment":[36],"cancers;":[38],"however,":[39],"their":[40],"efficacies":[41],"are":[42,123,190],"limited":[43],"due":[44],"to":[45,54,164,202,221],"various":[46],"resistance":[47],"mechanisms.":[48],"There":[49],"an":[51],"urgent":[52],"need":[53],"develop":[55],"novel":[56,204],"targeted":[57],"covalent":[58,68,148,205,226],"inhibitors.":[59],"Here":[60],"we":[61],"report":[62],"a":[63,196],"systematic":[64,223],"study":[65],"ligandabilities":[69,175,227],"(ARAF,":[75,108],"BRAF,":[76,109],"CRAF,":[77,110],"KSR1,":[78,111],"KSR2,":[79],"MEK1,":[80],"MEK2,":[81],"ERK1,":[82],"ERK2)":[84],"using":[85],"constant":[86],"pH":[87],"molecular":[88],"dynamics":[89],"titration":[90],"pocket":[92],"analysis.":[93],"Our":[94,193],"data":[95],"revealed":[96],"that":[97,130],"hinge":[99],"GK":[100],"(gate":[101],"keeper)+3":[102],"cysteine":[103,118,169,179,185],"family":[106],"KSR2)":[113],"back":[116,167],"loop":[117,168],"MEK1":[120],"MEK2":[122],"reactive":[124],"ligandable.":[126],"Structure":[127],"analysis":[128],"suggests":[129],"type":[132,157],"II":[133],"belvarafenib":[135],"GW5074":[137],"may":[138,161],"be":[139,162,219],"used":[140],"as":[141],"scaffolds":[142],"designing":[144],"pan-RAF":[145],"or":[146],"CRAF-selective":[147],"directed":[150],"at":[151],"GK+3":[153],"cysteine,":[154],"while":[155],"III":[158],"inhibitor":[159],"cobimetinib":[160],"modified":[163],"label":[165],"MEK1/2.":[171],"reactivities":[173],"remote":[178],"MEK1/2":[181,187],"DFG-1":[184],"ERK1/2":[189],"also":[191],"discussed.":[192],"work":[194],"provides":[195],"starting":[197],"point":[198],"medicinal":[200],"chemists":[201],"design":[203],"kinases.":[211],"computational":[213],"protocol":[214],"general":[216],"can":[218],"applied":[220],"evaluation":[224],"human":[230],"cysteinome.":[231]},"counts_by_year":[{"year":2024,"cited_by_count":3},{"year":2023,"cited_by_count":4}],"updated_date":"2025-12-19T19:40:27.379048","created_date":"2025-10-10T00:00:00"}
