Structure-Based Design of 5-Methylpyrimidopyridone Derivatives as New Wild-Type Sparing Inhibitors of the Epidermal Growth Factor Receptor Triple Mutant (EGFR L858R/T790M/C797S )
Tertiary EGFRc797s mutation induced resistance against osimertinib (1) is an emerging "unmet clinical need" for non-small-cell lung cancer (NSCLC) patients. A series of 5-methylpyrimidopyridone derivatives were designed and synthesized as new selective EGFR(L858R/T790M/C797S) inhibitors. A...
Saved in:
| Published in | Journal of medicinal chemistry Vol. 62; no. 15; pp. 7302 - 7308 |
|---|---|
| Main Authors | , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
WASHINGTON
Amer Chemical Soc
08.08.2019
|
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Abstract | Tertiary EGFRc797s mutation induced resistance against osimertinib (1) is an emerging "unmet clinical need" for non-small-cell lung cancer (NSCLC) patients. A series of 5-methylpyrimidopyridone derivatives were designed and synthesized as new selective EGFR(L858R/T790M/C797S) inhibitors. A representative compound, 8r-B, exhibited an ICso of 27.5 nM against the EGFR(L858R/T790M/C797S) mutant, while being a significantly less potent for EGFRwr (IC50 > 1.0 NM). Cocrystallographic structure determination and computational investigation were conducted to elucidate its target selectivity. |
|---|---|
| AbstractList | Tertiary EGFR
mutation induced resistance against osimertinib (
) is an emerging "unmet clinical need" for non-small-cell lung cancer (NSCLC) patients. A series of 5-methylpyrimidopyridone derivatives were designed and synthesized as new selective EGFR
inhibitors. A representative compound,
, exhibited an IC
of 27.5 nM against the EGFR
mutant, while being a significantly less potent for EGFR
(IC
> 1.0 μM). Cocrystallographic structure determination and computational investigation were conducted to elucidate its target selectivity. Tertiary EGFRc797s mutation induced resistance against osimertinib (1) is an emerging "unmet clinical need" for non-small-cell lung cancer (NSCLC) patients. A series of 5-methylpyrimidopyridone derivatives were designed and synthesized as new selective EGFR(L858R/T790M/C797S) inhibitors. A representative compound, 8r-B, exhibited an ICso of 27.5 nM against the EGFR(L858R/T790M/C797S) mutant, while being a significantly less potent for EGFRwr (IC50 > 1.0 NM). Cocrystallographic structure determination and computational investigation were conducted to elucidate its target selectivity. Tertiary EGFRC797S mutation induced resistance against osimertinib (1) is an emerging "unmet clinical need" for non-small-cell lung cancer (NSCLC) patients. A series of 5-methylpyrimidopyridone derivatives were designed and synthesized as new selective EGFRL858R/T790M/C797S inhibitors. A representative compound, 8r-B, exhibited an IC50 of 27.5 nM against the EGFRL858R/T790M/C797S mutant, while being a significantly less potent for EGFRWT (IC50 > 1.0 μM). Cocrystallographic structure determination and computational investigation were conducted to elucidate its target selectivity.Tertiary EGFRC797S mutation induced resistance against osimertinib (1) is an emerging "unmet clinical need" for non-small-cell lung cancer (NSCLC) patients. A series of 5-methylpyrimidopyridone derivatives were designed and synthesized as new selective EGFRL858R/T790M/C797S inhibitors. A representative compound, 8r-B, exhibited an IC50 of 27.5 nM against the EGFRL858R/T790M/C797S mutant, while being a significantly less potent for EGFRWT (IC50 > 1.0 μM). Cocrystallographic structure determination and computational investigation were conducted to elucidate its target selectivity. |
| Author | Xie, Hua Lai, Mengzhen Ding, Jian Yun, Cai-Hong Lu, Xiaoyun Tong, Linjiang Xu, Wei Shen, Jiayi Zhu, Su-Jie Wu, Ruibo Sun, Min Zhang, Rong Zhang, Tao Ding, Ke |
| Author_xml | – sequence: 1 givenname: Jiayi surname: Shen fullname: Shen, Jiayi organization: International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Discovery of Chinese Ministry of Education (MOE), Guangzhou City Key Laboratory of Precision Chemical Drug Development, School of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China – sequence: 2 givenname: Tao surname: Zhang fullname: Zhang, Tao organization: Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China – sequence: 3 givenname: Su-Jie surname: Zhu fullname: Zhu, Su-Jie organization: Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China – sequence: 4 givenname: Min surname: Sun fullname: Sun, Min organization: Jiangsu Aosaikang Pharmacceutical Co. Ltd., No. 699 Kejian Road, Jiangsu Science Park, Nanjing 211112, China – sequence: 5 givenname: Linjiang surname: Tong fullname: Tong, Linjiang organization: Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China – sequence: 6 givenname: Mengzhen surname: Lai fullname: Lai, Mengzhen organization: Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China – sequence: 7 givenname: Rong surname: Zhang fullname: Zhang, Rong organization: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China – sequence: 8 givenname: Wei surname: Xu fullname: Xu, Wei organization: International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Discovery of Chinese Ministry of Education (MOE), Guangzhou City Key Laboratory of Precision Chemical Drug Development, School of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China – sequence: 9 givenname: Ruibo surname: Wu fullname: Wu, Ruibo organization: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China – sequence: 10 givenname: Jian surname: Ding fullname: Ding, Jian organization: Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China – sequence: 11 givenname: Cai-Hong orcidid: 0000-0002-5880-8307 surname: Yun fullname: Yun, Cai-Hong organization: Department of Biochemistry and Biophysics, Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China – sequence: 12 givenname: Hua surname: Xie fullname: Xie, Hua organization: Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China – sequence: 13 givenname: Xiaoyun orcidid: 0000-0001-7931-6873 surname: Lu fullname: Lu, Xiaoyun organization: International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Discovery of Chinese Ministry of Education (MOE), Guangzhou City Key Laboratory of Precision Chemical Drug Development, School of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China – sequence: 14 givenname: Ke orcidid: 0000-0001-9016-812X surname: Ding fullname: Ding, Ke organization: International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Discovery of Chinese Ministry of Education (MOE), Guangzhou City Key Laboratory of Precision Chemical Drug Development, School of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31298540$$D View this record in MEDLINE/PubMed |
| BookMark | eNqNks-O0zAQxi20iO0uvAFCPi5CaSfOHyfcltKWlVqQ2iKOkeNMtl6lcbCdrfpaPCGO2nLggDiNJf--mdF83w25anWLhLwNYRwCCydC2vHTHiu5w_04LwESnr4gozBhEMQZxFdkBMBYwFIWXZMba58AIApZ9Ipc-5JnSQwj8mvjTC9dbzD4JCxW9DNa9dhSXdMkWKHbHZvuaNReVXqold_BI0Y9C6ee0VJh6Vc80B-qqYLtsUO66YRR7SN9aHeqVE4bO_RyO6SzTlVo9qKhC6MPbkfnQvp_ukaJ3fDYGtU1SFe9E62jd7PFfE2XWZKtJ1uew2oy5Tnf0PevyctaNBbfnOst-T6fbadfguW3xcP0fhnIiEcuyNKyTCFMal6nkFYIFbI6qiqIJdYZFzzJykjmIGWCWY0hK1MZQQplCBJ5lEW35O7UtzP6Z4_WFXtlJTaNaFH3tmAs4Rwgjwf03RntS29J0fmLCXMsLnf2QHYCDljq2kqFrcQ_mDfGO5aAn-4ty6fK-evqdqr71nnph_-XevrjiZZGW2uwLuS5mzNCNUUIxZCewqenuKSnOKfHi-O_xJcx_5T9Brx7y3g |
| CitedBy_id | crossref_primary_10_1021_acsomega_3c06225 crossref_primary_10_1021_acsmedchemlett_1c00555 crossref_primary_10_1021_acs_jmedchem_2c01246 crossref_primary_10_1016_j_ejmech_2022_114381 crossref_primary_10_1080_14756366_2023_2218602 crossref_primary_10_1038_s41392_021_00572_w crossref_primary_10_3390_ijms21239323 crossref_primary_10_1016_j_ejmech_2024_116590 crossref_primary_10_1016_j_ejmech_2025_117323 crossref_primary_10_1080_07391102_2020_1844801 crossref_primary_10_3389_fcell_2022_872729 crossref_primary_10_1016_j_bioorg_2022_106057 crossref_primary_10_3390_molecules28073014 crossref_primary_10_1021_acs_jmedchem_9b01566 crossref_primary_10_1016_j_ejmech_2020_112995 crossref_primary_10_1016_j_ejmech_2021_113523 crossref_primary_10_1142_S2737416524500054 crossref_primary_10_1016_j_ejmech_2020_113023 crossref_primary_10_1111_cbdd_70039 crossref_primary_10_1016_j_ejmech_2021_113300 crossref_primary_10_1186_s13065_024_01279_z crossref_primary_10_3390_molecules25040895 crossref_primary_10_1021_acs_jmedchem_0c00200 crossref_primary_10_1021_acs_jmedchem_2c00168 crossref_primary_10_1186_s13045_022_01311_6 crossref_primary_10_1021_acs_jmedchem_0c02005 crossref_primary_10_1021_acs_jmedchem_1c00876 crossref_primary_10_1021_acs_jmedchem_0c00507 crossref_primary_10_1016_j_ejmech_2024_117178 crossref_primary_10_1248_cpb_c22_00653 crossref_primary_10_1039_D3RA02347H crossref_primary_10_1039_D4MD00384E crossref_primary_10_1002_cmdc_202000646 crossref_primary_10_1016_j_ejmech_2020_113019 crossref_primary_10_1021_acs_jmedchem_3c00277 crossref_primary_10_1055_s_0043_1764218 crossref_primary_10_1016_j_ejmech_2022_114889 crossref_primary_10_1126_sciadv_adl0026 crossref_primary_10_3390_molecules27248901 crossref_primary_10_3390_ph15070857 |
| Cites_doi | 10.1038/nrd1612 10.1002/anie.201603736 10.1021/acs.jmedchem.6b00883 10.1158/2159-8290.CD-15-0399 10.1126/science.1099314 10.1038/ncomms14768 10.1158/2159-8290.CD-18-0903 10.1016/j.ejmech.2016.12.006 10.1007/s40265-013-0111-6 10.1021/acsmedchemlett.8b00373 10.1039/C5MD00208G 10.1186/s13045-016-0290-1 10.1158/1078-0432.CCR-15-1211 10.1056/NEJMoa0810699 10.1158/1078-0432.CCR-15-0560 10.1007/s40265-016-0606-z 10.1158/2159-8290.CD-14-0337 10.1016/S1470-2045(17)30608-3 10.1038/nature17960 10.1002/anie.201703389 10.1056/NEJMoa1713137 10.1038/nm.3854 10.1021/acsmedchemlett.5b00475 10.1039/c5md00208g |
| ContentType | Journal Article |
| DBID | AAYXX CITATION 17B 1KM AAWJD BLEPL DTL EGQ NPM 7X8 |
| DOI | 10.1021/acs.jmedchem.9b00576 |
| DatabaseName | CrossRef Web of Knowledge Index Chemicus Web of Science - Science Citation Index Expanded - 2019 Web of Science Core Collection Science Citation Index Expanded Web of Science Primary (SCIE, SSCI & AHCI) PubMed MEDLINE - Academic |
| DatabaseTitle | CrossRef Web of Science PubMed MEDLINE - Academic |
| DatabaseTitleList | PubMed Web of Science MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 1KM name: Index Chemicus url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/woscc/search-with-editions?editions=WOS.IC sourceTypes: Enrichment Source Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Chemistry Pharmacy, Therapeutics, & Pharmacology |
| EISSN | 1520-4804 |
| EndPage | 7308 |
| ExternalDocumentID | 31298540 000480500600029 10_1021_acs_jmedchem_9b00576 |
| Genre | Research Support, Non-U.S. Gov't Journal Article |
| GrantInformation_xml | – fundername: National Natural Science Foundation of China; National Natural Science Foundation of China (NSFC) grantid: 81820108029; 21572230; 81673285; 81425021; 21702075 – fundername: Guangzhou City grantid: 201805010007 – fundername: Guangdong Province grantid: 2015A030312014; 2015A030306042; 2016A050502041; 2018A050506043; 2017A030310253 – fundername: Jinan University |
| GroupedDBID | --- -~X .K2 4.4 55A 5GY 5RE 5VS 6P2 7~N AABXI AAHBH AAYXX ABBLG ABJNI ABLBI ABMVS ABOCM ABQRX ABUCX ACGFO ACGFS ACJ ACS ADHLV AEESW AENEX AFEFF AGXLV AHGAQ ALMA_UNASSIGNED_HOLDINGS AQSVZ BAANH CITATION CS3 CUPRZ DU5 EBS ED~ EJD F5P GGK GNL IH2 IH9 IHE JG~ L7B LG6 P2P ROL TN5 UI2 VF5 VG9 W1F WH7 XSW YQT YZZ ZY4 17B 1KM BLEPL DTL GROUPED_WOS_SCIENCE_CITATION_INDEX_EXPANDED GROUPED_WOS_WEB_OF_SCIENCE ABTAH NPM 7X8 |
| ID | FETCH-LOGICAL-c373t-86bb6015f7f606de0de2f3dd04cef87a758b3c90cc5e8fe12b6c3060b10ce7383 |
| IEDL.DBID | ACS |
| ISICitedReferencesCount | 42 |
| ISICitedReferencesURI | https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestApp=WOS&DestLinkType=CitingArticles&UT=000480500600029 |
| ISSN | 0022-2623 1520-4804 |
| IngestDate | Fri Jul 11 00:45:55 EDT 2025 Thu Apr 03 07:08:09 EDT 2025 Wed Jul 09 17:52:02 EDT 2025 Fri Aug 29 16:17:26 EDT 2025 Tue Jul 01 00:43:01 EDT 2025 Thu Apr 24 23:11:34 EDT 2025 |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 15 |
| Keywords | LUNG-CANCER EGFR INHIBITORS GEFITINIB RESISTANCE OPTIMIZATION MUTATIONS DISCOVERY AZD9291 |
| Language | English |
| License | https://doi.org/10.15223/policy-029 https://doi.org/10.15223/policy-037 https://doi.org/10.15223/policy-045 |
| LinkModel | DirectLink |
| LogoURL | https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg |
| MergedId | FETCHMERGED-LOGICAL-c373t-86bb6015f7f606de0de2f3dd04cef87a758b3c90cc5e8fe12b6c3060b10ce7383 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ORCID | 0000-0001-7931-6873 0000-0002-5880-8307 0000-0001-9016-812X |
| PMID | 31298540 |
| PQID | 2257700948 |
| PQPubID | 23479 |
| PageCount | 7 |
| ParticipantIDs | crossref_citationtrail_10_1021_acs_jmedchem_9b00576 proquest_miscellaneous_2257700948 webofscience_primary_000480500600029CitationCount pubmed_primary_31298540 crossref_primary_10_1021_acs_jmedchem_9b00576 webofscience_primary_000480500600029 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 2019-08-08 |
| PublicationDateYYYYMMDD | 2019-08-08 |
| PublicationDate_xml | – month: 08 year: 2019 text: 2019-08-08 day: 08 |
| PublicationDecade | 2010 |
| PublicationPlace | WASHINGTON |
| PublicationPlace_xml | – name: WASHINGTON – name: United States |
| PublicationTitle | Journal of medicinal chemistry |
| PublicationTitleAbbrev | J MED CHEM |
| PublicationTitleAlternate | J Med Chem |
| PublicationYear | 2019 |
| Publisher | Amer Chemical Soc |
| Publisher_xml | – name: Amer Chemical Soc |
| References | ref9/cit9 ref17/cit17 ref6/cit6 ref10/cit10 ref3/cit3 ref18/cit18 ref19/cit19 ref21/cit21 ref11/cit11 ref12/cit12 ref15/cit15 ref16/cit16 ref22/cit22 ref23/cit23 ref13/cit13 ref14/cit14 ref8/cit8 ref5/cit5 ref2/cit2 ref4/cit4 ref1/cit1 ref24/cit24 ref20/cit20 ref7/cit7 Gunther, M (WOS:000383473600069) 2016; 55 Wu, YL (WOS:000414134100053) 2017; 18 Engel, J (WOS:000368566900001) 2016; 7 Dungo, RT (WOS:000324324200010) 2013; 73 Lu, XY (WOS:000449888400011) 2018; 9 Park, H (WOS:000403017000055) 2017; 56 Cross, DAE (WOS:000343121400027) 2014; 4 Dowell, J (WOS:000226153200009) 2005; 4 Uchibori, K (WOS:000396231400001) 2017; 8 Mok, TS (WOS:000269480400004) 2009; 361 Ayeni, D (WOS:000361910000003) 2015; 21 Kim, ES (WOS:000379497000007) 2016; 76 Jia, Y (WOS:000376962300048) 2016; 534 Niederst, MJ (WOS:000361910000016) 2015; 21 To, C (WOS:000473530600021) 2019; 9 Soria, JC (WOS:000419971600005) 2018; 378 Thress, KS (WOS:000355778300011) 2015; 21 Piotrowska, Z (WOS:000359316800021) 2015; 5 Wang, SH (WOS:000380317100002) 2016; 9 Xu, TF (WOS:000360639300015) 2015; 6 Paez, JG (WOS:000221795800043) 2004; 304 Smaill, JB (WOS:000383111300029) 2016; 59 Yu, L (WOS:000396804600085) 2017; 126 |
| References_xml | – ident: ref3/cit3 doi: 10.1038/nrd1612 – ident: ref19/cit19 doi: 10.1002/anie.201603736 – ident: ref9/cit9 – ident: ref6/cit6 doi: 10.1021/acs.jmedchem.6b00883 – ident: ref10/cit10 doi: 10.1158/2159-8290.CD-15-0399 – ident: ref2/cit2 doi: 10.1126/science.1099314 – ident: ref18/cit18 doi: 10.1038/ncomms14768 – ident: ref21/cit21 doi: 10.1158/2159-8290.CD-18-0903 – ident: ref23/cit23 doi: 10.1016/j.ejmech.2016.12.006 – ident: ref4/cit4 doi: 10.1007/s40265-013-0111-6 – ident: ref22/cit22 doi: 10.1021/acsmedchemlett.8b00373 – ident: ref24/cit24 doi: 10.1039/C5MD00208G – ident: ref15/cit15 doi: 10.1186/s13045-016-0290-1 – ident: ref16/cit16 doi: 10.1158/1078-0432.CCR-15-1211 – ident: ref1/cit1 doi: 10.1056/NEJMoa0810699 – ident: ref12/cit12 doi: 10.1158/1078-0432.CCR-15-0560 – ident: ref7/cit7 doi: 10.1007/s40265-016-0606-z – ident: ref14/cit14 doi: 10.1158/2159-8290.CD-14-0337 – ident: ref5/cit5 doi: 10.1016/S1470-2045(17)30608-3 – ident: ref17/cit17 doi: 10.1038/nature17960 – ident: ref20/cit20 doi: 10.1002/anie.201703389 – ident: ref8/cit8 doi: 10.1056/NEJMoa1713137 – ident: ref13/cit13 doi: 10.1038/nm.3854 – ident: ref11/cit11 doi: 10.1021/acsmedchemlett.5b00475 – volume: 59 start-page: 8103 year: 2016 ident: WOS:000383111300029 article-title: Tyrosine Kinase Inhibitors. 20. Optimization of Substituted Quinazoline and Pyrido[3,4-d]pyrimidine Derivatives as Orally Active, Irreversible Inhibitors of the Epidermal Growth Factor Receptor Family publication-title: JOURNAL OF MEDICINAL CHEMISTRY doi: 10.1021/acs.jmedchem.6b00883 – volume: 73 start-page: 1503 year: 2013 ident: WOS:000324324200010 article-title: Afatinib: First Global Approval publication-title: DRUGS doi: 10.1007/s40265-013-0111-6 – volume: 4 start-page: 13 year: 2005 ident: WOS:000226153200009 article-title: Erlotinib hydrochloride publication-title: NATURE REVIEWS DRUG DISCOVERY doi: 10.1038/nrd1612 – volume: 56 start-page: 7634 year: 2017 ident: WOS:000403017000055 article-title: Discovery of EGF Receptor Inhibitors That Are Selective for the d746-750/T790M/C797S Mutant through Structure-Based de Novo Design publication-title: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION doi: 10.1002/anie.201703389 – volume: 21 start-page: 3924 year: 2015 ident: WOS:000361910000016 article-title: The Allelic Context of the C797S Mutation Acquired upon Treatment with Third-Generation EGFR Inhibitors Impacts Sensitivity to Subsequent Treatment Strategies publication-title: CLINICAL CANCER RESEARCH doi: 10.1158/1078-0432.CCR-15-0560 – volume: 55 start-page: 10890 year: 2016 ident: WOS:000383473600069 article-title: Lung Cancer: EGFR Inhibitors with Low Nanomolar Activity against a Therapy-Resistant L858R/T790M/C797S Mutant publication-title: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION doi: 10.1002/anie.201603736 – volume: 76 start-page: 1153 year: 2016 ident: WOS:000379497000007 article-title: Olmutinib: First Global Approval publication-title: DRUGS doi: 10.1007/s40265-016-0606-z – volume: 9 start-page: 926 year: 2019 ident: WOS:000473530600021 article-title: Single and Dual Targeting of Mutant EGFR with an Allosteric Inhibitor publication-title: CANCER DISCOVERY doi: 10.1158/2159-8290.CD-18-0903 – volume: 7 start-page: 2 year: 2016 ident: WOS:000368566900001 article-title: Hope and Disappointment: Covalent Inhibitors to Overcome Drug Resistance in Non-Small Cell Lung Cancer publication-title: ACS MEDICINAL CHEMISTRY LETTERS doi: 10.1021/acsmedchemlett.5b00475 – volume: 4 start-page: 1046 year: 2014 ident: WOS:000343121400027 article-title: AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer publication-title: CANCER DISCOVERY doi: 10.1158/2159-8290.CD-14-0337 – volume: 5 start-page: 713 year: 2015 ident: WOS:000359316800021 article-title: Heterogeneity Underlies the Emergence of EGFR(T790) Wild-Type Clones Following Treatment of T790M-Positive Cancers with a Third-Generation EGFR Inhibitor publication-title: CANCER DISCOVERY doi: 10.1158/2159-8290.CD-15-0399 – volume: 534 start-page: 129 year: 2016 ident: WOS:000376962300048 article-title: Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors publication-title: NATURE doi: 10.1038/nature17960 – volume: 361 start-page: 947 year: 2009 ident: WOS:000269480400004 article-title: Gefitinib or Carboplatin-Paclitaxel in Pulmonary Adenocarcinoma. publication-title: NEW ENGLAND JOURNAL OF MEDICINE doi: 10.1056/NEJMoa0810699 – volume: 18 start-page: 1454 year: 2017 ident: WOS:000414134100053 article-title: Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial publication-title: LANCET ONCOLOGY doi: 10.1016/S1470-2045(17)30608-3 – volume: 9 start-page: 1123 year: 2018 ident: WOS:000449888400011 article-title: Discovery of JND3229 as a New EGFR(C797S) Mutant Inhibitor with In Vivo Monodrug Efficacy publication-title: ACS MEDICINAL CHEMISTRY LETTERS doi: 10.1021/acsmedchemlett.8b00373 – volume: 304 start-page: 1497 year: 2004 ident: WOS:000221795800043 article-title: EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy publication-title: SCIENCE doi: 10.1126/science.1099314 – volume: 21 start-page: 3818 year: 2015 ident: WOS:000361910000003 article-title: Emerging Agents and New Mutations in EGFR-Mutant Lung Cancer publication-title: CLINICAL CANCER RESEARCH doi: 10.1158/1078-0432.CCR-15-1211 – volume: 126 start-page: 1107 year: 2017 ident: WOS:000396804600085 article-title: A structure-guided optimization of pyrido[2,3-d]pyrimidin-7-ones as selective inhibitors of EGFR(L858R/T790M) mutant with improved pharmacokinetic properties publication-title: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY doi: 10.1016/j.ejmech.2016.12.006 – volume: 6 start-page: 1693 year: 2015 ident: WOS:000360639300015 article-title: C5-substituted pyrido[2,3-d]pyrimidin-7-ones as highly specific kinase inhibitors targeting the clinical resistance-related EGFR(T790M) mutant publication-title: MEDCHEMCOMM doi: 10.1039/c5md00208g – volume: 21 start-page: 560 year: 2015 ident: WOS:000355778300011 article-title: Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M publication-title: NATURE MEDICINE doi: 10.1038/nm.3854 – volume: 378 start-page: 113 year: 2018 ident: WOS:000419971600005 article-title: Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer publication-title: NEW ENGLAND JOURNAL OF MEDICINE doi: 10.1056/NEJMoa1713137 – volume: 8 start-page: ARTN 14768 year: 2017 ident: WOS:000396231400001 article-title: Brigatinib combined with anti-EGFR antibody overcomes osimertinib resistance in EGFR-mutated non-small-cell lung cancer publication-title: NATURE COMMUNICATIONS doi: 10.1038/ncomms14768 – volume: 9 start-page: ARTN 59 year: 2016 ident: WOS:000380317100002 article-title: EGFR C797S mutation mediates resistance to third-generation inhibitors in T790M-positive non-small cell lung cancer publication-title: JOURNAL OF HEMATOLOGY & ONCOLOGY doi: 10.1186/s13045-016-0290-1 |
| SSID | ssj0003123 |
| Score | 2.4801877 |
| Snippet | Tertiary EGFRc797s mutation induced resistance against osimertinib (1) is an emerging "unmet clinical need" for non-small-cell lung cancer (NSCLC) patients. A... Tertiary EGFR mutation induced resistance against osimertinib ( ) is an emerging "unmet clinical need" for non-small-cell lung cancer (NSCLC) patients. A... Tertiary EGFRC797S mutation induced resistance against osimertinib (1) is an emerging "unmet clinical need" for non-small-cell lung cancer (NSCLC) patients. A... |
| Source | Web of Science |
| SourceID | proquest pubmed webofscience crossref |
| SourceType | Aggregation Database Index Database Enrichment Source |
| StartPage | 7302 |
| SubjectTerms | Chemistry, Medicinal Life Sciences & Biomedicine Pharmacology & Pharmacy Science & Technology |
| Title | Structure-Based Design of 5-Methylpyrimidopyridone Derivatives as New Wild-Type Sparing Inhibitors of the Epidermal Growth Factor Receptor Triple Mutant (EGFR L858R/T790M/C797S ) |
| URI | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestApp=WOS&DestLinkType=FullRecord&UT=000480500600029 https://www.ncbi.nlm.nih.gov/pubmed/31298540 https://www.proquest.com/docview/2257700948 |
| Volume | 62 |
| WOS | 000480500600029 |
| WOSCitedRecordID | wos000480500600029 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV1Zb9NAEF6hvsALR7lCAQ1SVYHUTdZrr9d-LCFpQQSqJpX6Ztl7NIXUiRIHFH4Wv5BZHwlQEOXJlrxeazTjOTSz30fIrtJCByLmNJRa0iDlisYsNlQGIbN-wFnV0R18CI9Og3dn4mxTKP7ewedeJ1WL9ic3rDg2l-0Kwa9E2JaBg8o_6A7Xjtf3uN-Ag3MM681Jub9s8mskupJe_jESlVGnf4d8bM7uVMMmn9vLImurb1ehHK8p0F1yu05A4aCymHvkhsm3yc1uw_u2TfaOKzTr1T6MNoezFvuwB8cbnOvVffJ9WGLPLueGvsZYqOFNOQ0CUwuCDgxawGS2cqxheuquepobXDIv6dS-mAWkC0AXC-iXNHXlMAwdI2J-Dm_z8UV24WiA3F6YoULP8djipydwOJ9-LcbQL2mCAJNeM3M3o7lrGMBg6UiR4WXvsH8C7yMRnXRGMmaDTlfGcgivHpDTfm_UPaI1BQRVvvQLGoVZhiWjsNJipaUN04ZbX2sWKGMjmWK1k_kqZkoJE1nj8SxUWASxzGPKSKy-H5KtHMV7TECw0IaKpTwIbWBtmqmUWxGqONOh8C1rEb8xh0TV-OiOpmOSlH167iWouKRRXFIrrkXo-q1ZhQ_yj_UvGktLUK-uO5PmZrpcJOhYpXSDnlGLPKpMcL0jWnYcYW7dIrs_2-T6eQUNIBy4jmuztoh3nWXdWkqHflA8-U9BdsgtzB3jchYyekq20OLMM8zPiux5-Vf-AHOpOEE |
| linkProvider | American Chemical Society |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Structure-Based+Design+of+5-Methylpyrimidopyridone+Derivatives+as+New+Wild-Type+Sparing+Inhibitors+of+the+Epidermal+Growth+Factor+Receptor+Triple+Mutant+%28EGFR+L858R%2FT790M%2FC797S+%29&rft.jtitle=Journal+of+medicinal+chemistry&rft.au=Shen%2C+Jiayi&rft.au=Zhang%2C+Tao&rft.au=Zhu%2C+Su-Jie&rft.au=Sun%2C+Min&rft.date=2019-08-08&rft.issn=0022-2623&rft.eissn=1520-4804&rft.volume=62&rft.issue=15&rft.spage=7302&rft.epage=7308&rft_id=info:doi/10.1021%2Facs.jmedchem.9b00576&rft.externalDBID=n%2Fa&rft.externalDocID=10_1021_acs_jmedchem_9b00576 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0022-2623&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0022-2623&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0022-2623&client=summon |