1. Rotow, J.; Bivona, T.G. Understanding and targeting resistance mechanisms in NSCLC.  Nat. Rev. Cancer  **2017** ,  17  , 637–658. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Understanding+and+targeting+resistance+mechanisms+in+NSCLC&author=Rotow,+J.&author=Bivona,+T.G.&publication_year=2017&journal=Nat.+Rev.+Cancer&volume=17&pages=637%E2%80%93658&doi=10.1038/nrc.2017.84&pmid=29068003) ] [ [ CrossRef ](https://doi.org/10.1038/nrc.2017.84) ] [ [ PubMed ](https://www.ncbi.nlm.nih.gov/pubmed/29068003) ] 
  2. Soda, M.; Choi, Y.L.; Enomoto, M.; Takada, S.; Yamashita, Y.; Ishikawa, S.; Fujiwara, S.; Watanabe, H.; Kurashina, K.; Hatanaka, H.; et al. Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer.  Nature  **2007** ,  448  , 561–566. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Identification+of+the+transforming+EML4%E2%80%93ALK+fusion+gene+in+non-small-cell+lung+cancer&author=Soda,+M.&author=Choi,+Y.L.&author=Enomoto,+M.&author=Takada,+S.&author=Yamashita,+Y.&author=Ishikawa,+S.&author=Fujiwara,+S.&author=Watanabe,+H.&author=Kurashina,+K.&author=Hatanaka,+H.&publication_year=2007&journal=Nature&volume=448&pages=561%E2%80%93566&doi=10.1038/nature05945&pmid=17625570) ] [ [ CrossRef ](https://doi.org/10.1038/nature05945) ] [ [ PubMed ](https://www.ncbi.nlm.nih.gov/pubmed/17625570) ] 
  3. He, Y.; Sheng, W.; Hu, W.; Lin, J.; Liu, J.; Yu, B.; Mao, X.; Zhang, L.; Huang, J.; Wang, G. Different types of ROS1 fusion partners yield comparable efficacy to crizotinib.  Oncol. Res.  **2019** ,  27  , 901–910. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Different+types+of+ROS1+fusion+partners+yield+comparable+efficacy+to+crizotinib&author=He,+Y.&author=Sheng,+W.&author=Hu,+W.&author=Lin,+J.&author=Liu,+J.&author=Yu,+B.&author=Mao,+X.&author=Zhang,+L.&author=Huang,+J.&author=Wang,+G.&publication_year=2019&journal=Oncol.+Res.&volume=27&pages=901%E2%80%93910&doi=10.3727/096504019X15509372008132&pmid=30940295) ] [ [ CrossRef ](https://doi.org/10.3727/096504019X15509372008132) ] [ [ PubMed ](https://www.ncbi.nlm.nih.gov/pubmed/30940295) ] 
  4. Davare, M.A.; Vellore, N.A.; Wagner, J.P.; Eide, C.A.; Goodman, J.R.; Drilon, A.; Deininger, M.W.; O’Hare, T.; Druker, B.J. Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitors.  Proc. Natl. Acad. Sci. USA  **2015** ,  112  , E5381–E5390. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Structural+insight+into+selectivity+and+resistance+profiles+of+ROS1+tyrosine+kinase+inhibitors&author=Davare,+M.A.&author=Vellore,+N.A.&author=Wagner,+J.P.&author=Eide,+C.A.&author=Goodman,+J.R.&author=Drilon,+A.&author=Deininger,+M.W.&author=O%E2%80%99Hare,+T.&author=Druker,+B.J.&publication_year=2015&journal=Proc.+Natl.+Acad.+Sci.+USA&volume=112&pages=E5381%E2%80%93E5390&doi=10.1073/pnas.1515281112) ] [ [ CrossRef ](https://doi.org/10.1073/pnas.1515281112) ] 
  5. Awad, M.M.; Katayama, R.; McTigue, M.; Liu, W.; Deng, Y.L.; Brooun, A.; Friboulet, L.; Huang, D.; Falk, M.D.; Timofeevski, S.; et al. Acquired resistance to crizotinib from a mutation in CD74–ROS1.  N. Engl. J. Med.  **2013** ,  368  , 2395–2401. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Acquired+resistance+to+crizotinib+from+a+mutation+in+CD74%E2%80%93ROS1&author=Awad,+M.M.&author=Katayama,+R.&author=McTigue,+M.&author=Liu,+W.&author=Deng,+Y.L.&author=Brooun,+A.&author=Friboulet,+L.&author=Huang,+D.&author=Falk,+M.D.&author=Timofeevski,+S.&publication_year=2013&journal=N.+Engl.+J.+Med.&volume=368&pages=2395%E2%80%932401&doi=10.1056/NEJMoa1215530) ] [ [ CrossRef ](https://doi.org/10.1056/NEJMoa1215530) ] 
  6. Zou, H.Y.; Li, Q.; Engstrom, L.D.; West, M.; Appleman, V.; Wong, K.A.; McTigue, M.; Deng, Y.L.; Liu, W.; Brooun, A.; et al. PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations.  Proc. Natl. Acad. Sci. USA  **2015** ,  112  , 3493–3498. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=PF-06463922+is+a+potent+and+selective+next-generation+ROS1/ALK+inhibitor+capable+of+blocking+crizotinib-resistant+ROS1+mutations&author=Zou,+H.Y.&author=Li,+Q.&author=Engstrom,+L.D.&author=West,+M.&author=Appleman,+V.&author=Wong,+K.A.&author=McTigue,+M.&author=Deng,+Y.L.&author=Liu,+W.&author=Brooun,+A.&publication_year=2015&journal=Proc.+Natl.+Acad.+Sci.+USA&volume=112&pages=3493%E2%80%933498&doi=10.1073/pnas.1420785112) ] [ [ CrossRef ](https://doi.org/10.1073/pnas.1420785112) ] 
  7. Davare, M.A.; Saborowski, A.; Eide, C.A.; Tognon, C.; Smith, R.L.; Elferich, J.; Agarwal, A.; Tyner, J.W.; Shinde, U.P.; Lowe, S.W.; et al. Foretinib is a potent inhibitor of oncogenic ROS1 fusion proteins.  Proc. Natl. Acad. Sci. USA  **2013** ,  110  , 19519–19524. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Foretinib+is+a+potent+inhibitor+of+oncogenic+ROS1+fusion+proteins&author=Davare,+M.A.&author=Saborowski,+A.&author=Eide,+C.A.&author=Tognon,+C.&author=Smith,+R.L.&author=Elferich,+J.&author=Agarwal,+A.&author=Tyner,+J.W.&author=Shinde,+U.P.&author=Lowe,+S.W.&publication_year=2013&journal=Proc.+Natl.+Acad.+Sci.+USA&volume=110&pages=19519%E2%80%9319524&doi=10.1073/pnas.1319583110) ] [ [ CrossRef ](https://doi.org/10.1073/pnas.1319583110) ] 
  8. Bailey, M.H.; Tokheim, C.; Porta-Pardo, E.; Sengupta, S.; Bertrand, D.; Weerasinghe, A.; Colaprico, A.; Wendl, M.C.; Kim, J.; Reardon, B.; et al. Comprehensive characterization of cancer driver genes and mutations.  Cell  **2018** ,  173  , 371–385. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Comprehensive+characterization+of+cancer+driver+genes+and+mutations&author=Bailey,+M.H.&author=Tokheim,+C.&author=Porta-Pardo,+E.&author=Sengupta,+S.&author=Bertrand,+D.&author=Weerasinghe,+A.&author=Colaprico,+A.&author=Wendl,+M.C.&author=Kim,+J.&author=Reardon,+B.&publication_year=2018&journal=Cell&volume=173&pages=371%E2%80%93385&doi=10.1016/j.cell.2018.02.060) ] [ [ CrossRef ](https://doi.org/10.1016/j.cell.2018.02.060) ] 
  9. van Kempen, L.C.; Wang, H.; Aguirre, M.L.; Spatz, A.; Kasymjanova, G.; Vilacha, J.F.; Groves, M.R.; Agulnik, J.; Small, D. Afatinib in osimertinib-resistant EGFR ex19del/T790M/P794L mutated NSCLC.  J. Thorac. Oncol.  **2018** ,  13  , e161–e163. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Afatinib+in+osimertinib-resistant+EGFR+ex19del/T790M/P794L+mutated+NSCLC&author=van+Kempen,+L.C.&author=Wang,+H.&author=Aguirre,+M.L.&author=Spatz,+A.&author=Kasymjanova,+G.&author=Vilacha,+J.F.&author=Groves,+M.R.&author=Agulnik,+J.&author=Small,+D.&publication_year=2018&journal=J.+Thorac.+Oncol.&volume=13&pages=e161%E2%80%93e163&doi=10.1016/j.jtho.2018.04.020) ] [ [ CrossRef ](https://doi.org/10.1016/j.jtho.2018.04.020) ] 
  10. Yosaatmadja, Y.; Silva, S.; Dickson, J.M.; Patterson, A.V.; Smaill, J.B.; Flanagan, J.U.; McKeage, M.J.; Squire, C.J. Binding mode of the breakthrough inhibitor AZD9291 to epidermal growth factor receptor revealed.  J. Struct. Biol.  **2015** ,  192  , 539–544. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Binding+mode+of+the+breakthrough+inhibitor+AZD9291+to+epidermal+growth+factor+receptor+revealed&author=Yosaatmadja,+Y.&author=Silva,+S.&author=Dickson,+J.M.&author=Patterson,+A.V.&author=Smaill,+J.B.&author=Flanagan,+J.U.&author=McKeage,+M.J.&author=Squire,+C.J.&publication_year=2015&journal=J.+Struct.+Biol.&volume=192&pages=539%E2%80%93544&doi=10.1016/j.jsb.2015.10.018) ] [ [ CrossRef ](https://doi.org/10.1016/j.jsb.2015.10.018) ] 
  11. Klaeger, S.; Heinzlmeir, S.; Wilhelm, M.; Polzer, H.; Vick, B.; Koenig, P.A.; Reinecke, M.; Ruprecht, B.; Petzoldt, S.; Meng, C.; et al. The target landscape of clinical kinase drugs.  Science  **2017** ,  358  , eaan4368. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=The+target+landscape+of+clinical+kinase+drugs&author=Klaeger,+S.&author=Heinzlmeir,+S.&author=Wilhelm,+M.&author=Polzer,+H.&author=Vick,+B.&author=Koenig,+P.A.&author=Reinecke,+M.&author=Ruprecht,+B.&author=Petzoldt,+S.&author=Meng,+C.&publication_year=2017&journal=Science&volume=358&pages=eaan4368&doi=10.1126/science.aan4368&pmid=29191878) ] [ [ CrossRef ](https://doi.org/10.1126/science.aan4368) ] [ [ PubMed ](https://www.ncbi.nlm.nih.gov/pubmed/29191878) ] 
  12. Petrovic, D.; Scott, J.S.; Bodnarchuk, M.S.; Lorthioir, O.; Boyd, S.; Hughes, G.M.; Lane, J.; Wu, A.; Hargreaves, D.; Robinson, J.; et al. Virtual screening in the cloud identifies potent and selective ROS1 kinase inhibitors.  J. Chem. Inf. Model.  **2022** ,  62  , 3832–3843. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Virtual+screening+in+the+cloud+identifies+potent+and+selective+ROS1+kinase+inhibitors&author=Petrovic,+D.&author=Scott,+J.S.&author=Bodnarchuk,+M.S.&author=Lorthioir,+O.&author=Boyd,+S.&author=Hughes,+G.M.&author=Lane,+J.&author=Wu,+A.&author=Hargreaves,+D.&author=Robinson,+J.&publication_year=2022&journal=J.+Chem.+Inf.+Model.&volume=62&pages=3832%E2%80%933843&doi=10.1021/acs.jcim.2c00644&pmid=35920716) ] [ [ CrossRef ](https://doi.org/10.1021/acs.jcim.2c00644) ] [ [ PubMed ](https://www.ncbi.nlm.nih.gov/pubmed/35920716) ] 
  13. D’Abramo, M.; Besker, N.; Chillemi, G.; Grottesi, A. Modeling conformational transitions in kinases by molecular dynamics simulations: Achievements, difficulties, and open challenges.  Front. Genet.  **2014** ,  5  , 128. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Modeling+conformational+transitions+in+kinases+by+molecular+dynamics+simulations:+Achievements,+difficulties,+and+open+challenges&author=D%E2%80%99Abramo,+M.&author=Besker,+N.&author=Chillemi,+G.&author=Grottesi,+A.&publication_year=2014&journal=Front.+Genet.&volume=5&pages=128&doi=10.3389/fgene.2014.00128&pmid=24860596) ] [ [ CrossRef ](https://doi.org/10.3389/fgene.2014.00128) ] [ [ PubMed ](https://www.ncbi.nlm.nih.gov/pubmed/24860596) ] 
  14. Vilachã, J.F.; Mitchel, S.C.; Akele, M.Z.; Evans, S.; Groves, M.R. Making NSCLC crystal clear: How kinase structures revolutionized lung cancer treatment.  Crystals  **2020** ,  10  , 725. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Making+NSCLC+crystal+clear:+How+kinase+structures+revolutionized+lung+cancer+treatment&author=Vilach%C3%A3,+J.F.&author=Mitchel,+S.C.&author=Akele,+M.Z.&author=Evans,+S.&author=Groves,+M.R.&publication_year=2020&journal=Crystals&volume=10&pages=725&doi=10.3390/cryst10090725) ] [ [ CrossRef ](https://doi.org/10.3390/cryst10090725) ] 
  15. Cui, J.J.; Tran-Dubé, M.; Shen, H.; Nambu, M.; Kung, P.P.; Pairish, M.; Jia, L.; Meng, J.; Funk, L.; Botrous, I.; et al. Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal–epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK).  J. Med. Chem.  **2011** ,  54  , 6342–6363. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Structure+based+drug+design+of+crizotinib+\(PF-02341066\),+a+potent+and+selective+dual+inhibitor+of+mesenchymal%E2%80%93epithelial+transition+factor+\(c-MET\)+kinase+and+anaplastic+lymphoma+kinase+\(ALK\)&author=Cui,+J.J.&author=Tran-Dub%C3%A9,+M.&author=Shen,+H.&author=Nambu,+M.&author=Kung,+P.P.&author=Pairish,+M.&author=Jia,+L.&author=Meng,+J.&author=Funk,+L.&author=Botrous,+I.&publication_year=2011&journal=J.+Med.+Chem.&volume=54&pages=6342%E2%80%936363&doi=10.1021/jm2007613&pmid=21812414) ] [ [ CrossRef ](https://doi.org/10.1021/jm2007613) ] [ [ PubMed ](https://www.ncbi.nlm.nih.gov/pubmed/21812414) ] 
  16. Tian, Y.; Yu, Y.; Shen, Y.; Wan, H.; Chang, S.; Zhang, T.; Wan, S.; Zhang, J. Molecular simulation studies on the binding selectivity of Type-I inhibitors in the complexes with ROS1 versus ALK.  J. Chem. Inf. Model.  **2017** ,  57  , 977–987. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Molecular+simulation+studies+on+the+binding+selectivity+of+Type-I+inhibitors+in+the+complexes+with+ROS1+versus+ALK&author=Tian,+Y.&author=Yu,+Y.&author=Shen,+Y.&author=Wan,+H.&author=Chang,+S.&author=Zhang,+T.&author=Wan,+S.&author=Zhang,+J.&publication_year=2017&journal=J.+Chem.+Inf.+Model.&volume=57&pages=977%E2%80%93987&doi=10.1021/acs.jcim.7b00019) ] [ [ CrossRef ](https://doi.org/10.1021/acs.jcim.7b00019) ] 
  17. Zhao, L.; Xiao, S.; Jiang, S.; Jin, Y.; Fang, W.; Wang, Z. Detailed structural investigation of Crizotinib and the exploration of its antitumor potential by DFT calculations and molecular docking.  J. Mol. Struct.  **2022** ,  1248  , 131530. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Detailed+structural+investigation+of+Crizotinib+and+the+exploration+of+its+antitumor+potential+by+DFT+calculations+and+molecular+docking&author=Zhao,+L.&author=Xiao,+S.&author=Jiang,+S.&author=Jin,+Y.&author=Fang,+W.&author=Wang,+Z.&publication_year=2022&journal=J.+Mol.+Struct.&volume=1248&pages=131530&doi=10.1016/j.molstruc.2021.131530) ] [ [ CrossRef ](https://doi.org/10.1016/j.molstruc.2021.131530) ] 
  18. Chen, W.; Jin, D.; Shi, Y.; Zhang, Y.; Zhou, H.; Li, G. The underlying mechanisms of lorlatinib penetration across the blood–brain barrier and the distribution characteristics of lorlatinib in the brain.  Cancer Med.  **2020** ,  9  , 4350–4359. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=The+underlying+mechanisms+of+lorlatinib+penetration+across+the+blood%E2%80%93brain+barrier+and+the+distribution+characteristics+of+lorlatinib+in+the+brain&author=Chen,+W.&author=Jin,+D.&author=Shi,+Y.&author=Zhang,+Y.&author=Zhou,+H.&author=Li,+G.&publication_year=2020&journal=Cancer+Med.&volume=9&pages=4350%E2%80%934359&doi=10.1002/cam4.3061) ] [ [ CrossRef ](https://doi.org/10.1002/cam4.3061) ] 
  19. Collier, T.L.; Normandin, M.D.; Stephenson, N.A.; Livni, E.; Liang, S.H.; Wooten, D.W.; Esfahani, S.A.; Stabin, M.G.; Mahmood, U.; Chen, J.; et al. Synthesis and preliminary PET imaging of 11C and 18F isotopologues of the ROS1/ALK inhibitor lorlatinib.  Nat. Commun.  **2017** ,  8  , 15761. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Synthesis+and+preliminary+PET+imaging+of+11C+and+18F+isotopologues+of+the+ROS1/ALK+inhibitor+lorlatinib&author=Collier,+T.L.&author=Normandin,+M.D.&author=Stephenson,+N.A.&author=Livni,+E.&author=Liang,+S.H.&author=Wooten,+D.W.&author=Esfahani,+S.A.&author=Stabin,+M.G.&author=Mahmood,+U.&author=Chen,+J.&publication_year=2017&journal=Nat.+Commun.&volume=8&pages=15761&doi=10.1038/ncomms15761) ] [ [ CrossRef ](https://doi.org/10.1038/ncomms15761) ] 
  20. Faber, E.B.; Georg, G.I. DFG-1 Binding: A New Residue for Developing Selective Kinase Inhibitors.  J. Med. Chem.  **2020** ,  63  , 10221–10223. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=DFG-1+Binding:+A+New+Residue+for+Developing+Selective+Kinase+Inhibitors&author=Faber,+E.B.&author=Georg,+G.I.&publication_year=2020&journal=J.+Med.+Chem.&volume=63&pages=10221%E2%80%9310223&doi=10.1021/acs.jmedchem.0c01501) ] [ [ CrossRef ](https://doi.org/10.1021/acs.jmedchem.0c01501) ] 
  21. Johnson, T.W.; Gallego, R.A.; Brooun, A.; Gehlhaar, D.; McTigue, M. Reviving B-Factors: Retrospective normalized B-factor analysis of c-ros oncogene 1 receptor tyrosine kinase and anaplastic lymphoma kinase L1196M with crizotinib and lorlatinib.  ACS Med. Chem. Lett.  **2018** ,  9  , 878–883. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Reviving+B-Factors:+Retrospective+normalized+B-factor+analysis+of+c-ros+oncogene+1+receptor+tyrosine+kinase+and+anaplastic+lymphoma+kinase+L1196M+with+crizotinib+and+lorlatinib&author=Johnson,+T.W.&author=Gallego,+R.A.&author=Brooun,+A.&author=Gehlhaar,+D.&author=McTigue,+M.&publication_year=2018&journal=ACS+Med.+Chem.+Lett.&volume=9&pages=878%E2%80%93883&doi=10.1021/acsmedchemlett.8b00147&pmid=30258534) ] [ [ CrossRef ](https://doi.org/10.1021/acsmedchemlett.8b00147) ] [ [ PubMed ](https://www.ncbi.nlm.nih.gov/pubmed/30258534) ] 
  22. Xu, M.; Shen, C.; Yang, J.; Wang, Q.; Huang, N. Systematic investigation of docking failures in large-scale structure-based virtual screening.  ACS Omega  **2022** ,  7  , 39417–39428. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Systematic+investigation+of+docking+failures+in+large-scale+structure-based+virtual+screening&author=Xu,+M.&author=Shen,+C.&author=Yang,+J.&author=Wang,+Q.&author=Huang,+N.&publication_year=2022&journal=ACS+Omega&volume=7&pages=39417%E2%80%9339428&doi=10.1021/acsomega.2c05826&pmid=36340123) ] [ [ CrossRef ](https://doi.org/10.1021/acsomega.2c05826) ] [ [ PubMed ](https://www.ncbi.nlm.nih.gov/pubmed/36340123) ] 
  23. Grebner, C.; Malmerberg, E.; Shewmaker, A.; Batista, J.; Nicholls, A.; Sadowski, J. Virtual screening in the cloud: How big is big enough?  J. Chem. Inf. Model.  **2019** ,  60  , 4274–4282. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Virtual+screening+in+the+cloud:+How+big+is+big+enough?&author=Grebner,+C.&author=Malmerberg,+E.&author=Shewmaker,+A.&author=Batista,+J.&author=Nicholls,+A.&author=Sadowski,+J.&publication_year=2019&journal=J.+Chem.+Inf.+Model.&volume=60&pages=4274%E2%80%934282&doi=10.1021/acs.jcim.9b00779&pmid=31682421) ] [ [ CrossRef ](https://doi.org/10.1021/acs.jcim.9b00779) ] [ [ PubMed ](https://www.ncbi.nlm.nih.gov/pubmed/31682421) ] 
  24. Menichincheri, M.; Ardini, E.; Magnaghi, P.; Avanzi, N.; Banfi, P.; Bossi, R.; Buffa, L.; Canevari, G.; Ceriani, L.; Colombo, M.; et al. Discovery of entrectinib: A new 3-aminoindazole as a potent anaplastic lymphoma kinase (ALK), c-ros oncogene 1 kinase (ROS1), and pan-tropomyosin receptor kinases (Pan-TRKs) inhibitor.  J. Med. Chem.  **2016** ,  59  , 3392–3408. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Discovery+of+entrectinib:+A+new+3-aminoindazole+as+a+potent+anaplastic+lymphoma+kinase+\(ALK\),+c-ros+oncogene+1+kinase+\(ROS1\),+and+pan-tropomyosin+receptor+kinases+\(Pan-TRKs\)+inhibitor&author=Menichincheri,+M.&author=Ardini,+E.&author=Magnaghi,+P.&author=Avanzi,+N.&author=Banfi,+P.&author=Bossi,+R.&author=Buffa,+L.&author=Canevari,+G.&author=Ceriani,+L.&author=Colombo,+M.&publication_year=2016&journal=J.+Med.+Chem.&volume=59&pages=3392%E2%80%933408&doi=10.1021/acs.jmedchem.6b00064&pmid=27003761) ] [ [ CrossRef ](https://doi.org/10.1021/acs.jmedchem.6b00064) ] [ [ PubMed ](https://www.ncbi.nlm.nih.gov/pubmed/27003761) ] 
  25. Salifu, E.Y.; Issahaku, A.R.; Agoni, C.; Ibrahim, M.A.; Manimbulu, N.; Soliman, M.E. Prioritizing the Catalytic Gatekeepers through Pan-Inhibitory Mechanism of Entrectinib against ALK, ROS1 and TRKA Tyrosine Kinases.  Cell Biochem. Biophys.  **2022** ,  80  , 11–21. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Prioritizing+the+Catalytic+Gatekeepers+through+Pan-Inhibitory+Mechanism+of+Entrectinib+against+ALK,+ROS1+and+TRKA+Tyrosine+Kinases&author=Salifu,+E.Y.&author=Issahaku,+A.R.&author=Agoni,+C.&author=Ibrahim,+M.A.&author=Manimbulu,+N.&author=Soliman,+M.E.&publication_year=2022&journal=Cell+Biochem.+Biophys.&volume=80&pages=11%E2%80%9321&doi=10.1007/s12013-021-01052-2&pmid=35040089) ] [ [ CrossRef ](https://doi.org/10.1007/s12013-021-01052-2) ] [ [ PubMed ](https://www.ncbi.nlm.nih.gov/pubmed/35040089) ] 
  26. Huse, M.; Kuriyan, J. The conformational plasticity of protein kinases.  Cell  **2002** ,  109  , 275–282. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=The+conformational+plasticity+of+protein+kinases&author=Huse,+M.&author=Kuriyan,+J.&publication_year=2002&journal=Cell&volume=109&pages=275%E2%80%93282&doi=10.1016/S0092-8674\(02\)00741-9&pmid=12015977) ] [ [ CrossRef ](https://doi.org/10.1016/S0092-8674\(02\)00741-9) ] [ [ PubMed ](https://www.ncbi.nlm.nih.gov/pubmed/12015977) ] 
  27. Collie, G.W.; Koh, C.M.; O’Neill, D.J.; Stubbs, C.J.; Khurana, P.; Eddershaw, A.; Snijder, A.; Mauritzson, F.; Barlind, L.; Dale, I.L.; et al. Structural and molecular insight into resistance mechanisms of first generation cMET inhibitors.  ACS Med. Chem. Lett.  **2019** ,  10  , 1322–1327. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Structural+and+molecular+insight+into+resistance+mechanisms+of+first+generation+cMET+inhibitors&author=Collie,+G.W.&author=Koh,+C.M.&author=O%E2%80%99Neill,+D.J.&author=Stubbs,+C.J.&author=Khurana,+P.&author=Eddershaw,+A.&author=Snijder,+A.&author=Mauritzson,+F.&author=Barlind,+L.&author=Dale,+I.L.&publication_year=2019&journal=ACS+Med.+Chem.+Lett.&volume=10&pages=1322%E2%80%931327&doi=10.1021/acsmedchemlett.9b00276) ] [ [ CrossRef ](https://doi.org/10.1021/acsmedchemlett.9b00276) ] 
  28. Zhou, Y.; Xiang, S.; Yang, F.; Lu, X. Targeting gatekeeper mutations for kinase drug discovery.  J. Med. Chem.  **2022** ,  65  , 15540–15558. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Targeting+gatekeeper+mutations+for+kinase+drug+discovery&author=Zhou,+Y.&author=Xiang,+S.&author=Yang,+F.&author=Lu,+X.&publication_year=2022&journal=J.+Med.+Chem.&volume=65&pages=15540%E2%80%9315558&doi=10.1021/acs.jmedchem.2c01361) ] [ [ CrossRef ](https://doi.org/10.1021/acs.jmedchem.2c01361) ] 
  29. Wu, X.; Fu, Y.; Wang, Y.; Wan, S.; Zhang, J. Gaining insight into crizotinib resistance mechanisms caused by L2026M and G2032R mutations in ROS1 via molecular dynamics simulations and free-energy calculations.  J. Mol. Model.  **2017** ,  23  , 141. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Gaining+insight+into+crizotinib+resistance+mechanisms+caused+by+L2026M+and+G2032R+mutations+in+ROS1+via+molecular+dynamics+simulations+and+free-energy+calculations&author=Wu,+X.&author=Fu,+Y.&author=Wang,+Y.&author=Wan,+S.&author=Zhang,+J.&publication_year=2017&journal=J.+Mol.+Model.&volume=23&pages=141&doi=10.1007/s00894-017-3314-z) ] [ [ CrossRef ](https://doi.org/10.1007/s00894-017-3314-z) ] 
  30. Chuang, Y.C.; Huang, B.Y.; Chang, H.W.; Yang, C.N. Molecular modeling of ALK L1198F and/or G1202R mutations to determine differential crizotinib sensitivity.  Sci. Rep.  **2019** ,  9  , 11390. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Molecular+modeling+of+ALK+L1198F+and/or+G1202R+mutations+to+determine+differential+crizotinib+sensitivity&author=Chuang,+Y.C.&author=Huang,+B.Y.&author=Chang,+H.W.&author=Yang,+C.N.&publication_year=2019&journal=Sci.+Rep.&volume=9&pages=11390&doi=10.1038/s41598-019-46825-1) ] [ [ CrossRef ](https://doi.org/10.1038/s41598-019-46825-1) ] 
  31. Chen, C.; He, Z.; Xie, D.; Zheng, L.; Zhao, T.; Zhang, X.; Cheng, D. Molecular mechanism behind the resistance of the G1202R-Mutated anaplastic lymphoma kinase to the approved drug Ceritinib.  J. Phys. Chem. B  **2018** ,  122  , 4680–4692. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Molecular+mechanism+behind+the+resistance+of+the+G1202R-Mutated+anaplastic+lymphoma+kinase+to+the+approved+drug+Ceritinib&author=Chen,+C.&author=He,+Z.&author=Xie,+D.&author=Zheng,+L.&author=Zhao,+T.&author=Zhang,+X.&author=Cheng,+D.&publication_year=2018&journal=J.+Phys.+Chem.+B&volume=122&pages=4680%E2%80%934692&doi=10.1021/acs.jpcb.8b02040&pmid=29648831) ] [ [ CrossRef ](https://doi.org/10.1021/acs.jpcb.8b02040) ] [ [ PubMed ](https://www.ncbi.nlm.nih.gov/pubmed/29648831) ] 
  32. Sun, H.; Li, Y.; Tian, S.; Wang, J.; Hou, T. P-loop conformation governed crizotinib resistance in G2032R-mutated ROS1 tyrosine kinase: Clues from free energy landscape.  PLoS Comput. Biol.  **2014** ,  10  , e1003729. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=P-loop+conformation+governed+crizotinib+resistance+in+G2032R-mutated+ROS1+tyrosine+kinase:+Clues+from+free+energy+landscape&author=Sun,+H.&author=Li,+Y.&author=Tian,+S.&author=Wang,+J.&author=Hou,+T.&publication_year=2014&journal=PLoS+Comput.+Biol.&volume=10&pages=e1003729&doi=10.1371/journal.pcbi.1003729&pmid=25033171) ] [ [ CrossRef ](https://doi.org/10.1371/journal.pcbi.1003729) ] [ [ PubMed ](https://www.ncbi.nlm.nih.gov/pubmed/25033171) ] 
  33. Wu, X.; Wang, Y.; Wan, S.; Zhang, J. Investigation on the binding mechanism of loratinib with the c-ros oncogene 1 (ROS1) receptor tyrosine kinase via molecular dynamics simulation and binding free energy calculations.  J. Biomol. Struct. Dyn.  **2018** ,  36  , 3106–3113. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Investigation+on+the+binding+mechanism+of+loratinib+with+the+c-ros+oncogene+1+\(ROS1\)+receptor+tyrosine+kinase+via+molecular+dynamics+simulation+and+binding+free+energy+calculations&author=Wu,+X.&author=Wang,+Y.&author=Wan,+S.&author=Zhang,+J.&publication_year=2018&journal=J.+Biomol.+Struct.+Dyn.&volume=36&pages=3106%E2%80%933113&doi=10.1080/07391102.2017.1378127&pmid=28893136) ] [ [ CrossRef ](https://doi.org/10.1080/07391102.2017.1378127) ] [ [ PubMed ](https://www.ncbi.nlm.nih.gov/pubmed/28893136) ] 
  34. Drilon, A.; Somwar, R.; Wagner, J.P.; Vellore, N.A.; Eide, C.A.; Zabriskie, M.S.; Arcila, M.E.; Hechtman, J.F.; Wang, L.; Smith, R.S.; et al. A novel crizotinib-resistant solvent-front mutation responsive to cabozantinib therapy in a patient with ROS1-rearranged lung cancer.  Clin. Cancer Res.  **2016** ,  22  , 2351–2358. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=A+novel+crizotinib-resistant+solvent-front+mutation+responsive+to+cabozantinib+therapy+in+a+patient+with+ROS1-rearranged+lung+cancer&author=Drilon,+A.&author=Somwar,+R.&author=Wagner,+J.P.&author=Vellore,+N.A.&author=Eide,+C.A.&author=Zabriskie,+M.S.&author=Arcila,+M.E.&author=Hechtman,+J.F.&author=Wang,+L.&author=Smith,+R.S.&publication_year=2016&journal=Clin.+Cancer+Res.&volume=22&pages=2351%E2%80%932358&doi=10.1158/1078-0432.CCR-15-2013&pmid=26673800) ] [ [ CrossRef ](https://doi.org/10.1158/1078-0432.CCR-15-2013) ] [ [ PubMed ](https://www.ncbi.nlm.nih.gov/pubmed/26673800) ] 
  35. Tamirat, M.Z.; Kurppa, K.J.; Elenius, K.; Johnson, M.S. Structural basis for the functional changes by EGFR exon 20 insertion mutations.  Cancers  **2021** ,  13  , 1120. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Structural+basis+for+the+functional+changes+by+EGFR+exon+20+insertion+mutations&author=Tamirat,+M.Z.&author=Kurppa,+K.J.&author=Elenius,+K.&author=Johnson,+M.S.&publication_year=2021&journal=Cancers&volume=13&pages=1120&doi=10.3390/cancers13051120) ] [ [ CrossRef ](https://doi.org/10.3390/cancers13051120) ] 
  36. Facchinetti, F.; Loriot, Y.; Kuo, M.S.; Mahjoubi, L.; Lacroix, L.; Planchard, D.; Besse, B.; Farace, F.; Auger, N.; Remon, J.; et al. Crizotinib-resistant ROS1 mutations reveal a predictive kinase inhibitor sensitivity model for ROS1-and ALK-rearranged lung cancers.  Clin. Cancer Res.  **2016** ,  22  , 5983–5991. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=Crizotinib-resistant+ROS1+mutations+reveal+a+predictive+kinase+inhibitor+sensitivity+model+for+ROS1-and+ALK-rearranged+lung+cancers&author=Facchinetti,+F.&author=Loriot,+Y.&author=Kuo,+M.S.&author=Mahjoubi,+L.&author=Lacroix,+L.&author=Planchard,+D.&author=Besse,+B.&author=Farace,+F.&author=Auger,+N.&author=Remon,+J.&publication_year=2016&journal=Clin.+Cancer+Res.&volume=22&pages=5983%E2%80%935991&doi=10.1158/1078-0432.CCR-16-0917) ] [ [ CrossRef ](https://doi.org/10.1158/1078-0432.CCR-16-0917) ] 
  37. Drilon, A.; Jenkins, C.; Iyer, S.; Schoenfeld, A.; Keddy, C.; Davare, M.A. ROS1-dependent cancers—Biology, diagnostics and therapeutics.  Nat. Rev. Clin. Oncol.  **2021** ,  18  , 35–55. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=ROS1-dependent+cancers%E2%80%94Biology,+diagnostics+and+therapeutics&author=Drilon,+A.&author=Jenkins,+C.&author=Iyer,+S.&author=Schoenfeld,+A.&author=Keddy,+C.&author=Davare,+M.A.&publication_year=2021&journal=Nat.+Rev.+Clin.+Oncol.&volume=18&pages=35%E2%80%9355&doi=10.1038/s41571-020-0408-9) ] [ [ CrossRef ](https://doi.org/10.1038/s41571-020-0408-9) ] 
  38. Gendarme, S.; Bylicki, O.; Chouaid, C.; Guisier, F. ROS-1 fusions in non-small-cell lung cancer: Evidence to date.  Curr. Oncol.  **2022** ,  29  , 641–658. [ [ Google Scholar ](https://scholar.google.com/scholar_lookup?title=ROS-1+fusions+in+non-small-cell+lung+cancer:+Evidence+to+date&author=Gendarme,+S.&author=Bylicki,+O.&author=Chouaid,+C.&author=Guisier,+F.&publication_year=2022&journal=Curr.+Oncol.&volume=29&pages=641%E2%80%93658&doi=10.3390/curroncol29020057) ] [ [ CrossRef ](https://doi.org/10.3390/curroncol29020057) ]