Targeting oncogenic KRasG13C with nucleotide-based covalent inhibitors.
Elife
Goebel, Lisa L; Kirschner, Tonia T; Koska, Sandra S; Rai, Amrita A; Janning, Petra P; Maffini, Stefano S; Vatheuer, Helge H; Czodrowski, Paul P; Goody, Roger S RS; Müller, Matthias P MP; Rauh, Daniel D
Fragment Optimization of Reversible Binding to the Switch II Pocket on KRAS Leads to a Potent, In Vivo Active KRASG12C Inhibitor.
Journal Of Medicinal Chemistry
Bröker, Joachim J; Waterson, Alex G AG; Smethurst, Chris C; Kessler, Dirk D; Böttcher, Jark J; Mayer, Moriz M; Gmaschitz, Gerhard G; Phan, Jason J; Little, Andrew A; Abbott, Jason R JR; Sun, Qi Q; Gmachl, Michael M; Rudolph, Dorothea D; Arnhof, Heribert H; Rumpel, Klaus K; Savarese, Fabio F; Gerstberger, Thomas T; Mischerikow, Nikolai N; Treu, Matthias M; Herdeis, Lorenz L; Wunberg, Tobias T; Gollner, Andreas A; Weinstabl, Harald H; Mantoulidis, Andreas A; Krämer, Oliver O; McConnell, Darryl B DB; W Fesik, Stephen S
Oncogenic KRAS G12C: Kinetic and redox characterization of covalent inhibition.
The Journal Of Biological Chemistry
Huynh, Minh V MV; Parsonage, Derek D; Forshaw, Tom E TE; Chirasani, Venkat R VR; Hobbs, G Aaron GA; Wu, Hanzhi H; Lee, Jingyun J; Furdui, Cristina M CM; Poole, Leslie B LB; Campbell, Sharon L SL
Proceedings Of The National Academy Of Sciences Of The United States Of America
Ingólfsson, Helgi I HI; Neale, Chris C; Carpenter, Timothy S TS; Shrestha, Rebika R; López, Cesar A CA; Tran, Timothy H TH; Oppelstrup, Tomas T; Bhatia, Harsh H; Stanton, Liam G LG; Zhang, Xiaohua X; Sundram, Shiv S; Di Natale, Francesco F; Agarwal, Animesh A; Dharuman, Gautham G; Kokkila Schumacher, Sara I L SIL; Turbyville, Thomas T; Gulten, Gulcin G; Van, Que N QN; Goswami, Debanjan D; Jean-Francois, Frantz F; Agamasu, Constance C; Chen, De ; Hettige, Jeevapani J JJ; Travers, Timothy T; Sarkar, Sumantra S; Surh, Michael P MP; Yang, Yue Y; Moody, Adam A; Liu, Shusen S; Van Essen, Brian C BC; Voter, Arthur F AF; Ramanathan, Arvind A; Hengartner, Nicolas W NW; Simanshu, Dhirendra K DK; Stephen, Andrew G AG; Bremer, Peer-Timo PT; Gnanakaran, S S; Glosli, James N JN; Lightstone, Felice C FC; McCormick, Frank F; Nissley, Dwight V DV; Streitz, Frederick H FH
Proceedings Of The National Academy Of Sciences Of The United States Of America
Ingólfsson, Helgi I HI; Neale, Chris C; Carpenter, Timothy S TS; Shrestha, Rebika R; López, Cesar A CA; Tran, Timothy H TH; Oppelstrup, Tomas T; Bhatia, Harsh H; Stanton, Liam G LG; Zhang, Xiaohua X; Sundram, Shiv S; Di Natale, Francesco F; Agarwal, Animesh A; Dharuman, Gautham G; Kokkila Schumacher, Sara I L SIL; Turbyville, Thomas T; Gulten, Gulcin G; Van, Que N QN; Goswami, Debanjan D; Jean-Francois, Frantz F; Agamasu, Constance C; Chen, De ; Hettige, Jeevapani J JJ; Travers, Timothy T; Sarkar, Sumantra S; Surh, Michael P MP; Yang, Yue Y; Moody, Adam A; Liu, Shusen S; Van Essen, Brian C BC; Voter, Arthur F AF; Ramanathan, Arvind A; Hengartner, Nicolas W NW; Simanshu, Dhirendra K DK; Stephen, Andrew G AG; Bremer, Peer-Timo PT; Gnanakaran, S S; Glosli, James N JN; Lightstone, Felice C FC; McCormick, Frank F; Nissley, Dwight V DV; Streitz, Frederick H FH
The Q61H mutation decouples KRAS from upstream regulation and renders cancer cells resistant to SHP2 inhibitors.
Nature Communications
Gebregiworgis, Teklab T; Kano, Yoshihito Y; St-Germain, Jonathan J; Radulovich, Nikolina N; Udaskin, Molly L ML; Mentes, Ahmet A; Huang, Richard R; Poon, Betty P K BPK; He, Wenguang W; Valencia-Sama, Ivette I; Robinson, Claire M CM; Huestis, Melissa M; Miao, Jinmin J; Yeh, Jen Jen JJ; Zhang, Zhong-Yin ZY; Irwin, Meredith S MS; Lee, Jeffrey E JE; Tsao, Ming-Sound MS; Raught, Brian B; Marshall, Christopher B CB; Ohh, Michael M; Ikura, Mitsuhiko M
NMR 1H, 13C, 15N backbone resonance assignments of the T35S and oncogenic T35S/Q61L mutants of human KRAS4b in the active, GppNHp-bound conformation.
Biomolecular Nmr Assignments
Sharma, Alok K AK; Dyba, Marcin M; Tonelli, Marco M; Smith, Brian B; Gillette, William K WK; Esposito, Dominic D; Nissley, Dwight V DV; McCormick, Frank F; Maciag, Anna E AE
Targeted Therapy of Papillary Thyroid Cancer: A Comprehensive Genomic Analysis.
Frontiers In Endocrinology
Hescheler, Daniel A DA; Riemann, Burkhard B; Hartmann, Milan J M MJM; Michel, Maximilian M; Faust, Michael M; Bruns, Christiane J CJ; Alakus, Hakan H; Chiapponi, Costanza C
Rudack, Till T; Teuber, Christian C; Scherlo, Marvin M; Güldenhaupt, Jörn J; Schartner, Jonas J; Lübben, Mathias M; Klare, Johann J; Gerwert, Klaus K; Kötting, Carsten C
Spatially interacting phosphorylation sites and mutations in cancer.
Nature Communications
Huang, Kuan-Lin KL; Scott, Adam D AD; Zhou, Daniel Cui DC; Wang, Liang-Bo LB; Weerasinghe, Amila A; Elmas, Abdulkadir A; Liu, Ruiyang R; Wu, Yige Y; Wendl, Michael C MC; Wyczalkowski, Matthew A MA; Baral, Jessika J; Sengupta, Sohini S; Lai, Chin-Wen CW; Ruggles, Kelly K; Payne, Samuel H SH; Raphael, Benjamin B; Fenyö, David D; Chen, Ken K; Mills, Gordon G; Ding, Li L
KRAS interaction with RAF1 RAS-binding domain and cysteine-rich domain provides insights into RAS-mediated RAF activation.
Nature Communications
Tran, Timothy H TH; Chan, Albert H AH; Young, Lucy C LC; Bindu, Lakshman L; Neale, Chris C; Messing, Simon S; Dharmaiah, Srisathiyanarayanan S; Taylor, Troy T; Denson, John-Paul JP; Esposito, Dominic D; Nissley, Dwight V DV; Stephen, Andrew G AG; McCormick, Frank F; Simanshu, Dhirendra K DK
Computationally Empowered Workflow Identifies Novel Covalent Allosteric Binders for KRASG12C.
Chemmedchem
Mortier, Jérémie J; Friberg, Anders A; Badock, Volker V; Moosmayer, Dieter D; Schroeder, Jens J; Steigemann, Patrick P; Siegel, Franziska F; Gradl, Stefan S; Bauser, Marcus M; Hillig, Roman C RC; Briem, Hans H; Eis, Knut K; Bader, Benjamin B; Nguyen, Duy D; Christ, Clara D CD
Identification of targeted therapy options for gastric adenocarcinoma by comprehensive analysis of genomic data.
Gastric Cancer : Official Journal Of The International Gastric Cancer Association And The Japanese Gastric Cancer Association
Hescheler, Daniel A DA; Plum, Patrick S PS; Zander, Thomas T; Quaas, Alexander A; Korenkov, Michael M; Gassa, Asmae A; Michel, Maximilian M; Bruns, Christiane J CJ; Alakus, Hakan H
Proceedings Of The National Academy Of Sciences Of The United States Of America
Kessler, Dirk D; Gmachl, Michael M; Mantoulidis, Andreas A; Martin, Laetitia J LJ; Zoephel, Andreas A; Mayer, Moriz M; Gollner, Andreas A; Covini, David D; Fischer, Silke S; Gerstberger, Thomas T; Gmaschitz, Teresa T; Goodwin, Craig C; Greb, Peter P; Häring, Daniela D; Hela, Wolfgang W; Hoffmann, Johann J; Karolyi-Oezguer, Jale J; Knesl, Petr P; Kornigg, Stefan S; Koegl, Manfred M; Kousek, Roland R; Lamarre, Lyne L; Moser, Franziska F; Munico-Martinez, Silvia S; Peinsipp, Christoph C; Phan, Jason J; Rinnenthal, Jörg J; Sai, Jiqing J; Salamon, Christian C; Scherbantin, Yvonne Y; Schipany, Katharina K; Schnitzer, Renate R; Schrenk, Andreas A; Sharps, Bernadette B; Siszler, Gabriella G; Sun, Qi Q; Waterson, Alex A; Wolkerstorfer, Bernhard B; Zeeb, Markus M; Pearson, Mark M; Fesik, Stephen W SW; McConnell, Darryl B DB
Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS-SOS1 interaction.
Proceedings Of The National Academy Of Sciences Of The United States Of America
Hillig, Roman C RC; Sautier, Brice B; Schroeder, Jens J; Moosmayer, Dieter D; Hilpmann, André A; Stegmann, Christian M CM; Werbeck, Nicolas D ND; Briem, Hans H; Boemer, Ulf U; Weiske, Joerg J; Badock, Volker V; Mastouri, Julia J; Petersen, Kirstin K; Siemeister, Gerhard G; Kahmann, Jan D JD; Wegener, Dennis D; Böhnke, Niels N; Eis, Knut K; Graham, Keith K; Wortmann, Lars L; von Nussbaum, Franz F; Bader, Benjamin B
Tyrosyl phosphorylation of KRAS stalls GTPase cycle via alteration of switch I and II conformation.
Nature Communications
Kano, Yoshihito Y; Gebregiworgis, Teklab T; Marshall, Christopher B CB; Radulovich, Nikolina N; Poon, Betty P K BPK; St-Germain, Jonathan J; Cook, Jonathan D JD; Valencia-Sama, Ivette I; Grant, Benjamin M M BMM; Herrera, Silvia Gabriela SG; Miao, Jinmin J; Raught, Brian B; Irwin, Meredith S MS; Lee, Jeffrey E JE; Yeh, Jen Jen JJ; Zhang, Zhong-Yin ZY; Tsao, Ming-Sound MS; Ikura, Mitsuhiko M; Ohh, Michael M
Dynamics of Membrane-Bound G12V-KRAS from Simulations and Single-Molecule FRET in Native Nanodiscs.
Biophysical Journal
Prakash, Priyanka P; Litwin, Douglas D; Liang, Hong H; Sarkar-Banerjee, Suparna S; Dolino, Drew D; Zhou, Yong Y; Hancock, John F JF; Jayaraman, Vasanthi V; Gorfe, Alemayehu A AA
Integrative omics analyses broaden treatment targets in human cancer.
Genome Medicine
Sengupta, Sohini S; Sun, Sam Q SQ; Huang, Kuan-Lin KL; Oh, Clara C; Bailey, Matthew H MH; Varghese, Rajees R; Wyczalkowski, Matthew A MA; Ning, Jie J; Tripathi, Piyush P; McMichael, Joshua F JF; Johnson, Kimberly J KJ; Kandoth, Cyriac C; Welch, John J; Ma, Cynthia C; Wendl, Michael C MC; Payne, Samuel H SH; Fenyö, David D; Townsend, Reid R RR; Dipersio, John F JF; Chen, Feng F; Ding, Li L
Precise characterization of KRAS4b proteoforms in human colorectal cells and tumors reveals mutation/modification cross-talk.
Proceedings Of The National Academy Of Sciences Of The United States Of America
Ntai, Ioanna I; Fornelli, Luca L; DeHart, Caroline J CJ; Hutton, Josiah E JE; Doubleday, Peter F PF; LeDuc, Richard D RD; van Nispen, Alexandra J AJ; Fellers, Ryan T RT; Whiteley, Gordon G; Boja, Emily S ES; Rodriguez, Henry H; Kelleher, Neil L NL
A KRAS GTPase K104Q Mutant Retains Downstream Signaling by Offsetting Defects in Regulation.
The Journal Of Biological Chemistry
Yin, Guowei G; Kistler, Samantha S; George, Samuel D SD; Kuhlmann, Nora N; Garvey, Leslie L; Huynh, Minh M; Bagni, Rachel K RK; Lammers, Michael M; Der, Channing J CJ; Campbell, Sharon L SL
LowMACA: exploiting protein family analysis for the identification of rare driver mutations in cancer.
Bmc Bioinformatics
Melloni, Giorgio E M GE; de Pretis, Stefano S; Riva, Laura L; Pelizzola, Mattia M; Céol, Arnaud A; Costanza, Jole J; Müller, Heiko H; Zammataro, Luca L
Oncogenic and RASopathy-associated K-RAS mutations relieve membrane-dependent occlusion of the effector-binding site.
Proceedings Of The National Academy Of Sciences Of The United States Of America
Mazhab-Jafari, Mohammad T MT; Marshall, Christopher B CB; Smith, Matthew J MJ; Gasmi-Seabrook, Geneviève M C GM; Stathopulos, Peter B PB; Inagaki, Fuyuhiko F; Kay, Lewis E LE; Neel, Benjamin G BG; Ikura, Mitsuhiko M
Martelotto, Luciano G LG; Ng, Charlotte Ky CK; De Filippo, Maria R MR; Zhang, Yan Y; Piscuoglio, Salvatore S; Lim, Raymond S RS; Shen, Ronglai R; Norton, Larry L; Reis-Filho, Jorge S JS; Weigelt, Britta B
Age-related mutations associated with clonal hematopoietic expansion and malignancies.
Nature Medicine
Xie, Mingchao M; Lu, Charles C; Wang, Jiayin J; McLellan, Michael D MD; Johnson, Kimberly J KJ; Wendl, Michael C MC; McMichael, Joshua F JF; Schmidt, Heather K HK; Yellapantula, Venkata V; Miller, Christopher A CA; Ozenberger, Bradley A BA; Welch, John S JS; Link, Daniel C DC; Walter, Matthew J MJ; Mardis, Elaine R ER; Dipersio, John F JF; Chen, Feng F; Wilson, Richard K RK; Ley, Timothy J TJ; Ding, Li L