Small Molecule KRAS Agonist for Mutant KRAS Cancer Therapy
Identifieur interne : 000385 ( Pmc/Checkpoint ); précédent : 000384; suivant : 000386Small Molecule KRAS Agonist for Mutant KRAS Cancer Therapy
Auteurs : Ke Xu [États-Unis] ; Dongkyoo Park [États-Unis] ; Andrew T. Magis [États-Unis] ; Jun Zhang [États-Unis] ; Wei Zhou [États-Unis] ; Gabriel L. Sica [États-Unis] ; Suresh S. Ramalingam [États-Unis] ; Walter J. Curran [États-Unis] ; Xingming Deng [États-Unis]Source :
- Molecular Cancer [ 1476-4598 ] ; 2019.
Abstract
Lung cancer patients with KRAS mutation(s) have a poor prognosis due in part to the development of resistance to currently available therapeutic interventions. Development of a new class of anticancer agents that directly targets KRAS may provide a more attractive option for the treatment of KRAS-mutant lung cancer.
Here we identified a small molecule KRAS agonist, KRA-533, that binds the GTP/GDP-binding pocket of KRAS. In vitro GDP/GTP exchange assay reveals that KRA-533 activates KRAS by preventing the cleavage of GTP into GDP, leading to the accumulation of GTP-KRAS, an active form of KRAS. Treatment of human lung cancer cells with KRA-533 resulted in increased KRAS activity and suppression of cell growth. Lung cancer cell lines with KRAS mutation were relatively more sensitive to KRA-533 than cell lines without KRAS mutation. Mutating one of the hydrogen-bonds among the KRA-533 binding amino acids in KRAS (mutant K117A) resulted in failure of KRAS to bind KRA-533. KRA-533 had no effect on the activity of K117A mutant KRAS, suggesting that KRA-533 binding to K117 is required for KRA-533 to enhance KRAS activity. Intriguingly, KRA-533-mediated KRAS activation not only promoted apoptosis but also autophagic cell death. In mutant KRAS lung cancer xenografts and genetically engineered mutant KRAS-driven lung cancer models, KRA-533 suppressed malignant growth without significant toxicity to normal tissues.
The development of this KRAS agonist as a new class of anticancer drug offers a potentially effective strategy for the treatment of lung cancer with KRAS mutation and/or mutant KRAS-driven lung cancer.
The online version of this article (10.1186/s12943-019-1012-4) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/s12943-019-1012-4
PubMed: 30971271
PubMed Central: 6456974
Affiliations:
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<author><name sortKey="Deng, Xingming" sort="Deng, Xingming" uniqKey="Deng X" first="Xingming" last="Deng">Xingming Deng</name>
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p id="Par1">Lung cancer patients with KRAS mutation(s) have a poor prognosis due in part to the development of resistance to currently available therapeutic interventions. Development of a new class of anticancer agents that directly targets KRAS may provide a more attractive option for the treatment of KRAS-mutant lung cancer.</p>
</sec>
<sec><title>Results</title>
<p id="Par2">Here we identified a small molecule KRAS agonist, KRA-533, that binds the GTP/GDP-binding pocket of KRAS. In vitro GDP/GTP exchange assay reveals that KRA-533 activates KRAS by preventing the cleavage of GTP into GDP, leading to the accumulation of GTP-KRAS, an active form of KRAS. Treatment of human lung cancer cells with KRA-533 resulted in increased KRAS activity and suppression of cell growth. Lung cancer cell lines with KRAS mutation were relatively more sensitive to KRA-533 than cell lines without KRAS mutation. Mutating one of the hydrogen-bonds among the KRA-533 binding amino acids in KRAS (mutant K117A) resulted in failure of KRAS to bind KRA-533. KRA-533 had no effect on the activity of K117A mutant KRAS, suggesting that KRA-533 binding to K117 is required for KRA-533 to enhance KRAS activity. Intriguingly, KRA-533-mediated KRAS activation not only promoted apoptosis but also autophagic cell death. In mutant KRAS lung cancer xenografts and genetically engineered mutant KRAS-driven lung cancer models, KRA-533 suppressed malignant growth without significant toxicity to normal tissues.</p>
</sec>
<sec><title>Conclusions</title>
<p id="Par3">The development of this KRAS agonist as a new class of anticancer drug offers a potentially effective strategy for the treatment of lung cancer with KRAS mutation and/or mutant KRAS-driven lung cancer.</p>
</sec>
<sec><title>Electronic supplementary material</title>
<p>The online version of this article (10.1186/s12943-019-1012-4) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
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</author>
<author><name sortKey="Maltese, Wa" uniqKey="Maltese W">WA Maltese</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hancock, Jf" uniqKey="Hancock J">JF Hancock</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Downward, J" uniqKey="Downward J">J Downward</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Stephen, Ag" uniqKey="Stephen A">AG Stephen</name>
</author>
<author><name sortKey="Esposito, D" uniqKey="Esposito D">D Esposito</name>
</author>
<author><name sortKey="Bagni, Rk" uniqKey="Bagni R">RK Bagni</name>
</author>
<author><name sortKey="Mccormick, F" uniqKey="Mccormick F">F McCormick</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cox, Ad" uniqKey="Cox A">AD Cox</name>
</author>
<author><name sortKey="Fesik, Sw" uniqKey="Fesik S">SW Fesik</name>
</author>
<author><name sortKey="Kimmelman, Ac" uniqKey="Kimmelman A">AC Kimmelman</name>
</author>
<author><name sortKey="Luo, J" uniqKey="Luo J">J Luo</name>
</author>
<author><name sortKey="Der, Cj" uniqKey="Der C">CJ Der</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Welsch, Me" uniqKey="Welsch M">ME Welsch</name>
</author>
<author><name sortKey="Kaplan, A" uniqKey="Kaplan A">A Kaplan</name>
</author>
<author><name sortKey="Chambers, Jm" uniqKey="Chambers J">JM Chambers</name>
</author>
<author><name sortKey="Stokes, Me" uniqKey="Stokes M">ME Stokes</name>
</author>
<author><name sortKey="Bos, Ph" uniqKey="Bos P">PH Bos</name>
</author>
<author><name sortKey="Zask, A" uniqKey="Zask A">A Zask</name>
</author>
<author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name>
</author>
<author><name sortKey="Sanchez Martin, M" uniqKey="Sanchez Martin M">M Sanchez-Martin</name>
</author>
<author><name sortKey="Badgley, Ma" uniqKey="Badgley M">MA Badgley</name>
</author>
<author><name sortKey="Huang, Cs" uniqKey="Huang C">CS Huang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hall, Be" uniqKey="Hall B">BE Hall</name>
</author>
<author><name sortKey="Bar Sagi, D" uniqKey="Bar Sagi D">D Bar-Sagi</name>
</author>
<author><name sortKey="Nassar, N" uniqKey="Nassar N">N Nassar</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Scheele, Js" uniqKey="Scheele J">JS Scheele</name>
</author>
<author><name sortKey="Rhee, Jm" uniqKey="Rhee J">JM Rhee</name>
</author>
<author><name sortKey="Boss, Gr" uniqKey="Boss G">GR Boss</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Okudela, K" uniqKey="Okudela K">K Okudela</name>
</author>
<author><name sortKey="Hayashi, H" uniqKey="Hayashi H">H Hayashi</name>
</author>
<author><name sortKey="Ito, T" uniqKey="Ito T">T Ito</name>
</author>
<author><name sortKey="Yazawa, T" uniqKey="Yazawa T">T Yazawa</name>
</author>
<author><name sortKey="Suzuki, T" uniqKey="Suzuki T">T Suzuki</name>
</author>
<author><name sortKey="Nakane, Y" uniqKey="Nakane Y">Y Nakane</name>
</author>
<author><name sortKey="Sato, H" uniqKey="Sato H">H Sato</name>
</author>
<author><name sortKey="Ishi, H" uniqKey="Ishi H">H Ishi</name>
</author>
<author><name sortKey="Keqin, X" uniqKey="Keqin X">X KeQin</name>
</author>
<author><name sortKey="Masuda, A" uniqKey="Masuda A">A Masuda</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Okudela, K" uniqKey="Okudela K">K Okudela</name>
</author>
<author><name sortKey="Woo, T" uniqKey="Woo T">T Woo</name>
</author>
<author><name sortKey="Kitamura, H" uniqKey="Kitamura H">H Kitamura</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ding, L" uniqKey="Ding L">L Ding</name>
</author>
<author><name sortKey="Getz, G" uniqKey="Getz G">G Getz</name>
</author>
<author><name sortKey="Wheeler, Da" uniqKey="Wheeler D">DA Wheeler</name>
</author>
<author><name sortKey="Mardis, Er" uniqKey="Mardis E">ER Mardis</name>
</author>
<author><name sortKey="Mclellan, Md" uniqKey="Mclellan M">MD McLellan</name>
</author>
<author><name sortKey="Cibulskis, K" uniqKey="Cibulskis K">K Cibulskis</name>
</author>
<author><name sortKey="Sougnez, C" uniqKey="Sougnez C">C Sougnez</name>
</author>
<author><name sortKey="Greulich, H" uniqKey="Greulich H">H Greulich</name>
</author>
<author><name sortKey="Muzny, Dm" uniqKey="Muzny D">DM Muzny</name>
</author>
<author><name sortKey="Morgan, Mb" uniqKey="Morgan M">MB Morgan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Park, Mj" uniqKey="Park M">MJ Park</name>
</author>
<author><name sortKey="Park, Sh" uniqKey="Park S">SH Park</name>
</author>
<author><name sortKey="Park, Pw" uniqKey="Park P">PW Park</name>
</author>
<author><name sortKey="Seo, Yh" uniqKey="Seo Y">YH Seo</name>
</author>
<author><name sortKey="Kim, Kh" uniqKey="Kim K">KH Kim</name>
</author>
<author><name sortKey="Jeong, Jh" uniqKey="Jeong J">JH Jeong</name>
</author>
<author><name sortKey="Kim, Mj" uniqKey="Kim M">MJ Kim</name>
</author>
<author><name sortKey="Ahn, Jy" uniqKey="Ahn J">JY Ahn</name>
</author>
<author><name sortKey="Lee, Jh" uniqKey="Lee J">JH Lee</name>
</author>
<author><name sortKey="Park, J" uniqKey="Park J">J Park</name>
</author>
<author><name sortKey="Hong, J" uniqKey="Hong J">J Hong</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Al Kzayer, Lf" uniqKey="Al Kzayer L">LF Al-Kzayer</name>
</author>
<author><name sortKey="Sakashita, K" uniqKey="Sakashita K">K Sakashita</name>
</author>
<author><name sortKey="Al Jadiry, Mf" uniqKey="Al Jadiry M">MF Al-Jadiry</name>
</author>
<author><name sortKey="Al Hadad, Sa" uniqKey="Al Hadad S">SA Al-Hadad</name>
</author>
<author><name sortKey="Ghali, Hh" uniqKey="Ghali H">HH Ghali</name>
</author>
<author><name sortKey="Uyen Le, Tn" uniqKey="Uyen Le T">TN Uyen le</name>
</author>
<author><name sortKey="Liu, T" uniqKey="Liu T">T Liu</name>
</author>
<author><name sortKey="Matsuda, K" uniqKey="Matsuda K">K Matsuda</name>
</author>
<author><name sortKey="Abdulkadhim, Jm" uniqKey="Abdulkadhim J">JM Abdulkadhim</name>
</author>
<author><name sortKey="Al Shujairi, Ta" uniqKey="Al Shujairi T">TA Al-Shujairi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Burmer, Gc" uniqKey="Burmer G">GC Burmer</name>
</author>
<author><name sortKey="Loeb, La" uniqKey="Loeb L">LA Loeb</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Almoguera, C" uniqKey="Almoguera C">C Almoguera</name>
</author>
<author><name sortKey="Shibata, D" uniqKey="Shibata D">D Shibata</name>
</author>
<author><name sortKey="Forrester, K" uniqKey="Forrester K">K Forrester</name>
</author>
<author><name sortKey="Martin, J" uniqKey="Martin J">J Martin</name>
</author>
<author><name sortKey="Arnheim, N" uniqKey="Arnheim N">N Arnheim</name>
</author>
<author><name sortKey="Perucho, M" uniqKey="Perucho M">M Perucho</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tam, Iy" uniqKey="Tam I">IY Tam</name>
</author>
<author><name sortKey="Chung, Lp" uniqKey="Chung L">LP Chung</name>
</author>
<author><name sortKey="Suen, Ws" uniqKey="Suen W">WS Suen</name>
</author>
<author><name sortKey="Wang, E" uniqKey="Wang E">E Wang</name>
</author>
<author><name sortKey="Wong, Mc" uniqKey="Wong M">MC Wong</name>
</author>
<author><name sortKey="Ho, Kk" uniqKey="Ho K">KK Ho</name>
</author>
<author><name sortKey="Lam, Wk" uniqKey="Lam W">WK Lam</name>
</author>
<author><name sortKey="Chiu, Sw" uniqKey="Chiu S">SW Chiu</name>
</author>
<author><name sortKey="Girard, L" uniqKey="Girard L">L Girard</name>
</author>
<author><name sortKey="Minna, Jd" uniqKey="Minna J">JD Minna</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sanders, Hr" uniqKey="Sanders H">HR Sanders</name>
</author>
<author><name sortKey="Albitar, M" uniqKey="Albitar M">M Albitar</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Meng, D" uniqKey="Meng D">D Meng</name>
</author>
<author><name sortKey="Yuan, M" uniqKey="Yuan M">M Yuan</name>
</author>
<author><name sortKey="Li, X" uniqKey="Li X">X Li</name>
</author>
<author><name sortKey="Chen, L" uniqKey="Chen L">L Chen</name>
</author>
<author><name sortKey="Yang, J" uniqKey="Yang J">J Yang</name>
</author>
<author><name sortKey="Zhao, X" uniqKey="Zhao X">X Zhao</name>
</author>
<author><name sortKey="Ma, W" uniqKey="Ma W">W Ma</name>
</author>
<author><name sortKey="Xin, J" uniqKey="Xin J">J Xin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Riely, Gj" uniqKey="Riely G">GJ Riely</name>
</author>
<author><name sortKey="Marks, J" uniqKey="Marks J">J Marks</name>
</author>
<author><name sortKey="Pao, W" uniqKey="Pao W">W Pao</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Janakiraman, M" uniqKey="Janakiraman M">M Janakiraman</name>
</author>
<author><name sortKey="Vakiani, E" uniqKey="Vakiani E">E Vakiani</name>
</author>
<author><name sortKey="Zeng, Z" uniqKey="Zeng Z">Z Zeng</name>
</author>
<author><name sortKey="Pratilas, Ca" uniqKey="Pratilas C">CA Pratilas</name>
</author>
<author><name sortKey="Taylor, Bs" uniqKey="Taylor B">BS Taylor</name>
</author>
<author><name sortKey="Chitale, D" uniqKey="Chitale D">D Chitale</name>
</author>
<author><name sortKey="Halilovic, E" uniqKey="Halilovic E">E Halilovic</name>
</author>
<author><name sortKey="Wilson, M" uniqKey="Wilson M">M Wilson</name>
</author>
<author><name sortKey="Huberman, K" uniqKey="Huberman K">K Huberman</name>
</author>
<author><name sortKey="Ricarte Filho, Jc" uniqKey="Ricarte Filho J">JC Ricarte Filho</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Stolze, B" uniqKey="Stolze B">B Stolze</name>
</author>
<author><name sortKey="Reinhart, S" uniqKey="Reinhart S">S Reinhart</name>
</author>
<author><name sortKey="Bulllinger, L" uniqKey="Bulllinger L">L Bulllinger</name>
</author>
<author><name sortKey="Frohling, S" uniqKey="Frohling S">S Frohling</name>
</author>
<author><name sortKey="Scholl, C" uniqKey="Scholl C">C Scholl</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Overmeyer, Jh" uniqKey="Overmeyer J">JH Overmeyer</name>
</author>
<author><name sortKey="Kaul, A" uniqKey="Kaul A">A Kaul</name>
</author>
<author><name sortKey="Johnson, Ee" uniqKey="Johnson E">EE Johnson</name>
</author>
<author><name sortKey="Maltese, Wa" uniqKey="Maltese W">WA Maltese</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bhanot, H" uniqKey="Bhanot H">H Bhanot</name>
</author>
<author><name sortKey="Young, Am" uniqKey="Young A">AM Young</name>
</author>
<author><name sortKey="Overmeyer, Jh" uniqKey="Overmeyer J">JH Overmeyer</name>
</author>
<author><name sortKey="Maltese, Wa" uniqKey="Maltese W">WA Maltese</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Khokhlatchev, A" uniqKey="Khokhlatchev A">A Khokhlatchev</name>
</author>
<author><name sortKey="Rabizadeh, S" uniqKey="Rabizadeh S">S Rabizadeh</name>
</author>
<author><name sortKey="Xavier, R" uniqKey="Xavier R">R Xavier</name>
</author>
<author><name sortKey="Nedwidek, M" uniqKey="Nedwidek M">M Nedwidek</name>
</author>
<author><name sortKey="Chen, T" uniqKey="Chen T">T Chen</name>
</author>
<author><name sortKey="Zhang, Xf" uniqKey="Zhang X">XF Zhang</name>
</author>
<author><name sortKey="Seed, B" uniqKey="Seed B">B Seed</name>
</author>
<author><name sortKey="Avruch, J" uniqKey="Avruch J">J Avruch</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Peeters, K" uniqKey="Peeters K">K Peeters</name>
</author>
<author><name sortKey="Van Leemputte, F" uniqKey="Van Leemputte F">F Van Leemputte</name>
</author>
<author><name sortKey="Fischer, B" uniqKey="Fischer B">B Fischer</name>
</author>
<author><name sortKey="Bonini, Bm" uniqKey="Bonini B">BM Bonini</name>
</author>
<author><name sortKey="Quezada, H" uniqKey="Quezada H">H Quezada</name>
</author>
<author><name sortKey="Tsytlonok, M" uniqKey="Tsytlonok M">M Tsytlonok</name>
</author>
<author><name sortKey="Haesen, D" uniqKey="Haesen D">D Haesen</name>
</author>
<author><name sortKey="Vanthienen, W" uniqKey="Vanthienen W">W Vanthienen</name>
</author>
<author><name sortKey="Bernardes, N" uniqKey="Bernardes N">N Bernardes</name>
</author>
<author><name sortKey="Gonzalez Blas, Cb" uniqKey="Gonzalez Blas C">CB Gonzalez-Blas</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yun, J" uniqKey="Yun J">J Yun</name>
</author>
<author><name sortKey="Mullarky, E" uniqKey="Mullarky E">E Mullarky</name>
</author>
<author><name sortKey="Lu, C" uniqKey="Lu C">C Lu</name>
</author>
<author><name sortKey="Bosch, Kn" uniqKey="Bosch K">KN Bosch</name>
</author>
<author><name sortKey="Kavalier, A" uniqKey="Kavalier A">A Kavalier</name>
</author>
<author><name sortKey="Rivera, K" uniqKey="Rivera K">K Rivera</name>
</author>
<author><name sortKey="Roper, J" uniqKey="Roper J">J Roper</name>
</author>
<author><name sortKey="Chio, Ii" uniqKey="Chio I">II Chio</name>
</author>
<author><name sortKey="Giannopoulou, Eg" uniqKey="Giannopoulou E">EG Giannopoulou</name>
</author>
<author><name sortKey="Rago, C" uniqKey="Rago C">C Rago</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Telang, S" uniqKey="Telang S">S Telang</name>
</author>
<author><name sortKey="Yalcin, A" uniqKey="Yalcin A">A Yalcin</name>
</author>
<author><name sortKey="Clem, Al" uniqKey="Clem A">AL Clem</name>
</author>
<author><name sortKey="Bucala, R" uniqKey="Bucala R">R Bucala</name>
</author>
<author><name sortKey="Lane, An" uniqKey="Lane A">AN Lane</name>
</author>
<author><name sortKey="Eaton, Jw" uniqKey="Eaton J">JW Eaton</name>
</author>
<author><name sortKey="Chesney, J" uniqKey="Chesney J">J Chesney</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Corcoran, Rb" uniqKey="Corcoran R">RB Corcoran</name>
</author>
<author><name sortKey="Cheng, Ka" uniqKey="Cheng K">KA Cheng</name>
</author>
<author><name sortKey="Hata, An" uniqKey="Hata A">AN Hata</name>
</author>
<author><name sortKey="Faber, Ac" uniqKey="Faber A">AC Faber</name>
</author>
<author><name sortKey="Ebi, H" uniqKey="Ebi H">H Ebi</name>
</author>
<author><name sortKey="Coffee, Em" uniqKey="Coffee E">EM Coffee</name>
</author>
<author><name sortKey="Greninger, P" uniqKey="Greninger P">P Greninger</name>
</author>
<author><name sortKey="Brown, Rd" uniqKey="Brown R">RD Brown</name>
</author>
<author><name sortKey="Godfrey, Jt" uniqKey="Godfrey J">JT Godfrey</name>
</author>
<author><name sortKey="Cohoon, Tj" uniqKey="Cohoon T">TJ Cohoon</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zhang, J" uniqKey="Zhang J">J Zhang</name>
</author>
<author><name sortKey="Park, D" uniqKey="Park D">D Park</name>
</author>
<author><name sortKey="Shin, Dm" uniqKey="Shin D">DM Shin</name>
</author>
<author><name sortKey="Deng, X" uniqKey="Deng X">X Deng</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Spiegel, J" uniqKey="Spiegel J">J Spiegel</name>
</author>
<author><name sortKey="Cromm, Pm" uniqKey="Cromm P">PM Cromm</name>
</author>
<author><name sortKey="Zimmermann, G" uniqKey="Zimmermann G">G Zimmermann</name>
</author>
<author><name sortKey="Grossmann, Tn" uniqKey="Grossmann T">TN Grossmann</name>
</author>
<author><name sortKey="Waldmann, H" uniqKey="Waldmann H">H Waldmann</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ball, Ed" uniqKey="Ball E">ED Ball</name>
</author>
<author><name sortKey="Sorenson, Gd" uniqKey="Sorenson G">GD Sorenson</name>
</author>
<author><name sortKey="Pettengill, Os" uniqKey="Pettengill O">OS Pettengill</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Deng, X" uniqKey="Deng X">X Deng</name>
</author>
<author><name sortKey="Ruvolo, P" uniqKey="Ruvolo P">P Ruvolo</name>
</author>
<author><name sortKey="Carr, B" uniqKey="Carr B">B Carr</name>
</author>
<author><name sortKey="May, Ws" uniqKey="May W">WS May</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chang, Km" uniqKey="Chang K">KM Chang</name>
</author>
<author><name sortKey="Chen, Sh" uniqKey="Chen S">SH Chen</name>
</author>
<author><name sortKey="Kuo, Cj" uniqKey="Kuo C">CJ Kuo</name>
</author>
<author><name sortKey="Chang, Ck" uniqKey="Chang C">CK Chang</name>
</author>
<author><name sortKey="Guo, Rt" uniqKey="Guo R">RT Guo</name>
</author>
<author><name sortKey="Yang, Jm" uniqKey="Yang J">JM Yang</name>
</author>
<author><name sortKey="Liang, Ph" uniqKey="Liang P">PH Liang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mackenzie, Gg" uniqKey="Mackenzie G">GG Mackenzie</name>
</author>
<author><name sortKey="Bartels, Le" uniqKey="Bartels L">LE Bartels</name>
</author>
<author><name sortKey="Xie, G" uniqKey="Xie G">G Xie</name>
</author>
<author><name sortKey="Papayannis, I" uniqKey="Papayannis I">I Papayannis</name>
</author>
<author><name sortKey="Alston, N" uniqKey="Alston N">N Alston</name>
</author>
<author><name sortKey="Vrankova, K" uniqKey="Vrankova K">K Vrankova</name>
</author>
<author><name sortKey="Ouyang, N" uniqKey="Ouyang N">N Ouyang</name>
</author>
<author><name sortKey="Rigas, B" uniqKey="Rigas B">B Rigas</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="De Rooij, J" uniqKey="De Rooij J">J de Rooij</name>
</author>
<author><name sortKey="Bos, Jl" uniqKey="Bos J">JL Bos</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ostrem, Jm" uniqKey="Ostrem J">JM Ostrem</name>
</author>
<author><name sortKey="Peters, U" uniqKey="Peters U">U Peters</name>
</author>
<author><name sortKey="Sos, Ml" uniqKey="Sos M">ML Sos</name>
</author>
<author><name sortKey="Wells, Ja" uniqKey="Wells J">JA Wells</name>
</author>
<author><name sortKey="Shokat, Km" uniqKey="Shokat K">KM Shokat</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Shima, F" uniqKey="Shima F">F Shima</name>
</author>
<author><name sortKey="Yoshikawa, Y" uniqKey="Yoshikawa Y">Y Yoshikawa</name>
</author>
<author><name sortKey="Ye, M" uniqKey="Ye M">M Ye</name>
</author>
<author><name sortKey="Araki, M" uniqKey="Araki M">M Araki</name>
</author>
<author><name sortKey="Matsumoto, S" uniqKey="Matsumoto S">S Matsumoto</name>
</author>
<author><name sortKey="Liao, J" uniqKey="Liao J">J Liao</name>
</author>
<author><name sortKey="Hu, L" uniqKey="Hu L">L Hu</name>
</author>
<author><name sortKey="Sugimoto, T" uniqKey="Sugimoto T">T Sugimoto</name>
</author>
<author><name sortKey="Ijiri, Y" uniqKey="Ijiri Y">Y Ijiri</name>
</author>
<author><name sortKey="Takeda, A" uniqKey="Takeda A">A Takeda</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jin, L" uniqKey="Jin L">L Jin</name>
</author>
<author><name sortKey="Li, D" uniqKey="Li D">D Li</name>
</author>
<author><name sortKey="Alesi, Gn" uniqKey="Alesi G">GN Alesi</name>
</author>
<author><name sortKey="Fan, J" uniqKey="Fan J">J Fan</name>
</author>
<author><name sortKey="Kang, Hb" uniqKey="Kang H">HB Kang</name>
</author>
<author><name sortKey="Lu, Z" uniqKey="Lu Z">Z Lu</name>
</author>
<author><name sortKey="Boggon, Tj" uniqKey="Boggon T">TJ Boggon</name>
</author>
<author><name sortKey="Jin, P" uniqKey="Jin P">P Jin</name>
</author>
<author><name sortKey="Yi, H" uniqKey="Yi H">H Yi</name>
</author>
<author><name sortKey="Wright, Er" uniqKey="Wright E">ER Wright</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="You, S" uniqKey="You S">S You</name>
</author>
<author><name sortKey="Li, R" uniqKey="Li R">R Li</name>
</author>
<author><name sortKey="Park, D" uniqKey="Park D">D Park</name>
</author>
<author><name sortKey="Xie, M" uniqKey="Xie M">M Xie</name>
</author>
<author><name sortKey="Sica, Gl" uniqKey="Sica G">GL Sica</name>
</author>
<author><name sortKey="Cao, Y" uniqKey="Cao Y">Y Cao</name>
</author>
<author><name sortKey="Xiao, Zq" uniqKey="Xiao Z">ZQ Xiao</name>
</author>
<author><name sortKey="Deng, X" uniqKey="Deng X">X Deng</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Deng, X" uniqKey="Deng X">X Deng</name>
</author>
<author><name sortKey="Gao, F" uniqKey="Gao F">F Gao</name>
</author>
<author><name sortKey="Flagg, T" uniqKey="Flagg T">T Flagg</name>
</author>
<author><name sortKey="Anderson, J" uniqKey="Anderson J">J Anderson</name>
</author>
<author><name sortKey="May, Ws" uniqKey="May W">WS May</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Deng, X" uniqKey="Deng X">X Deng</name>
</author>
<author><name sortKey="Xiao, L" uniqKey="Xiao L">L Xiao</name>
</author>
<author><name sortKey="Lang, W" uniqKey="Lang W">W Lang</name>
</author>
<author><name sortKey="Gao, F" uniqKey="Gao F">F Gao</name>
</author>
<author><name sortKey="Ruvolo, P" uniqKey="Ruvolo P">P Ruvolo</name>
</author>
<author><name sortKey="May, Ws" uniqKey="May W">WS May</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kabeya, Y" uniqKey="Kabeya Y">Y Kabeya</name>
</author>
<author><name sortKey="Mizushima, N" uniqKey="Mizushima N">N Mizushima</name>
</author>
<author><name sortKey="Ueno, T" uniqKey="Ueno T">T Ueno</name>
</author>
<author><name sortKey="Yamamoto, A" uniqKey="Yamamoto A">A Yamamoto</name>
</author>
<author><name sortKey="Kirisako, T" uniqKey="Kirisako T">T Kirisako</name>
</author>
<author><name sortKey="Noda, T" uniqKey="Noda T">T Noda</name>
</author>
<author><name sortKey="Kominami, E" uniqKey="Kominami E">E Kominami</name>
</author>
<author><name sortKey="Ohsumi, Y" uniqKey="Ohsumi Y">Y Ohsumi</name>
</author>
<author><name sortKey="Yoshimori, T" uniqKey="Yoshimori T">T Yoshimori</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Oltersdorf, T" uniqKey="Oltersdorf T">T Oltersdorf</name>
</author>
<author><name sortKey="Elmore, Sw" uniqKey="Elmore S">SW Elmore</name>
</author>
<author><name sortKey="Shoemaker, Ar" uniqKey="Shoemaker A">AR Shoemaker</name>
</author>
<author><name sortKey="Armstrong, Rc" uniqKey="Armstrong R">RC Armstrong</name>
</author>
<author><name sortKey="Augeri, Dj" uniqKey="Augeri D">DJ Augeri</name>
</author>
<author><name sortKey="Belli, Ba" uniqKey="Belli B">BA Belli</name>
</author>
<author><name sortKey="Bruncko, M" uniqKey="Bruncko M">M Bruncko</name>
</author>
<author><name sortKey="Deckwerth, Tl" uniqKey="Deckwerth T">TL Deckwerth</name>
</author>
<author><name sortKey="Dinges, J" uniqKey="Dinges J">J Dinges</name>
</author>
<author><name sortKey="Hajduk, Pj" uniqKey="Hajduk P">PJ Hajduk</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Li, R" uniqKey="Li R">R Li</name>
</author>
<author><name sortKey="Ding, C" uniqKey="Ding C">C Ding</name>
</author>
<author><name sortKey="Zhang, J" uniqKey="Zhang J">J Zhang</name>
</author>
<author><name sortKey="Xie, M" uniqKey="Xie M">M Xie</name>
</author>
<author><name sortKey="Park, D" uniqKey="Park D">D Park</name>
</author>
<author><name sortKey="Ding, Y" uniqKey="Ding Y">Y Ding</name>
</author>
<author><name sortKey="Chen, G" uniqKey="Chen G">G Chen</name>
</author>
<author><name sortKey="Zhang, G" uniqKey="Zhang G">G Zhang</name>
</author>
<author><name sortKey="Gilbert Ross, M" uniqKey="Gilbert Ross M">M Gilbert-Ross</name>
</author>
<author><name sortKey="Zhou, W" uniqKey="Zhou W">W Zhou</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ji, H" uniqKey="Ji H">H Ji</name>
</author>
<author><name sortKey="Ramsey, Mr" uniqKey="Ramsey M">MR Ramsey</name>
</author>
<author><name sortKey="Hayes, Dn" uniqKey="Hayes D">DN Hayes</name>
</author>
<author><name sortKey="Fan, C" uniqKey="Fan C">C Fan</name>
</author>
<author><name sortKey="Mcnamara, K" uniqKey="Mcnamara K">K McNamara</name>
</author>
<author><name sortKey="Kozlowski, P" uniqKey="Kozlowski P">P Kozlowski</name>
</author>
<author><name sortKey="Torrice, C" uniqKey="Torrice C">C Torrice</name>
</author>
<author><name sortKey="Wu, Mc" uniqKey="Wu M">MC Wu</name>
</author>
<author><name sortKey="Shimamura, T" uniqKey="Shimamura T">T Shimamura</name>
</author>
<author><name sortKey="Perera, Sa" uniqKey="Perera S">SA Perera</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Shackelford, Db" uniqKey="Shackelford D">DB Shackelford</name>
</author>
<author><name sortKey="Abt, E" uniqKey="Abt E">E Abt</name>
</author>
<author><name sortKey="Gerken, L" uniqKey="Gerken L">L Gerken</name>
</author>
<author><name sortKey="Vasquez, Ds" uniqKey="Vasquez D">DS Vasquez</name>
</author>
<author><name sortKey="Seki, A" uniqKey="Seki A">A Seki</name>
</author>
<author><name sortKey="Leblanc, M" uniqKey="Leblanc M">M Leblanc</name>
</author>
<author><name sortKey="Wei, L" uniqKey="Wei L">L Wei</name>
</author>
<author><name sortKey="Fishbein, Mc" uniqKey="Fishbein M">MC Fishbein</name>
</author>
<author><name sortKey="Czernin, J" uniqKey="Czernin J">J Czernin</name>
</author>
<author><name sortKey="Mischel, Ps" uniqKey="Mischel P">PS Mischel</name>
</author>
<author><name sortKey="Shaw, Rj" uniqKey="Shaw R">RJ Shaw</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Han, B" uniqKey="Han B">B Han</name>
</author>
<author><name sortKey="Park, D" uniqKey="Park D">D Park</name>
</author>
<author><name sortKey="Li, R" uniqKey="Li R">R Li</name>
</author>
<author><name sortKey="Xie, M" uniqKey="Xie M">M Xie</name>
</author>
<author><name sortKey="Owonikoko, Tk" uniqKey="Owonikoko T">TK Owonikoko</name>
</author>
<author><name sortKey="Zhang, G" uniqKey="Zhang G">G Zhang</name>
</author>
<author><name sortKey="Sica, Gl" uniqKey="Sica G">GL Sica</name>
</author>
<author><name sortKey="Ding, C" uniqKey="Ding C">C Ding</name>
</author>
<author><name sortKey="Zhou, J" uniqKey="Zhou J">J Zhou</name>
</author>
<author><name sortKey="Magis, At" uniqKey="Magis A">AT Magis</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Park, D" uniqKey="Park D">D Park</name>
</author>
<author><name sortKey="Magis, At" uniqKey="Magis A">AT Magis</name>
</author>
<author><name sortKey="Li, R" uniqKey="Li R">R Li</name>
</author>
<author><name sortKey="Owonikoko, Tk" uniqKey="Owonikoko T">TK Owonikoko</name>
</author>
<author><name sortKey="Sica, Gl" uniqKey="Sica G">GL Sica</name>
</author>
<author><name sortKey="Sun, Sy" uniqKey="Sun S">SY Sun</name>
</author>
<author><name sortKey="Ramalingam, Ss" uniqKey="Ramalingam S">SS Ramalingam</name>
</author>
<author><name sortKey="Khuri, Fr" uniqKey="Khuri F">FR Khuri</name>
</author>
<author><name sortKey="Curran, Wj" uniqKey="Curran W">WJ Curran</name>
</author>
<author><name sortKey="Deng, X" uniqKey="Deng X">X Deng</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Xin, M" uniqKey="Xin M">M Xin</name>
</author>
<author><name sortKey="Li, R" uniqKey="Li R">R Li</name>
</author>
<author><name sortKey="Xie, M" uniqKey="Xie M">M Xie</name>
</author>
<author><name sortKey="Park, D" uniqKey="Park D">D Park</name>
</author>
<author><name sortKey="Owonikoko, Tk" uniqKey="Owonikoko T">TK Owonikoko</name>
</author>
<author><name sortKey="Sica, Gl" uniqKey="Sica G">GL Sica</name>
</author>
<author><name sortKey="Corsino, Pe" uniqKey="Corsino P">PE Corsino</name>
</author>
<author><name sortKey="Zhou, J" uniqKey="Zhou J">J Zhou</name>
</author>
<author><name sortKey="Ding, C" uniqKey="Ding C">C Ding</name>
</author>
<author><name sortKey="White, Ma" uniqKey="White M">MA White</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yoshii, Saori R" uniqKey="Yoshii S">Saori R. Yoshii</name>
</author>
<author><name sortKey="Mizushima, Noboru" uniqKey="Mizushima N">Noboru Mizushima</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Liang, C" uniqKey="Liang C">C Liang</name>
</author>
<author><name sortKey="Feng, P" uniqKey="Feng P">P Feng</name>
</author>
<author><name sortKey="Ku, B" uniqKey="Ku B">B Ku</name>
</author>
<author><name sortKey="Dotan, I" uniqKey="Dotan I">I Dotan</name>
</author>
<author><name sortKey="Canaani, D" uniqKey="Canaani D">D Canaani</name>
</author>
<author><name sortKey="Oh, Bh" uniqKey="Oh B">BH Oh</name>
</author>
<author><name sortKey="Jung, Ju" uniqKey="Jung J">JU Jung</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jackson, El" uniqKey="Jackson E">EL Jackson</name>
</author>
<author><name sortKey="Willis, N" uniqKey="Willis N">N Willis</name>
</author>
<author><name sortKey="Mercer, K" uniqKey="Mercer K">K Mercer</name>
</author>
<author><name sortKey="Bronson, Rt" uniqKey="Bronson R">RT Bronson</name>
</author>
<author><name sortKey="Crowley, D" uniqKey="Crowley D">D Crowley</name>
</author>
<author><name sortKey="Montoya, R" uniqKey="Montoya R">R Montoya</name>
</author>
<author><name sortKey="Jacks, T" uniqKey="Jacks T">T Jacks</name>
</author>
<author><name sortKey="Tuveson, Da" uniqKey="Tuveson D">DA Tuveson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tuveson, Da" uniqKey="Tuveson D">DA Tuveson</name>
</author>
<author><name sortKey="Shaw, At" uniqKey="Shaw A">AT Shaw</name>
</author>
<author><name sortKey="Willis, Na" uniqKey="Willis N">NA Willis</name>
</author>
<author><name sortKey="Silver, Dp" uniqKey="Silver D">DP Silver</name>
</author>
<author><name sortKey="Jackson, El" uniqKey="Jackson E">EL Jackson</name>
</author>
<author><name sortKey="Chang, S" uniqKey="Chang S">S Chang</name>
</author>
<author><name sortKey="Mercer, Kl" uniqKey="Mercer K">KL Mercer</name>
</author>
<author><name sortKey="Grochow, R" uniqKey="Grochow R">R Grochow</name>
</author>
<author><name sortKey="Hock, H" uniqKey="Hock H">H Hock</name>
</author>
<author><name sortKey="Crowley, D" uniqKey="Crowley D">D Crowley</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Frese, Kk" uniqKey="Frese K">KK Frese</name>
</author>
<author><name sortKey="Tuveson, Da" uniqKey="Tuveson D">DA Tuveson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hopkins, Al" uniqKey="Hopkins A">AL Hopkins</name>
</author>
<author><name sortKey="Groom, Cr" uniqKey="Groom C">CR Groom</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Patricelli, Mp" uniqKey="Patricelli M">MP Patricelli</name>
</author>
<author><name sortKey="Janes, Mr" uniqKey="Janes M">MR Janes</name>
</author>
<author><name sortKey="Li, Ls" uniqKey="Li L">LS Li</name>
</author>
<author><name sortKey="Hansen, R" uniqKey="Hansen R">R Hansen</name>
</author>
<author><name sortKey="Peters, U" uniqKey="Peters U">U Peters</name>
</author>
<author><name sortKey="Kessler, Lv" uniqKey="Kessler L">LV Kessler</name>
</author>
<author><name sortKey="Chen, Y" uniqKey="Chen Y">Y Chen</name>
</author>
<author><name sortKey="Kucharski, Jm" uniqKey="Kucharski J">JM Kucharski</name>
</author>
<author><name sortKey="Feng, J" uniqKey="Feng J">J Feng</name>
</author>
<author><name sortKey="Ely, T" uniqKey="Ely T">T Ely</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lito, P" uniqKey="Lito P">P Lito</name>
</author>
<author><name sortKey="Solomon, M" uniqKey="Solomon M">M Solomon</name>
</author>
<author><name sortKey="Li, Ls" uniqKey="Li L">LS Li</name>
</author>
<author><name sortKey="Hansen, R" uniqKey="Hansen R">R Hansen</name>
</author>
<author><name sortKey="Rosen, N" uniqKey="Rosen N">N Rosen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Smith, G" uniqKey="Smith G">G Smith</name>
</author>
<author><name sortKey="Bounds, R" uniqKey="Bounds R">R Bounds</name>
</author>
<author><name sortKey="Wolf, H" uniqKey="Wolf H">H Wolf</name>
</author>
<author><name sortKey="Steele, Rj" uniqKey="Steele R">RJ Steele</name>
</author>
<author><name sortKey="Carey, Fa" uniqKey="Carey F">FA Carey</name>
</author>
<author><name sortKey="Wolf, Cr" uniqKey="Wolf C">CR Wolf</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Mol Cancer</journal-id>
<journal-id journal-id-type="iso-abbrev">Mol. Cancer</journal-id>
<journal-title-group><journal-title>Molecular Cancer</journal-title>
</journal-title-group>
<issn pub-type="epub">1476-4598</issn>
<publisher><publisher-name>BioMed Central</publisher-name>
<publisher-loc>London</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">30971271</article-id>
<article-id pub-id-type="pmc">6456974</article-id>
<article-id pub-id-type="publisher-id">1012</article-id>
<article-id pub-id-type="doi">10.1186/s12943-019-1012-4</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research</subject>
</subj-group>
</article-categories>
<title-group><article-title>Small Molecule KRAS Agonist for Mutant KRAS Cancer Therapy</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Xu</surname>
<given-names>Ke</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Park</surname>
<given-names>Dongkyoo</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Magis</surname>
<given-names>Andrew T.</given-names>
</name>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhang</surname>
<given-names>Jun</given-names>
</name>
<xref ref-type="aff" rid="Aff3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhou</surname>
<given-names>Wei</given-names>
</name>
<xref ref-type="aff" rid="Aff4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sica</surname>
<given-names>Gabriel L.</given-names>
</name>
<xref ref-type="aff" rid="Aff5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ramalingam</surname>
<given-names>Suresh S.</given-names>
</name>
<xref ref-type="aff" rid="Aff4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Curran</surname>
<given-names>Walter J.</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Deng</surname>
<given-names>Xingming</given-names>
</name>
<address><phone>(404)778-3398</phone>
<email>xdeng4@emory.edu</email>
</address>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<aff id="Aff1"><label>1</label>
<institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0941 6502</institution-id>
<institution-id institution-id-type="GRID">grid.189967.8</institution-id>
<institution>Division of Cancer Biology, Department of Radiation Oncology,</institution>
<institution>Emory University School of Medicine and Winship Cancer Institute of Emory University,</institution>
</institution-wrap>
Atlanta, GA 30322 USA</aff>
<aff id="Aff2"><label>2</label>
<institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0463 2320</institution-id>
<institution-id institution-id-type="GRID">grid.64212.33</institution-id>
<institution>Institute for Systems Biology,</institution>
</institution-wrap>
Seattle, WA 98109 USA</aff>
<aff id="Aff3"><label>3</label>
<institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 8294</institution-id>
<institution-id institution-id-type="GRID">grid.214572.7</institution-id>
<institution>Division of Hematology, Oncology and Blood & Marrow Transplantation, Department of Internal Medicine, Holden Comprehensive Cancer Center,</institution>
<institution>University of Iowa Carver College of Medicine,</institution>
</institution-wrap>
Iowa City, IA 52242 USA</aff>
<aff id="Aff4"><label>4</label>
<institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0941 6502</institution-id>
<institution-id institution-id-type="GRID">grid.189967.8</institution-id>
<institution>Department of Hematology and Medical Oncology,</institution>
<institution>Emory University School of Medicine and Winship Cancer Institute of Emory University,</institution>
</institution-wrap>
Atlanta, GA 30322 USA</aff>
<aff id="Aff5"><label>5</label>
<institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0941 6502</institution-id>
<institution-id institution-id-type="GRID">grid.189967.8</institution-id>
<institution>Department of Pathology and Laboratory Medicine,</institution>
<institution>Emory University School of Medicine and Winship Cancer Institute of Emory University,</institution>
</institution-wrap>
Atlanta, GA 30322 USA</aff>
</contrib-group>
<pub-date pub-type="epub"><day>10</day>
<month>4</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>10</day>
<month>4</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="collection"><year>2019</year>
</pub-date>
<volume>18</volume>
<elocation-id>85</elocation-id>
<history><date date-type="received"><day>4</day>
<month>12</month>
<year>2018</year>
</date>
<date date-type="accepted"><day>25</day>
<month>3</month>
<year>2019</year>
</date>
</history>
<permissions><copyright-statement>© The Author(s). 2019</copyright-statement>
<license license-type="OpenAccess"><license-p><bold>Open Access</bold>
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">http://creativecommons.org/publicdomain/zero/1.0/</ext-link>
) applies to the data made available in this article, unless otherwise stated.</license-p>
</license>
</permissions>
<abstract id="Abs1"><sec><title>Background</title>
<p id="Par1">Lung cancer patients with KRAS mutation(s) have a poor prognosis due in part to the development of resistance to currently available therapeutic interventions. Development of a new class of anticancer agents that directly targets KRAS may provide a more attractive option for the treatment of KRAS-mutant lung cancer.</p>
</sec>
<sec><title>Results</title>
<p id="Par2">Here we identified a small molecule KRAS agonist, KRA-533, that binds the GTP/GDP-binding pocket of KRAS. In vitro GDP/GTP exchange assay reveals that KRA-533 activates KRAS by preventing the cleavage of GTP into GDP, leading to the accumulation of GTP-KRAS, an active form of KRAS. Treatment of human lung cancer cells with KRA-533 resulted in increased KRAS activity and suppression of cell growth. Lung cancer cell lines with KRAS mutation were relatively more sensitive to KRA-533 than cell lines without KRAS mutation. Mutating one of the hydrogen-bonds among the KRA-533 binding amino acids in KRAS (mutant K117A) resulted in failure of KRAS to bind KRA-533. KRA-533 had no effect on the activity of K117A mutant KRAS, suggesting that KRA-533 binding to K117 is required for KRA-533 to enhance KRAS activity. Intriguingly, KRA-533-mediated KRAS activation not only promoted apoptosis but also autophagic cell death. In mutant KRAS lung cancer xenografts and genetically engineered mutant KRAS-driven lung cancer models, KRA-533 suppressed malignant growth without significant toxicity to normal tissues.</p>
</sec>
<sec><title>Conclusions</title>
<p id="Par3">The development of this KRAS agonist as a new class of anticancer drug offers a potentially effective strategy for the treatment of lung cancer with KRAS mutation and/or mutant KRAS-driven lung cancer.</p>
</sec>
<sec><title>Electronic supplementary material</title>
<p>The online version of this article (10.1186/s12943-019-1012-4) contains supplementary material, which is available to authorized users.</p>
</sec>
</abstract>
<kwd-group xml:lang="en"><title>Keywords</title>
<kwd>KRAS</kwd>
<kwd>Agonist</kwd>
<kwd>Apoptosis</kwd>
<kwd>Autophagy</kwd>
<kwd>NSCLC</kwd>
<kwd>Therapy</kwd>
</kwd-group>
<funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">http://dx.doi.org/10.13039/100000054</institution-id>
<institution>National Cancer Institute</institution>
</institution-wrap>
</funding-source>
<award-id>1R01CA193828</award-id>
<principal-award-recipient><name><surname>Deng</surname>
<given-names>Xingming</given-names>
</name>
</principal-award-recipient>
</award-group>
</funding-group>
<funding-group><award-group><funding-source><institution>National Institute of Health</institution>
</funding-source>
<award-id>2R01CA136534</award-id>
<award-id>1R01CA200905</award-id>
<principal-award-recipient><name><surname>Deng</surname>
<given-names>Xingming</given-names>
</name>
</principal-award-recipient>
</award-group>
</funding-group>
<custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name>
<meta-value>© The Author(s) 2019</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Géorgie (États-Unis)</li>
<li>Iowa</li>
<li>Washington (État)</li>
</region>
</list>
<tree><country name="États-Unis"><region name="Géorgie (États-Unis)"><name sortKey="Xu, Ke" sort="Xu, Ke" uniqKey="Xu K" first="Ke" last="Xu">Ke Xu</name>
</region>
<name sortKey="Curran, Walter J" sort="Curran, Walter J" uniqKey="Curran W" first="Walter J." last="Curran">Walter J. Curran</name>
<name sortKey="Deng, Xingming" sort="Deng, Xingming" uniqKey="Deng X" first="Xingming" last="Deng">Xingming Deng</name>
<name sortKey="Magis, Andrew T" sort="Magis, Andrew T" uniqKey="Magis A" first="Andrew T." last="Magis">Andrew T. Magis</name>
<name sortKey="Park, Dongkyoo" sort="Park, Dongkyoo" uniqKey="Park D" first="Dongkyoo" last="Park">Dongkyoo Park</name>
<name sortKey="Ramalingam, Suresh S" sort="Ramalingam, Suresh S" uniqKey="Ramalingam S" first="Suresh S." last="Ramalingam">Suresh S. Ramalingam</name>
<name sortKey="Sica, Gabriel L" sort="Sica, Gabriel L" uniqKey="Sica G" first="Gabriel L." last="Sica">Gabriel L. Sica</name>
<name sortKey="Zhang, Jun" sort="Zhang, Jun" uniqKey="Zhang J" first="Jun" last="Zhang">Jun Zhang</name>
<name sortKey="Zhou, Wei" sort="Zhou, Wei" uniqKey="Zhou W" first="Wei" last="Zhou">Wei Zhou</name>
</country>
</tree>
</affiliations>
</record>
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