1 Rational re-engineering of a C-Kit kinase inhibitor to promote activity over toxicity: From in silico design to animal model Ariel Fernández 1,2,3 # * , Angela Sanguino 3 # , Zhenghong Peng 4 , Eylem Ozturk 3,5 , Jianping Chen 2 , Alejandro Crespo 1 , Aleksander Shavrin 4 , Chaoping Qin 6 , David Maxwell 4 ,Jianpeng Ma 1,6,7 , Jonathan Trent 8 , Yvonne Lin 9 , Juri Gelovani 4 , William Bornmann 4 , Anil Sood 9,10 and Gabriel Lopez-Berestein 3 ( 1 ) Department of Bioengineering, Rice University, Houston, TX 77005 ( 2 ) Applied Physics Division, Rice Quantum Institute, Rice University Houston, TX 77005 ( 3 ) Experimental Therapeutics, M. D. Anderson Cancer Center, 1515 Holcombe, Box 422, Houston, TX 77030 ( 4 ) Experimental Diagnostic Imaging, Chemistry Section, M. D. Anderson Cancer Center, 1515 Holcombe, Box 603, Houston, TX 77030 ( 5 ) Chemistry Department, Hacettepe University, 06800 Ankara, Turkey ( 6 ) Graduate Program of Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, TX77030 ( 7 ) Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX77030 ( 8 ) Division of Cancer Medicine, Department of Sarcoma Medical Oncology, M. D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030 ( 9 ) Department of Cancer Biology, M. D. Anderson Cancer Center, 7777 Knight Road, Houston, TX 77054 ( 10 ) Department of Gynecologic Oncology, M. D. Anderson Cancer Center, 1155 Herman Pressler, Unit 1362, Houston, TX 77054 ( # ) These authors contributed equally to the work. (*) Corresponding author: arifer@rice.edu