"Like virtually all proteins, KIT has packing defects that leave some hydrogen bonds poorly shielded from water attack," Fernandez said. "These bonds, which are called dehydrons, are in the twilight zone between order and disorder."
In KIT, there is a dehydron near the active site that plays a key role in drug resistance. WBZ-7 seals off this dehydron.
Fernandez said WBZ-7 is identical to imatinib, save for the addition of four atoms a carbon and three hydrogens at a key point. Though the change appears to be minimal at first glance, finding a method to synthesize the compound was complex and challenging, Fernandez said. The task fell on Bornmann, a director of the Center for Targeted Therapy's Translational Chemistry Service, and his colleagues Shimei Wang and Zhenghong Peng who dubbed the compound WBZ-7 based on their initials and the fact that it was the seventh compound they'd made together.
Following the drug's synthesis, a second team of M. D. Anderson researchers, led by Lopez-Berestein, a professor in the Department of Experimental Therapeutics, and including Angela Sanguino and Eylem Ozturk, embarked on a comprehensive testing program. In the first stage of testing, WBZ-7's effects were tested against more than 250 catalytic proteins called kinases, which are in the same class of proteins as KIT, to make sure the drug would not have unintended consequences. Finally, a range of in vitro tests were conducted. The tests confirmed that WBZ-7 was just as effective against both non-resistant and drug-resistant strains of gastrointestinal cancer cells.
WBZ-7 is not yet available for human testing, and a date for human trials has not been set. Fernandez said the research team is preparing for the next phase of testing in laboratory animals.