@misc{10481/71659,
year = {2021},
month = {8},
url = {http://hdl.handle.net/10481/71659},
abstract = {Despite the approval of several multikinase inhibitors that
target SRC and the overwhelming evidence of the role of SRC in
the progression and resistance mechanisms of many solid malignancies,
inhibition of its kinase activity has thus far failed to
improve patient outcomes. Here we report the small molecule
eCF506 locks SRC in its native inactive conformation, thereby
inhibiting both enzymatic and scaffolding functions that prevent
phosphorylation and complex formation with its partner FAK.
This mechanism of action resulted in highly potent and selective
pathway inhibition in culture and in vivo. Treatment with
eCF506 resulted in increased antitumor efficacy and tolerability
in syngeneic murine cancer models, demonstrating significant
therapeutic advantages over existing SRC/ABL inhibitors. Therefore,
this mode of inhibiting SRC could lead to improved
treatment of SRC-associated disorders.
Significance: Small molecule–mediated inhibition of SRC
impairing both catalytic and scaffolding functions confers increased
anticancer properties and tolerability compared with other
SRC/ABL inhibitors.},
organization = {Spanish Ministry of Science, Innovation, and Universities	RTI2018-099318-B-I00},
organization = {European Commission},
organization = {Cancer Research UK},
organization = {Molecular Interactions Facility funds at the CIB-CSIC},
organization = {Vice-Rectorate for Research of the University of Granada},
organization = {CRUK Career Development Fellowship	C49791/A17367},
organization = {European Research Council (ERC)	716379},
organization = {CRUK Programme Grant	C157/A15703},
organization = {CMVM of the University of Edinburgh},
organization = {Wellcome Trust},
organization = {European Commission		
H2020-MSCA-IF-2016-749299},
publisher = {American Association for Cancer Research},
title = {A Conformation Selective Mode of Inhibiting SRC Improves Drug Efficacy and Tolerability},
doi = {10.1158/0008-5472.CAN-21-0613},
author = {Temps, Carolin and Valero Griñán, María Teresa},
}