TY - JOUR
T1 - Discovery of novel anti-angiogenesis agents. Part 9
T2 - Multiplex inhibitors suppressing compensatory activations of RTKs
AU - Shan, Yuanyuan
AU - Si, Ru
AU - Wang, Jin
AU - Zhang, Qingqing
AU - Zhou, Huaxin
AU - Song, Jie
AU - Zhang, Jie
AU - Chen, Qinhua
N1 - Publisher Copyright:
© 2018 Elsevier Masson SAS
PY - 2019/2/15
Y1 - 2019/2/15
N2 - Aberrant angiogenesis is a hallmark of various diseases including cancers. VEGFR-2 inhibitors have been utilized as anti-angiogenic agents for several years. However, compensatory activation of various receptor tyrosine kinases (RTK) could induce the occurrence of resistance. We previously reported a series of multi-target inhibitors of VEGFR-2, Tie-2, and EphB4 as anti-angiogenic agents. These inhibitors might be a promising strategy to overcome the resistance induced by compensatory activation. In order to expand the structural diversity of these multiple RTK inhibitors, we described herein the design, synthesis, and evaluation of a novel class of triplet VEGFR-2/TIE-2/EphB4 inhibitors. The biological evaluation indicated that five compounds (6b, 6d, 6e, 7e, and 7g) exhibited simultaneous VEGFR-2/Tie-2/EphB4 inhibitory activities with IC50 values less than 50 nM.
AB - Aberrant angiogenesis is a hallmark of various diseases including cancers. VEGFR-2 inhibitors have been utilized as anti-angiogenic agents for several years. However, compensatory activation of various receptor tyrosine kinases (RTK) could induce the occurrence of resistance. We previously reported a series of multi-target inhibitors of VEGFR-2, Tie-2, and EphB4 as anti-angiogenic agents. These inhibitors might be a promising strategy to overcome the resistance induced by compensatory activation. In order to expand the structural diversity of these multiple RTK inhibitors, we described herein the design, synthesis, and evaluation of a novel class of triplet VEGFR-2/TIE-2/EphB4 inhibitors. The biological evaluation indicated that five compounds (6b, 6d, 6e, 7e, and 7g) exhibited simultaneous VEGFR-2/Tie-2/EphB4 inhibitory activities with IC50 values less than 50 nM.
KW - 1,2,3-Triazole
KW - Anti-angiogenic agents
KW - Compensatory activation
KW - Multi-target
KW - RTK inhibitors
UR - https://www.scopus.com/pages/publications/85059466914
U2 - 10.1016/j.ejmech.2018.12.067
DO - 10.1016/j.ejmech.2018.12.067
M3 - 文章
C2 - 30616052
AN - SCOPUS:85059466914
SN - 0223-5234
VL - 164
SP - 440
EP - 447
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
ER -
