Design and synthesis of tetrahydropyridothieno[2,3-d]pyrimidine scaffold based epidermal growth factor receptor (EGFR) kinase inhibitors: The role of side chain chirality and michael acceptor group for maximal potency
Wu C.-H.,Institute of Biotechnology and Pharmaceutical Research |
Wu C.-H.,National Tsing Hua University |
Coumar M.S.,Institute of Biotechnology and Pharmaceutical Research |
Chu C.-Y.,Institute of Biotechnology and Pharmaceutical Research |
And 22 more authors.
Journal of Medicinal Chemistry | Year: 2010
HTS hit 7 was modified through hybrid design strategy to introduce a chiral side chain followed by introduction of Michael acceptor group to obtain potent EGFR kinase inhibitors 11 and 19. Both 11 and 19 showed over 3 orders of magnitude enhanced HCC827 antiproliferative activity compared to HTS hit 7 and also inhibited gefitinib-resistant double mutant (DM, T790M/L858R) EGFR kinase at nanomolar concentration. Moreover, treatment with 19 shrinked tumor in nude mice xenograft model. © 2010 American Chemical Society.
Chang C.-I.,National Pingtung University of Science and Technology |
Li Y.-C.,National Taiwan University |
Yang C.-S.,China Medical University at Taichung |
Chao C.-Y.,Asia University, Taiwan |
And 7 more authors.
Helvetica Chimica Acta | Year: 2015
Two new labdane-type diterpene acids, (12S)-12-hydroxylabda-8(17),13(16),14-trien-18-oic acid (1) and (12R)-12-hydroxy-15,16-epoxylabda-8(17),13-dien-18-oic acid (2), along with a known labdane-type diterpene, (11E)-15,16-bisnor-13-oxolabda-8(17),11-dien-19-oic acid (3), were isolated from the MeOH extract of the wood of Cunninghamia konishii. Their structures were determined by analysis of spectroscopic data and comparison with the data of known analogs. © 2015 Verlag Helvetica Chimica Acta AG, Zürich.
PubMed | National Health Research Institute and Institute of Biotechnology and Pharmaceutical Research
Type: | Journal: Cell transplantation | Year: 2016
C-X-C chemokine receptor type 4 (CXCR4) is a receptor for a pleiotropic chemokine CXCL12. Previous studies have shown that the acute administration of the CXCR4 antagonist AMD3100 reduced neuroinflammation in stroke brain and mobilized bone marrow hematopoietic stem cells (HSCs). The purpose of this study was to characterize the neuroprotective and neurotrophic effect of a novel CXCR4 antagonist CX549. We demonstrated that CX549 had a higher affinity for CXCR4 and was more potent than AMD3100 to inhibit CXCL12 -mediated chemotaxis in culture. CX549 effectively reduced the activation of microglia and improved neuronal survival after injury in neuron/microglia co-cultures. Early post-stroke treatment with CX549 significantly improved behavioral function, reduced brain infarction, and suppressed the expression of inflammatory markers. Compared to AMD3100, CX549 has a higher affinity for CXCR4, is more efficient to mobilize HSCs for transplantation, and induces behavioral improvement. Our data support that CX549 is a potent anti-inflammatory agent, is neuroprotective against ischemic brain injury, and may have clinical implications for the treatment of stroke.