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901.
Hüseyin Çavdar Oktay Talaz Deniz Ekinci 《Bioorganic & medicinal chemistry letters》2012,22(24):7499-7503
Here we synthesized four novel indole conduritol derivatives 1–4 for the first time in the literature and probed their biological activities with the α and β-glucosidases. The compounds showed quite effective glucosidase inhibitory action. IC50 values of the compounds were compared with the known glucosidase inhibitor acarbose and it was determined that newly synthesized indole conduritols had more powerful effect against β-glucosidase in addition to exhibiting moderate influence against α-glucosidase. Our molecules thus constitute an important starting point for the design and exploitation of novel glucosidase inhibitors since glucosidase inhibitors have widespread applications in the treatment of diabetes, viral infections, lysosomal storage diseases and cancers. 相似文献
902.
903.
Deniz A. Ucar Elena Kurenova Timothy J. Garrett William G. Cance Carl Nyberg Audrey Cox Nicole Massoll David A. Ostrov Nicholas Lawrence Said M. Sebti Maria Zajac-Kaye Steven N. Hochwald 《Cell cycle (Georgetown, Tex.)》2012,11(17):3250-3259
FAK (focal adhesion kinase) and IGF-1R (insulin-like growth factor receptor-1) directly interact with each other and thereby activate crucial signaling pathways that benefit cancer cells. Inhibition of FAK and IGF-1R function has been shown to significantly decrease cancer cell proliferation and increase sensitivity to chemotherapy and radiation treatment. As a novel approach in human melanoma, we evaluated the effect of a small-molecule compound that disrupts the protein interaction of FAK and IGF-1R.
Previously, using virtual screening and functional testing, we identified a lead compound (INT2–31) that targets the known FAK-IGF-1R protein interaction site. We studied the ability of this compound to disrupt FAK-IGF-1R protein interactions, inhibit downstream signaling, decrease human melanoma cell proliferation, alter cell cycle progression, induce apoptosis and decrease tumor growth in vivo.
INT2–31 blocked the interaction of FAK and IGF-1R in vitro and in vivo in melanoma cells and tumor xenografts through precluding the activation of IRS-1, leading to reduced phosphorylation of AKT upon IGF-1 stimulation. As a result, INT2–31 significantly inhibited cell proliferation and viability (range 0.05–10 μM). More importantly, 15 mg/kg of INT2–31 given for 21 d via intraperitoneal injection disrupted the interaction of FAK and IGF-1R and effectively decreased phosphorylation of tumor AKT, resulting in significant melanoma tumor regression in vivo.
Our data suggest that the FAK-IGF-1R protein interaction is an important target, and disruption of this interaction with a novel small molecule (INT2–31) has potential anti-neoplastic therapeutic effects in human melanoma. 相似文献
904.
905.
Preparation of fungal material for microscopical examination of their conidiogenous structures is described below. A modification to the existing methods used coupled with a sporulation medium has proved to be simple to use and successful for the induction of sporulation and subsequent examination of conidiogenous structures in a range of xylariaceous species and in endophytic fungi. 相似文献
906.
907.
Abstract On a reed-stem, collected in April 1992 in Lake Köycegiz (SW Turkey), numerous gemmules of Spongilla alba were found on and between the tubes of the marine polychaete Ficopomatus enigmaticus. 相似文献
908.
909.
910.
Natali L. Chanaday Elena Nosyreva Ok-Ho Shin Hua Zhang Iltan Aklan Deniz Atasoy Ilya Bezprozvanny Ege T. Kavalali 《Neuron》2021,109(8):1314-1332.e5
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