1474030-92-6Relevant academic research and scientific papers
Design, synthesis and molecular mechanisms of novel dual inhibitors of heat shock protein 90/phosphoinositide 3-kinase alpha (Hsp90/PI3Kα) against cutaneous melanoma
Qin, Feifei,Wang, Yali,Jiang, Xian,Wang, Yujia,Zhang, Nan,Wen, Xiang,Wang, Lian,Jiang, Qinglin,He, Gu
, p. 909 - 926 (2019/04/13)
Overexpression of heat shock protein 90 (Hsp90) is common in various types of cancer. In cutaneous melanoma, a cancer with one of the high levels of Hsp90 overexpression, such expression was correlated with a panel of protein kinases, thus offering an opportunity to identify Hsp90-based multi-kinase inhibitors for novel cancer therapies. Towards this goal, we utilized a 2,4-dihydroxy-5-isopropylbenzate-based Hsp90 inhibitor scaffold and thieno[2,3-d]pyrimidine-based kinase inhibitor scaffold to develop a Hsp90-inhibiting compound library. Our inhibitory compound named 8m inhibited Hsp90 and PI3Kα with an IC50 value of 38.6 nM and 48.4 nM, respectively; it displayed improved cellular activity which could effectively induce cell cycle arrest and apoptosis in melanoma cells and lead to the inhibition of cell proliferation, colony formation, migration and invasion. Our results demonstrated 8m to be a promising lead compound for further therapeutic potential assessment of Hsp90/PI3Kα dual inhibitors in melanoma targeted therapy.
Quinazoline and tetrahydropyridothieno[2,3-d]pyrimidine derivatives as irreversible EGFR tyrosine kinase inhibitors: Influence of the position 4 substituent
Hamed, Mostafa M.,Abou El Ella, Dalal A.,Keeton, Adam B.,Piazza, Gary A.,Engel, Matthias,Hartmann, Rolf W.,Abadi, Ashraf H.
supporting information, p. 1202 - 1207 (2013/08/23)
Herein, we describe new quinazoline and tetrahydropyridothieno[2,3-d] pyrimidine derivatives with an acrylamido group at positions 6 and 7 respectively, and with variable anilino, sulfonamido and cycloalkylamino substituents at position 4. The lipophilic and steric properties of the position 4 substituent seem crucial for activity. Several compounds were more active than gefitinib in inhibiting the wild type EGFR enzyme, the autophosphorylation of the mutant EGFR expressing cell line (H1975), and the growth of cell lines with wild type and mutant EGFR tyrosine kinase. Moreover, a novel synthesis of the quinazoline nucleus from a formimidate derivative is described.
