16622-59-6Relevant academic research and scientific papers
Structure-based virtual screening, synthesis and biological evaluation of potential FAK-FAT domain inhibitors for treatment of metastatic cancer
Hiscox, Stephen E.,Jones, Samuel R.,Kandil, Sahar B.,Smith, Sonia,Westwell, Andrew D.
, (2020/08/28)
Focal adhesion kinase (FAK) is a tyrosine kinase that is overexpressed and activated in several advanced-stage solid cancers. In cancer cells, FAK promotes the progression and metastasis of tumours. In this study, we used structure-based virtual screening to filter a library of more than 210K compounds against the focal adhesion targeting FAK-focal adhesion targeting (FAT) domain to identify 25 virtual hit compounds which were screened in the invasive breast cancer line (MDA-MB-231). Most notably, compound I showed low micromolar antiproliferative activity, as well as antimigratory activity. Moreover, examination in a model of triple negative breast cancer (TNBC), revealed that, despite not effecting FAK phosphorylation, compound I significantly impairs proliferation whilst impairing focal adhesion growth and turnover leading to reduced migration. Further optimisation and synthesis of analogues of the lead compound I using a four-step synthetic procedure was performed, and analogues were assessed for their antiproliferative activity against three breast cancer (MDA-MB-231, T47D, BT474) cell lines and one pancreatic cancer (MIAPaCa2) cell line. Compound 5f was identified as a promising lead compound with IC50 values in the range of 4.59–5.28 μM in MDA-MB-231, T47D, BT474, and MIAPaCa2. Molecular modelling and pharmacokinetic studies provided more insight into the therapeutic features of this new series.
Chiral gating for size- And shape-selective asymmetric catalysis
Li, Xiaowei,Zhao, Yan
, p. 13749 - 13752 (2019/08/26)
A poor or mediocre stereoselectivity is a key roadblock for a chiral catalyst to find practical adoptions. We report a facile method to create a tunable chiral space near a chiral catalyst to augment its selectivity. The space was created rationally throu
Stabilities of Carbonium Ions. IV. Steric Effects in the Solvolysis of Substituted Diphenylmethyl Chlorides
Bolton, Roger,Burley, Rita E.,Williams, Nigel J.
, p. 625 - 634 (2007/10/02)
The replacement of ortho-hydrogen atoms by methyl groups in diphenylmethyl chloride has three distinguishable results upon the rate of solvolysis.Firstly, the alkyl group activates by its electronic effect; secondly, steric interactions diminish all obsse
