7A04

Structure of human CKa1 in complex with compound b

7A04 の概要

• エントリーDOI: 10.2210/pdb7a04/pdb
• 分子名称: Choline kinase alpha, 1-(phenylmethyl)-4-pyrrolidin-1-yl-pyridin-1-ium, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: choline kinase, drugs, cancer, anti proliferative effect, half molecules, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 90697.92

構造登録者

Serran-Aguilera, L.,Mariotto, E.,Rubbini, G.,Castro Navas, F.C.,Marco, C.,Carrasco-Jimenez, M.P.,Ballarotto, M.,Macchiarulo, A.,Hurtado-Guerrero, R.,Viola, G.,Lopez-Cara, L.C. (登録日: 2020-08-06, 公開日: 2020-09-09, 最終更新日: 2024-01-31)

主引用文献

Serran-Aguilera, L.,Mariotto, E.,Rubbini, G.,Castro Navas, F.F.,Marco, C.,Carrasco-Jimenez, M.P.,Ballarotto, M.,Macchiarulo, A.,Hurtado-Guerrero, R.,Viola, G.,Lopez-Cara, L.C.
Synthesis, biological evaluation, in silico modeling and crystallization of novel small monocationic molecules with potent antiproliferative activity by dual mechanism.
Eur.J.Med.Chem., 207:112797-112797, 2020

PubMed Abstract: Seeking for new anticancer drugs with strong antiproliferative activity and simple molecular structure, we designed a novel series of compounds based on our previous reported pharmacophore model composed of five moieties. Antiproliferative assays on four tumoral cell lines and evaluation of Human Choline Kinase CKα1 enzymatic activity was performed for these compounds. Among tested molecules, those ones with biphenyl spacer showed betters enzymatic and antiproliferative activities (n-v). Docking and crystallization studies validate the hypothesis and confirm the results. The most active compound (t) induces a significant arrest of the cell cycle in G0/G1 phase that ultimately lead to apoptosis, following the mitochondrial pathway, as demonstrated for other choline kinase inhibitors. However additional assays reveal that the inhibition of choline uptake could also be involved in the antiproliferative outcome of this class of compounds.

PubMed: 32977218
DOI: 10.1016/j.ejmech.2020.112797

実験手法

X-RAY DIFFRACTION (2.15 Å)