7A06

Structure of human CKa1 in complex with compound o

Summary for 7A06

• Entry DOI: 10.2210/pdb7a06/pdb
• Descriptor: Choline kinase alpha, 1-[(4-phenylphenyl)methyl]-4-pyrrolidin-1-yl-pyridine, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: choline kinase, drugs, cancer, anti proliferative effect, half molecules, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 46392.20

Authors

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. (deposition date: 2020-08-06, release date: 2020-09-09, Last modification date: 2024-01-31)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.8 Å)