Choline kinase inhibitors

Crilly, K.S., Tomono, M. and Kiss, Z. (1998) The choline kinase inhibitor hemicholinium-3 can inhibit mitogen-induced DNA synthesis independent of its effect on phosphocholine formation. Archives of Biochemistry and Biophysics 352, 137-143. 

N. M. S. Al-Saffar, H. Troy, A. Ramirez de Molina, L. E. Jackson, B. Madhu, J. R. Griffiths, M. O. Leach, P. Workman, J. C. Lacal, 1. R. Judson and Y.-L. Chung, Noninvasive magnetic resonance spectroscopic pharmacodynamic markers of the choline kinase inhibitor MN58b in human carcinoma models. Cancer Res., 2006,66,427-434. 

Gomez-Perez V, McSorley T, See Too WC, Konrad M, Campos JM. Novel 4-Amino Bis-p3nidinium and bis-quinolinium derivatives as choline kinase inhibitors with antiproliferative activity against the human breast cancer SKBR-3 cell line. ChemMed-Chem2012 7, 663-669. Doi 10.1002/cmdc.201100505. 

Conejo-Garci a A, Campos JM, Smchez-Martin RM, Gallo MA, Espinosa A. Bis-pyri-dinium cyclophanes novel templates for human choline kinase inhibitors. Journal of Medicinal Chemistry 2003 46 3754-3757. Doi 10.1021/jm030792i. 

Phosphatidylcholine is preferentially synthesized in lactating mammary tissue (Kinsella, 1973), possibly regulated by the differential activities of choline kinase and ethanolamine kinase. Choline kinase has a lower Km and a higher Vmax with its substrate than does ethanolamine kinase. Also, choline kinase is inhibited slightly by ethanolamine, whereas choline is a potent competitive inhibitor of ethanolamine kinase. Thus, the intracellular concentration of choline probably regulates the synthesis of these two phos-phoglycerides (Infante and Kinsella, 1976). 

We will discuss small molecule inhibitors of three main classes of nonprotein kinases sugar kinases, nucleoside kinases and lipid kinases. This chapter will be limited to discussion of the inhibition of human kinases. Several non-human non-protein kinases have been the focus of drug development efforts as well, including choline kinase for inhibition of Plasmodium, uridine-cytidine kinase as an anti-parasitic target and thymidine kinase inhibitors as an anti-mycobacterial treatment or for treatment of Herpes simplex viral infections. These applications will not be discussed in this chapter. Peptide... 

Choline kinase phosphorylates choline to give a phosphocholine and participates in glycine, serine and threonine metabolism and glycerophospholipid metabolism. Hemicholinium-7 is the prototypical tool compound used to inhibit CHK. Based on inhibitor studies, it has been proposed that CHK is important for the regulation of cell proliferation. Inhibition of choline kinase is also used to target plasmodium and develop novel antimalarials. A series of papers on pyridinium based inhibitors have been published, but no disclosures of more drug-like molecules have been made. 

Glycine max (L.) Merrill G. soja Sieb. Zucc. Da Dou Ye Da Dou (Soybean) (seed) Protein, isoflavone derivatives, genisteine, daidzein, riboflavin, thiamine, niacin, pantothenic acid, choline.33,67 Phytoestrogenic, elevate the vasomotor system, prevent cancer, a potent inhibitor of protein tyrosine kinase. 

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