60750-75-6Relevant academic research and scientific papers
Chemical Inhibition of Human Thymidylate Kinase and Structural Insights into the Phosphate Binding Loop and Ligand-Induced Degradation
Chen, Yi-Hsuan,Hsu, Hua-Yi,Yeh, Ming-Tyng,Chen, Chen-Cheng,Huang, Chang-Yu,Chung, Ying-Hsuan,Chang, Zee-Fen,Kuo, Wei-Chen,Chan, Nei-Li,Weng, Jui-Hsia,Chung, Bon-Chu,Chen, Yu-Ju,Jian, Cheng-Bang,Shen, Ching-Chieh,Tai, Hwan-Ching,Sheu, Sheh-Yi,Fang, Jim-Min
, p. 9906 - 9918 (2016/11/19)
Targeting thymidylate kinase (TMPK) that catalyzes the phosphotransfer reaction for formation of dTDP from dTMP is a new strategy for anticancer treatment. This study is to understand the inhibitory mechanism of a previously identified human TMPK (hTMPK) inhibitor YMU1 (1a) by molecular docking, isothermal titration calorimetry, and photoaffinity labeling. The molecular dynamics simulation suggests that 1a prefers binding at the catalytic site of hTMPK, whereas the hTMPK inhibitors that bear pyridino[d]isothiazolone or benzo[d]isothiazolone core structure in lieu of the dimethylpyridine-fused isothiazolone moiety in 1a can have access to both the ATP-binding and catalytic sites. The binding sites of hTMPK inhibitors were validated by photoaffinity labeling and mass spectrometric studies. Taking together, 1a and its analogues stabilize the conformation of ligand-induced degradation (LID) region of hTMPK and block the catalytic site or ATP-binding site, thus attenuating the ATP binding-induced closed conformation that is required for phosphorylation of dTMP.
TARGETING HUMAN THYMIDYLATE KINASE INDUCES DNA REPAIR TOXICITY IN MALIGNANT TUMOR CELLS
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Page/Page column 64, (2012/06/16)
The present invention relates to novel TMPK inhibitor compositions and their methods of use. In particular, it relates to novel TMPK inhibitor compositions and therapeutics that lead to dUTP-mediated DNA repair in tumor cells and acts as a novel chemosensitizer, which are useful in methods for treating or preventing cancers
Synthesis and anorectic activity of 2H-4,6-dimethyl-2-[(4-phenylpiperazin-1-yl)methyl]-3-oxo-2,3 -dihydroisothiazolo[5,4-b]pyridine
Malinka,Rutkowska
, p. 595 - 601 (2007/10/03)
The synthesis of 2H-4,6-dimethyl-2-[(4-phenylpiperazin-1-yl)methyl]-3-oxo-2,3 -dihydroisothiazolo[5,4-b]pyridine (3) and its biological properties are described. Compound 3 pharmacologically evaluated in vivo by use of behavioral tests showed to have a profile of activity characteristic of stimulation of the central serotoninergic system, mostly 5-HT(2A) receptors (anorectic action: 2 mg/kg ip, 8.5 mg/kg po). However, receptor activity of isothiazolopyridine 3 was not confirmed in vitro using 5-HT(2A) and 5-HT(1A) receptor binding technique. Molecular modeling studies demonstrated that it is difficult to predict bioactive conformation of title molecule 3.
Heterocyclen-Synthesen mit Monothiomalonsaeure-Amiden: Synthese von 3-Oxo-2,3-dihydroisothiazolopyridinen und 3-Oxo-2,3-dihydroisothiazolopyrimidinen
Schaper, Wolfgang
, p. 861 - 867 (2007/10/02)
The monothiomalonic acid amides 5, prepared from cyanoacetamides 4 and hydrogen sulphide, react with diketones 6 or aldehyde derivatives 7 to give the 2-thioxo-1,2-dihydropyridine-3-carboxamides 8 which can be cyclised to the 3-oxo-2,3-dihydroisothiazolo
SYNTHESIS OF 3-OXOISOTHIAZOLOPYRIDINES
Krauze, A. A.,Bomika, Z. A.,Pelcher, Yu. E.,Mazheika, I. B.,Dubur, G. Ya.
, p. 385 - 390 (2007/10/02)
3-Oxoisothiazolopyridines were synthesized for the first time by the reaction of 3-cyanopyridine-2-thiones or bis(3-cyanopyridyl) disulfides with concentrated sulfuric acid.It is demonstrated that 3-carbamoylpyridine-2-thiones are formed as intermediates.The 3-oxoisothiazolopyridines were converted to 3-bromoisothiazolopyridines and pyridine-2-thiones.The bromination of pyridine-2-thione was studied.
