Discovery of 3-(trifluoromethyl)-1H-pyrazole-5-carboxamide activators of the M2 isoform of pyruvate kinase (PKM2)
| Autor: | Xiao-Hui Liu, Hendrickson Thomas, Kevin Wright, Adrianne Clifford, Michael V. McCullar, Rebecca N. Nix, Steven B. Kanner, Michael Saunders, Jeremy Bullough, Jason M. Foulks, Yong Xu, Scott Pearce, K. Mark Parnell, Koc-Kan Ho |
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| Rok vydání: | 2014 |
| Předmět: |
Gene isoform
Thyroid Hormones Clinical Biochemistry Pharmaceutical Science PKM2 Biochemistry Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Humans Molecular Biology Trifluoromethyl Organic Chemistry Membrane Proteins Warburg effect Small molecule Enzyme Activation Isoenzymes chemistry Cancer cell Pyrazoles Molecular Medicine Bioisostere Carrier Proteins Pyruvate kinase |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 24:515-519 |
| ISSN: | 0960-894X |
| Popis: | Activators of the pyruvate kinase M2 (PKM2) are currently attracting significant interest as potential anticancer therapies. They may achieve a novel antiproliferation response in cancer cells through modulation of the classic ‘Warburg effect’ characteristic of aberrant metabolism. In this Letter, we describe the optimization of a weakly active screening hit to a structurally novel series of small molecule 3-(trifluoromethyl)-1H-pyrazole-5-carboxamides as potent PKM2 activators. |
| Databáze: | OpenAIRE |
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