1186653-94-0Relevant articles and documents
Evaluation of thieno[3,2-b]pyrrole[3,2-d]pyridazinones as activators of the tumor cell specific M2 isoform of pyruvate kinase
Jiang, Jian-kang,Boxer, Matthew B.,Vander Heiden, Matthew G.,Shen, Min,Skoumbourdis, Amanda P.,Southall, Noel,Veith, Henrike,Leister, William,Austin, Christopher P.,Park, Hee Won,Inglese, James,Cantley, Lewis C.,Auld, Douglas S.,Thomas, Craig J.
supporting information; experimental part, p. 3387 - 3393 (2010/08/20)
Cancer cells have distinct metabolic needs that are different from normal cells and can be exploited for development of anti-cancer therapeutics. Activation of the tumor specific M2 form of pyruvate kinase (PKM2) is a potential strategy for returning cancer cells to a metabolic state characteristic of normal cells. Here, we describe activators of PKM2 based upon a substituted thieno[3,2-b]pyrrole[3,2-d]pyridazinone scaffold. The synthesis of these agents, structure-activity relationships, analysis of activity at related targets (PKM1, PKR and PKL) and examination of aqueous solubility are investigated. These agents represent the second reported chemotype for activation of PKM2.