Abstract: The present invention pertains to a method for identifying anti-cancer compounds. The invention is based on the finding that a direct protein-protein interaction between 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4) and (F-box protein 28) FBXO28 silences a ubiquitin E3 ligase activity of FBXO28 towards HIF1a. Interfering with this protein-protein interaction leads to a strong induction of HIF1a proteasomal degradation and cell death in tumors, and therefore, compounds screened according to the present invention harbour therapeutic potential for the treatment of proliferative diseases such as cancer. The invention provides a screening method for cancer therapeutics based on the interaction of PFKFB4 and FBXO28, as well medical applications thereof.

Abstract: The present invention relates to a method for detecting (D)-2-hydroxyglutarate or (D)-2-hydroxyadipic acid in a sample, the method comprising the steps of: a) contacting a sample with a reagent mixture, wherein said reagent mixture comprises: (i) a solvent, (ii) a dye having an oxidized state and a reduced state, wherein the reduced state can be distinguished from the oxidized state and wherein the dye is initially present in the oxidized state, (iii) an electron transfer agent, (iv) a (D)-2-hydroxyglutarate dehydrogenase enzyme, and (v) a cofactor; and b) detecting (D)-2-hydroxyglutarate or (D)-2-hydroxyadipic acid by measuring the production of the reduced state of the dye. The invention further pertains to a method for diagnosing and/or monitoring a (D)-2-hydroxy-glutarate-associated disease in a subject. Encompassed by the invention is also a method for diagnosing a mutation in an isocitrate dehydrogenase (IDH) gene or in a (D)-2-hydroxyglutarate (D2HG) dehydrogenase enzyme gene in a subject.

Abstract: The present invention relates to a method for detecting (D)-2-hydroxyglutarate or (D)-2-hydroxyadipic acid in a sample, the method comprising the steps of: a) contacting a sample with a reagent mixture, wherein said reagent mixture comprises: (i) a solvent, (ii) a dye having an oxidized state and a reduced state, wherein the reduced state can be distinguished from the oxidized state and wherein the dye is initially present in the oxidized state, (iii) an electron transfer agent, (iv) a (D)-2-hydroxyglutarate dehydrogenase enzyme, and (v) a cofactor; and b) detecting (D)-2-hydroxyglutarate or (D)-2-hydroxyadipic acid by measuring the production of the reduced state of the dye. The invention further pertains to a method for diagnosing and/or monitoring a (D)-2-hydroxy-glutarate-associated disease in a subject. Encompassed by the invention is also a method for diagnosing a mutation in an isocitrate dehydrogenase (IDH) gene or in a (D)-2-hydroxyglutarate (D2HG) dehydrogenase enzyme gene in a subject.