2.7.1.105 (2E)-1-(pyridin-4-yl)-3-(quinolin-2-yl)prop-2-en-1-one - 213172 2.7.1.105 (2E)-3-(pyridin-3-yl)-1-(pyridin-4-yl)prop-2-en-1-one - 213171 2.7.1.105 1-(3-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one - 232532 2.7.1.105 1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one the inhibitor causes a rapid induction of apoptosis in transformed cells, has adequate pharmacokinetic properties, suppresses the glucose uptake and growth of Lewis lung carcinomas in syngeneic mice and yields anti-tumor effects in three human xenograft models of cancer in athymic mice that are comparable to FDA-approved chemotherapeutic agents 213169 2.7.1.105 1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one - 213169 2.7.1.105 2,5-anhydro-D-mannitol 6-phosphate - 19904 2.7.1.105 2-((5-bromo-6-oxo-1-phenyl-1,6-dihydropyridazin-4-yl)amino)acetamide - 197128 2.7.1.105 2-(2-bromoacetamido)ethyl phosphate an irreversible inhibitor of PFK-2 in several cancer cell lines 213170 2.7.1.105 2-(5-bromo-6-oxo-1-phenyl-1,6-dihydropyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline-5-carbonitrile - 197126 2.7.1.105 2-hydroxy-4-[(naphthalen-1-ylsulfonyl)amino]benzoic acid - 213174 2.7.1.105 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), small-molecule inhibitor, mixed inhibition mechanism, both competitive and uncompetitive inhibition, suppresses glycolytic flux and is cytostatic to neoplastic cells, inhibits activity of recombinantly expressed PFKFB3 68159 2.7.1.105 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one - 68159 2.7.1.105 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one the PFKFB3 inhibitor, 3PO, increases p27 protein in Lewis lung carcinoma cells in vitro and in vivo 68159 2.7.1.105 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one 3PO, a weak competitive inhibitor of PFKFB3, reduces the glucose metabolism and proliferation of cancer cells 68159 2.7.1.105 3-phosphoglycerate - 194 2.7.1.105 3H-benzo[e]indol-2-yl(pyridin-4-yl)methanone - 213173 2.7.1.105 4-(4-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-5-bromo-6-oxopyridazin-1(6H)-yl)benzonitrile - 197135 2.7.1.105 4-bromo-2-phenyl-5-(((tetrahydrofuran-2-yl)methyl)amino)pyridazin-3(2H)-one - 197129 2.7.1.105 4-bromo-2-phenyl-5-(2-oxa-6-azaspiro[3.3]heptan-6-yl)pyridazin-3(2H)-one - 197127 2.7.1.105 4-bromo-5-morpholino-2-phenylpyridazin-3(2H)-one - 197125 2.7.1.105 5,6,7,8-tetrahydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one - 197145 2.7.1.105 5,6,7,8-tetrahydroxy-2-(4-hydroxyphenyl)chromen-4-one - 256639 2.7.1.105 5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-2-benzyl-4-bromopyridazin-3(2H)-one - 197139 2.7.1.105 5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-2-benzylpyridazin-3(2H)-one - 197140 2.7.1.105 5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(3-phenylpropyl)pyridazin-3(2H)-one - 197143 2.7.1.105 5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(4-((2-(dimethylamino)ethyl)-amino)benzyl)pyridazin-3(2H)-one - 197144 2.7.1.105 5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(4-(trifluoromethoxy)phenyl)-pyridazin-3(2H)-one - 197136 2.7.1.105 5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(4-chlorophenyl)pyridazin-3(2H)-one - 197137 2.7.1.105 5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(4-iodobenzyl)pyridazin-3(2H)-one - 197141 2.7.1.105 5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(pyrimidin-5-yl)pyridazin-3(2H)-one - 197138 2.7.1.105 5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-phenethylpyridazin-3(2H)-one - 197142 2.7.1.105 5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-phenylpyridazin-3(2H)-one - 197124 2.7.1.105 5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-chloro-2-phenylpyridazin-3(2H)-one - 197130 2.7.1.105 5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-ethoxy-2-phenylpyridazin-3(2H)-one - 197133 2.7.1.105 5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-iodo-2-phenylpyridazin-3(2H)-one - 197131 2.7.1.105 5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-isopropyl-2-phenylpyridazin-3(2H)-one - 197132 2.7.1.105 5-(N-(8-methoxy-4-quinolyl)amino)pentyl nitrate - 256636 2.7.1.105 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside AICAR, associated with phosphorylation of PFK-2 on Ser-32, phosphorylation increased of both wild-type and overexpressed PFK-2 protein in hepatocytes 6097 2.7.1.105 7,8-dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one - 256640 2.7.1.105 7,8-dihydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one - 199173 2.7.1.105 ADP kinetics 13 2.7.1.105 ADP product inhibition 13 2.7.1.105 ADP - 13 2.7.1.105 AMP not 30 2.7.1.105 AMP weak 30 2.7.1.105 ATP at low concentrations of Mg2+ and fructose 6-phosphate 4 2.7.1.105 ATP free form 4 2.7.1.105 ATP not 4 2.7.1.105 AZ67 potent and specific PFKFB3 inhibitor 256635 2.7.1.105 beta-D-fructose 2,6-bisphosphate product inhibition 4125 2.7.1.105 beta-D-fructose 2,6-bisphosphate kinetics 4125 2.7.1.105 beta-D-fructose 2,6-bisphosphate - 4125 2.7.1.105 beta-D-fructose 6-phosphate modeling of beta-D-fructose 6-phosphate as inhibitor 633 2.7.1.105 citrate - 131 2.7.1.105 citrate not 131 2.7.1.105 citrate heart enzyme is more sensitive than liver enzyme 131 2.7.1.105 citrate at physiological concentrations 131 2.7.1.105 citrate skeletal muscle enzyme is more sensitive than liver enzyme 131 2.7.1.105 citrate phosphorylation enhances sensitivity 131 2.7.1.105 citrate weak 131 2.7.1.105 citrate 60% inhibition at 1 mM 131 2.7.1.105 citrate strong 131 2.7.1.105 dibutyryl cAMP slightly inhibits the complex formation between the enzyme and glucokinase 13026 2.7.1.105 dihydroxyacetone phosphate weak 278 2.7.1.105 dihydroxyacetone phosphate - 278 2.7.1.105 diphosphate - 17 2.7.1.105 diphosphate not phosphate 17 2.7.1.105 ethyl 1-(6-oxo-1-phenyl-5-(2-oxa-6-azaspiro[3.3]heptan-6-yl)-1,6-dihydropyridazin-4-yl)-1H-1,2,3-triazole-4-carboxylate - 197134 2.7.1.105 ethyl 7-hydroxy-2-oxo-2H-1-benzopyran-3-carboxylate - 256641 2.7.1.105 glucagon the native and the recombinant wild-type and mutant enzymes are phosphorylated after incubation with glucagon inactivating the enzyme 1399 2.7.1.105 glucagon phosphorylation of PFK2 on Ser-32 in liver 1399 2.7.1.105 glycerate 2-phosphate - 9175 2.7.1.105 Glycerol 2-phosphate - 2993 2.7.1.105 glycerol 3-phosphate 20% inhibition at 2mM 445 2.7.1.105 glycolate 2-phosphate - 30055 2.7.1.105 guanidine inactivation, unfolding 2023 2.7.1.105 m-periodate strong, DTT protects or reverses 113757 2.7.1.105 Mg2+ MgATP 6 2.7.1.105 MgATP inhibited by, structure determination reveals substrate inhibition due to sequential binding of two MgATP molecules per subunit, the first at the usual site occupied by the nucleotide in homologous enzymes and the second at the allosteric site, making a number of direct and Mg-mediated interactions with the first, two configurations observed for the second MgATP, one of which involves interactions with Tyr-23 from the adjacent subunit in the dimer and the other making an unusual non-Watson-Crick base pairing with the adenine in the substrate ATP 8247 2.7.1.105 MgATP2- allosteric inhibition, important regulation of in vivo carbohydrate metabolism under gluconeogenic conditions 108 2.7.1.105 MgATP2- E190Q mutant presents alterations in the inhibition by MgATP2- and phosphate 108 2.7.1.105 MgATP2- allosteric inhibition 108 2.7.1.105 MgNTP strain DF903, substrate inhibition, most effective: MgATP2, at low fructose concentration 98496 2.7.1.105 MoO42- - 2413 2.7.1.105 additional information phosphorylation by cAMP-dependent protein kinase causes inactivation of liver enzyme 2 2.7.1.105 additional information phosphorylation at lower pH-values; phosphorylation by cAMP-dependent protein kinase causes inactivation of liver enzyme 2 2.7.1.105 additional information - 2 2.7.1.105 additional information phosphorylation site: Ser-32 2 2.7.1.105 additional information phosphorylation by cAMP-dependent protein kinase causes inactivation of liver enzyme; phosphorylation of foetal liver enzyme by protein kinase C, but no effect on adult liver cells 2 2.7.1.105 additional information not: cAMP or protein kinase alone; phosphorylation at pH 6.6, not at pH 8; phosphorylation by cAMP-dependent protein kinase causes inactivation of liver enzyme 2 2.7.1.105 additional information phosphorylation by cAMP-dependent protein kinase causes inactivation of liver enzyme; phosphorylation by cAMP-dependent protein kinase of liver enzyme, not of skeletal muscle enzyme, since the phosphorylation site target Ser-32 of the liver isozyme is replaced by Ala in the muscle isozyme 2 2.7.1.105 additional information phosphorylation by cAMP-dependent protein kinase causes inactivation of liver enzyme; rat liver enzyme is inhibited by phosphorylation by cAMP-dependent protein kinase, but not rat skeletal muscle, bovine and rat heart enzyme 2 2.7.1.105 additional information no inhibition by protein kinase C; phosphorylation by cAMP-dependent protein kinase causes inactivation of liver enzyme; rat liver enzyme is inhibited by phosphorylation by cAMP-dependent protein kinase but not rat kidney, testis and skeletal muscle enzyme and bovine and rat heart enzyme 2 2.7.1.105 additional information no inhibition by protein kinase C; phosphorylation by cAMP-dependent protein kinase causes inactivation of liver enzyme 2 2.7.1.105 additional information no inhibition by lactate, glyceraldehyde 3-phosphate, beta-D-fructose 1,6-bisphosphate 2 2.7.1.105 additional information phosphorylation by cAMP-dependent protein kinase, but no inhibition 2 2.7.1.105 additional information no inhibition by protein kinase C; phosphorylation by cAMP-dependent protein kinase, but no inhibition 2 2.7.1.105 additional information not: ITP, GTP, UTP, CTP, strain DF905; phosphorylation by cAMP-dependent protein kinase causes inactivation 2 2.7.1.105 additional information phosphorylation by cAMP-dependent protein kinase causes inactivation of liver enzyme; phosphorylation by cAMP-dependent protein kinase causes inactivation of liver enzyme, not of heart and skeletal muscle enzyme 2 2.7.1.105 additional information phosphorylation by cAMP-dependent protein kinase causes inactivation 2 2.7.1.105 additional information loss of phosphorylation-dependent reduction of enzyme by deletion of the N-terminal residues of enzyme. The deletion of 7 N-terminal amino acids causes a 75% decrease in activity; phosphorylation site: Ser-32 2 2.7.1.105 additional information phosphorylation by cAMP-dependent protein kinase causes inactivation of liver enzyme, not skeletal muscle enzyme 2 2.7.1.105 additional information phosphorylation by cAMP-dependent protein kinase causes 35% inactivation of isozyme L of adipose tissue, not isozyme M 2 2.7.1.105 additional information kinetic of phosphorylation by cAMP-dependent protein kinase 2 2.7.1.105 additional information enzyme is not affected by protein kinase C 2 2.7.1.105 additional information enzyme structure-activity relationships, screening of a small-molecule library, and design and synthesis of 5-triazolo-2-arylpyridazinone analogus inhibitors, molecular docking using the X-ray structure for human PFKFB3, PDB ID 2AXN, overview 2 2.7.1.105 additional information synthesis and screening of 3PO inhibitor derivatives for inhibitory potency against isozyme PFKFB3, overview. 1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one displays improved pharmacokinetic properties relative to 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one 2 2.7.1.105 additional information not inhibited by up to 0.75 mM 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one 2 2.7.1.105 additional information phosphorylation by cAMP-dependent protein kinase causes 80% decrease in activity of the liver cells but not of hepatoma cells; phosphorylation by cAMP-dependent protein kinase causes inactivation of liver enzyme 2 2.7.1.105 additional information phosphorylation by cAMP-dependent protein kinase causes inactivation of liver enzyme; phosphorylation by cAMP-dependent protein kinase causes inactivation of liver enzyme, not of kidney, testis and heart enzyme 2 2.7.1.105 additional information the islet enzyme lacks protein kinase A and C phosphorylation sites 2 2.7.1.105 additional information no inhibition by phosphorylation with Ca2+/calmodulin dependent protein kinase; no inhibition by protein kinase C 2 2.7.1.105 N-(1-pyrenil)maleimide complete loss of catalytic activity, but modified enzyme is able to bind beta-D-fructose 6-phosphate, the presence of MgATP2- completely protects the enzyme activity, the modified enzyme elutes as a monomer 113834 2.7.1.105 N-bromoacetylethanolamine repetitive administration affects inhibition of glycolysis and lipid metabolism, causing suppression of body weight gain 10724 2.7.1.105 N-bromoacetylethanolamine specific active site-directed inactivator of enzyme, in vitro and in vivo 10724 2.7.1.105 N-bromoacetylethanolamine phosphate - 118611 2.7.1.105 o-phthalaldehyde kinetics, DTT or substrates do not protect 5587 2.7.1.105 PFK-15 i.e. 1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one 256637 2.7.1.105 PFK-158 potent and specific inhibitor 256638 2.7.1.105 phosphate inhibits wild-type and mutant enzym E190Q. E190 contributs to the mechanism of phosphate inhibition in Pfk-2. E190Q mutant presents alterations in the inhibition by MgATP2- and phosphate 16 2.7.1.105 phosphoenolpyruvate - 51 2.7.1.105 phosphoenolpyruvate kinetics 51 2.7.1.105 phosphoenolpyruvate not 51 2.7.1.105 phosphoenolpyruvate mixed-type inhibitory effect, phosphorylation enhances sensitivity 51 2.7.1.105 phosphoenolpyruvate weak 51 2.7.1.105 phosphoenolpyruvate HBP1 and HBP2, the bifunctional enzyme is regulated via inhibition by phosphoenolpyruvate, uncompetitive against ATP, noncompetitive against beta-D-fructose 6-phosphate 51 2.7.1.105 phosphoenolpyruvate strong 51 2.7.1.105 protein kinase A inactivation via a 7fold increase in Km for fructose 6-phosphate without alteration of Vmax 7521 2.7.1.105 pyrene maleimide incorporation of 2 mol per mol of enzyme subunit, modifiying Cys-238 and Cys-295, leads to rapid inactivation, MgATP2- protects Cys295, modification of Cys238 does not abolish activity 127336 2.7.1.105 SeO42- - 5615 2.7.1.105 sn-glycerol 3-phosphate - 422 2.7.1.105 sn-glycerol 3-phosphate stimulates phosphatase activity 422 2.7.1.105 sn-glycerol 3-phosphate heart enzyme is less sensitive than liver 422 2.7.1.105 sn-glycerol 3-phosphate i.e. alpha-glycerol phosphate 422 2.7.1.105 sn-glycerol 3-phosphate not 422 2.7.1.105 sn-glycerol 3-phosphate heart enzyme is less sensitive than liver; liver enzyme 422 2.7.1.105 sn-glycerol 3-phosphate most potent inhibitor of phosphorylated liver enzyme, phosphorylation enhances sensitivity 422 2.7.1.105 sn-glycerol 3-phosphate most potent inhibitor of phosphorylated liver enzyme, phosphorylation enhances sensitivity; skeletal muscle enzyme is not sensitive to inhibition 422 2.7.1.105 sn-glycerol 3-phosphate 75% decrease in activity of liver enzyme but not hepatoma cells 422 2.7.1.105 SO42- - 245 2.7.1.105 VO42- - 98285 2.7.1.105 WO42- - 10810