LY294002
Encyclopedia
LY294002 is a morpholine
derivative of quercetin
. It is a potent inhibitor of phosphoinositide 3-kinase
s (PI3Ks). Two of these are the proto-oncogene serine/threonine-protein kinase (PIM1
) and the phosphatidylinositol-4,5-bisphosphate 3-kinase
catalytic subunit gamma isoform. With an IC50
of 1.4uM it is somewhat less potent than wortmannin
, another well-known PI3 kinase inhibitor However, LY294002 is a reversible inhibitor of PI3K whereas wortmannin acts irreversibly. Application of LY294002 causes a substantial acceleration of MEPP frequency (150 μM) at the frog neuromuscular junction through a mechanism that is independent of intraterminal calcium. LY294002 causes the release of MEPPs through a perturbation of synaptotagmin function.
Morpholine
Morpholine is an organic chemical compound having the chemical formula O2NH. This heterocycle, pictured at right, features both amine and ether functional groups. Because of the amine, morpholine is a base; its conjugate acid is called morpholinium...
derivative of quercetin
Quercetin
Quercetin , a flavonol, is a plant-derived flavonoid found in fruits, vegetables, leaves and grains. It also may be used as an ingredient in supplements, beverages or foods.-Occurrence:...
. It is a potent inhibitor of phosphoinositide 3-kinase
Phosphoinositide 3-kinase
Phosphatidylinositol 3-kinases are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. In response to lipopolysaccharide, PI3K phosphorylates p65, inducing...
s (PI3Ks). Two of these are the proto-oncogene serine/threonine-protein kinase (PIM1
PIM1
Proto-oncogene serine/threonine-protein kinase Pim-1 is an enzyme that in humans is encoded by the PIM1 gene.Pim-1 is a proto-oncogene which encodes for the serine/threonine kinase of the same name. The pim-1 oncogene was first described in relation to murine T-cell lymphomas, as it was the locus...
) and the phosphatidylinositol-4,5-bisphosphate 3-kinase
Phosphatidylinositol-4,5-bisphosphate 3-kinase
In enzymology, a phosphatidylinositol-4,5-bisphosphate 3-kinase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are ATP and 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate, whereas its two products are ADP and 1-phosphatidyl-1D-myo-inositol...
catalytic subunit gamma isoform. With an IC50
IC50
The half maximal inhibitory concentration is a measure of the effectiveness of a compound in inhibiting biological or biochemical function. This quantitative measure indicates how much of a particular drug or other substance is needed to inhibit a given biological process by half...
of 1.4uM it is somewhat less potent than wortmannin
Wortmannin
Wortmannin, a furanosteroid metabolite of the fungi Penicillium funiculosum, Talaromyces wortmannii,is a specific, covalent inhibitor of phosphoinositide 3-kinases . It has an in vitro inhibitory concentration of around 5 nM, making it a more potent inhibitor than LY294002, another commonly...
, another well-known PI3 kinase inhibitor However, LY294002 is a reversible inhibitor of PI3K whereas wortmannin acts irreversibly. Application of LY294002 causes a substantial acceleration of MEPP frequency (150 μM) at the frog neuromuscular junction through a mechanism that is independent of intraterminal calcium. LY294002 causes the release of MEPPs through a perturbation of synaptotagmin function.