LY294002 is a
morpholine-containing chemical compound that is a potent inhibitor of numerous proteins, and a strong inhibitor of
phosphoinositide 3-kinases (PI3Ks).
It is generally considered a non-selective research tool, and should not be used for experiments aiming to target PI3K uniquely.
Two of these are the proto-oncogene serine/threonine-protein kinase (
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 ...
) and the
phosphatidylinositol-4,5-bisphosphate 3-kinase
In enzymology, a phosphatidylinositol-4,5-bisphosphate 3-kinase () is an enzyme that catalyzes the chemical reaction:
:ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate \rightleftharpoons ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphospha ...
P110 gamma, catalytic subunit gamma isoform.
With an
IC50 of 1.4 μM it is somewhat less potent than
wortmannin, another well-known
PI3 kinase inhibitor
Phosphoinositide 3-kinase inhibitors (PI3K inhibitors) are a class of medical drugs that are mainly used to treat advanced cancers. They function by inhibiting one or more of the phosphoinositide 3-kinase (PI3K) enzymes, which are part of the PI3 ...
. However, LY294002 is a reversible inhibitor of PI3K whereas wortmannin acts irreversibly.
Application of LY294002 causes a substantial acceleration of
MEPP
End plate potentials (EPPs) are the voltages which cause depolarization of skeletal muscle fibers caused by neurotransmitters binding to the postsynaptic membrane in the neuromuscular junction. They are called "end plates" because the postsynapti ...
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.
LY294002 is also a
BET inhibitor
BET inhibitors are a class of drugs that reversibly bind the bromodomains of Bromodomain and Extra-Terminal motif (BET) proteins BRD2, BRD3, BRD4, and BRDT, and prevent protein-protein interaction between BET proteins and acetylated histones and ...
(e.g. of BRD2, BRD3, and BRD4).
Application
Research
It has been shown that LY294002 administration has an additive effect on
quercetin
Quercetin is a plant flavonol from the flavonoid group of polyphenols. It is found in many fruits, vegetables, leaves, seeds, and grains; capers, red onions, and kale are common foods containing appreciable amounts of it. It has a bitter flavor ...
antiviral activity against
hepatitis C virus
The hepatitis C virus (HCV) is a small (55–65 nm in size), enveloped, positive-sense single-stranded RNA virus of the family '' Flaviviridae''. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer (hepatoc ...
.
[{{cite journal , author = Pisonero-Vaquero S , title = Modulation of PI3K-LXRα-dependent lipogenesis mediated by oxidative/nitrosative stress contributes to inhibition of HCV replication by quercetin. , journal = Lab. Invest. , volume = 94 , issue = 3 , date=Mar 2014 , pmid = 24492281 , pages = 262–274 , doi=10.1038/labinvest.2013.156, doi-access = free ]
References
4-Morpholinyl compunds
Chromones
Phosphoinositide 3-kinase inhibitors