LY294002

LY294002 is a morpholine-containing chemical compound that is a potent inhibitor of numerous proteins, and a strong inhibitor of phosphoinositide 3-kinases (PI3Ks).[1] It is generally considered a non-selective research tool, and should not be used for experiments aiming to target PI3K uniquely.[2]

LY294002
Names
Preferred IUPAC name
2-(Morpholin-4-yl)-8-phenyl-4H-1-benzopyran-4-one
Other names
2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
UNII
  • InChI=1S/C19H17NO3/c21-17-13-18(20-9-11-22-12-10-20)23-19-15(7-4-8-16(17)19)14-5-2-1-3-6-14/h1-8,13H,9-12H2 ☒N
    Key: CZQHHVNHHHRRDU-UHFFFAOYSA-N ☒N
  • InChI=1/C19H17NO3/c21-17-13-18(20-9-11-22-12-10-20)23-19-15(7-4-8-16(17)19)14-5-2-1-3-6-14/h1-8,13H,9-12H2
    Key: CZQHHVNHHHRRDU-UHFFFAOYAM
  • C1COCCN1C2=CC(=O)C3=C(O2)C(=CC=C3)C4=CC=CC=C4
Properties
C19H17NO3
Molar mass 307.349 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)
Infobox references

Two of these are the proto-oncogene serine/threonine-protein kinase (PIM1) and the phosphatidylinositol-4,5-bisphosphate 3-kinase P110 gamma|catalytic subunit gamma isoform.[3] With an IC50 of 1.4 μM 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.[4]

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.[5]

LY294002 is also a BET inhibitor (e.g. of BRD2, BRD3, and BRD4).[6]

Application

Research

It has been shown that LY294002 administration has an additive effect on quercetin antiviral activity against hepatitis C virus.[7]

References
  1. Maira; et al. (2009). "PI3K inhibitors for cancer treatment: where do we stand?". Biochemical Society Transactions. 37 (Pt 1): 265–272. doi:10.1042/BST0370265. PMID 19143644.
  2. Arrowsmith, Cheryl H.; Audia, James E.; Austin, Christopher; Baell, Jonathan; Bennett, Jonathan; Blagg, Julian; Bountra, Chas; Brennan, Paul E.; Brown, Peter J. (2015-08-01). "The promise and peril of chemical probes". Nature Chemical Biology. 11 (8): 536–541. doi:10.1038/nchembio.1867. ISSN 1552-4450. PMC 4706458. PMID 26196764.
  3. "Card for LY294002 in DrugBank". DrugBank. Retrieved 2009-09-25.
  4. Chris J. Vlahos; et al. (1994). "A Specific Inhibitor of Phosphatidylinositol 3-Kinase, 2-(4-Morpholinyl)-8-phenyl-4H-l-benzopyran-4-one (LY294002)". Journal of Biological Chemistry. 269 (7): 5241–5248. doi:10.1016/S0021-9258(17)37680-9. PMID 8106507.
  5. Searl TJ, Silinsky EM (Dec 2005). "LY 294002 inhibits adenosine receptor activation by a mechanism independent of effects on PI-3 kinase or casein kinase II". Purinergic Signal. 1 (4): 389–94. doi:10.1007/s11302-005-0778-6. PMC 2096559. PMID 18404524.
  6. Dittmann, Antje; Werner, Thilo; Chung, Chun-Wa; Savitski, Mikhail M.; Fälth Savitski, Maria; Grandi, Paola; Hopf, Carsten; Lindon, Matthew; Neubauer, Gitte; Prinjha, Rabinder K.; Bantscheff, Marcus; Drewes, Gerard (2013). "The Commonly Used PI3-Kinase Probe LY294002 is an Inhibitor of BET Bromodomains". ACS Chemical Biology. 9 (2): 495–502. doi:10.1021/cb400789e. PMID 24533473.
  7. Pisonero-Vaquero S (Mar 2014). "Modulation of PI3K-LXRα-dependent lipogenesis mediated by oxidative/nitrosative stress contributes to inhibition of HCV replication by quercetin". Lab. Invest. 94 (3): 262–274. doi:10.1038/labinvest.2013.156. PMID 24492281.
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