LY294002

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
CAS Number	154447-36-6 ;
3D model (JSmol)	Interactive image;
ChEMBL	ChEMBL98350 ;
ChemSpider	3835 ;
IUPHAR/BPS	6004;
PubChem CID	3973;
UNII	31M2U1DVID ;
CompTox Dashboard (EPA)	DTXSID6042650 ;
	InChI 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 Key: CZQHHVNHHHRRDU-UHFFFAOYSA-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;
	SMILES C1COCCN1C2=CC(=O)C3=C(O2)C(=CC=C3)C4=CC=CC=C4;
Properties
Chemical formula	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). verify (what is ?) Infobox references

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]

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

^ Maira SM, Stauffer F, Schnell C, García-Echeverría C (February 2009). "PI3K inhibitors for cancer treatment: where do we stand?". Biochemical Society Transactions. 37 (Pt 1): 265–272. doi:10.1042/BST0370265. PMID 19143644.
^ Arrowsmith CH, Audia JE, Austin C, Baell J, Bennett J, Blagg J, et al. (August 2015). "The promise and peril of chemical probes". Nature Chemical Biology. 11 (8): 536–541. doi:10.1038/nchembio.1867. PMC 4706458. PMID 26196764.
^ "LY294002". DrugBank. Retrieved 2009-09-25.
^ Vlahos CJ, Matter WF, Hui KY, Brown RF (February 1994). "A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002)". The Journal of Biological Chemistry. 269 (7): 5241–5248. doi:10.1016/S0021-9258(17)37680-9. PMID 8106507.
^ Searl TJ, Silinsky EM (December 2005). "LY 294002 inhibits adenosine receptor activation by a mechanism independent of effects on PI-3 kinase or casein kinase II". Purinergic Signalling. 1 (4): 389–394. doi:10.1007/s11302-005-0778-6. PMC 2096559. PMID 18404524.
^ Dittmann A, Werner T, Chung CW, Savitski MM, Fälth Savitski M, Grandi P, et al. (February 2014). "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.
^ Pisonero-Vaquero S, García-Mediavilla MV, Jorquera F, Majano PL, Benet M, Jover R, et al. (March 2014). "Modulation of PI3K-LXRα-dependent lipogenesis mediated by oxidative/nitrosative stress contributes to inhibition of HCV replication by quercetin". Laboratory Investigation; A Journal of Technical Methods and Pathology. 94 (3): 262–274. doi:10.1038/labinvest.2013.156. PMID 24492281.

[Maira2009-1] Maira SM, Stauffer F, Schnell C, García-Echeverría C (February 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 CH, Audia JE, Austin C, Baell J, Bennett J, Blagg J, et al. (August 2015). "The promise and peril of chemical probes". Nature Chemical Biology. 11 (8): 536–541. doi:10.1038/nchembio.1867. PMC 4706458. PMID 26196764.

[titleCard_for_LY294002_in_DrugBank_|_DB02656-3] "LY294002". DrugBank. Retrieved 2009-09-25.

[4] Vlahos CJ, Matter WF, Hui KY, Brown RF (February 1994). "A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002)". The Journal of Biological Chemistry. 269 (7): 5241–5248. doi:10.1016/S0021-9258(17)37680-9. PMID 8106507.

[pmid18404524-5] Searl TJ, Silinsky EM (December 2005). "LY 294002 inhibits adenosine receptor activation by a mechanism independent of effects on PI-3 kinase or casein kinase II". Purinergic Signalling. 1 (4): 389–394. doi:10.1007/s11302-005-0778-6. PMC 2096559. PMID 18404524.

[6] Dittmann A, Werner T, Chung CW, Savitski MM, Fälth Savitski M, Grandi P, et al. (February 2014). "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.

[pmid_=_24492281-7] Pisonero-Vaquero S, García-Mediavilla MV, Jorquera F, Majano PL, Benet M, Jover R, et al. (March 2014). "Modulation of PI3K-LXRα-dependent lipogenesis mediated by oxidative/nitrosative stress contributes to inhibition of HCV replication by quercetin". Laboratory Investigation; A Journal of Technical Methods and Pathology. 94 (3): 262–274. doi:10.1038/labinvest.2013.156. PMID 24492281.

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