LY294002
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MedKoo CAT#: 201795

CAS#: 154447-36-6

Description: LY294002 is a morpholine derivative of quercetin. It is a potent inhibitor of phosphoinositide 3-kinases (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 1.4 uM 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.


Chemical Structure

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LY294002
CAS# 154447-36-6

Theoretical Analysis

MedKoo Cat#: 201795
Name: LY294002
CAS#: 154447-36-6
Chemical Formula: C19H17NO3
Exact Mass: 307.12084
Molecular Weight: 307.34
Elemental Analysis: C, 74.25; H, 5.58; N, 4.56; O, 15.62

Price and Availability

Size Price Availability Quantity
200.0mg USD 130.0 Same day
500.0mg USD 280.0 Same day
1.0g USD 520.0 Same day
2.0g USD 950.0 Same day
5.0g USD 2250.0 Same day
10.0g USD 4050.0 2 Weeks
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Synonym: LY294002; LY-294002; LY 294002

IUPAC/Chemical Name: 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one

InChi Key: CZQHHVNHHHRRDU-UHFFFAOYSA-N

InChi Code: 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

SMILES Code: O=C1C=C(N2CCOCC2)OC3=C(C4=CC=CC=C4)C=CC=C13

Appearance: Solid powder

Purity: >99% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not soluble in water.

Shelf Life: >5 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: LY294002 is a PI3K inhibitor with IC50s of 0.5, 0.57, and 0.97 μM for PI3Kα, PI3Kδ and PI3Kβ, respectively.
In vitro activity: The inhibitory effect of LY294002 on proliferation of multiple myeloma cell U266 was explored. U266 cell viability was reduced in time- and dose-dependent manner after treatment with 5, 10, 20 µmol/L of LY294002 for 24, 48, 72 h. The 5, 10, 20 µmol/L LY294002 leaded to cell nucleus dense and thick, and the cell cycle arrested in the G1 phase (P<0.01). The expressions of BCL-2, Cyclin D1, Cyclin E, PI3K and p-AKT were down-regulated (P<0.01), and the expression of BAX up-regulated (P<0.01). These results indicate that LY294002 can inhibit U266 cell proliferation via suppresion of activation of PI3K/AKT signal pathway. Reference: Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2017 Aug;25(4):1092-1096. https://pubmed.ncbi.nlm.nih.gov/28823274/
In vivo activity: The effects of LY294002 on Tourette syndrome (TS) in rats were evaluated. TS model was induced in rats by DOI (the selective 5-HT2A/2C agonist 1- (2, 5- dimethoxy -4 - iodophenyl) -2- aminopropane). Behavior was assessed by stereotypic score and autonomic activity. Inflammatory cytokines such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in serum and striatum were detected. The protein levels of PI3K/Akt/NF-B in striatum were detected by Western Blot. LY294002 treatment significantly reduced IL-6, IL-1β and TNF-α in serum and striatum of TS rats, Also, highly expressed P-PI3K, P-Akt, P-NF-κBp65, P-IκBα in TS rats were restored respectively by LY294002 treatment as indicted in western blot analysis and immunohistochemistry analysis. Thus, it was supposed that the protective effect of LY294002 against TS in rat might be associated with the regulation of PI3K/Akt/NF-B pathway. Reference: Metab Brain Dis. 2017 Oct;32(5):1619-1625. https://link.springer.com/article/10.1007%2Fs11011-017-0051-z

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
Ethanol 61.0 198.48
DMSO 51.34 167.05
DMSO:PBS (pH 7.2) (1:1) 0.5 1.63

Preparing Stock Solutions

The following data is based on the product molecular weight 307.34 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Wang YQ, Lin Y, Zhao JD, Yang YT. [Inhibitory Effect of LY294002 on Proliferation of Multiple Myeloma Cells and Its Mechanism]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2017 Aug;25(4):1092-1096. Chinese. doi: 10.7534/j.issn.1009-2137.2017.04.023. PMID: 28823274. 2. Chen P, Wen X, Wang B, Hou D, Zou H, Yuan Q, Yang H, Xie J, Huang H. PI3K/Akt inhibitor LY294002 potentiates homoharringtonine antimyeloma activity in myeloma cells adhered to stromal cells and in SCID mouse xenograft. Ann Hematol. 2018 May;97(5):865-875. doi: 10.1007/s00277-018-3247-3. Epub 2018 Feb 15. PMID: 29450644. 3. Hongyan L, Chunyan W, Yue'e Y. LY294002, a PI3K inhibitor, attenuates Tourette syndrome in rats. Metab Brain Dis. 2017 Oct;32(5):1619-1625. doi: 10.1007/s11011-017-0051-z. Epub 2017 Jun 18. PMID: 28624893.
In vitro protocol: 1. Wang YQ, Lin Y, Zhao JD, Yang YT. [Inhibitory Effect of LY294002 on Proliferation of Multiple Myeloma Cells and Its Mechanism]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2017 Aug;25(4):1092-1096. Chinese. doi: 10.7534/j.issn.1009-2137.2017.04.023. PMID: 28823274. 2. Chen P, Wen X, Wang B, Hou D, Zou H, Yuan Q, Yang H, Xie J, Huang H. PI3K/Akt inhibitor LY294002 potentiates homoharringtonine antimyeloma activity in myeloma cells adhered to stromal cells and in SCID mouse xenograft. Ann Hematol. 2018 May;97(5):865-875. doi: 10.1007/s00277-018-3247-3. Epub 2018 Feb 15. PMID: 29450644.
In vivo protocol: 1. Hongyan L, Chunyan W, Yue'e Y. LY294002, a PI3K inhibitor, attenuates Tourette syndrome in rats. Metab Brain Dis. 2017 Oct;32(5):1619-1625. doi: 10.1007/s11011-017-0051-z. Epub 2017 Jun 18. PMID: 28624893. 2. Chen P, Wen X, Wang B, Hou D, Zou H, Yuan Q, Yang H, Xie J, Huang H. PI3K/Akt inhibitor LY294002 potentiates homoharringtonine antimyeloma activity in myeloma cells adhered to stromal cells and in SCID mouse xenograft. Ann Hematol. 2018 May;97(5):865-875. doi: 10.1007/s00277-018-3247-3. Epub 2018 Feb 15. PMID: 29450644.

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  1: Welling A, Hofmann F, Wegener JW. Inhibition of L-type Cav1.2 Ca2+ channels by 2,(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) and 2-[1-(3-dimethyl-aminopropyl)-5-methoxyindol-3-yl]-3-(1H-indol-3-yl) maleimide (Go6983). Mol Pharmacol. 2005 Feb;67(2):541-4. Epub 2004 Nov 10. PubMed PMID: 15537868.

2: Guo M, Joiakim A, Reiners JJ Jr. Suppression of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated aryl hydrocarbon receptor transformation and CYP1A1 induction by the phosphatidylinositol 3-kinase inhibitor 2-(4-morpholinyl)-8-phenyl-4H-1- benzopyran-4-one (LY294002). Biochem Pharmacol. 2000 Sep 1;60(5):635-42. PubMed PMID: 10927021.

3: Jung YD, Kim MS, Lee KS, Kang IC, Nah AS, Song DU, Yang SY, Kim JK, Ahn BW. 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) inhibits nitric oxide production in cultured murine astrocytes. Pharmacol Res. 1999 Nov;40(5):423-7. PubMed PMID: 10527657.

4: Chasserot-Golaz S, Hubert P, Thiersé D, Dirrig S, Vlahos CJ, Aunis D, Bader MF. Possible involvement of phosphatidylinositol 3-kinase in regulated exocytosis: studies in chromaffin cells with inhibitor LY294002. J Neurochem. 1998 Jun;70(6):2347-56. PubMed PMID: 9603199.

5: Rousse S, Montarras D, Pinset C, Dubois C. Up-regulation of insulin-like growth factor binding protein-5 is independent of muscle cell differentiation, sensitive to rapamycin, but insensitive to wortmannin and LY294002. Endocrinology. 1998 Apr;139(4):1487-93. PubMed PMID: 9528925.

6: Nakamura M, Nakashima S, Katagiri Y, Nozawa Y. Effect of wortmannin and 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) on N-formyl-methionyl-leucyl-phenylalanine-induced phospholipase D activation in differentiated HL60 cells: possible involvement of phosphatidylinositol 3-kinase in phospholipase D activation. Biochem Pharmacol. 1997 Jun 15;53(12):1929-36. PubMed PMID: 9256168.

7: Yano H, Agatsuma T, Nakanishi S, Saitoh Y, Fukui Y, Nonomura Y, Matsuda Y. Biochemical and pharmacological studies with KT7692 and LY294002 on the role of phosphatidylinositol 3-kinase in Fc epsilon RI-mediated signal transduction. Biochem J. 1995 Nov 15;312 ( Pt 1):145-50. PubMed PMID: 7492304; PubMed Central PMCID: PMC1136237.

8: Smith LK, Vlahos CJ, Reddy KK, Falck JR, Garner CW. Wortmannin and LY294002 inhibit the insulin-induced down-regulation of IRS-1 in 3T3-L1 adipocytes. Mol Cell Endocrinol. 1995 Aug 30;113(1):73-81. PubMed PMID: 8674815.

9: Yamamoto-Honda R, Tobe K, Kaburagi Y, Ueki K, Asai S, Yachi M, Shirouzu M, Yodoi J, Akanuma Y, Yokoyama S, et al. Upstream mechanisms of glycogen synthase activation by insulin and insulin-like growth factor-I. Glycogen synthase activation is antagonized by wortmannin or LY294002 but not by rapamycin or by inhibiting p21ras. J Biol Chem. 1995 Feb 10;270(6):2729-34. PubMed PMID: 7852343.

10: Vlahos CJ, Matter WF, Hui KY, Brown RF. A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J Biol Chem. 1994 Feb 18;269(7):5241-8. PubMed PMID: 8106507.

LY294002

200.0mg / USD 130.0


Additional Information

LY294002 is a potent inhibitor of phosphoinositide 3-kinases (PI3K), two of which 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.  
 
Research data showed that LY294002 inhibited the phosphorylating of Akt (S473), cell proliferation, and induced apoptosis in CNE-2Z cells. Moreover, the apoptosis-induced LY294002 was directly regulated by caspase-9 activation pathway, which suggested that PI3K inhibitor, LY294002, induced apoptosis by caspase-9 activation pathway and might be as a potentially useful target for therapeutic intervention in nasopharyngeal carcinoma patients. Fro detail see: http://www.ncbi.nlm.nih.gov/pubmed/20412566.