154447-36-6

Basic information

• Product Name: LY 294002 HYDROCHLORIDE
• Synonyms: LY 294002;LY 294002 HYDROCHLORIDE;2-[4-MORPHOLINYL]-8-PHENYL-1[4H]-BENZOPYRAN-4-ONE;2-(4-MORPHOLINYL)-8-PHENYL-4H-1-BENZOPYRAN-4-ONE;2-(4-MORPHOLINYL)-8-PHENYL-4H-1-BENZOPYRAN-4-ONE HYDROCHLORIDE;2-(4-MORPHOLINO)-8-PHENYL-4H-1-BENZOPYRAN-4-ONE;LY 294002, 99+%;LY294002HCl
• CAS NO: 154447-36-6
• Molecular Formula: C₁₉H₁₇NO₃
• Molecular Weight: 343.8
• EINECS: 1312995-182-4
• Product Categories: Lipid signaling;Signalling;Cell Cycle Regulation;apis;Inhibitor;Anti-cancer&immunity;PI3K/Akt/mTOR;Inhibitors;Akt;mTOR;PI3K
• Mol File: 154447-36-6.mol
• Article Data: 5

Chemical Properties

• Melting Point: 183-185℃
• Boiling Point: 494.6 °C at 760 mmHg
• Flash Point: 253 °C
• Appearance: white to off-white/solid
• Density: 1.266
• Vapor Pressure: 6.33E-10mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: DMSO: >5 mg/mL
• PKA: 0.55±0.20(Predicted)
• Water Solubility: Soluble in DMSO at 5mg/ml. Insoluble in water
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 4 months.
• CAS DataBase Reference: LY 294002 HYDROCHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: LY 294002 HYDROCHLORIDE(154447-36-6)
• EPA Substance Registry System: LY 294002 HYDROCHLORIDE(154447-36-6)

Safety Data

• Safety Statements: 24-25
• WGK Germany: 3
• Hazardous Substances Data: 154447-36-6(Hazardous Substances Data)

Usage

Description

LY294002 Hydrochloride is a selective phosphatidylinositol 3-kinase (PI3K) inhibitor, which is a salt analogue of LY294002 (L486590). It is a chromone substituted with a phenyl group at position 8 and a morpholine group at position 2. LY 294002 HYDROCHLORIDE has a 2.7-fold greater potency than quercetin and inhibits purified PI3K with an IC50 of 1.4 μM.

Uses

Used in Pharmaceutical Industry:
LY294002 Hydrochloride is used as a potent PI3K inhibitor for blocking the PI 3-kinase/Akt signaling pathway. This inhibition is crucial in the development of targeted therapies against various cancers, as the PI3K/Akt pathway is often dysregulated in malignant cells, contributing to uncontrolled cell growth and survival.
Used in Cancer Research:
LY294002 Hydrochloride is used as a research tool for studying the role of PI3K in cancer cell biology. It helps researchers understand the molecular mechanisms underlying tumor growth, survival, and resistance to conventional treatments. This knowledge can be applied to develop novel therapeutic strategies and identify potential biomarkers for patient stratification.
Used in Preclinical Models:
LY294002 Hydrochloride is used as a PI3K inhibitor in preclinical models, such as SCID mice, to investigate its effects on tumor tissue formation and the inhibition of multiple myeloma-induced osteoclast formation and osteolysis. These studies provide valuable insights into the potential therapeutic applications of LY294002 Hydrochloride in the treatment of bone-related malignancies.
Used in Drug Development:
LY294002 Hydrochloride is used as a lead compound in the development of new PI3K inhibitors with improved pharmacological properties, such as better selectivity, bioavailability, and reduced off-target effects. These next-generation inhibitors may offer enhanced efficacy and safety profiles for the treatment of various cancers.

Biological Activity

A highly selective inhibitor of phosphatidylinositol 3-kinase (IC 50 values are 0.31, 0.73, 1.06 and 6.60 μ M for PI3K β , PI3K α , PI3K δ and PI3K γ respectively). Inhibits proliferation and induces apoptosis in human colon cancer cells in vitro and in vivo .

References

1) Vlahos et al. (1994) A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY 294002); J. Biol. Chem., 269 5241

InChI: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

Upstream product

• 2411-83-8 methyl-2,3-dihydroxybenzoate 
• 15159-40-7 4-morpholinocarbonyl chloride 
• 21424-82-8 1-(2-hydroxy-[1,1'-biphenyl]-3-yl)ethanone 
• 90-43-7 2-Phenylphenol 
• 132939-03-8 Diethylcarbamic acid, <1,1'-biphenyl>-2-yl ester 
• 63992-45-0 N,N-diethyl-2-hydroxy-[1,1'-biphenyl]-3-carboxamide 
• 503469-17-8 trifluoromethanesulfonic acid 2-hydroxy-3-(3-morpholin-4-yl-3-oxopropionyl)phenyl ester 
• 688745-54-2 1-(2-hydroxy-3-methoxyphenyl)-3-morpholin-4-yl-3-oxopropan-1-one 
• 130735-95-4 8-Hydroxy-2-(4-morpholinyl)-4H-1-benzopyran-4-one 
• 351002-09-0 2-hydroxy-3-trifluoromethanesulfonyloxybenzoic acid methyl ester 
• 130766-15-3 8-methoxy-2-morpholin-4-yl-4H-chromen-4-one 
• 304-06-3 3-phenylsalicylic acid 
• 6342-70-7 3-methoxymethylsalicylate 
• 877-22-5 3-methoxysalicylic acid 

Downstream Products

• 778643-67-7 C₂₇H₂₃N₂O₄⁽¹⁺⁾ 
• 778643-68-8 A₀₄₀-70 
• 1174428-99-9 4-ethoxy-2-morpholino-8-phenylchromenylium chloride 
• 1174428-98-8 4-(3-hydroxypropoxy)-2-morpholino-8-phenylchromenylium chloride 
• 1174428-97-7 4-chloro-2-morpholino-8-phenylchromenylium chloride 
• 1202494-02-7 C₁₉H₁₇NO₄ 
• 1202494-01-6 C₁₉H₁₇NO₄ 
• 778643-66-6 C₂₇H₂₄NO₅⁽¹⁺⁾ 
• 778643-65-5 C₂₈H₂₃N₂O₅⁽¹⁺⁾ 
• 778643-09-7 C₂₈H₂₃N₂O₅S⁽¹⁺⁾*I^(1-) 

Relevant articles and documents

Lithiation of a silyl ether: Formation of an ortho-fries hydroxyketone

A hydroxy-directed alkylation of an N,N-diethylarylamide using CIPE-assisted α-silyl carbanions (CIPE=complex-induced proximity effect) has been developed using a simple reagent combination of LDA (lithium diisopropylamide) and chlorosilane. A study of the mechanism, and the application of the procedure to an anionic Snieckus-Fries rearrangement for a highly efficient synthesis of the potent phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, are reported.

Selective benzopyranone and pyrimido[2,1-α]isoquinolin-4-one inhibitors of DNA-dependent protein kinase: Synthesis, structure-activity studies, and radiosensitization of a human tumor cell line in vitro

A diverse range of chromen-2-one, chromen-4-one and pyrimidoisoquinolin-4- one derivatives was synthesized and evaluated for inhibitory activity against the DNA repair enzyme DNA-dependent protein kinase (DNA-PK), with a view to elucidating structure-activity relationships for potency and kinase selectivity. DNA-PK inhibitory activity varied widely over the series of compounds evaluated (IC50 values ranged from 0.19 to >10 μM), with excellent activity being observed for the 7,8-benzochromen-4-one and pyrimido[2,1-a] isoquinolin-4-one templates. By contrast, inhibitors based on the benzochromen-2-one (coumarin) or 2-aryl-7,8-benzochromen-4-one (flavone) scaffolds were less potent. Crucially, these studies revealed a very constrained structure-activity relationship at the 2-position of the benzopyranone and pyrimido[2,1-a]-isoquinolin-4-one pharmacophore, with only a 2-morpholino or 2-(2′-methylmorpholino) group being tolerated at this position. More detailed biological studies conducted with the most potent inhibitor NU7163 (48; IC50 = 0.19 μM) demonstrated ATP-competitive DNA-PK inhibition, with a Ki value of 24 nM, and 48 exhibited selectivity for DNA-PK compared with the related enzymes ATM, ATR, mTOR, and PI 3-K (p110alpha). Compound 48 sensitized the HeLa human tumor cell line to the cytotoxic effects of ionizing radiation in vitro, a dose modification factor of 2.3 at 10% survival being observed with an inhibitor concentration of 5 μM. This study identified these structural classes as novel DNA-PK inhibitors and delineated initial structure-activity relationships against DNA-PK.

Synthetic studies of the phosphatidylinositol 3-kinase inhibitor LY294002 and related analogues

Synthetic methodologies have been developed for the direct and high-yielding preparation of the phosphatidyl-inositol 3-kinase inhibitor LY294002. These methods are readily amenable to the efficient generation of analogues, which will facilitate a detailed investigation of this important family of enzymes.