2-(morpholin-4-yl)-8-phenyl-4H-chromen-4-one

• ChemBase编号: 2382
• 分子式: C19H17NO3
• 平均质量: 307.34318
• 单一同位素质量: 307.12084341
• SMILES: N1(CCOCC1)c1oc2c(cccc2c2ccccc2)c(=O)c1
• Canonical SMILES: O=c1cc(oc2c1cccc2c1ccccc1)N1CCOCC1
• 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
• InChIKey: CZQHHVNHHHRRDU-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 2-(morpholin-4-yl)-8-phenyl-4H-chromen-4-one
• IUPAC传统名: 2-(morpholin-4-yl)-8-phenylchromen-4-one
• 别名: 2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; 2-(4-Morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride; LY-294,002 hydrochloride; 2-(4-Morpholinyl)-8-Phenyl-4h-1-Benzopyran-4-One; LY294002

登记号

• CAS号: 154447-36-6; 934389-88-5
• MDL号: MFCD00270881
• PubChem SID: 160965833; 46504762; 24278828
• PubChem CID: 3973
• CHEMBL: 98350
• 维基百科标题: LY294002

理论计算性质

JChem

• Acid pKa: 15.94608
• 质子受体: 4
• 质子供体: 0
• LogD (pH = 5.5): 3.4085917
• LogD (pH = 7.4): 3.4125834
• Log P: 3.4126344
• 摩尔折射率: 98.5041 cm^3
• 极化性: 35.035717 Å^3
• 极化表面积: 38.77 Å^2
• 可自由旋转的化学键: 2
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 3.46
• LOG S: -3.38
• 溶解度: 1.27e-01 g/l

分子性质

理化性质

• 溶解度: DMSO; DMSO: >5 mg/mL; H2O: insoluble
• 外观: white to off-white solid

安全信息

• 保存条件: -20°C
• 德国WGK号: 3
• 个人保护装置: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter
• 保存温度: 2-8°C

药理学性质

• 作用靶点: PI3K

产品相关信息

• 纯度: ≥98% (HPLC)
• 成盐信息: Free Base

详细说明

DrugBank - DB02656

Drug information: experimental

Selleck Chemicals - S1105

Research Area

• Description: Cancer

Biological Activity

• Description: LY294002 is a PI3K inhibitor for p110α, p110δ and p110β with IC50 of 0.5 μM, 0.57 μM and 0.97 μM, respectively.
• Targets: p110α; p110δ; p110β
• IC50: 0.5 μM; 0.57 μM; 0.97 μM^[1]
• In Vitro: LY294002 inactivates Akt/PKB, consequently inhibiting cell proliferation and inducing apoptosis. LY294002 demonstrates a remarkable growth-inhibitory and apoptosis-inducing effect in these colon cancer cell lines, with decreased expression of phosphorylated Akt (Ser473). ^[2]LY294002 induces marked nuclear pyknosis and diminished cytoplasmic volume in the tumor cells. Thus, LY294002 markedly inhibits ovarian cancer cell proliferation in vitro. LY294002 induces specific G1 arrest in cell growth, leading to almost complete inhibition of melanoma cell proliferation and partial inhibition of MG-63 (osteosarcoma cell line) proliferation. The effect of LY294002 on cell cycle progression may provide insights into a possible link between the PI3K activation pathway and cancer cell cycle regulation. ^[3]
• In Vivo: LY294002 also resultes in suppression of tumor growth and induction of apoptosis, especially in the LoVo tumors, and therefore shows remarkable effectiveness in the mouse peritonitis carcinomatosa model. ^[2] LY294002 significantly inhibits growth and ascites formation of ovarian carcinoma. ^[3]
• Clinical Trials: LY294002 is currently in Phase I clinical trials in patients with cancers.

Protocol

• Protocol: Kinase Assay ^[4]
• kinase assays: PI3K inhibition by LY294002 is determined in a radiometric assay using purified, recombinant enzymes with 1?μM ATP. The kinase reaction is carried out for 1?hour at room temperature (24^oC) and is terminated by addition of PBS. IC50 values are subsequently determined using a sigmoidal dose–response curve fit (variable slope). CK2 and GSK3β (glycogen synthase kinase 3β) inhibition is established by kinase selectivity screening. LY294002 is tested against the Upstate panel of kinases in 10?μM ATP.
• Protocol: Cell Assay ^[2]
• Cell Lines: Colon cancer cell lines DLD-1, LoVo, HCT15, and Colo205
• Concentrations: 0–50 μM
• Incubation Time: 0–48 hours
• Methods: 1.0×10^5 cells (100 μL volume/well) are inoculated into 96-well microtiter plates. LY294002 is added to triplicate wells and cultured at 37^oC for 0–48 hours. After treatment, 10 μL of Premix WST-1 are added to each microculture well, and the plates are incubated for 60 minutes at 37^oC, after which absorbance at 450 nm is measured with a microplate reader.
• Protocol: Animal Study ^[3]
• Animal Models: Two groups of athymic nude mice (5–7 weeks) are inoculated i.p. with OVCAR-3 cells
• Formulation: Dissolved in DMSO plus 0.25 ml of PBS
• Doses: 0–100 mg/kg
• Administration: Administered via i.p.

References

• References: [1] Chaussade C, et al. Biochem J, 2007, 404(3), 449-58.
• References: [2] Semba S, et al. Clin Cancer Res, 2002, 8(6), 1957-63.
• References: [3] Hu L, et al. Clin Cancer Res, 2000, 6(3), 880-6.
• References: [4] Gharbi SI, et al. Biochem J, 2007, 404(1), 15-21.

Sigma Aldrich - L9908

Frequently Asked Questions
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Biochem/physiol Actions
Specific cell permeable phosphatidylinositol 3-kinase inhibitor.

参考文献

• Semba S, et al. Clin Cancer Res, 2002, 8(6), 1957-63.
• Hu L, et al. Clin Cancer Res, 2000, 6(3), 880-6.
• Gharbi SI, et al. Biochem J, 2007, 404(1), 15-21.
• Chaussade C, et al. Biochem J, 2007, 404(3), 449-58.