(1R,3R,6R,8S,10R,12S,13S,16S,17R)-8-tert-butyl-6,12,17-trihydroxy-16-methyl-2,4,14,19-tetraoxahexacyclo[8.7.2.0^{1,11}.0^{3,7}.0^{7,11}.0^{13,17}]nonadecane-5,15,18-trione

• ChemBase编号: 72628
• 分子式: C20H24O10
• 平均质量: 424.39856
• 单一同位素质量: 424.13694697
• SMILES: C123[C@@H]([C@H]4[C@@]([C@@]51O[C@H]1C2([C@@H](C[C@@H]3OC5=O)C(C)(C)C)[C@H](C(=O)O1)O)([C@@H](C(=O)O4)C)O)O
• Canonical SMILES: O=C1O[C@@H]2[C@@]([C@@H]1C)(O)[C@@]13C4([C@@H]2O)[C@@H](OC3=O)C[C@H](C24[C@H](O1)OC(=O)[C@@H]2O)C(C)(C)C
• InChI: InChI=1S/C20H24O10/c1-6-12(23)28-11-9(21)18-8-5-7(16(2,3)4)17(18)10(22)13(24)29-15(17)30-20(18,14(25)27-8)19(6,11)26/h6-11,15,21-22,26H,5H2,1-4H3/t6-,7+,8-,9-,10+,11+,15+,17?,18?,19-,20-/m1/s1
• InChIKey: SQOJOAFXDQDRGF-RLAVLKHASA-N

名称和登记号

名称

• IUPAC标准名: (1R,3R,6R,8S,10R,12S,13S,16S,17R)-8-tert-butyl-6,12,17-trihydroxy-16-methyl-2,4,14,19-tetraoxahexacyclo[8.7.2.0^{1,11}.0^{3,7}.0^{7,11}.0^{13,17}]nonadecane-5,15,18-trione
• IUPAC传统名: (1R,3R,6R,8S,10R,12S,13S,16S,17R)-8-tert-butyl-6,12,17-trihydroxy-16-methyl-2,4,14,19-tetraoxahexacyclo[8.7.2.0^{1,11}.0^{3,7}.0^{7,11}.0^{13,17}]nonadecane-5,15,18-trione
• 别名: BN 52021; Ginkgolide B

登记号

• CAS号: 15291-77-7
• PubChem SID: 162037553
• PubChem CID: 17751009

理论计算性质

• Acid pKa: 11.709941
• 质子受体: 7
• 质子供体: 3
• LogD (pH = 5.5): -0.5822128
• LogD (pH = 7.4): -0.5822338
• Log P: -0.58221257
• 摩尔折射率: 91.382 cm^3
• 极化性: 38.405952 Å^3
• 极化表面积: 148.82 Å^2
• 可自由旋转的化学键: 1
• 里宾斯基五规则: true

分子性质

安全信息

• 保存条件: -20°C

药理学性质

• 作用靶点: PAFR

产品相关信息

• 成盐信息: Free Base

详细说明

Selleck Chemicals - S1343

Research Area

• Description: Cancer

Biological Activity

• Description: Ginkgolide B (BN 52021) is a PAFR antagonist with IC50 of 3.6 μM.
• Targets: PAFR
• IC50: 3.6 μM ^[1]
• In Vitro: Ginkgolide B potently inhibits a platelet-activating factor (PAF) receptor. ^[1] Treatment of PMN with ginkgolide B (0.5 μM -12 μM) stimulates a rapid and weak production of reactive oxygen species determined by chemiluminescence. Ginkgolide B potentiates the CL response induced by fMet-Leu-Phe and zymosan. ^[2] Ginkgolide B induces cyst cell differentiation and alteres the Ras/MAPK signaling pathway. ^[3] Ginkgolide B promotes the proliferation and endothelial gene expression, and markedly enhances vascular endothelial growth factor-induced migration response and the capability to incorporate into the vascular networks in EPCs. Ginkgolide B protects EPCs from H₂O₂-induced cell death. Ginkgolide B induces the phosphorylation of eNOS, Akt and p38, which in turn promotes cell proliferation and function. ^[4]
• In Vivo: Ginkgolide B (2 μM) significantly inhibits MDCK cyst formation dose dependently, with up to 69% reduction. Ginkgolide B also significantly inhibits cyst enlargement in the MDCK cyst model, embryonic kidney cyst model, and PKD mouse model.^[3] Preischemic application of Ginkgolide B (50 mg/kg p.o.) significantly reduces neuronal damage.^[5] 30 minutes of pretreatment with Ginkgolide B (100 mg/kg, s. c.) reduces the infarct area in the mouse model of focal ischemia. In primary cultures of hippocampal neurons and astrocytes from neonatal rats, Ginkgolide B (1 μM) protects the neurons against damage caused by glutamate. Ginkgolide B (100 μM) reduces apoptotic damage induced by staurosporine. ^[6] In pentobarbitone or ethyl carbamate-anaesthetized animals, Ginkgolide B (1 mg/kg i.v. or 10 mg/kg p.o.) inhibits bronchoconstriction, the hematocrit increase and the accompanying thrombopenia and leukopenia induced by PAF-acether (33 ng/kg–100 ng/kg). Ginkgolide B at a dose of 3 mg/kg reduces the bronchoconstriction induced by aerosolized PAF-acether. Ginkgolide B at a dose of 300 μM also inhibits the superoxide production by PAF-acether-stimulated alveolar macrophages. Ginkgolide B blocks the formation of thromboxane-triggered by PAF-acether (100 ng) injected into perfused lung.Pretreatment of parenchyma lung strips with Ginkgolide B (100 μM) partially inhibits the contraction induced by PAF-acether (0.1 μM) and suppresses the accompanying release of thromboxane. ^[7] Ginkgolide B inhibits the maturation of ischemic injury. ^[8] Ginkgolide B treatment reveals marked reduction in infarction volume, brain edema and neurological deficits. Ginkgolide B also inhibitsischemia/reperfusion (I/R) induced NF-κB, microglia activation and production of pro-inflammatory cytokines. Ginkgolide B reducesBax protein levels and increases Bcl-2 protein levels in the post-ischemic brains. ^[9] Ginkgolide B attenuates platelet aggregation and inhibits phosphatidylinositol 3 kinase (PI3K) activation and Akt phosphorylation in thrombin- and collagen-activated platelets.Ginkgolide B decreases plasma PF4 and RANTES levels in ApoE^?/? mice.Ginkgolide B diminishes P-selectin, PF4, RANTES, and CD40L expression in aortic plaque in ApoE^?/? mice.Moreover, ginkgolide B suppresses macrophage and vascular cell adhesion protein 1 (VCAM-1) expression in aorta lesions in ApoE^?/? mice.^[10]

Protocol

• Protocol: Animal Study ^[10]
• Animal Models: Eight-week-old male ApoE^?/? mice
• Formulation: PBS
• Doses: 0.6 mg/day
• Administration: Intragastric administration

References

• References: [1] Lamant V, et al. BiochemPharmacol, 1987, 36(17), 2749-2752.
• References: [2] Lenoir M, et al. BiochemPharmacol, 2002, 63(7), 1241-1249.
• References: [3] Zhou H, et al. Am J Physiol Renal Physiol, 2012, 302(10), F1234-F1242.
• References: [4] Tang Y, et al. Eur Cell Mater, 2011, 21, 459-469.
• References: [5] OberpichlerH, et al. J Cereb Blood Flow Metab, 1990, 10(1), 133-135.
• References: [6] Ahlemeyer B, et al. Pharmacopsychiatry, 2003, Suppl 1, S8-S14.
• References: [7] Desquand S, et al. Eur J Pharmacol, 1986, 127(1-2), 83-95.
• References: [8] Birkle DL,et al. J Neurochem, 1988, 51(6), 1900-1905.
• References: [9] Gu JH, et al. Eur J Pharm Sci, 2012, 47(4), 652-660.
• References: [10] Liu X,et al. PLoS One, 2012, 7(5), e36237.

参考文献

• Lamant V, et al. BiochemPharmacol, 1987, 36(17), 2749-2752.
• Lenoir M, et al. BiochemPharmacol, 2002, 63(7), 1241-1249.
• Zhou H, et al. Am J Physiol Renal Physiol, 2012, 302(10), F1234-F1242.
• Tang Y, et al. Eur Cell Mater, 2011, 21, 459-469.
• OberpichlerH, et al. J Cereb Blood Flow Metab, 1990, 10(1), 133-135.
• Ahlemeyer B, et al. Pharmacopsychiatry, 2003, Suppl 1, S8-S14.
• Desquand S, et al. Eur J Pharmacol, 1986, 127(1-2), 83-95.
• Birkle DL,et al. J Neurochem, 1988, 51(6), 1900-1905.
• Gu JH, et al. Eur J Pharm Sci, 2012, 47(4), 652-660.
• Liu X,et al. PLoS One, 2012, 7(5), e36237.