BQ-788 钠盐 | 156161-89-6

• 物质功能分类: 生物 - 生物化学试剂 - 拮抗剂
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: BQ-788 钠盐
• 中文别名: BQ-788钠盐
• 英文名称: BQ-788 sodium salt
• CAS: 156161-89-6
• 化学式: C34H51N5NaO7
• 分子量: 664.8
• InChiKey: IASLQTYUGYPLFB-FUKQNADPSA-N

物化性质

• 溶解度：
  在乙腈中的溶解度：0.3 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  4.44
• 重原子数：
  47
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  159
• 氢给体数：
  4
• 氢受体数：
  7

安全信息

• WGK Germany：
  3
• 海关编码：
  2923900090

制备方法与用途

生物活性

BQ-788 sodium salt 是一种有效，选择性的 ETB 受体拮抗剂，在人类 Girrardi 心脏细胞中抑制 ET-1 与 ETB 受体结合的 IC50 为 1.2 nM。

靶点

IC50: 1.2 nM (ETB)

体外研究

BQ-788 potently and competitively inhibits ¹²⁵ I-labeled ET-1 binding to ETB receptors in human Girrardi heart cells with an IC ₅₀ of 1.2 nM, but only poorly inhibits the binding to ETA receptors in human neuro-blastoma cell line SK-N-MC cells (IC ₅₀ , 1300 nM). BQ-788 shows no agonistic activity up to 10 μM and competitively inhibits thevasoconstriction induced by an ETB-selective agonist (pA2, 8.4). BQ-788 also inhibits several bioactivities of ET-1, such as bronchoconstriction, cell proliferation, and clearance of perfused ET-1.

体内研究

BQ-788 (3 mg/kg/h, i.v.) completely inhibits a pharmacological dose of ET-1- or sarafotoxin6c (0.5 nmol/kg, i.v.)-induced ETB receptor-mediated depressor, but not pressor responses in conscious rats. Furthermore, BQ-788 markedly increases the plasma concentration of ET-1, which is considered an index of potential ETB receptor blockade in vivo. In Dahl salt-sensitive hypertensive (DS) rats, BQ-788 (3 mg/kg/h, i.v.) increases blood pressure by about 20 mm Hg. It is reported that BQ-788 also inhibits ET-1-induced bronchoconstriction, tumor growth and lipopolysaccharide-induced organfailure. BQ 788 (3 mg/kg) results in an eightfold leftward shift in the ET-1 dose-response curve, suggesting a significant involvement of ETB dilator receptors. Mice are treated with 30 nmol BQ-788 by intraplantar, reduce mechanical hyperalgesia (47% and 42%), thermal hyperalgesia (68% and 76%), oedema (50% and 30%); myeloperoxidase activity (64% and 32%), and overt-pain like behaviours. Additionally, intraplantar treatment with clazosentan or BQ-788 decreases spinal (45% and 41%) and peripheral (47% and 47%) superoxide anion production as well as spinal (47% and 47%) and peripheral (33% and 54%) lipid peroxidation, respectively.

文献信息

• COMPOSITIONS AND METHODS FOR TREATMENT OF DISEASES AND CONDITIONS EMPLOYING ORAL ADMINISTRATION OF SODIUM PENTOSAN POLYSULFATE AND OTHER PENTOSAN POLYSULFATE SALTS
  申请人：PARSONS C. Lowell

  公开号：US20170189443A1

  公开（公告）日：2017-07-06

  The present invention is directed to a pharmaceutical composition comprising: (1) a therapeutically effective quantity of sodium pentosan polysulfate; (2) a quantity of a penetration enhancer sufficient to improve the bioavailability of the sodium pentosan polysulfate; and (3) optionally, a pharmaceutically acceptable carrier and to methods for the oral administration of sodium pentosan polysulfate with improved bioavailability for the treatment of interstitial cystitis and other urinary tract diseases and conditions. Such compositions and methods allow the administration of sodium pentosan polysulfate at lower dosages to reduce the frequency and severity of side effects.