Histrelin Acetate | 220810-26-4

• 物质功能分类: 生物化工 - 多肽
• 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
• 英文名称: Histrelin Acetate
• 英文别名: acetic acid;(2S)-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2R)-3-(1-benzylimidazol-4-yl)-1-[[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-[(2S)-2-(ethylcarbamoyl)pyrrolidin-1-yl]-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]-5-oxopyrrolidine-2-carboxamide
• CAS: 220810-26-4
• 化学式: C70H94N18O16
• 分子量: 1443.6
• InChiKey: BKEMVGVBBDMHKL-VYFXDUNUSA-N

物化性质

• 溶解度：
  DMF：30mg/mL； DMSO：30mg/mL；乙醇：0.25mg/mL； PBS（pH 7.2）：10 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  -0.81
• 重原子数：
  104
• 可旋转键数：
  34
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  524
• 氢给体数：
  17
• 氢受体数：
  19

ADMET

代谢

使用人肝细胞进行的体外药物代谢研究中，发现了一个由C端脱烷基化产生的histrelin代谢物。由水解产生的肽片段也可能是代谢物。

An in vitro drug metabolism study using human hepatocytes identified a single histrelin metabolite resulting from C-terminal dealkylation. Peptide fragments resulting from hydrolysis are also likely metabolites.

来源:DrugBank

毒理性

• 蛋白质结合

对于Vantas产品，在体外测量的血浆中未结合药物的分数为29.5% ± 8.9%（平均值 ± 标准差）。

For the product Vantas, the fraction of drug unbound in plasma measured in vitro was 29.5% ± 8.9% (mean ± SD).

来源:DrugBank

吸收、分配和排泄

• 吸收

在17名晚期前列腺癌患者中，皮下植入一种醋酸亮丙瑞林植入剂（商品名：Vantas）后，血清中醋酸亮丙瑞林的平均峰浓度为1.10 ± 0.375 ng/mL（平均值 ± 标准差），中位达峰时间为12小时。持续的皮下释放明显，血清水平在整个52周给药期间保持稳定（见图1）。52周治疗结束时，血清中醋酸亮丙瑞林的平均浓度为0.13 ± 0.065 ng/mL。

Following subcutaneous insertion of one histrelin implant as the product Vantas in advanced prostate cancer patients (n = 17), peak serum concentrations of 1.10 ± 0.375 ng/mL (mean ± SD) occurred at a median of 12 hours. Continuous subcutaneous release was evident, as serum levels were sustained throughout the 52 week dosing period (see Figure 1). The mean serum histrelin concentration at the end of the 52 week treatment duration was 0.13 ± 0.065 ng/mL.

来源:DrugBank

吸收、分配和排泄

• 分布容积

皮下注射.histrelin后，健康志愿者体内分布容积为58.4±7.86 L。

The apparent volume of distribution of histrelin following a subcutaneous bolus dose of histrelin as the product Vantas (500 mcg) in healthy volunteers was 58.4 ± 7.86 L

来源:DrugBank

吸收、分配和排泄

• 清除

在17名前列腺癌患者中植入50毫克（作为醋酸组氨酸）的Vantas植入剂后，表观清除率为174毫升/分钟。

The apparent clearance following a 50 mg (as histrelin acetate) Vantas implant in 17 prostate cancer patients was 174 mL/min.

来源:DrugBank

文献信息

• Prostate cancer-associated secreted proteins
  申请人：Battelle Memorial Institute

  公开号：US10725053B2

  公开（公告）日：2020-07-28

  Methods are provided for treating a subject with prostate cancer and/or diagnosing a subject at risk for prostate cancer, which can include measuring increased expression of at least two prostate cancer-related molecules in a sample obtained from a subject, including the prostate cancer-related molecules AGR2, AGR3, CRISP3, CCL3, CEACAM5, CEACAM6, IL24, MMP9, CXCL14, CD90, POSTN, and SFRP4. The methods can include administering at therapy to a subject with prostate cancer. Methods are provided for treating a subject with intermediate- or high-risk prostate cancer, which can include measuring increased expression of MMP9 in a sample obtained from a subject compared to a control representing expression of MMP9 expected in a sample from a subject who has low-risk prostate cancer.

  提供了治疗前列腺癌受试者和/或诊断前列腺癌风险受试者的方法，其中可包括测量从受试者处获得的样本中至少两种前列腺癌相关分子的增加表达，包括前列腺癌相关分子AGR2、AGR3、CRISP3、CCL3、CEACAM5、CEACAM6、IL24、MMP9、CXCL14、CD90、POSTN和SFRP4。这些方法可包括对前列腺癌患者进行治疗。提供了治疗中危或高危前列腺癌受试者的方法，其中可包括与代表低危前列腺癌受试者样本中预期 MMP9 表达量的对照相比，测量受试者样本中 MMP9 表达量的增加。
• Gene panel to predict response to androgen deprivation in prostate cancer
  申请人：Rutgers, The State University of New Jersey

  公开号：US11299786B2

  公开（公告）日：2022-04-12

  Methods for predicting the response of prostate cancer to androgen deprivation therapy (ADT) using a gene signature of five genes (CSPG5, FKBP6, FOSB, STMN1, and TTC27) is provided. Also provided are sets containing specific binding molecules for each of CSPG5, FKBP6, FOSB, STMN1, and TTC27 and kits containing such sets.

  提供了利用五个基因（CSPG5、FKBP6、FOSB、STMN1 和 TTC27）的基因特征预测前列腺癌对雄激素剥夺疗法（ADT）反应的方法。此外，还提供了含有 CSPG5、FKBP6、FOSB、STMN1 和 TTC27 中每种基因的特异性结合分子的试剂盒以及含有这些试剂盒的试剂盒。
• PROTEIN PANELS FOR THE EARLY DIAGNOSIS/PROGNOSIS AND TREATMENT OF AGGRESSIVE PROSTATE CANCER
  申请人：Battelle Memorial Institute

  公开号：EP4017993A2

  公开（公告）日：2022-06-29
• IMMUNO-MALDI TO MEASURE AKT1 AND AKT2 PHOSPHORYLATION
  申请人：UVic Industry Partnerships Inc.

  公开号：US20170299606A1

  公开（公告）日：2017-10-19

  This application relates to methods of quantifying AKT1 and AKT2 and determining AKT1 and AKT2 phosphorylation status. The disclosed methods allow for selection of cancer therapy.
• PROSTATE CANCER-ASSOCIATED SECRETED PROTEINS
  申请人：Battelle Memorial Institute

  公开号：US20180164329A1

  公开（公告）日：2018-06-14

  Methods are provided for treating a subject with prostate cancer and/or diagnosing a subject at risk for prostate cancer, which can include measuring increased expression of at least two prostate cancer-related molecules in a sample obtained from a subject, including the prostate cancer-related molecules AGR2, AGR3, CRISP3, CCL3, CEACAM5, CEACAM6, IL24, MMP9, CXCL14, CD90, POSTN, and SFRP4. The methods can include administering at therapy to a subject with prostate cancer. Methods are provided for treating a subject with intermediate- or high-risk prostate cancer, which can include measuring increased expression of MMP9 in a sample obtained from a subject compared to a control representing expression of MMP9 expected in a sample from a subject who has low-risk prostate cancer.