Ac-DEVD-pNA | 189684-50-2

• 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: Ac-DEVD-pNA
• 英文别名: acetyl-Asp-Glu-Val-Asp p-nitroanilide；N-Acetyl-Asp-Glu-Val-Asp p-nitroanilide；(4S)-4-[[(2S)-2-acetamido-3-carboxypropanoyl]amino]-5-[[(2S)-1-[[(2S)-3-carboxy-1-(4-nitroanilino)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxopentanoic acid
• CAS: 189684-50-2
• 化学式: C₂₆H₃₄N₆O₁₃
• mdl: MFCD00792707
• 分子量: 638.588
• InChiKey: GGXRLUDNGFFUKI-ORGXJRBJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  45
• 可旋转键数：
  17
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.461
• 拓扑面积：
  303
• 氢给体数：
  8
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  Ac-DEVD-pNA 在 human caspase-3 作用下， 以 aq. buffer 为溶剂， 生成 4-硝基苯胺
  参考文献：
  名称：

  Effect of a Procaspase-Activating Compound on the Catalytic Activity of Mature Caspase-3

  摘要：

  半胱天冬酶-3（Caspase-3）是一种具有二聚结构的凋亡执行酶，其酶原（procaspase-3）是利用合成化合物进行癌症化疗的靶蛋白。先前的研究表明，PAC-1（第一种促活化酶原的化合物）通过Zn2+螯合机制影响癌细胞中procaspase-3的激活。然而，我们发现该化合物在没有Zn2+的情况下也增强了成熟半胱天冬酶-3的活性。PAC-1对成熟半胱天冬酶-3活性的增强呈现出与化合物浓度相关的米哈利斯-门腾型饱和依赖性。PAC-1诱导了成熟半胱天冬酶-3的紫外-可见光谱的变化。根据这些发现，我们提出PAC-1与蛋白质核心之间存在直接的结构相互作用。根据PAC-1与成熟半胱天冬酶-3复合物的分子动力学计算，PAC-1可能结合于成熟半胱天冬酶-3二聚结构之间的界面。建议在PAC-1与影响成熟半胱天冬酶-3催化活性的氨基酸残基之间存在相互作用。在这项研究中，揭示了该促凋亡化合物的多种功能。

  DOI：

  10.1246/bcsj.20150139
• 作为产物：
  描述：

  N-乙酰基-L-天冬氨酸 4-叔丁酯 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.17h， 生成 Ac-DEVD-pNA
  参考文献：
  名称：

  Using Peptidic Inhibitors to Systematically Probe the S1‘ Site of Caspase-3 and Caspase-7

  摘要：

  Fifteen ketone-containing peptides were designed, synthesized, and used to probe the effect of substitution at the P1' position on caspase-3 and -7 inhibition. Even with the large bias of Ac-Asp-Glu-Val-Asp at the P4-P1 positions, certain peptides with cyclic functionality in the P1' position show a dramatically reduced ability to inhibit these caspases. Additionally, trends toward isozyme selectivity were also uncovered for particular P1' substituents. The data indicate that substitution in the P1' position can drastically affect both caspase inhibition and selectivity.

  DOI：

  10.1021/ol051287d

文献信息

• [EN] NOVEL HYDROGEN PEROXIDE-ACTIVABLE, ANTI-OXIDANT COMPOUNDS AND METHODS USING SAME<br/>[FR] NOUVEAUX COMPOSÉS ANTI-OXYDANTS ACTIVABLES PAR PEROXYDE D'HYDROGÈNE, COMPOSÉS ANTI-OXYDANTS ET PROCÉDÉS LES UTILISANT
  申请人：BETH ISRAEL HOSPITAL

  公开号：WO2016073357A1

  公开（公告）日：2016-05-12

  The present invention includes 4-(hydroxymethyl)phenylboronic esters, which react with hydrogen peroxide to form 4-hydroxybenzyl alcohol, which is an anti-inflammatory and/or anti-oxidant compound. In certain embodiments, the compositions of the invention may be used to treat or prevent oxidative stress and/or inflammation, including ischemic disease.

  本发明包括4-(羟甲基)苯硼酸酯，它们与过氧化氢反应形成4-羟基苯甲醇，这是一种抗炎和/或抗氧化剂化合物。在某些实施例中，本发明的组合物可用于治疗或预防氧化应激和/或炎症，包括缺血性疾病。
• DESIGN, SYNTHESIS AND EVALUATION OF PROCASPASE ACTIVATING COMPOUNDS AS PERSONALIZED ANTI-CANCER DRUGS
  申请人：Hergenrother Paul J.

  公开号：US20140315915A1

  公开（公告）日：2014-10-23

  Compositions and methods are disclosed in embodiments relating to induction of cell death such as in cancer cells. Compounds and related methods for synthesis and use thereof, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells are disclosed. Compounds are disclosed that have lower neurotoxicity effects than other compounds.

  本实施例揭示了与诱导细胞死亡有关的组合物和方法，例如在癌细胞中。揭示了用于合成和使用相关方法的化合物，包括在治疗癌症和选择性诱导细胞凋亡方面使用化合物的方法。揭示了具有比其他化合物更低神经毒性影响的化合物。
• PROCASPASE ACTIVATING COMPOUNDS
  申请人：The Board of Trustees of the University of Illinois

  公开号：US20150344452A1

  公开（公告）日：2015-12-03

  Compositions and methods are disclosed in embodiments relating to induction of cell death such as in cancer cells. Compounds and related methods for synthesis and use thereof, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells are disclosed. Compounds are disclosed that have lower neurotoxicity effects than other compounds.

  本实施例揭示了与细胞死亡诱导有关的组合物和方法，例如在癌细胞中。揭示了合成和使用相关化合物的方法，包括在治疗癌症和选择性诱导细胞凋亡方面使用化合物的方法。揭示了具有较低神经毒性效应的化合物。
• Selective apoptotic induction in cancer cells including activation of procaspase-3
  申请人：The Board of Trustees of the University of Illinois

  公开号：EP2634581A1

  公开（公告）日：2013-09-04

  Compounds and related methods for synthesis, and the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells are disclosed. Compounds are disclosed in connection with modification of procaspases such as procaspase-3, and particular embodiments are capable of direct activation of procaspase-3 and procaspase-7 to the effector forms of caspase-3 and caspase-7. Procaspase-3 levels can vary among cancer cell types; several types have relatively high levels and can have increased susceptibility to chemotherapy by compounds and methods herein. Therapeutic applications are relevant for a variety of cancer conditions and cell types, e.g. breast, lung, brain, colon, renal, adrenal, melanoma, and others.

  公开了化合物和相关的合成方法，以及化合物在治疗癌症和选择性诱导细胞凋亡疗法中的用途。所公开的化合物涉及对原蛋白酶（如原蛋白酶-3）的修饰，特定的实施方案能够将原蛋白酶-3和原蛋白酶-7直接激活为caspase-3和caspase-7的效应形式。Procaspase-3 的水平可因癌细胞类型而异；有几种癌细胞类型的 Procaspase-3 水平相对较高，可增加对本文所述化合物和方法化疗的敏感性。治疗应用适用于多种癌症病症和细胞类型，如乳腺癌、肺癌、脑癌、结肠癌、肾癌、肾上腺癌、黑色素瘤等。
• Compounds and methods for the treatment of cancer
  申请人：The Board of Trustees of the University of Illinois

  公开号：US10166229B2

  公开（公告）日：2019-01-01

  Compositions and methods are disclosed in embodiments relating to induction of cell death such as in cancer cells. Compounds and related methods for synthesis and use thereof, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells are disclosed. Compounds are disclosed in connection with modification of procaspases such as procaspase-3. In embodiments, compositions are capable of activation of procaspase-3.

  在有关诱导细胞死亡（如癌细胞）的实施方案中，公开了化合物和方法。公开了化合物及其合成和使用的相关方法，包括在治疗癌症和选择性诱导细胞凋亡的疗法中使用化合物。所公开的化合物涉及对原蛋白酶（如原蛋白酶-3）的修饰。在实施方案中，组合物能够激活procaspase-3。