2-[[4-[4-[[3-[(2-甲基-6-苯并噻唑基)氨基]-3-氧代丙基]氨基]-4-氧代丁基]苯基]甲基]丙二酸 | 1370290-34-8

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 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: 2-[[4-[4-[[3-[(2-甲基-6-苯并噻唑基)氨基]-3-氧代丙基]氨基]-4-氧代丁基]苯基]甲基]丙二酸
• 英文名称: 2-(4-(4-((3-((2-methylbenzo[d]thiazol-6-yl)amino)-3-oxopropyl)amino)-4-oxobutyl)benzyl)malonic acid
• 英文别名: 2-(4-(4-(3-(2-methylbenzo[d]thiazol-6-ylamino)-3-oxopropylamino)-4-oxobutyl)benzyl)malonic acid；AZ-33；{4-[4-({3-[(2-Methyl-1,3-benzothiazol-6-YL)amino]-3-oxopropyl}amino)-4-oxobutyl]benzyl}propanedioic acid；2-[[4-[4-[[3-[(2-methyl-1,3-benzothiazol-6-yl)amino]-3-oxopropyl]amino]-4-oxobutyl]phenyl]methyl]propanedioic acid
• CAS: 1370290-34-8
• 化学式: C₂₅H₂₇N₃O₆S
• 分子量: 497.572
• InChiKey: SGFJAJFBGVAOFW-UHFFFAOYSA-N

物化性质

• 沸点：
  843.9±65.0 °C(Predicted)
• 密度：
  1.381±0.06 g/cm3(Predicted)
• 溶解度：
  DMF：30mg/mL；二甲基亚砜：30mg/mL；乙醇：2mg/mL； PBS (pH 7.2)：微溶

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  35
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  174
• 氢给体数：
  4
• 氢受体数：
  8

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

AZ-33（LDHA抑制剂33）是一种有效抑制乳酸脱氢酶A（LDHA）的化合物，其IC50值为0.5 μM。LDHA是参与厌氧糖酵解的关键酶，在人类恶性肿瘤中该酶经常失活。

靶点

Target	Value
LDHA (细胞自由测定)	0.5 μM

反应信息

• 作为反应物：
  描述：

  甲醇 、 2-[[4-[4-[[3-[(2-甲基-6-苯并噻唑基)氨基]-3-氧代丙基]氨基]-4-氧代丁基]苯基]甲基]丙二酸 在 sodium 作用下， 反应 5.0h， 以90%的产率得到dimethyl 2-(4-(4-((3-((2-methylbenzo[d]thiazol-6-yl)amino)-3-oxopropyl)amino)-4-oxobutyl)benzyl)malonate
  参考文献：
  名称：

  Design and Synthesis of Novel Lactate Dehydrogenase A Inhibitors by Fragment-Based Lead Generation

  摘要：

  Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate, utilizing NADH as a cofactor. It has been identified as a potential therapeutic target in the area of cancer metabolism. In this manuscript we report our progress using fragment-based lead generation (FBLG), assisted by X-ray crystallography to develop small molecule LDHA inhibitors. Fragment hits were identified through NMR and SPR screening and optimized into lead compounds with nanomolar binding affinities via fragment linking. Also reported is their modification into cellular active compounds suitable for target validation work.

  DOI：

  10.1021/jm201734r
• 作为产物：
  描述：

  4-苯基丁酸 在 咪唑 、 lithium hydroxide monohydrate 、 硫酸 、 水 、 N,N'-羰基二咪唑 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 215.0h， 生成 2-[[4-[4-[[3-[(2-甲基-6-苯并噻唑基)氨基]-3-氧代丙基]氨基]-4-氧代丁基]苯基]甲基]丙二酸
  参考文献：
  名称：

  Design and Synthesis of Novel Lactate Dehydrogenase A Inhibitors by Fragment-Based Lead Generation

  摘要：

  Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate, utilizing NADH as a cofactor. It has been identified as a potential therapeutic target in the area of cancer metabolism. In this manuscript we report our progress using fragment-based lead generation (FBLG), assisted by X-ray crystallography to develop small molecule LDHA inhibitors. Fragment hits were identified through NMR and SPR screening and optimized into lead compounds with nanomolar binding affinities via fragment linking. Also reported is their modification into cellular active compounds suitable for target validation work.

  DOI：

  10.1021/jm201734r

文献信息

• QUINOLINE BASED CYANINE DYE TURN-ON FLUORESCENT PROBES AND METHODS OF USE THEREOF
  申请人：YEDA RESEARCH AND DEVELOPMENT CO. LTD.

  公开号：US20210156867A1

  公开（公告）日：2021-05-27

  This invention is directed to a turn-on fluorescent probe, wherein said probe comprises a quinoline based cyanine dye derivative (QBC) and a specific protein binder covalently attached thereto directly or via a linker. This invention is further directed to His-tag binding compounds and uses thereof in the preparation of genetically targeted detectable molecules and sensors which can specifically bind tag-labeled proteins. This invention further describes methods for using these turn-on probes and compounds for detecting and labelling a wide range of proteins in their native environment.
• Design and Synthesis of Novel Lactate Dehydrogenase A Inhibitors by Fragment-Based Lead Generation
  作者：Richard A. Ward、Claire Brassington、Alexander L. Breeze、Alessandro Caputo、Susan Critchlow、Gareth Davies、Louise Goodwin、Giles Hassall、Ryan Greenwood、Geoffrey A. Holdgate、Michael Mrosek、Richard A. Norman、Stuart Pearson、Jonathan Tart、Julie A. Tucker、Martin Vogtherr、David Whittaker、Jonathan Wingfield、Jon Winter、Kevin Hudson

  DOI：10.1021/jm201734r

  日期：2012.4.12

  Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate, utilizing NADH as a cofactor. It has been identified as a potential therapeutic target in the area of cancer metabolism. In this manuscript we report our progress using fragment-based lead generation (FBLG), assisted by X-ray crystallography to develop small molecule LDHA inhibitors. Fragment hits were identified through NMR and SPR screening and optimized into lead compounds with nanomolar binding affinities via fragment linking. Also reported is their modification into cellular active compounds suitable for target validation work.