HA 130 | 1229652-21-4

• 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 - 苯类化合物 - 苯酚醚
• 英文名称: HA 130
• 英文别名: 3-[(4-{[3-(4-fluorobenzyl)-2,4-dioxo-1,3-thiazolan-5-yliden]methyl}phenoxy)methyl]benzeneboronic acid；3-(4-{[(5Z)-3-[(4-fluorophenyl)methyl]-2,4-dioxo-1,3-thiazolidin-5-ylidene]methyl}phenoxymethyl)phenylboronic acid；[3-[[4-[[3-[(4-fluorophenyl)methyl]-2,4-dioxo-1,3-thiazolidin-5-ylidene]methyl]phenoxy]methyl]phenyl]boronic acid
• CAS: 1229652-21-4
• 化学式: C₂₄H₁₉BFNO₅S
• 分子量: 463.294
• InChiKey: VTNKMYWFWQTEHE-UHFFFAOYSA-N

物化性质

• 溶解度：
  DMF:10.0(最大浓度 mg/mL);21.58(最大浓度 mM)DMSO:30.11(最大浓度 mg/mL);64.99(最大浓度 mM)乙醇:0.5(最大浓度 mg/mL);1.08(最大浓度 mM)

计算性质

• 辛醇/水分配系数(LogP)：
  3.32
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  7

安全信息

• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

制备方法与用途

用途

HA 130 是一种自分泌运动抑制剂，是一种选择性的 autotaxin (ATX) 抑制剂，其 IC50 值为 28 nM。

靶点

Autotaxin
28 nM (IC₅₀)

体外研究

HA130 完全抑制了 ATX 促进 TEM（跨内皮迁移）的能力。在浓度为 0.3 μM 时，HA130 完全消除了 ATX 对 TK1 尾足形成的作用。

体内研究

HA130 减缓了 T 细胞穿过淋巴结微血管内皮细胞的迁移速度。与对照组相比，治疗组的“外周微血管内皮细胞/中央微血管内皮细胞”比率降低了 3 至 4 倍。

此外，皮下注射 HA130 引起了显著的淋巴细胞在引流淋巴结微血管内皮细胞层及其下方的堆积。

反应信息

• 作为产物：
  描述：

  (3-((4-formylphenoxy)methyl)phenyl)boronic acid 、 3-[(4-氟苯基)甲基]-1,3-噻唑烷-2,4-二酮 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 22.0h， 以64%的产率得到HA 130
  参考文献：
  名称：

  Discovery and Optimization of Boronic Acid Based Inhibitors of Autotaxin

  摘要：

  Autotaxin (ATX) is an extracellular enzyme that hydrolyzes lysophosphatidylcholine (LPC) to produce the lipid mediator lysophosphatidic acid (LPA). The ATX LPA signaling axis has been implicated in diverse physiological and pathological processes, including vascular development, inflammation, fibrotic disease, and tumor progression. Therefore targeting ATX with small molecule inhibitors is an attractive therapeutic strategy. We recently reported that 2,4-thiazolidinediones inhibit ATX activity in the micromolar range. Interestingly, inhibitory potency was dramatically increased by introduction of a boronic acid moiety, designed to target the active site threonine in ATX. Here we report on the discovery and further optimization of boronic acid based ATX inhibitors. The most potent of these compounds inhibits ATX-mediated LPC hydrolysis in the nanomolar range (IC50 = 6 nM). The finding that ATX can be targeted by boronic acids may aid the development of ATX inhibitors for therapeutic use.

  DOI：

  10.1021/jm1005012

文献信息

• Discovery and Optimization of Boronic Acid Based Inhibitors of Autotaxin
  作者：Harald M. H. G. Albers、Laurens A. van Meeteren、David A. Egan、Erica W. van Tilburg、Wouter H. Moolenaar、Huib Ovaa

  DOI：10.1021/jm1005012

  日期：2010.7.8

  Autotaxin (ATX) is an extracellular enzyme that hydrolyzes lysophosphatidylcholine (LPC) to produce the lipid mediator lysophosphatidic acid (LPA). The ATX LPA signaling axis has been implicated in diverse physiological and pathological processes, including vascular development, inflammation, fibrotic disease, and tumor progression. Therefore targeting ATX with small molecule inhibitors is an attractive therapeutic strategy. We recently reported that 2,4-thiazolidinediones inhibit ATX activity in the micromolar range. Interestingly, inhibitory potency was dramatically increased by introduction of a boronic acid moiety, designed to target the active site threonine in ATX. Here we report on the discovery and further optimization of boronic acid based ATX inhibitors. The most potent of these compounds inhibits ATX-mediated LPC hydrolysis in the nanomolar range (IC50 = 6 nM). The finding that ATX can be targeted by boronic acids may aid the development of ATX inhibitors for therapeutic use.