H4541
HPI-4
≥98% (HPLC)
别名:
2,4-二氯-a-(3,4-二氢-4-氧代-2(1H)-喹唑啉基)-β-氧代苯丙腈, Ciliobrevin A, Hedgehog通路抑制剂4
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关于此项目
经验公式（希尔记法）:
C17H9Cl2N3O2
化学文摘社编号:
分子量:
358.18
NACRES:
NA.77
PubChem Substance ID:
UNSPSC Code:
51111800
MDL number:
产品名称
HPI-4, ≥98% (HPLC)
InChI key
SESYPWCSIZUIAS-FOWTUZBSSA-N
SMILES string
Clc1ccc(c(Cl)c1)C(=O)\C(C#N)=C2\NC(=O)c3ccccc3N2
InChI
1S/C17H9Cl2N3O2/c18-9-5-6-10(13(19)7-9)15(23)12(8-20)16-21-14-4-2-1-3-11(14)17(24)22-16/h1-7,21H,(H,22,24)/b16-12+
assay
≥98% (HPLC)
form
powder
color
off-white, off-white to orange
solubility
DMSO: 10 mg/mL, clear
storage temp.
2-8°C
Quality Level
Application
Hedgehog 通路抑制剂（HP1-4）已被用于抑制利什曼原虫中的动力蛋白 ATPase。
Biochem/physiol Actions
HPI-4 是一种 Hedgehog 途径抑制剂；纤毛生成抑制剂。
HPI-4 是一种 Hedgehog 途径抑制剂；纤毛生成抑制剂。Hedgehog（HH）信号传导途径是抗癌治疗的靶标。HH 途径中的关键信号分子 Smoothened 蛋白（Smo）已成为药理学干预的靶标，这导致产生了包括环巴胺在内的多种 Smo 拮抗剂。但是，Smo 的致癌形式对环巴胺具有抗性，因此鉴定下游效应蛋白（例如转录因子 Gli1 和 Gli2）的抑制剂非常重要。确定了四个抑制 Smo 下游 HH 途径的小分子，HPI-1、HPI-2、HPI-3 和 HPI-4。HPI-4 阻止了 SAG 激活 HH 途径，降低了 Smo 纤毛的积累，降低了组成型激活 HH 细胞系中的 HH 活性，并降低了 Gli1 和 Gli2 加工和稳定性。HPI-4 抑制小脑颗粒神经元前体细胞（HH 信号的重要模型）的增殖。HPI-4 处理的细胞中的纤毛被截断或缺失。据推测，HPI-4 的作用机制是直接通过纤毛的发生而引起的，从而导致 Gli1/Gli2 活性的破坏，这与环巴胺明显不同。
signalword
Warning
hcodes
Hazard Classifications
Acute Tox. 4 Oral - Aquatic Acute 1 - Aquatic Chronic 1
存储类别
11 - Combustible Solids
wgk
WGK 3
flash_point_f
Not applicable
flash_point_c
Not applicable
法规信息
新产品
此项目有
Effect of inhibition of axonemal dynein ATPases on the regulation of flagellar and ciliary waveforms in Leishmania parasites
Mukhopadhyay AG and Dey CS
Molecular and Biochemical Parasitology, 225, 27 -237 (2018)
Ivonne Bernal et al.
Journal of molecular biology, 431(19), 3787-3803 (2019-07-10)
Many medically relevant Gram-negative bacteria use the type III secretion system (T3SS) to translocate effector proteins into the host for their invasion and intracellular survival. A multi-protein complex located at the cytosolic interface of the T3SS is proposed to act
Characterization of ciliobrevin A mediated dynein ATPase inhibition on flagellar motility of Leishmania donovani
Reddy GS, et al.
Molecular and Biochemical Parasitology, 214, 75 -781 (2017)
Ivonne Bernal et al.
Protein science : a publication of the Protein Society, 28(10), 1888-1901 (2019-08-09)
Translocation of virulence effector proteins through the type III secretion system (T3SS) is essential for the virulence of many medically relevant Gram-negative bacteria. The T3SS ATPases are conserved components that specifically recognize chaperone-effector complexes and energize effector secretion through the
Wei Xiang et al.
Oncology reports, 32(4), 1622-1630 (2014-08-12)
Chondrosarcoma is a type of malignant bone tumor secreting cartilage-like matrix. In clinical treatment, there is no frequently used drug treatment option except for surgical resection. Hedgehog (HH) pathway is a classical signaling pathway that regulates normal cartilage cell development.
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