H4541
HPI-4
≥98% (HPLC)
Synonym(s):
2,4-Dichloro-a-(3,4-dihydro-4-oxo-2(1H)-quinazolinylidene)-β-oxo-benzenepropanenitrile, Ciliobrevin A, Hedgehog Pathway Inhibitor 4
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About This Item
Empirical Formula (Hill Notation):
C17H9Cl2N3O2
CAS Number:
Molecular Weight:
358.18
MDL number:
UNSPSC Code:
51111800
PubChem Substance ID:
NACRES:
NA.77
Recommended Products
Quality Level
Assay
≥98% (HPLC)
form
powder
color
off-white, off-white to orange
solubility
DMSO: 10 mg/mL, clear
storage temp.
2-8°C
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+
InChI key
SESYPWCSIZUIAS-FOWTUZBSSA-N
Application
Hedgehog pathway inhibitor (HP1-4) has been used for the inhibition of dynein ATPase in Leishmania.
Biochem/physiol Actions
HPI-4 is a Hedgehog pathway inhibitor; ciliogenesis inhibitor. The Hedgehog (HH) signaling pathway is targeted for anti-cancer therapeutics. A key signaling molecule in HH pathway, Smoothened (Smo), has been the target of pharmacological intervention, which has resulted in multiple Smo antagonists including Cyclopamine. However, the oncogenic form of Smo is resistant to Cyclopamine, so the identification of inhibitors of downstream effectors, such as the transcription factors Gli1 and Gli2, is important. Four small molecules were identified to inhibit HH downstream of Smo, HPI-1, HPI-2, HPI-3, and HPI-4. HPI-4 blocked HH pathway activation by SAG, decreased Smo ciliary accumulation, decreased HH activity in a consitutively active HH cell line, and decreased Gli1 and Gli2, processing, and stability. HPI-4 inhibited proliferation of cerebellar granula neuron precursor cells, an important model of HH signaling. Cilia in HPI-4-treated cells were either truncated or absent. The mechanism of action of HPI-4 is hypothesized to be directly through perturbation of ciliogenesis, leading to disruption of Gli1/Gli2 activity, which is distinctly different from that of Cyclopamine.
Signal Word
Warning
Hazard Statements
Precautionary Statements
Hazard Classifications
Acute Tox. 4 Oral - Aquatic Acute 1 - Aquatic Chronic 1
Storage Class Code
11 - Combustible Solids
WGK
WGK 3
Flash Point(F)
Not applicable
Flash Point(C)
Not applicable
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