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H4541

Sigma-Aldrich

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
Empirical Formula (Hill Notation):
C17H9Cl2N3O2
CAS Number:
Molecular Weight:
358.18
MDL number:
PubChem Substance ID:
NACRES:
NA.77

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.

Packaging

5, 25 mg in glass bottle

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.

Pictograms

Exclamation markEnvironment

Signal Word

Warning

Hazard 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

Certificate of Analysis

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Certificate of Origin

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