Home > Compound List > Product Information
HPI-4_Molecular_structure_CAS_302803-72-1)
Click picture or here to close

HPI-4

Catalog No. H4541 Name Sigma Aldrich
CAS Number 302803-72-1 Website http://www.sigmaaldrich.com
M. F. C17H9Cl2N3O2 Telephone 1-800-521-8956
M. W. 358.17826 Fax
Purity ≥98% (HPLC) Email
Storage Chembase ID: 154756

SYNONYMS

IUPAC name
3-(2,4-dichlorophenyl)-3-oxo-2-(4-oxo-1,2,3,4-tetrahydroquinazolin-2-ylidene)propanenitrile
IUPAC Traditional name
3-(2,4-dichlorophenyl)-3-oxo-2-(4-oxo-1,3-dihydroquinazolin-2-ylidene)propanenitrile
Synonyms
Ciliobrevin A
Hedgehog Pathway Inhibitor 4
2,4-Dichloro-a-(3,4-dihydro-4-oxo-2(1H)-quinazolinylidene)-β-oxo-benzenepropanenitrile

DATABASE IDS

CAS Number 302803-72-1
MDL Number MFCD01911757

PROPERTIES

Empirical Formula (Hill Notation) C17H9Cl2N3O2
Purity ≥98% (HPLC)
Apperance yellow powder
Solubility DMSO: >20 mg/mL
GHS Pictograms GHS07
GHS Pictograms GHS09
GHS Signal Word Warning
GHS Hazard statements H302-H410
European Hazard Symbols Harmful Harmful (Xn)
European Hazard Symbols Nature polluting Nature polluting (N)
MSDS Link Download
GHS Precautionary statements P273-P501
RID/ADR UN 3077 9/PG 3
Risk Statements 22-50/53
Safety Statements 60-61
Storage Temperature 2-8°C
Hazard Class 9
UN Number 3077
Packing Group 3
German water hazard class 3

DETAILS

Description (简体中文)
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.
Description (English)
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.

REFERENCES