H4541

HPI-4

≥98% (HPLC)

• Synonyme(s) : 2,4-Dichloro-a-(3,4-dihydro-4-oxo-2(1H)-quinazolinylidene)-β-oxo-benzenepropanenitrile, Ciliobrevin A, Hedgehog Pathway Inhibitor 4
• Formule empirique (notation de Hill) : C₁₇H₉Cl₂N₃O₂
• CAS Number: 302803-72-1
• Poids moléculaire : 358.18
• Numéro MDL: MFCD01911757
• Code UNSPSC : 51111800
• ID de substance PubChem : 329815127
• Nomenclature NACRES : NA.77

Propriétés

• Niveau de qualité: 100
• Essai: ≥98% (HPLC)
• Forme: powder
• Couleur: off-white, off-white to orange
• Solubilité: DMSO: 10 mg/mL, clear
• Température de stockage: 2-8°C
• Chaîne SMILES: 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+
• Clé InChI: SESYPWCSIZUIAS-FOWTUZBSSA-N

Description

Application

Hedgehog pathway inhibitor (HP1-4) has been used for the inhibition of dynein ATPase in Leishmania.

Actions biochimiques/physiologiques

HPI-4 is a Hedgehog pathway inhibitor; ciliogenesis inhibitor.

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.

Informations sur la sécurité

• Pictogrammes: GHS07,GHS09
• Mention d'avertissement: Warning
• Mentions de danger: H302,H410
• Conseils de prudence: P264 - P270 - P273 - P301 + P312 - P391 - P501
• Classification des risques: Acute Tox. 4 Oral - Aquatic Acute 1 - Aquatic Chronic 1
• Code de la classe de stockage: 11 - Combustible Solids
• Classe de danger pour l'eau (WGK): WGK 3
• Point d'éclair (°F): Not applicable
• Point d'éclair (°C): Not applicable