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
• Empirical Formula (Hill Notation): C₁₇H₉Cl₂N₃O₂
• CAS Number: 302803-72-1
• Molecular Weight: 358.18
• MDL number: MFCD01911757
• UNSPSC Code: 51111800
• PubChem Substance ID: 329815127
• NACRES: NA.77

Properties

• Quality Level: 100
• 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

Description

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.

Safety Information

• Pictograms: GHS07,GHS09
• Signal Word: Warning
• Hazard Statements: H302,H410
• Precautionary Statements: P264 - P270 - P273 - P301 + P312 - P391 - P501
• 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