H4541

HPI-4

≥98% (HPLC)

• 동의어(들): 2,4-Dichloro-a-(3,4-dihydro-4-oxo-2(1H)-quinazolinylidene)-β-oxo-benzenepropanenitrile, Ciliobrevin A, Hedgehog Pathway Inhibitor 4
• 실험식(Hill 표기법): C₁₇H₉Cl₂N₃O₂
• CAS Number: 302803-72-1
• Molecular Weight: 358.18
• MDL number: MFCD01911757
• UNSPSC 코드: 51111800
• PubChem Substance ID: 329815127
• NACRES: NA.77

속성

• Quality Level: 100
• 분석: ≥98% (HPLC)
• 양식: powder
• 색상: off-white, off-white to orange
• solubility: DMSO: 10 mg/mL, clear
• 저장 온도: 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

설명

애플리케이션

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

생화학적/생리학적 작용

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.

안전성 정보

• 픽토그램: GHS07,GHS09
• 신호어: Warning
• 유해 및 위험 성명서: H302,H410
• 예방조치 성명서: 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