Ciliobrevin A

SKU: orb1225379

Description

A small molecule Hedgehog pathway inhibitor (IC50=7 uM) that acts downstream of Su(fu) to modulate Gli processing, activation or trafficking; does not directly target Smo, blocks the proliferation of cerebellar granule neuron precursors expressing an oncogenic form of Smo; disrupts spindle pole assembly and kinetochore-microtubule attachment, inhibits melanosome aggregation and peroxisome motility in cultured cells; inhibits AAA+ ATPase motor cytoplasmic dynein.

Key Properties

• CAS Number: 302803-72-1
• MW: 358.1783
• Purity: >98% (HPLC)
• Formula: C₁₇H₉Cl₂N₃O₂
• SMILES: N#C/C(C(C1=CC=C(Cl)C=C1Cl)=O)=C(N2)/NC3=C(C=CC=C3)C2=O
• Target: Hedgehog (Hh)
• Solubility: DMSO: ≥ 34 mg/mL

Bioactivity

• In Vitro:
  Ciliobrevin A (HPI-4) also prevents an increase in the FLAG-Gli2 full-length/repressor ratio upon Shh stimulation, but HPI-2 and HPI-3 have no significant effect. Ciliobrevin A decreases FLAG-Gli1 stability in these cells, revealing another mechanism by which this small molecule can inhibit Hh target gene expression, while neither HPI-2 or HPI-3 has any significant effect on FLAG-Gli1 levels. Ciliobrevin A increases ciliary levels of FLAG-Gli2 in a manner disproportionate to their effects on total FLAG-Gli2 levels. In addition, Shh-EGFPFLAG-Gli2 cells cultured with Ciliobrevin A have truncated primary cilia, and this cellular organelle is absent in a significant fraction of Ciliobrevin A-treated cells. Ciliobrevin A also perturbs primary cilia formation in the Shh-LIGHT2FLAG-Gli1 cells and promotes accumulation of FLAG-Gli1 at the distal tip of this organelle. Ciliobrevin A significantly inhibits the proliferation of these neuronal progenitors, as measured by histone H3 phosphorylation (pH3) levels, and reduces cellular levels of cyclin D1 protein and Gli1, Gli2, and N-Myc transcripts in the CGNPs. Ciliobrevin A can block the proliferation of SmoM2-expressing CGNPs and should be equally potent against CGNPs lacking Su(fu) function, whereas the Smo inhibitor Cyclopamine is ineffective against either oncogenic lesion.
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Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

HPI-4 | HH pathway inhibitor 4

Quick Database Links

Gene Symbol

Hedgehog (Hh)