Ciliobrevin A

SKU: orb1304481

Description

Ciliobrevin A (HPI-4) is a cell-permeable small molecule inhibitor of the Hedgehog signaling pathway, exhibiting an IC50 below 10 μM. It is widely used in both in vitro and in vivo research to study ciliary function, developmental biology, and Hedgehog-related oncogenesis.

Research Area

Pharmacology & Drug Discovery, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 302803-72-1
• MW: 358.18
• Purity: 99.57%
• Formula: C₁₇H₉Cl₂N₃O₂
• SMILES: Clc1ccc(C(=O)C(\C#N)=C2\NC(=O)c3ccccc3N2)c(Cl)c1
• Target: Hedgehog/Smoothened
• Solubility: Ethanol:1 mg/mL (2.79 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (5.58 mM);DMSO:65 mg/mL (181.47 mM)

Bioactivity

• Target IC50:
  Hedgehog:>10 μM.
• In Vitro:
  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 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. Ciliobrevin A 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 increases ciliary levels of FLAG-Gli2 in a manner disproportionate to their effects on total FLAG-Gli2 levels.
• Cell Research:
  Using MTS-8 assay to measure cell proliferation and the toxicity of this drug. 2000 cells were plated in 96-well plates per well. HPI-4 was added to cells at concentrations of 0, 5 and 10 μM in 100 μl DMEM/F12 with 10% FBS and incubated for 0, 1, 3, 6 and 9 days. Then, 10 μl MST-8 was added to the media in each well and incubated in an environment without light for 90 min. The absorbance value was measured using an enzyme microplate reader at 450 nm wavelength. The relative viability of cells was expressed by OD value.(Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Ciliobrevin A, Hedgehog Pathway Inhibitor 4, Hedgehog, Inhibitor, HPI 4, HPI4, HPI-4, inhibit, Smoothened

Compound Identifiers

PubChem CID

135486395