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HPI-4

Cat. No. M6149
HPI-4 Structure
Synonym:

Hedgehog Pathway Inhibitor 4

Size Price Availability Quantity
10mg USD 100 In stock
25mg USD 220 In stock
50mg USD 400 In stock
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Quality Control
  • Current batch:
  • Purity >99%
  • COA
  • MSDS
Biological Activity

In vitro: HPI-4 does not directly target Smo. It counteracts the activities of endogenous Gli1 and Gli2 but does not directly act on transcription factor GLIs. HPI-4 significantly inhibited the proliferation of these neuronal progenitors, as measured by histone H3 phosphorylation (pH3) levels, It also reduced cellular levels of cyclin D1 protein and Gli1, Gli2, and N-Myc transcripts in the Cerebellar Granule Neuron Precursors. HPI-4 acts by perturbing ciliogenesis. Treatment with HH pathway inhibitor-4 (HPI-4) could significantly decrease human chondrosarcoma cell proliferation, invasion and migration ability. Furthermore, HPI-4 could distinctly disturb HH pathway-mediated ciliogenesis and suppress primary cilia-related protein intraflagellar transport protein IFT88 expression. HH downstream effect molecular GLI2 was restrained to block parathyroid hormone-related protein and affect MAPK/ERK-regulated matrix metalloproteinases (MMP2 and MMP9). HPI-4(ciliobrevin A) is also a small molecule inhibitor of the catalytic heavy chain subunit of cytoplasmic dynein.

In vivo: Pancreatic fibrosis and destruction were effectively prevented by the treatment of HPI-4, a ciliogenesis inhibitor, in zebrafish model.

Protocol
Cell Experiment
Cell lines The human chondrosarcoma cell line SW1353
Preparation method 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.
Concentrations 0, 5 and 10 μM
Incubation time 0, 1, 3, 6 and 9 days
Animal Experiment
Animal models zebrafish
Formulation water
Dosages 5 uM
Administration
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 358.18
Formula C17H9Cl2N3O2
CAS Number 302803-72-1
Purity >99%
Solubility 71 mg/mL in DMSO
Storage at -20°C
References

Hedgehog pathway inhibitor-4 suppresses malignant properties of chondrosarcoma cells by disturbing tumor ciliogenesis.
Xiang W, et al. Oncol Rep. 2014 Oct;32(4):1622-30. PMID: 25110171.

Aberrant Hedgehog ligands induce progressive pancreatic fibrosis by paracrine activation of myofibroblasts and ductular cells in transgenic zebrafish.
Jung IH, et al. PLoS One. 2011;6(12):e27941. PMID: 22164219.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: HPI-4, Hedgehog Pathway Inhibitor 4 supplier, Hedgehog, inhibitors

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