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.
|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|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|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.
|Solubility||71 mg/mL in DMSO|
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.
|Related Hedgehog Products|
|Smoothened Agonist (SAG) HCl
Smoothened Agonist (SAG) HCl is a cell-permeable Smoothened (Smo) agonist with EC50 of 3 nM in Shh-LIGHT2 cells.
LDE225 Diphosphate is a Smoothened (Smo) antagonist, inhibiting Hedgehog (Hh) signaling with IC50 of 1.3 nM (mouse) and 2.5 nM (human), respectively.
Jervine is a naturally occuring steroidal alkaloid that causes cyclopia by blocking sonic hedgehog signaling.
GANT61 is an inhibitor for GLI1 as well as GLI2-induced transcription, inhibits hedgehog with IC50 of 5 μM.
PF-5274857 is a novel Smoothened antagonist, inhibits Hedgehog signaling with IC50 and Ki values of 5.8 nM and 4.6 nM, respectively.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.