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HPI-4 (Ciliobrevin A) Hedgehog/Smoothened inhibitor

Name: HPI-4 (Ciliobrevin A)
Brand: Selleck Chemicals
SKU: S8249
Availability: InStock
Rating: 5 (9 reviews)

Cat.No.S8249

HPI-4 (Ciliobrevin A, Hedgehog Pathway Inhibitor 4) is a hedgehog (Hh) pathway antagonist. It blocks Sonic hedgehog (Shh)-induced Hh pathway activation (IC50 = 7 μM) downstream of Smo.

Chemical Structure

Molecular Weight: 358.18

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Quality Control

Batch: S824901 DMSO]71 mg/mL]false]Ethanol]1 mg/mL]false]Water]Insoluble]false Purity: 99.63%

Cited in Nature Medicine for its top-tier quality
COA
NMR
HPLC
SDS
Datasheet

99.63

Related Targets	JAK TGF-beta/Smad Wnt/beta-catenin ERK GSK-3 ROCK PKA Secretase STAT Casein Kinase
Other Hedgehog/Smoothened Inhibitors	SAG (Smoothened Agonist) Hydrochloride Purmorphamine Cyclopamine (11-Deoxojervine) GANT61 SAG (Smoothened Agonist) SANT-1 BMS-833923 Taladegib (LY2940680) Ciliobrevin D Jervine

Solubility

In vitro
Batch:

DMSO : 71 mg/mL (198.22 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 1 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	3.55mg/ml (9.91mM)	Taking the 1 mL working solution as an example, add 50 μL of 71 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.51mg/ml (1.42mM)	Taking the 1 mL working solution as an example, add 50 μL of 10.2 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

% Tween 80

% ddH₂O

% DMSO

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	358.18	Formula	C₁₇H₉Cl₂N₃O₂	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	302803-72-1	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	Hedgehog Pathway Inhibitor 4			Smiles	C1=CC=C2C(=C1)C(=O)NC(=N2)C(=C(C3=C(C=C(C=C3)Cl)Cl)O)C#N

Mechanism of Action

Targets/IC₅₀/Ki	Hedgehog
In vitro	HPI-4 (Ciliobrevin A) does not directly target Smo. It counteracts the activities of endogenous Gli1 and Gli2 but does not directly act on transcription factor GLIs. This compound 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. It acts by perturbing ciliogenesis. Treatment with this inhibitor could significantly decrease human chondrosarcoma cell proliferation, invasion and migration ability. Furthermore, it 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). It is also a small molecule inhibitor of the catalytic heavy chain subunit of cytoplasmic dynein.
In vivo	In a zebrafish model, treatment with HPI-4 (Ciliobrevin A), a ciliogenesis inhibitor, effectively prevented pancreatic fibrosis and destruction.
References	[1] https://pubmed.ncbi.nlm.nih.gov/19666565/ [2] https://pubmed.ncbi.nlm.nih.gov/25110171/ [3] https://pubmed.ncbi.nlm.nih.gov/22164219/

Applications

Methods	Biomarkers	Images	PMID
Western blot	β-catenin		26515592
Growth inhibition assay	Cell viability		26515592

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