| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 500mg | |||
| 1g | |||
| Other Sizes |
Purity: ≥98%
| Targets |
Ciliobrevin A targets the Hedgehog signaling pathway, acting downstream of Smoothened (Smo). It also targets the AAA+ ATPase motor protein cytoplasmic dynein, inhibiting its ATPase activity. By inhibiting dynein, it disrupts microtubule-based processes. Its mechanism involves the modulation of Gli processing, activation, or trafficking.
|
|---|---|
| ln Vitro |
While HPI-2 and HPI-3 exhibited no discernible effect, ciliobrevin A (HPI-4) likewise stopped the rise in the FLAG-Gli2 full-length/repressor protein ratio following Shh stimulation. While HPI-2 or HPI-3 had no discernible influence on FLAG-Gli1 levels, Ciliobrevin A decreased the stability of FLAG-Gli1 in these cells, exposing a different mechanism by which this small chemical inhibits Hh target gene production. The effect of ciliobrevin A on ciliary FLAG-Gli2 levels is greater than that of the compound on total FLAG-Gli2 levels. Additionally, primary cilia in Shh-EGFPFLAG-Gli2 cells cultivated with Ciliobrevin A were shortened, and in the majority of Ciliobrevin A-treated cells, this organelle was gone. Additionally, in Shh-LIGHT2FLAG-Gli1 cells, ciliobrevin A interferes with the development of primary cilia and encourages FLAG-Gli1 accumulation at the distal end of this organelle. As shown by histone H3 phosphorylation (pH3), cleiobrevin A markedly suppressed the proliferation of these neural progenitor cells. It also decreased the amounts of cyclin D1 protein, Gli1, Gli2, and N-Myc transcripts in CGNPs. While Cyclopamine, a Smo inhibitor, is ineffective against any oncogenic lesions, Ciliobrevin A effectively inhibits the proliferation of SmoM2-expressing CGNPs and is also effective against CGNPs lacking Su(fu) function [1].
In vitro, Ciliobrevin A significantly inhibits the proliferation of neuronal progenitors, as measured by histone H3 phosphorylation levels. It reduces cellular levels of cyclin D1 protein and Gli1, Gli2, and N-Myc transcripts in Cerebellar Granule Neuron Precursors. Treatment with HPI-4 significantly decreases human chondrosarcoma cell proliferation, invasion, and migration ability. |
| ln Vivo |
In vivo, Ciliobrevin A has been studied for its effects on Hedgehog signaling and dynein function. As an inhibitor of the Hedgehog pathway, it has potential anticancer activity. It is used as a research tool to study the role of Hedgehog signaling and dynein in various biological processes.
|
| Enzyme Assay |
In vitro assays for Ciliobrevin A typically measure its inhibition of Hedgehog pathway activation. Reporter gene assays using Gli-responsive luciferase constructs are used. Cells are treated with Shh and the compound, and luciferase activity is measured. IC50 values are calculated. Dynein ATPase activity is assessed using ATPase assays.
|
| Cell Assay |
Cellular assays for Ciliobrevin A are performed using neuronal progenitors or cancer cell lines. Cells are treated with the compound, and proliferation is assessed by measuring histone H3 phosphorylation or by using proliferation assays. Gli1, Gli2, and N-Myc expression is measured by qRT-PCR. Cell migration and invasion are assessed using transwell assays.
|
| Animal Protocol |
In vivo animal studies with Ciliobrevin A are conducted in models of Hedgehog-dependent cancers. The compound is administered to tumor-bearing animals. Tumor growth and Hedgehog pathway activity are assessed. Its efficacy in inhibiting tumor growth is evaluated.
|
| ADME/Pharmacokinetics |
Pharmacokinetic data for Ciliobrevin A are limited. Its molecular weight is 358.18 g/mol. The compound is cell-permeable. For research use, it is typically dissolved in DMSO for in vitro studies. Its oral bioavailability and metabolic stability have not been extensively characterized.
|
| Toxicity/Toxicokinetics |
Comprehensive toxicological data for Ciliobrevin A are limited. In cell-based assays, the compound shows activity at micromolar concentrations. No significant toxicity has been reported at the doses used for Hedgehog inhibition studies. The compound is intended for laboratory research only and should be handled with standard safety precautions.
|
| References | |
| Additional Infomation |
Ciliobrevin A is a research compound used as an inhibitor of the Hedgehog signaling pathway and cytoplasmic dynein. It is a valuable tool for studying the role of Hedgehog signaling in development and cancer. The compound is not approved for clinical use and is intended for laboratory research only.
|
| Molecular Formula |
C17H9CL2N3O2
|
|---|---|
| Molecular Weight |
358.178
|
| Exact Mass |
357.007
|
| CAS # |
302803-72-1
|
| Related CAS # |
302803-72-1;
|
| PubChem CID |
135535957
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
3.001
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
24
|
| Complexity |
637
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=CC=C2C(=C1)C(=O)NC(=N2)/C(=C(/C3=C(C=C(C=C3)Cl)Cl)\O)/C#N
|
| InChi Key |
UEZZGQDPOFILFH-QINSGFPZSA-N
|
| InChi Code |
InChI=1S/C17H9Cl2N3O2/c18-9-5-6-10(13(19)7-9)15(23)12(8-20)16-21-14-4-2-1-3-11(14)17(24)22-16/h1-7,21H,(H,22,24)/b16-12+
|
| Chemical Name |
(E)-3-(2,4-dichlorophenyl)-3-oxo-2-(4-oxo-3,4-dihydroquinazolin-2(1H)-ylidene)propanenitrile
|
| Synonyms |
Ciliobrevin A HPI-4 HPI 4 HPI4. Hedgehog Pathway Inhibitor 4.
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~279.19 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.98 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7919 mL | 13.9595 mL | 27.9189 mL | |
| 5 mM | 0.5584 mL | 2.7919 mL | 5.5838 mL | |
| 10 mM | 0.2792 mL | 1.3959 mL | 2.7919 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA