| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
The primary molecular target of CHIR 4531 is the mu-opioid receptor (MOR), a class A G protein-coupled receptor and the primary target for opioid analgesics. CHIR 4531 binds with high affinity (Ki = 6 nM) to MOR and functions as a potent and selective agonist. Activation of MOR leads to Gi-mediated inhibition of adenylyl cyclase, reduced neuronal excitability, and analgesia. The peptoid backbone confers resistance to proteolytic degradation, allowing sustained receptor engagement.
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|---|---|
| ln Vitro |
In vitro, CHIR 4531 binds to the mu-opioid receptor with a Ki of 6 nM, validated by competitive radioligand binding assays using [3H]-DAMGO. It activates Gi protein coupling, measured by [35S]GTPγS binding, and inhibits forskolin-stimulated cAMP accumulation in cells expressing MOR. The compound also induces β-arrestin recruitment and receptor internalization, providing a stable probe for extended time-course assays due to its protease-resistant peptoid scaffold.
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| ln Vivo |
In vivo studies with CHIR 4531 are anticipated based on its in vitro profile. As a potent MOR agonist with a protease-resistant backbone, it is expected to produce analgesic effects in animal models of pain. The peptoid scaffold may offer advantages over conventional peptide agonists like DAMGO by resisting rapid proteolytic degradation. In vivo characterization would assess analgesic efficacy, duration of action, and side-effect profile in relevant pain models.
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| Enzyme Assay |
For radioligand displacement assays, rat brain membranes or membranes from cells expressing recombinant MOR are incubated with a fixed concentration of [3H]-DAMGO (e.g., 1-2 nM) and varying concentrations of CHIR 4531 (10-11 M to 10-5 M) in assay buffer containing 50 mM Tris-HCl, pH 7.5, 20 mM NaCl, 5 mM EGTA, 2 mM MgCl2, and protease inhibitors. Incubation proceeds at 25°C for 60-90 minutes to reach equilibrium. Bound radioligand is separated by rapid filtration through glass fiber filters and measured by liquid scintillation counting. Ki values are calculated by nonlinear regression.
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| Cell Assay |
For functional assays, cells expressing MOR are pre-incubated with various concentrations of CHIR 4531 for 15-30 minutes. For cAMP assays, cells are stimulated with forskolin (10 µM) for 15-30 minutes, lysed, and intracellular cAMP is measured by enzyme immunoassay. For [35S]GTPγS binding, membranes are incubated with CHIR 4531, GDP, and [35S]GTPγS, and bound radioactivity is measured. β-Arrestin recruitment is assessed using a cell line engineered for β-arrestin recruitment assay, with luminescence or fluorescence readout after 60-90 minutes.
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| Animal Protocol |
For in vivo characterization, animal models of pain are used. CHIR 4531 is dissolved in DMSO and diluted in appropriate vehicle for administration. The compound is administered by intraperitoneal or intrathecal routes at doses determined from preliminary studies. Analgesic efficacy is assessed using the tail-flick test, hot plate test, or formalin test. Duration of action is monitored at multiple time points. Side effects including sedation, respiratory depression, and constipation are evaluated. Pharmacokinetic parameters are determined by LC-MS/MS.
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| References |
| Molecular Formula |
C36H38N4O6
|
|---|---|
| Molecular Weight |
622.71
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| Exact Mass |
622.279
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| CAS # |
158198-48-2
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| PubChem CID |
133042
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| Appearance |
Typically exists as solid at room temperature
|
| Density |
1.299g/cm3
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| Boiling Point |
801ºC at 760mmHg
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| Flash Point |
438.2ºC
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| Vapour Pressure |
1.12E-26mmHg at 25°C
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| Index of Refraction |
1.643
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| LogP |
4.608
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| tPSA |
148.42
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| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
14
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| Heavy Atom Count |
46
|
| Complexity |
960
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C([C@@H]([N@@](CCc1ccc(cc1)O)Cc1cc2OCOc2cc1)C(CN)=O)(=O)N(CC(c1ccccc1)c1ccccc1)C(CN)=O
|
| InChi Key |
GANLUHRILMMVRH-DHUJRADRSA-N
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| InChi Code |
InChI=1S/C36H38N4O6/c37-20-31(42)35(36(44)40(34(43)21-38)23-30(27-7-3-1-4-8-27)28-9-5-2-6-10-28)39(18-17-25-11-14-29(41)15-12-25)22-26-13-16-32-33(19-26)46-24-45-32/h1-16,19,30,35,41H,17-18,20-24,37-38H2/t35-/m0/s1
|
| Chemical Name |
(2S)-4-amino-N-(2-aminoacetyl)-2-[1,3-benzodioxol-5-ylmethyl-[2-(4-hydroxyphenyl)ethyl]amino]-N-(2,2-diphenylethyl)-3-oxobutanamide
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| Synonyms |
Chir-4531; Chir4531; Chir 4531
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6059 mL | 8.0294 mL | 16.0588 mL | |
| 5 mM | 0.3212 mL | 1.6059 mL | 3.2118 mL | |
| 10 mM | 0.1606 mL | 0.8029 mL | 1.6059 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.
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