| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
CCKBR agonist-1 is a Gq-biased cholecystokinin B receptor (CCKBR) agonist. By activating Gq proteins, it triggers the phospholipase C (PLC) pathway, leading to the generation of inositol trisphosphate (IP3) and diacylglycerol (DAG). This results in calcium mobilization from intracellular stores and activation of protein kinase C (PKC). This specific signaling cascade is linked to neuroprotection, enhanced synaptic plasticity, and anti-amyloidogenic processes.
|
|---|---|
| ln Vitro |
CCKBR agonist-1 shows potent and selective activation of the CCKBR. It has an EC50 of 35 pM for activating Gq signaling. This activation strongly protects neurons against various insults, with an EC50 of 37 pM for promoting neuronal survival. The compound significantly increases the activity of alpha-secretase (ADAM10) and upregulates the calcium signaling molecule phospholipase C beta 4 (PLCB4), which promotes the non-amyloidogenic processing of the amyloid precursor protein.
|
| ln Vivo |
In mouse models of Alzheimer's disease (AD), CCKBR agonist-1 demonstrates significant in vivo efficacy. It improves cognitive decline, reduces the number of amyloid-beta (Abeta) plaques in the brain, and promotes long-term potentiation (LTP), a cellular correlate of learning and memory. These effects are attributed to its Gq-mediated upregulation of alpha-secretase and PLCB4, which shift amyloid precursor protein processing away from the amyloidogenic pathway.
|
| Enzyme Assay |
Radioligand binding assays using [3H]-PD140376 are used to determine the binding affinity (Ki). CCKBR agonist-1 (various concentrations) is incubated with recombinant human CCKBR membranes and a fixed concentration of the radioligand. Gq activation is measured in cell-based assays. CHO-K1 cells co-expressing the CCKBR and a chimeric Galphaqi protein are seeded and treated with varying concentrations of CCKBR agonist-1. Calcium mobilization is measured using a fluorescent calcium-sensitive dye (e.g., Fluo-4 AM). The EC50 for Gq activation is 35 pM.
|
| Cell Assay |
Neuronal survival is assessed using primary cultures of mouse cortical or hippocampal neurons. Neurons are exposed to toxic agents (e.g., Abeta peptides) to induce cell death. Co-treatment with CCKBR agonist-1 (various concentrations) rescues neurons from toxicity. Cell viability is quantified via MTT reduction or measurement of lactate dehydrogenase (LDH) release. EC50 for neuroprotection is 37 pM. Western blot analysis of cell lysates confirms the increase in alpha-secretase (ADAM10) and PLCB4 protein levels.
|
| Animal Protocol |
In the Abeta-induced Alzheimer's disease mouse model, cognitive impairment is induced in male C57BL/6 mice via intracerebroventricular injection of aggregated Abeta1-42 peptides. Mice are randomized to receive either CCKBR agonist-1 (administered intracerebroventricularly or intraperitoneally) or vehicle control for 14 days. Spatial learning and memory are tested in the Morris water maze. Post-mortem brain analysis includes quantification of Abeta plaque burden by immunohistochemistry and measurement of long-term potentiation in hippocampal slices.
|
| ADME/Pharmacokinetics |
Pharmacokinetic data for CCKBR agonist-1 is not fully detailed. As a synthetic peptide (MW 699.59), its bioavailability after peripheral administration is expected to be limited. For many neuropeptides, direct central administration (e.g., intracerebroventricular injection) is required to achieve significant brain concentrations. Its in vivo effects in the AD mouse model were observed at doses used in research settings, but specific plasma half-life and volume of distribution are not reported.
|
| Toxicity/Toxicokinetics |
Comprehensive toxicology data are not available. In published research studies, CCKBR agonist-1 was well-tolerated at the administered doses. Standard safety precautions for handling synthetic peptides apply: store lyophilized at -20degC, avoid repeated freeze-thaw cycles, use PPE (gloves, lab coat, goggles), avoid inhalation and skin contact.
|
| References | |
| Additional Infomation |
CCKBR agonist-1 (CAS# 2923120-30-1) is a research-grade synthetic peptide serving as a Gq-biased CCKBR agonist. It is a valuable tool for studying Gq-mediated signaling pathways, neuroprotection, and the underlying mechanisms of Alzheimer's disease. It is not an FDA-approved drug. For research use only, not for diagnostic or therapeutic applications.
|
| Molecular Formula |
C32H39BRN6O7
|
|---|---|
| Molecular Weight |
699.59
|
| Exact Mass |
698.206
|
| CAS # |
2923120-30-1
|
| PubChem CID |
176060013
|
| Sequence |
Ac-Trp-{Nle}-Asp-{Phe(3-Br)}-NH2Ac-W-{Nle}-D-{Phe(3-Br)}-NH2
|
| Appearance |
Solid powder
|
| Hydrogen Bond Donor Count |
7
|
| Rotatable Bond Count |
17
|
| Heavy Atom Count |
46
|
| Complexity |
1090
|
| Defined Atom Stereocenter Count |
4
|
| SMILES |
CCCC[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC1=CC(=CC=C1)Br)C(=O)N)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)NC(=O)C
|
| InChi Key |
MUNNSMXBFGKXRU-FWEHEUNISA-N
|
| InChi Code |
InChI=1S/C32H39BrN6O7/c1-3-4-11-24(37-31(45)26(36-18(2)40)15-20-17-35-23-12-6-5-10-22(20)23)30(44)39-27(16-28(41)42)32(46)38-25(29(34)43)14-19-8-7-9-21(33)13-19/h5-10,12-13,17,24-27,35H,3-4,11,14-16H2,1-2H3,(H2,34,43)(H,36,40)(H,37,45)(H,38,46)(H,39,44)(H,41,42)/t24-,25-,26-,27-/m0/s1
|
| Chemical Name |
(3S)-3-[[(2S)-2-[[(2S)-2-acetamido-3-(1H-indol-3-yl)propanoyl]amino]hexanoyl]amino]-4-[[(2S)-1-amino-3-(3-bromophenyl)-1-oxopropan-2-yl]amino]-4-oxobutanoic acid
|
| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 : ≥ 50 mg/mL (~71.47 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.57 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 of PEG300 and mix thoroughly. Then add 50 μL of Tween-80 to the above system and mix thoroughly. Finally, add 450 μL of physiological saline to bring the volume to 1 mL. Preparation of physiological saline: Dissolve 0.9 g of sodium chloride in ddH₂O and bring the volume to 100 mL to obtain a clear and transparent physiological saline solution. 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 | 1.4294 mL | 7.1470 mL | 14.2941 mL | |
| 5 mM | 0.2859 mL | 1.4294 mL | 2.8588 mL | |
| 10 mM | 0.1429 mL | 0.7147 mL | 1.4294 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
