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Compound Sharing

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Long-acting CCK analogue

Category
ID
Amount per vial
CCK (only for in vitro studies)
NNC0368-0056
1000 nmol

PLEASE NOTE THAT THIS COMPOUND CAN ONLY BE USED FOR IN VITRO STUDIES (NOT IN VIVO)

Cholecystokinin (CCK) is a gut and brain peptide hormone that plays an important role in the regulation of energy balance. CCK binds to two G-protein-coupled receptors, the CCK 1 receptor and the CCK 2 receptor. Both receptors are found in the gastrointestinal tract and in the central nervous system. Activation of the CCK 1 receptor has effects on appetite regulation and a number of other effects (gallbladder contraction, pancreatic enzyme secretion, delay of gastric emptying).  The CCK 2 receptor has effects on anxiety, pain, attention, memory and the stimulation of gastric acid by gastrin is mediated by the activation of the CCK 2 receptor.  

NN0368-0056 is a long-acting and highly selective CCK-1R analogue.

PropertyNNC0368-0056CCK-8
MW (Da)1849.11107.2
pI (calculated)0.751.90
SequenceC18 diacid-gGlu-2xOEG-Asp-Phe(4sm)-Nle-Gly-Trp-Nle-DMeAsp-MePhe-NH2Asp-sTyr-Met-Gly-Trp-Met-Asp-Phe-NH2
Extinction coefficient (calculated, 280 nm)55006990

The structure of NNC0368-0056
2D sketch of NNC0368-0056. The compound has several substitutions and an N-terminal 2xOEG-gGlu-C18 diacid for protraction compared to the native reference. Please see 2D sketch of native reference for comparison.

The binding affinity to human CCK-1R and CCK-2R was measured by their ability to displace radio-labeled 125I-CCK-8 from the receptors in a plasma membrane-based scintillation proximity assay (SPA). The in vitro potencies were determined by measuring the accumulation of inositol 1 phosphate (IP1) in cells expressing human CCK-1R or CCK-2R. Please see the Sensfuss et al., 2019 reference listed in the reference section for further data and details regarding the experimental setup of the in vitro assays.


Binding (pIC50, M)



Compound
CCK-1R
CCK-2R
CCK-89.959.54
NNC0368-005610.28<5

Potency (pEC50, M)

CCK-1R
CCK-2R
CCK-8
10.369.30
NNC0368-00569.60<6
CCK-1R: cholecystokinin 1 receptor; CCK-2R: cholecystokinin 2 receptor

At present we have no available reference compound.

NNC0368-0056 can be dissolved in MilliQ water, neutral buffer or DMSO. Peptides and proteins have a tendency to adhere to glass and plastic surfaces. This may at low concentration impact the actual amount in solution. To minimize this unspecific adherence, adding detergents or inert proteins like e.g., ovalbumin or other serum albumins to the solution can minimize this phenomenon. In case albumins are added to peptide/protein solutions, ensure that the albumins are free of any proteases, but be aware that it will affect the apparent potency and affinity in in vitro assays in case a fatty acid is attached to the compound.

Sensfuss U et al.
Structure-Activity Relationships and Characterization of Highly Selective, Long-Acting, Peptide-Based Cholecystokinin 1 Receptor Agonists
J Med Chem 2019; 62; 1407-1419