Long-acting CCK analogue
Category
CCK (only for in vitro studies)
ID
NNC0368-0056
Amount per vial
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 (CCK-1R) and the CCK 2 receptor (CCK-2R). Both receptors are found in the gastrointestinal tract and in the central nervous system. Activation of CCK-1R has effects on appetite regulation and a number of other effects (gallbladder contraction, pancreatic enzyme secretion, delay of gastric emptying). The CCK-2R has effects on anxiety, pain, attention, memory and the stimulation of gastric acid by gastrin is mediated by the activation of the CCK-2R.
NN0368-0056 is a long-acting and highly selective CCK-1R analogue. In the Senfuss et al. 2019 reference listed in the reference section, NNC0368-0056 is compound 10 .
Due to unexpected finding in vivo (see the Nyborg et al. 2020 reference listed in the reference section), NNC0368-0056 can only be used for in vitro studies.
Category
CCK (only for in vitro studies)
ID
NNC0368-0056
Amount per vial
1000 nmol
In the Senfuss et al. 2019 reference listed in the reference section, NNC0368-0056 is compound 10 and CCK-8 is compound 1.
| Property | NNC0368-0056 | CCK-8 |
| MW (Da) | 1849.1 | 1107.2 |
| pI (calculated) | 0.75 | 1.90 |
| Sequence | C18 diacid-gGlu-2xOEG-Asp-Phe(4sm)-Nle-Gly-Trp-Nle-DMeAsp-MePhe-NH2 | Asp-sTyr-Met-Gly-Trp-Met-Asp-Phe-NH2 |
| Extinction coefficient (calculated, 280 nm) | 5500 | 6990 |
Figure 1
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.The binding affinity to human CCK-1R and CCK-2R was measured by the ability of the compounds to displace 125-iodine-labelled 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. Since albumin binding is a key mechanism for the design of NNC0368-0056, be aware that the apparent affinity and potency will be very dependent on whether the in vitro assays contain albumin or not. The assays below are performed in the absence of human serum albumin. 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.
| Affinity
(pIC50, M)
Mean (95% confidence interval) | ||
| Compound
| CCK-1R
| CCK-2R
|
| CCK-8 | 9.95 (9.90 to 10.01) | 9.54 (9.49 to 9.59) |
| NNC0368-0056 | 10.28 (10.17 to 10.38) | <5 |
| Potency
(pEC50, M)
Mean (95% confidence interval) | ||
| CCK-1R
| CCK-2R
| |
| CCK-8 | 10.36 (10.24 ro 10.48) | 9.30 (9.22 ro 9.37) |
| NNC0368-0056 | 9.60 (9.48 to 9.73) | <6 |