A-71623 TFA

A71623, a CCK-4-based peptide, is a potent and highly selective CCK-A full agonist. The IC50s for A-71623 are 3.7 nM in guinea pig pancreas (CCK-A) and 4500 nM in cerebral cortex (CCK-B) in radioligand binding assays, respectively[1].

Signaling Pathways >> GPCR/G Protein >> Cholecystokinin Receptor

Research Areas >> Metabolic Disease

IC50: 3.7 nM (CCKA receptor in radioligand binding assays)[1]

In guinea pig gastric glands, the affinities of A-71623 for the cholecystokinin (CCK)-B/gastrin receptor were 11 μM[1].

A71623 (A-63387; i.c.v., but not i.p., injections) reduces food intakes and suppresses intakes of a liquid diet in both deprived and sated rats[2]. A71623 dampens Purkinje neuron pathology and associates deficits in motor performance in Pcp2-ATXN1[30Q]D776;Cck-/- and Pcp2-AXTN1[82Q] mice[3]. A71623 improves motor performance of Pcp2-ATXN2[127Q] SCA2 mice[3]. Animal Model: Adult male, Sprague-Dawley rats[2] Dosage: 5 μL Administration: Intracerebroventricular (i.c.v) administration, A-71623 was infused using a 28 gauge injection cannula in a volume of 5uL over 60 s Result: Reduced food intakes and suppressed intakes of a liquid diet. Animal Model: ATXN1[30Q]-D776, ATXN1[82Q]-D776, ATXN2[127Q], and WT/FVB/NJ mice [3] Dosage: 0.02 mg/kg/day Administration: Osmotic minipumps containing either A71623 (0.02mg/kg/day) were implanted intraperitoneally (i.p.) Result: Treatment dampened Purkinje neuron pathology in ATXN1[30Q]D776;Cck-/- mice and ATXN1[82Q] mice. Improved motor performance in ATXN2[127Q] mice.

[1]. C W Lin, et al. Characterization of two novel cholecystokinin tetrapeptide (30-33) analogues, A-71623 and A-70874, that exhibit high potency and selectivity for cholecystokinin-A receptors. Mol Pharmacol. 1991 Mar;39(3):346-51.

[2]. K E Asin, et al. Effects of selective CCK receptor agonists on food intake after central or peripheral administration in rats. Brain Res. 1992 Jan 31;571(1):169-74.

[3]. Emily A.L. Wozniak, et al. Cholecystokinin 1 Receptor (Cck1R) Activates mTORC1 signaling and is Protective to Purkinje cells in SCA Mice.  bioRxiv. February 17, 2021.