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Metabolic Actions of the Type 1 Cholecystokinin Receptor: Its Potential as a Therapeutic Target

Laurence J Miller1, Aditya J Desai1

  • 1Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Scottsdale, AZ, 85259, USA.

Trends in Endocrinology and Metabolism: TEM
|May 9, 2016
PubMed

Insights

New strategies aim to effectively target the cholecystokinin type 1 receptor (CCK1R) for obesity treatment. These approaches focus on ligand-directed bias and positive allosteric modulators to improve efficacy and reduce side effects.

Area of Science:

  • Pharmacology
  • Endocrinology
  • Obesity Research

Background:

  • Cholecystokinin (CCK) is a hormone that regulates appetite and food intake via the CCK type 1 receptor (CCK1R).
  • Previous attempts to develop CCK1R agonists for obesity management have not succeeded in clinical practice.

Purpose of the Study:

  • To explore reasons for the lack of clinical success with CCK1R agonists for obesity.
  • To discuss novel strategies for more effective CCK1R targeting in obesity treatment.

Main Methods:

  • Examination of CCK1R signaling pathways.
  • Discussion of ligand-directed bias to separate satiety from side effects.
  • Exploration of allosteric modulation and positive allosteric modulators (PAMs) without intrinsic activity.

Main Results:

  • Identified challenges in developing effective CCK1R agonists.
  • Proposed new therapeutic strategies focusing on biased agonism and allosteric modulation.
  • Highlighted the potential of PAMs as a novel approach for obesity treatment.

Conclusions:

  • Novel CCK1R-targeting drugs, including biased agonists and PAMs, offer promising avenues for obesity management.
  • These agents could be used alone or in combination therapies for obesity.
Keywords:
biased agonistscholecystokininpositive allosteric modulatorssatietytype 1 cholecystokinin receptor

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