Description:

INV-14020

Background

Cannabinoid receptors type 1 (CB1), abundantly found in the brain, play diverse roles in physiological processes including learning, memory, motor control, energy homeostasis, and reward system response. The enhancers of CB1 receptor activity have the potential to treat diseases such as depression, anxiety, multiple sclerosis, and pain. CB1 inhibitors can treat metabolic syndrome as well as drug and alcohol addiction. 

CB1 inhibitor drugs have been developed for the treatment of type 2 diabetes, weight loss, smoking cessation, and osteoporosis however complete inhibition of CB1 causes adverse effects including suicidal thoughts, depression, and nausea. Besides potential adverse effects, reduction in the efficacy and reversal of the therapeutic effect can occur. Generating ligands with high receptor selectivity remains an issue. 

It has been suggested that the adverse effects of CB1 inhibition could be mitigated if a drug tunes down the excessive activity of the receptor rather than turning it off completely. Hence, new compounds with a different mechanism of action are needed to design new therapeutics targeting CB1 receptors. 

Technology Overview

Researchers at Northeastern invented a new class of compounds that work with a novel mechanism called allosteric modulation which can negatively or positively modulate responses of CB1. CB1 allosteric modulators have several advantages, including more subtle modulation or resetting of the receptor activity, thereby having fewer adverse effects. Since they act only in the presence of the natural ligand, they allow the CB1 receptor to maintain its normal function, such as neuroprotective effect in the presence of endogenous cannabinoids. CB1 allosteric modulators have more selectivity and tissue specificity and are more capable of distinguishing between similar receptors (e.g. different subtypes of cannabinoid receptors). Unlike CB1 antagonists/agonists, CB1 allosteric modulators do not have either excessive deactivation or desensitization effect due to extended and continued activation of the receptor. They also possess specific advantages considering the treatment of multifactorial diseases such as metabolic disorders. Taken together, allosteric modulation of CB1 can surmount the limitations of the current CB1 agonists/antagonists, and become an intriguing option for the treatment of a multitude of diseases. 

Benefits

  • Fewer side effects compared to antagonists 
  • More selectivity 
  • Not blocking the desirable effect of endogenous cannabinoids 

Applications

  • Used alone or as add-ons to conventional cannabinoid therapy, including treatment of metabolic disorders, obesity, and substance abuse 
  • Used as a diagnostic tool for analytical purposes of CB1 allosterism 

Opportunity

  • Research Collaboration
  • Partnering
  • License
Patent Information:
For Information, Contact:
Mark Saulich
Associate Director of Commercialization
Northeastern University
m.saulich@northeastern.edu
Inventors:
Ganeshsingh Thakur
Pushkar Kulkarni
Abhijit Kulkarni
Ritesh Tichkule
Keywords:
Chemistry
Drug Discovery & Development
Health
Pharmaceutical Composition