Corporate Banner
Satellite Banner
ADME Tox
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Nimbus Discovery Presents Preclinical Data on Sought-After ACC Inhibitors

Published: Tuesday, January 29, 2013
Last Updated: Tuesday, January 29, 2013
Bookmark and Share
Company successfully discovered and optimized the first small molecule allosteric inhibitors of ACC achieving excellent potency, selectivity and drug-like properties within 12 months.

Nimbus Discovery LLC, a biotechnology company discovering novel medicines against exciting but previously inaccessible drug targets, will present preclinical data today at the Keystone Symposia Conference: Adipose Tissue Biology in Keystone, Colo., that show that the company has identified a series of novel, highly potent, and highly selective Acetyl CoA Carboxylase (ACC)1/2 allosteric inhibitors. Inhibition of ACC reduces fatty acid synthesis and stimulates fatty acid oxidation and has the potential to favorably affect the morbidity and mortality associated with obesity, diabetes, and fatty liver diseases.

Most efforts to discover ACC inhibitors have focused on interactions within the carboxyltransferase (CT) domain of the enzyme active center resulting in poor drug-like properties and have thus failed to provide benefit to patients. In contrast, Nimbus focused on the biotin carboxylase (BC) domain where the natural product soraphen interacts. Nimbus ACC allosteric inhibitors demonstrate excellent drug-like properties and show liver-muscle exposure that is aligned with driving outstanding pharmacology in preclinical models of disease.

Key findings of the Nimbus compounds presented at the conference include:

•    Development of this series of ACC inhibitors has yielded deep structure-activity relationships, sub-nanomolar enzyme inhibition, functional activity in cellular assays and favorable drug-like properties leading to in vivo proof of concept.
•    ND-630, the Nimbus lead compound, potently inhibits hepatic fatty acid synthesis (ED50 = 0.14 mg/kg) in a highly dose-dependent manner and stimulates whole body fatty acid oxidation (minimum effective dose 3 mg/kg) in preclinical models of disease.

“Using our state-of-the art structure-based drug design approach, Nimbus was able to identify potent small molecule ACC inhibitors, with excellent pharmaceutical properties, 12 months after hits were generated from an in silico screen. We believe that we are the first company to create drug-like allosteric inhibitors against ACC. The impressive potency and selectivity of our molecules could translate into significant safety and efficacy benefits in the clinic,” said Rosana Kapeller, M.D., Ph.D., Chief Scientific Officer of Nimbus. “We are now conducting a detailed pharmacological evaluation of this broad portfolio of potent allosteric inhibitors, including ND-630, and will provide an update on these data in metabolic disease, diabetes and cancer tumor metabolism models in the near future.”


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,000+ scientific posters on ePosters
  • More than 4,500+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.


Scientific News
'Kidney on a Chip' Facilitates Safer Drug Dosing
University of Michigan researchers have used a "kidney on a chip" device to mimic the flow of medication through human kidneys and measure its effect on kidney cells.
Ketamine Metabolism Lifts Depression
NIH-funded team finds rapid-acting, non-addicting agent in mouse study.
Turning Skin Cells into Heart, Brain Cells
In a major breakthrough, scientists at the Gladstone Institutes transformed skin cells into heart cells and brain cells using a combination of chemicals.
Growing Stem Cells More Safely
Nurturing stem cells atop a bed of mouse cells works well, but is a non-starter for transplants to patients – Brown University scientists are developing a synthetic bed instead.
Cell Transplant Treats Parkinson’s in Mice
A University of Wisconsin—Madison neuroscientist has inserted a genetic switch into nerve cells so a patient can alter their activity by taking designer drugs that would not affect any other cell.
Understanding Female HIV Transmission
Glowing virus maps points of entry through entire female reproductive tract for first time.
Experimental Drug Cancels Effect from Key Intellectual Disability Gene
A University of Wisconsin—Madison researcher who studies the most common genetic intellectual disability has used an experimental drug to reverse — in mice — damage from the mutation that causes the syndrome.
Common Class of Cancer Drugs May Not Lead to Cognitive Decline
UCLA study refutes 2015 research suggesting anthracyclines could cause memory loss, other impairments.
Designing Better Drugs
A rational drug engineering approach could breathe new life into drug development.
Genetic Approach May Lead to New Treatments for Digestive Diseases
Researchers at UMass Medical School have identified a new molecular pathway critical for maintaining the smooth muscle tone that allows the passage of materials through the digestive system.
SELECTBIO

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!