Corporate Banner
Satellite Banner
Biomolecular Screening
Scientific Community
Become a Member | Sign in
Home>News>This Article

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
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 2,600+ scientific posters on ePosters
  • More than 3,800+ 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 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
Promising Drug Candidate to Treat Chronic Itch
In a new study, scientists from the Florida campus of The Scripps Research Institute (TSRI) describe a class of compounds with the potential to stop chronic itch without the adverse side effects normally associated with medicating the condition.
Are Changes to Current Colorectal Cancer Screening Guidelines Required?
Editorial suggests more research is needed to pinpoint age to end aggressive screening.
Assessing Cancer Patient Survival and Drug Sensitivity
RNA editing events another way to investigate biomarkers and therapy targets.
New Molecular Marker for Killer Cells
Cell marker enables prognosis about the course of infections.
Potential Target for Treatment of Autism
Grant of $2.4 million will support further research.
Sniffing Out Cancer
Scientists have been exploring new ways to “smell” signs of cancer by analyzing what’s in patients’ breath.
Inroads Against Leukaemia
Potential for halting disease in molecule isolated from sea sponges.
Molecular ‘Kiss Of Death’ Flags Pathogens For Destruction
Researchers have discovered that our bodies mark pathogen-containing vacuoles for destruction by using a molecule called ubiquitin, commonly known as the "kiss of death."
A New Single-Molecule Tool to Observe Enzymes at Work
A team of scientists at the University of Washington and the biotechnology company Illumina have created an innovative tool to directly detect the delicate, single-molecule interactions between DNA and enzymatic proteins.
Milestone Single-Biomolecule Imaging Technique May Advance Drug Design
The first nanometer resolved image of individual tobacco mosaic virions shows the potential of low-energy electron holography for imaging biomolecules at a single particle level; a milestone in structural biology and a potential new tool for drug design.

Skyscraper Banner
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
2,600+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos