• Assay Selection Tool

BellBrook Labs

  • Products
    • Transcreener® HTS Assays
      • Transcreener® ADP² Kinase Assay
      • Transcreener® ADO CD73 Assay
      • Transcreener® AMP²/GMP² Phosphodiesterase Assay
      • Transcreener® cGAMP cGAS Assay
      • Transcreener® GDP GTPase Assay Kits
      • Transcreener® UDP² Glycosyltransferase Assay
      • Transcreener® EPIGEN SAH Methyltransferase Assay
    • AptaFluor® HTS Assays
      • AptaFluor® SAH Methyltransferase Assay
    • HTS Assays by Target Family
      • Kinase Assay Kits
      • ATPase Assay Kits
      • Glycosyltransferase Assay Kits
      • GTPase Assay Kits
        • GAP Assay Kits
        • GEF Assay Kits
      • Methyltransferase Assay Kits
      • Ligase and Synthetase Assay Kits
      • Phosphodiesterase Assay Kits
    • HTS Assays by Target
      • AMPK Assay Kits
      • cGAS Assay Kits
      • CD39 Assay Kits
      • CD73 Assay Kits
      • ENPP1 Assay Kits
      • EZH2 Assay Kits
      • IKK-beta Assay Kits
      • JAK1 Assay Kits
      • JAK3 Assay Kits
      • TBK1 Assay Kits
    • Recombinant cGAS Enzyme
    • Assay Plates
    • Ordering Information
  • Services
    • Assay Development Services
    • Lead Discovery Services
    • GTPase Profiling Services
    • OAS1 Assay Services
  • Innate Immunity
    • cGAS Activity Assays
    • CD73 Activity Assays
    • CD39 Activity Assays
    • ENPP1 Activity Assays
    • IKK-beta Activity Assays
    • JAK1 Activity Assays
    • JAK3 Activity Assays
    • OAS1 Activity Assays
    • TBK1 Activity Assays
  • Resources
    • Application Notes
    • Transcreener® Assays – Instrument Compatibility
    • Posters and Presentations
    • Publications
    • Technical Manuals
    • Transcreener® FAQ’s
    • Guides
      • Residence Time Guide
      • Hit Prioritization Guide
  • Company
    • President’s Message
    • International Distributors
    • Careers
    • Downloads
    • Contact Us
  • Blog
  • MY CART
    No products in cart.

Acetyl-CoA Carboxylase Inhibitors: Transcreener ADP Assay Powers Drug Detection Strategy

by Bellbrook Labs / Wednesday, 19 September 2018 / Published in HTS Assays, Products, Success Stories
Acetyl-CoA Carboxylase Inhibitors

The impact of Acetyl-CoA carboxylases (ACCs) on eukaryotic metabolism and metabolic-related disease states is profound. ACCs catalyze the formation of malonyl-CoA by ATP-dependent carboxylation of acetyl-CoA. In humans, the two isoforms of ACC exhibit highly regulated, tissue-specific patterns of expression, with ACC1 being present in lipogenic tissues such as liver and adipose, and ACC2 being expressed in oxidative tissues such as liver, heart, and skeletal muscle¹. Thus, the ACC product malonyl-CoA serves as a critical signal, controlling synthesis and use of fatty acids – a shift that is sensitive to changes in diet and exercise, and which also controls the switch between carbohydrate and fatty acid utilization in liver and skeletal muscle1,2

Finding an Acetyl-CoA Carboxylase Inhibitor

Logically, it then follows that inhibition of ACC isoforms could be advantageous for lessening many cardiovascular risk factors linked to obesity, diabetes, insulin resistance, and metabolic syndrome. Several studies have supported this hypothesis, including studies of ACC2 knock-out mice that exhibited favorable metabolic shift and protection from diet-induced diabetes and obesity3,4, and the use of a non-isoform-selective inhibitor called CP-640186 which stimulated insulin sensitivity and fatty acid clearance in animal models.

This strategy has captured the attention of pharmaceutical giant Pfizer, which has filed a series of patent applications relating to ACC inhibitor compounds. Each patent and patent application details the use of Transcreener® ADP² FP Assay in a screen to measure inhibition of recombinant human ACC1 (rhACC1) in vitro. The first application, which was filed in 2011 and resulted in an issued patent in 2014, claims a series of substituted pyrazolospiroketone compounds as an Acetyl-CoA Carboxylase inhibitor and describes the use of the Transcreener ADP² FP Assay to screen for the inhibition of activity of rhACC1 expressed in Sf9 cells and purified using a His-tag5. A more recently published patent application filed in January, 2018 also describes the use of Transcreener ADP² FP Assay in similar fashion6.

More data including clinical studies are needed to assess the feasibility of ACC inhibitors for the prevention and/or treatment of various diseases and conditions such as metabolic syndrome2, diabetes, and other related conditions7. Assays amenable to high-throughput screens are an essential tool in this approach. The robust, sensitive performance of the Transcreener ADP² FP Assay has powered a set of investigations that – given the global impact of diabetes and related conditions – one can only hope will prove fruitful for discovering, validating and testing much-needed new therapies.

– Robyn M. Perrin, PhD

Learn more about the Trancsreener ADP² Assay

References
[1] Tong L, Harwood HJ. 2006. Acetyl-coenzyme A carboxylases: versatile targets for drug discovery. J Cell Biochem. 99(6): 10.1002/jcb.21077.

[2] Harwood HJ. 2005. Treating the metabolic syndrome: acetyl-CoA carboxylase inhibition. Expert Opin Ther Targets. 9:267–281.

[3] Abu-Elheiga L, Matzuk MM, Abo-Hashema KAH, Wakil SJ. 2001. Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2. Science.  291:2613–2616.

[4] Abu-Elheiga L, Oh W, Kordari P, Wakil SJ. 2003. Acetyl-CoA carboxylase 2 mutant mice are protected against obesity and diabetes induced by high-fat/high-carbohydrate diets. Proc Natl Acad Sci USA. 100:10207–10212.

[5] U.S. Pat. No. 8,859,577, issued October 14, 2014

[6] U.S. Pat. App. No. 20180162858, filed January 30, 2018.

[7] Luo DX, Tong DJ, Rajput S, Wang C, Liao DF, Cao D, Maser E. 2012. Targeting acetyl-CoA carboxylases: small molecular inhibitors and their therapeutic potential. Recent Pat Anticancer Drug Discov. 7(2):168-84.

Tagged under: Acetyl-CoA Carboxylase, Transcreener ADP ATPase Assay, Transcreener ADP Kinase Assay

What you can read next

Success Story: Development of a High Throughput Screening Assay to Identify Inhibitors of the de novo Purine Biosynthetic Pathway
What is a kinase assay
How Does a Biochemical Kinase Assay Work?
Webinar Slides Available: Integrated Instrument-Reagent Platform for Screening Kinases and Methyltransferases

Categories

  • Company
  • Emerging Targets
  • Epigenetics
  • HTS Assays
  • Neurodegenerative Diseases
  • News
  • Products
  • Resources
  • Success Stories
  • Uncategorized

Recent Posts

  • SLAS 2021

    Join Us for SLAS 2021 Virtual Conference

    BellBrook Labs will be exhibiting at SLAS 2021,...
  • New cGAS TR-FRET Assay

    New TR-FRET Readout Now Available with the Transcreener cGAMP cGAS Assay

    Launched in November 2019, the Transcreener cGA...
  • Webinar Graphic

    Previously Recorded Webinar – Streamline cGAS Inhibitor Discovery with the Transcreener® cGAS Assay

    The immune system uses the recognition of forei...
  • Lab IRAK4 Inhibitors Kinase Assay Kit

    Uncovering IRAK4 Inhibitors with a Transcreener Kinase Assay Kit

    Genentech discovers IRAK4 inhibitors using the ...
  • Assay Development Services - Two Scientists Working In the Lab

    Five Considerations When Choosing a Biochemical Assay Development Services CRO

    There are many options out there for choosing a...

Archives

BellBrook Labs
5500 Nobel Drive, Suite 230
Madison, Wisconsin 53711 USA
(608) 443-2400

info@bellbrooklabs.com

 Copyright © 2019 BellBrook Labs | All Rights Reserved | Privacy Policy | Terms of Use | FCOI | Sitemap

TOP