• Assay Selection Tool

BellBrook Labs

  • Products
    • Transcreener® HTS Assay Kits
      • Transcreener® ADP² Kinase Assay Kits
        • Transcreener® ADP2 Assay Kit – FP Readout
        • Transcreener® ADP2 Assay Kit – FI Readout
        • Transcreener® ADP2 Assay Kit – TR-FRET Readout
      • Transcreener® ADO CD73 Assay Kit
      • Transcreener® AMP²/GMP² Phosphodiesterase Assay Kits
        • Transcreener® AMP2/GMP2 FP Assay
        • Transcreener® AMP2/GMP2 Assay Kit – TR-FRET Readout
      • Transcreener® cGAMP cGAS Assay Kits
        • Transcreener® cGAMP Assay Kit – FP Readout
        • Transcreener® cGAMP Assay Kit – TR-FRET Readout
      • Transcreener dAMP Exonuclease Assay Kit
      • Transcreener® EPIGEN SAH Methyltransferase Assay Kit
      • Transcreener® GDP GTPase Assay Kits
        • Transcreener® GDP Assay Kit – FP Readout
        • Transcreener® GDP Assay Kit – FI Readout
        • Transcreener® GDP Assay Kit – TR-FRET Readout
      • Transcreener® UDP² Glycosyltransferase Assay Kits
        • Transcreener® UDP2 Assay Kit – FP Readout
        • Transcreener® UDP2 Assay Kit – FI Readout
        • Transcreener® UDP2 Assay Kit – TR-FRET Readout
      • Transcreener® 2-5A OAS Assay Kit
    • AptaFluor® HTS Assay Kits
      • AptaFluor® SAH Methyltransferase Assay Kit
    • Enzyme Assay Systems
      • TREX1 Assay System
    • Recombinant Enzymes
      • Human cGAS Enzyme
      • Mouse cGAS Enzyme
      • Human DDX3 Enzyme
      • Human OAS1 Enzyme
      • Human TREX1 Enzyme
    • Assay Plates
    • Ordering Information
  • Services
    • Assay Development Services
    • Lead Discovery Services
    • CD38 Assay Services
    • GTPase Profiling Services
    • ATPase Profiling Services
  • Assays by Target
    • Kinase Assays
      • ADK Assays – Application
      • AMPK Assays – Application
      • IKK-beta Assays – Application
      • IRAK4 Assays – Application
      • JAK1 Assays – Application
      • JAK3 Assays – Application
      • MAPK8 Assays – Application
      • PKR Assays – Application
      • RIPK1 Assays – Application
      • RIPK2 Assays – Application
      • TBK1 Assays – Application
    • GTPase Assays
      • GAP Assays – Application
      • GEF Assays – Application
      • KRAS Assays – Application
      • HRAS Assays – Application
      • NRAS Assays – Application
      • RRAS Assays – Application
      • Rac1 Assays – Application
      • RhoA Assays – Application
      • RhoC Assays – Application
      • Cdc42 Assays – Application
      • Ran Assays – Application
    • Methyltransferase Assays
      • EZH2 Assays – Application
      • G9a Assays – Application
      • SET7/9 Assays – Application
      • SET8 Assays – Application
      • PRMT1 Assays – Application
      • PRMT3 Assays – Application
      • PRMT4 Assay – Application
    • STING Pathway Assays
      • cGAS Assay Kits
      • ENPP1 Assays – Application
      • TREX1 Assay System
      • IKK-beta Assays – Application
      • TBK1 Assays – Application
    • Nucleotidase Assays
      • CD38 Assay Services
      • CD39 Assays – Application
      • CD73 Activity Assay Kits
    • Helicase / ATPase Assays
      • DDX3 Assays – Application
      • NSP13 Assays – Application
      • P97 Assays – Application
    • Glycosyltransferase Assays
      • Toxin B Assays – Application
      • GALNT2 Assays – Application
      • GALNT3 Assays – Application
      • BGalT1 Assays – Application
    • Phosphodiesterase Assays
      • PDE3 Assays – Application
      • PDE4 Assays – Application
      • PDE5 Assays – Application
      • PDE7 Assays – Application
    • Ligase and Synthetase Assays
      • SUMO E1 Assays – Application
      • Acyl CoA Synthetase Assays – Application
      • S-Acetyl CoA Synthetase Assays – Application
    • Exonuclease Assays
      • TREX1 Assay System
    • OAS Assays
      • OAS1 Assay Kits
    • Other Enzyme Assays
      • NUDT5 Assays – Application
  • Resources
    • Technical Manuals
    • Transcreener® Assays – Instrument Compatibility
    • Application Notes
    • Posters and Presentations
    • Publications
    • Transcreener® FAQ’s
    • Guides
      • Residence Time Guide
      • Hit Prioritization Guide
      • Kinases in Innate Immunity
  • 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

JNK1 And Cancer Pathogenesis
The Double-Edged Sword in Cancer Pathogenesis – JNK1
Transcreener Glycosyltransferase Assay Blog
New Transcreener UDP2 Assay with a Fluorescence Intensity Readout
Inhibitors of ENPP1 SLAS Discovery
New Publication by the Scientists at BellBrook Labs – Development of a High-Throughput Assay to Identify Inhibitors of ENPP1

Categories

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

Recent Posts

  • PARP1 as a Hero vs Villain

    Is PARP1 a Hero or Villain?

    Not counting histones, PARP1 [Poly(ADP-ribose) ...
  • Ongoing Puzzle of c-SRC in Cancer Treatment

    Advancements in The Ongoing Puzzle to Understand c-SRC

    Nearly a half-century ago, sequences from the R...
  • SLAS 2023 Conference Exhibitor Announcement

    SLAS 2023 – HTS Assays and Discovery Services

    BellBrook Labs will exhibit and present posters...
  • BTK's Involved in Systemic lupus erythematosus

    The Challenging Search for BTK Inhibitors

    Bruton’s Tyrosine Kinase (BTK) is a 76kDa...
  • SARM1 Causes Axonal Death

    SARM1 Forefronts Research into Major Neurological Diseases

    SARM1 [Sterile alpha & toll/interleukin rec...

Archives

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

info@bellbrooklabs.com

 Copyright © 2023 BellBrook Labs | All Rights Reserved | Privacy Policy | Terms of Use | FCOI | Sitemap

TOP