Navigation Links
First-ever covalent irreversible inhibition of a protease central to hepatitis C infection
Date:11/28/2010

WALTHAM, MA November 28, 2010 Avila Therapeutics, Inc., a biotechnology company developing novel targeted covalent drugs, has published research in Nature Chemical Biology demonstrating the first-ever selective irreversible inhibition of a viral protease using a targeted covalent drug. In the paper titled "Selective Irreversible Inhibition of a Protease by Targeting a Non-Catalytic Cysteine", Avila used its proprietary Avilomics platform to design covalent irreversible protease inhibitors that are highly selective, potent and with superior duration of action as compared to conventional protease inhibitors.

Importantly, the published research demonstrates that covalent drugs can be designed and targeted to irreversibly and covalently bond to molecular domains specific to proteases. This is the first report of the irreversible covalent approach being successfully extended to proteases, a very broad class of proteins that includes many important potential drug targets.

"This research elevates covalent drug design to a fundamentally new level," said Simon Campbell, PhD, CBE, FMedSci, FRS, a renowned scientist and former Senior Vice President for Worldwide Drug Discovery and Medicinal R&D Europe of Pfizer. "By creating extremely selective protease inhibitors with their platform, Avila is showing the remarkable therapeutic potential of irreversible covalent drugs to address a broad spectrum of drug targets."

"This publication showcases the creation of a whole new class of small molecule drugs," said Juswinder Singh, PhD, Chief Scientific Officer of Avila and a co-author of the paper. "This approach can make a difference to patients living with HCV infection, and we expect to make an impact in other important areas such as cancer and inflammatory disease."

In order to maximize selectivity and minimize off-target effects, the irreversible covalent inhibitors of HCV protease were designed to covalently target a unique structure in the HCV protease not found in human proteases. Key findings include:

  • A representative irreversible covalent inhibitor designed, by Avila, was shown to inhibit the HCV protease (also known as "NS3") in cells at a concentration of 6 nM .
  • Specific covalent bond formation between the drug and target protease was demonstrated through use of mass spectrometry and also x-ray crystallography.
  • Very high selectivity of the Avila compounds was demonstrated by showing no notable inhibition of a panel of human proteases in biochemical assays with additional specificity demonstrated in cellular assays; this was contrasted experimentally with Telaprevir, an HCV protease inhibitor in late-stage clinical testing which demonstrated off-target biochemical activity against several human targets.

Avila has subsequently optimized additional drug candidates, yielding current development candidates, AVL-181 and AVL-192, which have excellent pharmacokinetics and bind potently to wild- type HCV protease as well as multiple genotypes and mutant forms of HCV protease.


'/>"/>

Contact: Kathryn Morris
kathryn@theyatesnetwork.com
914-204-6412
Yates Public Relations
Source:Eurekalert

Related biology news :

1. First-ever blueprint of a minimal cell is more complex than expected
2. UBC researchers find first-ever wanderlust gene in tiny bony fish
3. Afghanistan releases its first-ever list of protected species
4. UBC researcher gives first-ever estimate of worldwide fish biomass and impact on climate change
5. First-ever socioeconomic study on coral reefs points to challenges of coastal resource management
6. New clues to how cancer-related proteins plasmin, thrombin lose inhibition
7. Gene signal GS-101 data shows safe and effective inhibition of ophthalmic blood vessel growth
8. HIV-1 protease inhibitor induced oxidative stress in pancreatic B-cells: thymoquinone protection
9. Researchers describe protease inhibitor that may aid in diabetic retinopathy treatment
10. New regional facility opened to advance stable isotope research in central Appalachians
11. Barrow scientists uncover clues on inflammation in central nervous system
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/11/2017)... April 11, 2017 NXT-ID, Inc. (NASDAQ: ... company, announces the appointment of independent Directors Mr. Robin ... its Board of Directors, furthering the company,s corporate governance and ... Gino Pereira ... look forward to their guidance and benefiting from their considerable ...
(Date:4/4/2017)... 4, 2017   EyeLock LLC , a leader ... United States Patent and Trademark Office (USPTO) has issued ... linking of an iris image with a face image ... the company,s 45 th issued patent. ... timely given the multi-modal biometric capabilities that have recently ...
(Date:3/29/2017)... the health IT company that operates the largest health ... today announced a Series B investment from BlueCross BlueShield ... investment and acquisition accelerates higi,s strategy to create the ... activities through the collection and workflow integration of ambient ... secures data today on behalf of over 36 million ...
Breaking Biology News(10 mins):
(Date:8/22/2017)... MA (PRWEB) , ... August 22, 2017 , ... ... new service pipeline built upon patented KBioBox technology, the extended GUIDE-Seq ananlysis. KBioBox ... source GUIDE-Seq computation pipeline to be provide scientists with easy to understand reports, ...
(Date:8/21/2017)... ... 2017 , ... Baltimore biotech firm, PathSensors, Inc., announced today ... proprietary CANARY pathogen detection technology and high throughput testing solutions to the Chinese ... undisclosed number of PathSensors’ Zephyr pathogen detection instruments and will act as a ...
(Date:8/18/2017)... (PRWEB) , ... August 18, 2017 , ... ... announce that they will feature Federal Hybrids, Inc. in an upcoming episode, scheduled ... , American Farmer will explore Federal Hybrids, the independent, family-owned seed company. ...
(Date:8/16/2017)... ... August 16, 2017 , ... Tunnell Consulting announced today that four ... ISPE Annual Meeting and Expo , to be held October 29 through November 1 ... “Driving innovation to advance patient therapies.” , The ISPE Annual Meeting and Expo will ...
Breaking Biology Technology: