Click chemistry reactions may boost cancer-fighting drug potency LA JOLLA, CA Feb. 16, 2018 Researchers at The Scripps Research Institute (TSRI) have developed a quick and easy way to simultaneously modify dozens of drugs or molecules to improve their disease-fighting properties. Using the approach, scientists exchanged one chemical group for another in 39 cancer drugs and discovered under lab conditions that the chemically altered versions of three of the drugs had more potent anti-cancer activity.
The results, published today in the Journal of the American Chemical Society, reveal a powerful application of so-called click chemistry to drug discovery.
Usually you have to make thousands or millions of molecules and go through a big screening process to find one or two molecules that are interesting and might work, says Peng Wu, PhD, a TSRI associate professor and one of the study's lead authors. With this new approach, you can save time and money by starting with drugs and molecules you know are already active and asking whether a quick modification makes any of them any better.
Our results suggest we will be able take a drug and make it more potent, faster acting, and hopefully with better bioavailability, adds Nobel laureate K. Barry Sharpless, PhD, who co-led the study.
Sharpless, the TSRI W.M. Keck Professor of Chemistry, first conceived of click chemistry in the 1990s. Click chemistry is the term for simple molecular reactions that can each be carried out in one container, undisturbed by water, and generate just one stable product at high yield. Sharpless compares the method to decorating molecules like Christmas trees, adding a new functional ornament to one of a molecule's branches, which he calls clickable hubs.
Instead of pursuing leads, which is the traditional method, SuFEx click chemistry is about connecting promising drug candidates directly with targets, says Sharpless.
One of the latest click chemistry reactions developed by Sharpless' group was Sulfur (VI) Fluoride Exchange (SuFEx), which transforms any phenol chemical group into a fluorosulfate. Because fluorosulfates have some benefits over phenols including tighter binding to proteins, and less ability to be modified in the cell the SuFEx reaction offers a way to potentially improve phenol drugs.
However, the transformation typically relies on sulfuryl fluoride gas, which makes it hard to perform on many different molecules at the same time; each reaction must be carried out in its own flask.
In the new paper, Sharpless and Wu show that sulfuryl fluoride gas can be dissolved in an organic solvent to make a liquid form of the reagent needed for SuFEx. Now, suddenly, we can use this in high-throughput experiments, says Wu.
To test the reaction's utility in drug discovery, Sharpless, Wu and their colleagues put 39 existing cancer drugs containing phenols into plates, added the liquid version of sulfuryl fluoride to each well, and exposed cancer cells to both the original compounds and the resulting fluorosulfate versions. In three instances, the new fluorosulfate drug killed more cancer cells than the original version. When modified with SuFEx, the breast cancer drug Fulvestrant had a great effect on estrogen receptors in breast cancer cells, and the cancer drug Combretastatin A4 was 70 times more potent against colon cancer cells.
Upon further examination, the researchers discovered that the new molecules bound to their molecular targets better and were less apt to be metabolized by the cells.
We think our approach is generally applicable to drug modification outside of just cancer drugs, says Wu. The team is already using the new high-throughput SuFEx to modify drugs targeting the immune system's T cells, he adds.
In addition to Wu and Sharpless, authors of the study, SuFEx click chemistry enabled late-stage drug functionalization, are Zilei Liu, Jie Li, Suhua Li and Gencheng Li of The Scripps Research Institute.
This work was supported by the National Institutes of Health (grants R01 GM117145, R01 GM111938 and R01GM113046).
About The Scripps Research Institute
The Scripps Research Institute (TSRI) is one of the worlds largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists including two Nobel laureates and 20 members of the National Academies of Science, Engineering or Medicine work toward their next discoveries. The institutes graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. In October 2016, TSRI announced a strategic affiliation with the California Institute for Biomedical Research (Calibr), representing a renewed commitment to the discovery and development of new medicines to address unmet medical needs. For more information, see www.scripps.edu.
# # #
For information:
Office of Communications
Tel: 858-784-2666
Fax: 858-784-8118
press@scripps.edu
North America Stories
24/04/2024
ATLANTA Mundo Hispano Digital has launched a new advertising product, MundoNow Connect, that is designed to help advertisers reach Hispanic audiences on connect...
24/04/2024
Epic Games has released a major new version of Unreal Engine, which has become a mainstay in virtual production, that includes new features and improvements to ...
24/04/2024
The National Association of Broadcasters welcomed the industry to its annual extravaganza last month in Las Vegas. The sights and sounds were similar to previou...
24/04/2024
NEW YORK Chptr and Gray Television have announced that they are introducing a new video solution for funeral homes and communities that will allow funeral direc...
24/04/2024
Adobe Charts the Future of Creativity and AI at MAX London
Brie Clayton April 24, 2024
0 Comments
Adobe is taking MAX, the world's largest creativ...
24/04/2024
National Association of Broadcasters president and CEO Curtis LeGeyt has agreed to a contract extension that keeps him at the trade association's helm throu...
24/04/2024
Jo Ann Ross, the long-running queen of television advertising sales, is stepping down from her role as chairman of Paramount Advertising at the end of the month...
24/04/2024
E.W. Scripps said it named James Galindo as station manager for KERO, the ABC affiliate in Bakersfield, California....
24/04/2024
Amazon Prime Video's Fallout topped TVision's Power Score rankings of shows on connected TV for the week of April 15....
24/04/2024
DoubleVerify said that it received accreditation from the Media Rating Council for its measurement of video viewable impressions and related metrics for connect...
24/04/2024
PlayBox Neo reports a successful and well attended 2024 NAB Show, held in mid April at the Las Vegas Convention Center. Now in its 101st year, the event attract...
24/04/2024
MPEG-5 LCEVC ecosystem support continues to grow and includes TVs and set-top boxes, gearing up for the deployment of TV3.0 in Brazil
New, never-before-seen ...
24/04/2024
At Integrate Middle East 2024 in Booth AR-F45, where the company is exhibiting along with its partner NOVO, Black Box will feature IP-based KVM and AV solution...
24/04/2024
FRANKFURT, Germany Software solutions provider manifold technologies has announced that its manifold CLOUD was selected by NEP Belgium to provide a signal proce...
24/04/2024
NEW YORK Integral Ad Science has announced that it has earned Media Rating Council (MRC) accreditation for its sophisticated invalid traffic (SIVT) filtration f...
24/04/2024
LOS GATOS, Calif. Streaming media company Plex has announced a partnership with the National Football League that will add the NFL Channel, the NFLs 24/7 free l...
24/04/2024
WASHINGTON, D.C. NAB President and CEO Curtis LeGeyt has agreed to a contract extension that will keep him at the helm of NAB through 2029, according to NAB Joi...
24/04/2024
GENEVA, Switzerland Software-defined video network (SDVN) platform specialist GlobalM and broadcast-quality content distribution expert scoopa have formed a str...
24/04/2024
Berklee Online to Hold 2024 Berklee Onsite Music Conference May 31-June 1 The in-person conference is open to Berklee Online students and the music community ...
24/04/2024
Kargo said it has launched a new product that gives advertisers more details about the connected TV campaigns they are buying....
24/04/2024
Mundo Hispano Digital said it has launched MundoNow Connect, which is designed to use first-party audience data to help advertisers reach Latino connected-TV vi...
24/04/2024
Brittney Griner, the WNBA star who spent 10 months in a Russian prison, sits with Robin Roberts for a primetime special on ABC Wednesday, May 1. The 20/20 speci...
24/04/2024
To give its subscribers more content to pick from, DirecTV Stream is making deals to carry streaming channels from Cineverse and additional digital multicast ch...
24/04/2024
Jenny Padura has been promoted to co-anchor on the 6 and 11 p.m. newscasts at WLTV Miami, known as Univision 23. She starts April 25 and will anchor with Ambros...
24/04/2024
Paris Schutz has joined WFLD Chicago, known as Fox 32, as a political reporter. He starts April 29 and will handle all political coverage for the station, repor...
24/04/2024
Plex has made a deal with the National Football League that will let users watch the NFL Channel, the league's free ad-supported streaming television (FAST)...
24/04/2024
Arnold Schwarzenegger and Sylvester Stallone sit for a chat when TMZ Presents: Arnold & Sly: Rivals, Friends, Icons debuts on Fox Tuesday, April 23. The pair di...
24/04/2024
Lionsgate Television said it signed a new multiyear employment agreement with executive VP, worldwide production, Gary Goodman....
24/04/2024
Miguelangel Lopez, WTMO Orlando (Florida) VP of news, has been named regional VP of news and content for WTMO, WRMD Tampa and WWDT Fort Myers, effective immedia...
24/04/2024
Howie Schwab - Beloved ESPN Researcher, Producer, and Trivia Star - Dies at 63 By SVG Staff
Wednesday, April 24, 2024 - 6:46 am
Print This Story | Subscri...
24/04/2024
Miss the SVG Venue Summit at Allegiant Stadium? All Panel Recordings Now Availab...
24/04/2024
Back to All News
My Oni Girl' Trailer Unveils a World Where Suppressed Emo...
24/04/2024
Editor's note: This post is part of the AI Decoded series, which demystifies AI by making the technology more accessible, and which showcases new hardware, ...
24/04/2024
Can machine learning help predict extreme weather events and climate change? Chr...
24/04/2024
To help customers make more efficient use of their AI computing resources, NVIDIA today announced it has entered into a definitive agreement to acquire Run:ai, ...
24/04/2024
To address the shift to electric vehicles, increased semiconductor demand, manufacturing onshoring, and ambitions for greater sustainability, manufacturers are ...
23/04/2024
IN ADDITION TO FICTION AND DOCUMENTARY FEATURES, THE SELECTION INCLUDES:
PRO...
23/04/2024
LONDON IBC is now accepting nominations for its IBC2024 Innovation Awards, which honor achievements in technological innovation and social impact media & entert...
23/04/2024
WASHINGTON, D.C. In response to the introduction of the Broadcast VOICES Act that seeks to encourage more diversity in the ownership of TV and radio stations, t...
23/04/2024
MIAMI, Fla. As part of a push to expand its FAST channel and streaming operations, Hemisphere Media Group has launched its free ad supported television (FAST) c...
23/04/2024
LOS ANGELES DirecTV is adding seven new channels to its rapidly expanding streaming lineup through new licensing agreements with Cineverse Corp. and Scripps Net...
23/04/2024
IBC is preparing to honour the highest achievements in technological innovation and social impact with the launch of its prestigious IBC2024 Innovation Awards, ...
23/04/2024
BREA, Calif. Bolin Technology is integrating Network Device Interface (NDI) across its product line, bringing support for the latest NDI technologies to its PTZ...
23/04/2024
WYOMISSING, Pa. PENN Entertainment has announced that longtime Disney and ESPN executive Aaron LaBerge has been named chief technology officer effective July 1,...
23/04/2024
In response to an FCC ruling in March proposing a $1.2 million fine against Nexstar and a ruling that Mission Broadcasting sell WPIX, Nexstar has filled a respo...
23/04/2024
Sony has announced new details about how the National Hot Rod Association (NHRA) is using Sony's Ci Media Cloud platform to streamline its workflows and spe...
23/04/2024
Esports' rapid rise to popularity can be attributed to many factors, from technological advancements that have enhanced the quality of modern gaming experie...
23/04/2024
OpenDrives, Inc., the global provider of software-defined media workflow solutions and data management capabilities, has been selected as a winner in the 2024 N...
23/04/2024
BCNEXXT is pleased to announce that Vpe has won the 2024 NAB Show Product of the Year Award in the Asset Management, Automation and Playout category. The offici...
Click chemistry reactions may boost cancer-fighting drug potency LA JOLLA, CA Feb. 16, 2018 Researchers at The Scripps Research Institute (TSRI) have developed a quick and easy way to simultaneously modify dozens of drugs or molecules to improve their disease-fighting properties. Using the approach, scientists exchanged one chemical group for another in 39 cancer drugs and discovered under lab conditions that the chemically altered versions of three of the drugs had more potent anti-cancer activity. 
