Therapeutic can seek and destroy potent opioid to treat overdoses Scripps Research chemists developed a new biologic to work against the synthetic opioid carfentanil, which is 100 times more potent than fentanyl.
April 17, 2023
LA JOLLA, CA A new therapeutic designed by Scripps Research chemists can alter the molecular structure of the potent opioid carfentanil, inactivating the opioid and reversing a carfentanil overdose. The compound, which is described in an ACS Pharmacology & Translational Science paper published on April 17, 2023, and hasn't yet been studied in humans, works in a fundamentally different way than existing treatments for opioid overdose.
Carfentanil is up to 10,000 times more potent than morphine and 100 times stronger than fentanyl, making it one of the deadliest opioids. It is typically only used as a tranquilizer for large animals like elephants and rhinoceroses, but it is known to be added to street drugs, ingested accidentally or used in terrorist attacks.
It has been a big challenge for the field to come up with ways to combat these incredibly strong synthetic opioids like carfentanil, says senior author Kim Janda, PhD, the Ely R. Callaway, Jr. Professor of Chemistry at Scripps Research. What is really different about our approach is that this antibody doesn't just sequester the opioid in the body; it actually inactivates it.
Opioid drugs including morphine, codeine, oxycodone, and fentanyl work by binding to opioid receptors in the brain and spinal cord. At low doses, they can act as painkillers and sedatives. At higher doses, they slow breathing and can cause death. In recent decades, the overuse and misuse of opioids has soared, with more than 71,000 deaths in the U.S. due to synthetic opioids in 2021 alone (CDC).
Overdoses of fentanyl, the most abused opioid, can be treated with naloxone (Narcan). Naloxone works by binding to the brain's opioid receptors, thereby kicking fentanyl off those receptors and blocking its effect on the body in the process. But carfentanil binds to the receptors more strongly and sticks around the body for longer than fentanyl. Naloxone does not work as well or works only temporarily to treat carfentanil overdoses.
In the past, Janda has developed vaccines to sequester opioids away from their receptors in the body. More recently, he wondered whether there was a way to fully inactivate carfentanil and related synthetic opioids. He was particularly interested in a chemical entity embedded within carfentanil's structure called a methyl ester. He knew that with the right machinery, this methyl ester could be converted to an acid, which he suspected would drastically change the properties of carfentanil and therefore make it unable to bind to the body's opioid receptors. Molecules that can accelerate a chemical reaction like the conversion of a methyl ester to an acid are called catalysts or described as catalytic.
Before we started designing a catalytic-biologic therapy to carry this reaction out, we had to make sure the drug would actually be inactive and unable to bind receptors without that methyl ester, says Janda. Going into this, no one knew whether that was the case.
In the new work, Janda and his colleagues showed that, indeed, the acid form of carfentanil is about 40,000 times less potent at binding to the opioid receptor compared to the methyl ester form.
Armed with that knowledge, the researchers created a transition-state of carfentanil partway toward the chemical conversion from a methyl ester to an acid. They then screened libraries of antibodies for one that would bind to this transition-state analogue, helping stabilize it. This kind of molecule, called a catalytic antibody or an abzyme, helps encourage a chemical reaction to proceed. Moreover, the better an antibody can bind to the transition state of carfentanil's ester hydrolysis, the more it will help usher all the carfentanil molecules to convert to an acid.
Janda's group pinpointed one promising catalytic antibody and showed that it was able to convert carfentanil to the acid form. What is more, treating a mouse respiratory depression model with the catalytic antibody reversed the symptoms of carfentanil overdose, boosting the animals' breathing and heart rate.
It was important that we not only showed the biochemistry of this catalytic antibody, but also that it could have translational value, says Janda. It is not quite ready for clinical trials, but we believe this proof of concept demonstrating a catalytic antibody degrading a synthetic opioid into an innocuous substance is a promising starting point, and it will help encourage other research groups to examine this line of research.
The researchers are also planning to test whether the catalytic enzyme works to inactivate other strong opioids, including lofentanil, which is slightly stronger than carfentanil and has a matching methyl ester.
In addition to Janda, authors of the study, Catalytic Antibody Blunts Carfentanil Induced Respiratory Depression, are Mingliang Lin, Lisa Eubanks, Nishant Karadkhelkar and Steven Blake of Scripps Research.
This work was supported by the Skaggs Institute for Chemical Biology at Scripps Research.
Chemistry Janda, Kim
Most recent headlines
06/10/2025
France T l visions, France's leading broadcaster, has received the 2025 EBU ...
04/09/2025
Monumental Sports & Entertainment (MSE), in collaboration with Dalet, has been a...
30/08/2025
WASHINGTON The Federal Communications Commission has adopted its FY 2025 Regulatory Fees Order that establishes the regulatory fee rates for the broadcast stati...
29/08/2025
Australian Red Cross and SBS launch training to help workplaces in the fight aga...
29/08/2025
The National Film and Video Foundation (NFVF), an agency of the Department of Sp...
29/08/2025
L3Harris Technologies has concentrated decades of expertise across the entire enterprise to develop affordable and reliable best-of-breed solutions to rapidly c...
29/08/2025
BURBANK, Calif. The CW Network and the Pac-12 Conference have announced a new media rights deal that will extend their broadcast partnership beginning with the ...
29/08/2025
NEW YORK Gracenote has released a new analysis of its global video dataset showing that the number of FAST channels grew nearly 14% from Q1 2025 and 76% since 2...
29/08/2025
SAN JOSE, Calif. Harmonic has announced a series of improvements to its live sports streaming solution that the company said will improve fan engagement, protec...
29/08/2025
NEW YORK and LOS ANGELES Fox Corp. and YouTube TV last night announced a renewal of the full portfolio of Fox networks, including Fox News Channel, Fox Business...
29/08/2025
Budapest, Hungary, August 2025 - The integration of Microsoft Teams Rooms (MTR) with Lightware's Taurus universal matrix switchers delivers a new level of f...
29/08/2025
Frequency, the engine behind many of the world's best-known streaming television channels, today announced it will launch Studio Live, a next-generation uni...
29/08/2025
In an era when AI and cyber resilience are essential, Scality will mark the 10th anniversary of Scality Day on October 16, 2025 in Paris. This flagship global e...
29/08/2025
Disguise's In-House Creative and Technical Teams Pre-Visualised, Programmed and Delivered Content for the Experience, All Powered by EX 3+
Technology solu...
29/08/2025
Disguise will be demonstrating the latest workflows for TV, film and live events on a number of partner booths at the show
Disguise, the industry-leading tech...
29/08/2025
STOCKHOLM, Sweden Accedo will showcase Accedo Compose, its AI agent-powered modular orchestration layer that assists streaming providers in transitioning client...
29/08/2025
LOS ANGELES Cineverse has announced that it is working with Xperi to bring four of its streaming channels to automobiles for the first time as part of the DTS A...
29/08/2025
DALLAS & ATLANTA Gray Media has announced an agreement with the sports streaming service Victory+ to simulcast 17 Dallas Stars NHL games in 15 television market...
29/08/2025
NEW YORK AND CULVER CITY Comcast NBCUniversal and Amazon have announced new and extended distribution agreements that will expand the content available on their...
29/08/2025
FOOTHILL RANCH, Calif. RED Digital Cinema will feature its Cine-Broadcast Module supporting live broadcast workflows during IBC2025, Sept. 12-15, at the RAI Ams...
29/08/2025
29 Aug 2025
Kyivstar Rings Opening Bell at Nasdaq Marking Landmark Listing and ...
29/08/2025
More than half of all NFL games live on Sky for the first timeFriday 29 August 2025
Sky Sports has announced a new three-year deal with the NFL, extending its ...
29/08/2025
Back to All News
RIV4LRIES: The Trailer of the New Series With Samuele Carrino ...
29/08/2025
Get ready for an inspiring and emotional insight into the world of competitive Irish dancing with My Story: Tomi Champion of the World airing on RT 2 this monda...
29/08/2025
RT has today announced that David McCullagh is to be the new presenter of RT Radio 1's flagship Today programme, which airs every weekday at 10am, replaci...
28/08/2025
By Kristin Feeley, Director, Documentary Film & Artist Programs
If you want to tell untold stories, if you want to give voice to the voiceless, you've got ...
28/08/2025
Directed by Steven Bognar and Julia Reichert, Sundance Institute-supported Amer...
28/08/2025
Corridos have been a cornerstone of M sica Mexicana for generations, telling stories rooted in everyday life. Now, a new chapter is taking shape: motivational c...
28/08/2025
Los corridos han sido un pilar de la M sica Mexicana durante generaciones, contando historias enraizadas en la vida cotidiana. Ahora, un nuevo cap tulo est tom...
28/08/2025
Earlier this month, we promised our Verano Forever party would bring the heat, a...
28/08/2025
L3Harris will provide the Polish F-16V fleet with the Viper Shield electronic warfare system as part of an upgrade program....
28/08/2025
Bilbao, August 26, 2025 - AgileTV, an international television and video technol...
28/08/2025
Ken Wilkinson is an Emmy Awards nominated New York audio engineer who specialises in production sound mixing for film, commercial, episodic and documentary work...
28/08/2025
NEW YORK FuboTV today announced that it will launch Fubo Sports, a skinny bundle that focuses on sports with a subscription price of $56 monthly....
28/08/2025
NEVADA City, Calif. At IBC2025, Sept. 12-15 at the RAI Amsterdam, Telestream will debut its new Global Ingest strategy, introducing a next-generation ingest arc...
28/08/2025
Dr. Rhoda Bernard Releases Groundbreaking Debut Book on Accessible Arts Educatio...
28/08/2025
TAG Video Systems, the leader in software-based IP end-to-end workflow monitoring, deep probing, and real-time visualization, has named Oliver Gappa as Sales Di...
28/08/2025
AI-based voice enhancement will be among a series of innovations making their IBC 2025 debut on the DHD stand B46 in Hall 8 at the RAI Amsterdam Convention Cent...
28/08/2025
Telef nica Servicios Audiovisuales (TSA), the leading system integrator and service provider in the media sector in Spain, with the support of Appear, the globa...
28/08/2025
To fully immerse sailing fans in the world's biggest offshore yacht race, production company, Optical Media turned to LiveU's On-site Production solutio...
28/08/2025
Working with Calrec on its most recent overhaul, radio and television broadcaster, WNED has migrated to a fully IP infrastructure with multiple Type R consoles,...
28/08/2025
Cleeng, the Subscriber Retention Management (SRM ) inventor, has unveiled Cleeng Pro, the first-ever direct-to-consumer (D2C) subscription management platform t...
28/08/2025
Zixi, the industry leader in live broadcast-quality video over IP, today announced that French media distribution platform OKAST has selected Zixi to enable rel...
28/08/2025
Solution offers a streamlined, speaker-free architecture to optimize integration with premium external loudspeakers and advanced loudness metering
Nixer Pro Au...
28/08/2025
Cinegy, the premier provider of software-defined television technology, has announced a strategic partnership with Vision One Touch Film Production Services L.L...
28/08/2025
Telestream, a global leader in media workflow technologies, will debut its new Global Ingest strategy at IBC2025, introducing a next-generation ingest architect...
28/08/2025
Tier 1 operator selects Broadpeak to power high-performance, unified CDN solution across Norway, Sweden and Finland
Broadpeak, a leader in streaming and moneti...
28/08/2025
Leading video software provider, Synamedia, today announced that 24 Frames Digital, one of India's leading live event streaming service providers, has chose...
28/08/2025
Meet VisualOn at IBC2025: See What's Next in AI-Powered Video Streaming Join VisualOn at IBC2025 and discover how our AI-driven Optimizer and advanced media...
Therapeutic can seek and destroy potent opioid to treat overdoses Scripps Research chemists developed a new biologic to work against the synthetic opioid carfentanil, which is 100 times more potent than fentanyl. 
