Scripps Research Institute Chemists Discover Structure of Cancer Drug Candidate LA JOLLA, CA May 19, 2014 Chemists at The Scripps Research Institute (TSRI) have determined the correct structure of a highly promising anticancer compound approved by the U.S. Food and Drug Administration (FDA) for clinical trials in cancer patients.
The new report, published this week by the international chemistry journal Angewandte Chemie, focuses on a compound called TIC10.
In the new study, the TSRI scientists show that TIC10's structure differs subtly from a version published by another group last year, and that the previous structure associated with TIC10 in fact describes a molecule that lacks TIC10's anticancer activity.
By contrast, the correct structure describes a molecule with potent anticancer effects in animals, representing a new family of biologically active structures that can now be explored for their possible therapeutic uses.
This new structure should generate much interest in the cancer research community, said Kim D. Janda, the Ely R. Callaway Jr. Professor of Chemistry and member of the Skaggs Institute for Chemical Biology at TSRI.
Antitumor Potential
TIC10 was first described in a paper in the journal Science Translational Medicine in early 2013. The authors identified the compound, within a library of thousands of molecules maintained by the National Cancer Institute (NCI), for its ability to boost cells' production of a powerful natural antitumor protein, TRAIL. (TIC10 means TRAIL-Inducing Compound #10.)
As a small molecule, TIC10 would be easier to deliver in a therapy than the TRAIL protein itself. The paper, which drew widespread media coverage, reported that TIC10 was orally active and dramatically shrank a variety of tumors in mice, including notoriously treatment-resistant glioblastomas.
Tumors can develop resistance to TRAIL, but Janda had been studying compounds that defeat this resistance. The news about TIC10 therefore got his attention. I thought, They have this molecule for upregulating TRAIL, and we have these molecules that can overcome tumor cell TRAIL resistance the combination could be important,' he said.
The original publication on TIC10 included a figure showing its predicted structure. I saw the figure and asked one of my postdocs, Jonathan Lockner, to make some, Janda said.
Although the other team had seemingly confirmed the predicted structure with a basic technique called mass spectrometry, no one had yet published a thorough characterization of the TIC10 molecule. There were no nuclear magnetic resonance data or X-ray crystallography data, and there was definitely no procedure for the synthesis, Lockner said. My background was chemistry, though, so I was able to find a way to synthesize it starting from simple compounds.
Surprising Inactivity
There was just one problem with Lockner's newly synthesized TIC10. When tested, it failed to induce TRAIL expression in cells, even at high doses.
Of course I was nervous, remembered Lockner. As a chemist, you never want to make a mistake and give biologists the wrong material.
To try to verify they had the right material, Janda's team obtained a sample of TIC10 directly from the NCI. When we got that sample and tested it, we saw that it had the expected TRAIL-upregulating effect, said Nicholas Jacob, a graduate student in the Janda Laboratory who, with Lockner, was a co-lead author of the new paper. That prompted us to look more closely at the structures of these two compounds.
The two researchers spent months characterizing their own synthesized material and the NCI material, using an array of sophisticated structural analysis tools. With Assistant Professor Vladimir V. Kravchenko of the TSRI Department of Immunology and Microbial Science, Jacob also tested the two compounds' biological effects.
The team eventually concluded that the TIC10 compound from the NCI library does boost TRAIL production in cells and remains promising as the basis for anticancer therapies, but it does not have the structure that was originally published.
The Right Structure
The originally published structure has a core made of three carbon-nitrogen rings in a straight line and does not induce TRAIL activity. The correct, TRAIL-inducing structure differs subtly, with an end ring that sticks out at an angle. In chemists' parlance, the two compounds are constitutional isomers: a linear imidazolinopyrimidinone and an angular imidazolinopyrimidinone.
Ironically, Lockner found that the angular TRAIL-inducing structure was easier to synthesize than the one originally described.
Now, with the correct molecule in hand and a solid understanding of its structure and synthesis, Janda and his team are moving forward with their original plan to study TIC10 in combination with TRAIL-resistance-thwarting molecules as an anticancer therapy.
The therapeutic implications of TIC10 may even go beyond cancer. The angular core of the TRAIL-inducing molecule discovered by Janda's team turns out to be a novel type of a biologically active structure or pharmacophore from which chemists may now be able to build a new class of candidate drugs, possibly for a variety of ailments.
One lesson from this has got to be: don't leave your chemists behind, said Janda.
Funding for the research, published in a paper titled Pharmacophore Reassignment for Induction of the Immunosurveillant TRAIL (DOI: 10.1002/anie.201), was provided by The Skaggs Institute for Chemical Biology and TSRI. For more information on the paper, see http://onlinelibrary.wiley.com/doi/10.1002/ange.201402133/abstract.
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
Most recent headlines
05/01/2027
Worlds first 802.15.4ab-UWB chip verified by Calterah and Rohde & Schwarz to be ...
04/08/2026
Dalet, a leading technology and service provider for media-rich organizations, t...
04/07/2026
April 7 2026, 19:00 (PDT) Detective Conan: Fallen Angel of the Highway Opens in...
01/06/2026
January 6 2026, 05:30 (PST) Dolby Sets the New Standard for Premium Entertainment at CES 2026
Throughout the week, Dolby brings to life the latest innovatio...
13/05/2026
New Adobe Premiere Color Grading Mode Accelerated on NVIDIA GPUs
Joel Pennington May 13, 2026
0 Comments
New NVIDIA RTX-accelerated features streamlin...
13/05/2026
Grass Valley announced that dB Broadcast has delivered new IP-based outside broadcast (OB) trucks for Cloudbass, featuring Grass Valley LDX 100 Series cameras a...
13/05/2026
Ikegami will exhibit the latest additions to its wide range of broadcast production cameras, control units, viewfinders and monitors on stand 5D3-1 at Broadcast...
13/05/2026
FISE, working with the founding members of the XR Sports Alliance (XRSA), Accedo, Qualcomm Technologies, Inc. and HBS, have collaborated to develop an immersive...
13/05/2026
Canon Unveils New EOS R6 V Full-Frame EOS Camera and RF20-50mm F4 L IS USM PZ Bu...
13/05/2026
Boston Conservatory at Berklee Honors Beth Morrison and Moses Pendleton at Comme...
13/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
13/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
13/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
13/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
13/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
13/05/2026
Creative software developer Foundry today announced the latest developments on Nuke Stage. A purpose-built application for end-to-end virtual production and in-...
13/05/2026
A definitive portrait of one of Ireland's most influential musicians
New TV documentary airs Monday 18 May on RT One and RT Player at 9.35pm
Watch the...
13/05/2026
Agentic AI is changing the way users get work done. Following the success of OpenClaw, the community is embracing new open source agentic frameworks. The latest...
13/05/2026
Reinforcement-learning agents - AI systems that learn by trial and error - can c...
12/05/2026
Beyond the Hype: A Strategic Post-Hoc Analysis of NAB 2026 If NAB Show 2026 had an underlying theme, it was a quiet, industry-wide pivot from the high-energy sp...
12/05/2026
Guntermann and Drunck (G&D), a Panoptec Technologies Group company, and CT Square, led by Chandresh Shah, have announced a joint venture to distribute G&D and V...
12/05/2026
With 30 days until the start of the FIFA World Cup 2026, Telemundo, the exclusive Spanish-language home of the tournament in the United States, has announced th...
12/05/2026
The NHL has announced the return of Stanley Pup for its third consecutive year, a 90-minute special featuring adoptable rescue dogs competing on a miniature rin...
12/05/2026
NBCUniversal presented its 2026 Upfront to advertisers at Radio City Music Hall, detailing upcoming programming across NBC, Peacock, Bravo, and Versant properti...
12/05/2026
FOX Sports has announced funding for the Fandom and Social Connection Initiative at Harvard Kennedy School's Shorenstein Center on Media, Politics, and Publ...
12/05/2026
TNDV and Live Media, both divisions of Live Media Group, supported live broadcast coverage around NCAA Final Four weekend in Indianapolis, including the March M...
12/05/2026
The European Football Alliance (EFA) has announced a content distribution agreement with Fubo Sports Network, the free ad-supported streaming TV (FAST) channel ...
12/05/2026
For the first time, Spanish-speaking fans in the U.S. will have two separate tel...
12/05/2026
CP Communications led a comprehensive spectrum management initiative on behalf of Churchill Downs during Kentucky Derby week, coordinating RF assets across the ...
12/05/2026
LiveU has announced a strategic partnership with DRONERESPONDERS, a 501(c)3 non-...
12/05/2026
Open Broadcast Systems has announced that BMC TV, a specialist in IP transport of broadcast content, has selected the Open Broadcast Systems 5G Flyaway solution...
12/05/2026
NEP Europe, part of NEP Group, has announced it will deliver broadcast solutions...
12/05/2026
Grass Valley has announced continued collaboration with Ravensbourne University ...
12/05/2026
Stats Perform has announced the launch of Opta Pulse, an AI-assisted video creation and distribution platform for leagues, rights holders, and broadcasters. The...
12/05/2026
FOX Sports has announced a collaboration with Sesame Workshop to integrate Sesame Street characters into FOX Sports' FIFA World Cup 2026 programming. Conten...
12/05/2026
To date, NHL Productions has produced 19 broadcasts with commentary in American Sign Language
NHL in ASL (American Sign Language) may be just one show, but the...
12/05/2026
Google's Brian Albert: creators, athletes, highlights, nostalgia, second-scr...
12/05/2026
A still from Past Lives by Celine Song, an official selection of the Premieres program at the 2023 Sundance Film Festival. (Courtesy of Sundance Institute | p...
12/05/2026
Spotify is where fans and artists come together, turning discovery into somethin...
12/05/2026
Features patented Marco-MMC clocking technology
Black Lion Audio's latest release combines the company's expertise in clocking with their renowned p...
12/05/2026
New Track Panel, sequencer upgrades & more
Following their recent public beta release, Reason Studios have announced the full release of Reason 14. With the...
12/05/2026
One month to go! SBS reveals expansive FIFA World Cup 2026 lineup beyond the pi...
12/05/2026
Rohde & Schwarz presents its advanced solutions for power electronics testing at...
12/05/2026
aconnic AG (ISIN: DE000A0LBKW6), Munich, has developed a modified fund raising p...
12/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
12/05/2026
Tyrell Corporation, specialists in high-end live sports and entertainment broadcasts, was tasked with delivering compelling broadcast coverage of premier equest...
12/05/2026
Registration is now open for IBC2026 as the global media, entertainment and technology community prepares to converge on the RAI Amsterdam from 11 14 September ...
12/05/2026
Ross Video, a global leader in live video production technology, will present its latest innovations and integrated production workflows at BroadcastAsia 2026, ...
12/05/2026
500 selected leaders from around the world across start-ups, corporates, and venture capital. Over 50bn in assets under management among attending investors, a...
Scripps Research Institute Chemists Discover Structure of Cancer Drug Candidate LA JOLLA, CA May 19, 2014 Chemists at The Scripps Research Institute (TSRI) have determined the correct structure of a highly promising anticancer compound approved by the U.S. Food and Drug Administration (FDA) for clinical trials in cancer patients.
