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By Dr. Chinta Sidharthan Reviewed by Danielle Ellis, B.Sc. Nov 21 2024

Researchers identify gliocidin, a blood-brain barrier-penetrating prodrug, that targets glioblastoma's unique metabolic vulnerability, offering a promising therapeutic strategy and extended survival in preclinical models. Study: Gliocidin is a nicotinamide-mimetic prodrug that targets glioblastoma. Image Credit: April stock/Shutterstock.com

In a recent study published in Nature, a team led by researchers from Memorial Sloan Kettering Cancer Center investigated the effects of the compound gliocidin in targeting glioblastoma, an aggressive form of brain tumor.

The study found that gliadin acts on specific cellular pathways to selectively kill glioblastoma cells without harming normal cells. Moreover, the compound can penetrate the blood-brain barrier, which highlights its potential as a treatment option for glioblastoma. Background

Glioblastoma is one of the most lethal forms of brain cancer and is known for its resistance to standard therapies. Despite significant advances in cancer therapies, currently used immunotherapies and targeted therapies have had minimal success in improving survival rates in glioblastoma. This resistance is believed to stem from several challenges unique to glioblastoma, such as its complex cellular heterogeneity and immune-evasive characteristics.

Additionally, crossing the blood-brain barrier to reach tumor cells remains a significant obstacle. Researchers are exploring novel metabolic pathways as potential therapeutic targets. Unlike typical cancer drugs that inhibit cell division, some emerging therapies aim to disrupt cancer-specific vulnerabilities. The use of prodrugs, which are converted into active drugs within the body, is gaining special attention due to their ability to target malignant cells while sparing healthy tissue selectively. About the study

In the present study, the researchers aimed to identify a compound that could selectively target glioblastoma cells. A high-throughput chemical screen of over 200,000 compounds was conducted using low-passage glioblastoma cells derived from genetically engineered mouse models. Compounds toxic to normal replicative cells were excluded. The screening identified gliocidin as a promising candidate due to its selective toxicity against glioblastoma cells.

To investigate the mechanism of action, the team then employed multiple experimental approaches. Genetic analyses were performed using clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) screens to identify pathways and enzymes essential for the activity of gliocidin.

Pharmacokinetics and biodistribution studies in animal models were used to determine the ability of gliocidin to cross the blood-brain barrier and maintain effective concentrations in the brain. The researchers used glioblastoma-bearing mouse models to test the brain penetration abilities and bioavailability of gliocidin. Drug administration was optimized using intraperitoneal injection, and tissue analysis was used to confirm its presence in the brain.

Additionally, the researchers used liquid chromatography-mass spectrometry (LC-MS) to measure the levels of intermediate compounds and final metabolites in cells and tissues to understand gliocidin metabolism. Related StoriesStudy defines three subtypes of Chiari type-1 malformation to guide treatmentSpecific redox protein identified as a critical regulator of ferroptosisCannabis use linked to brain changes in young adults at risk of psychosis

Structural studies, including cryo-electron microscopy, were also conducted to characterize the interaction between the active form of gliocidin, gliocidin-adenine dinucleotide (GAD), and the enzyme inosine monophosphate dehydrogenase 2 (IMPDH2), to understand the binding mechanisms involved in gliocidin activation and metabolism. Gliocidin was also tested in combination with temozolomide, a standard chemotherapeutic for glioblastoma, to evaluate potential synergistic effects. Results

The study found that gliocidin effectively targeted glioblastoma cells by exploiting specific metabolic vulnerabilities of the cancer cells. Gliocidin was metabolized into GAD within the NAD+ salvage pathway, which then indirectly inhibited IMPDH2, a key enzyme in the purine synthesis pathway. This inhibition was found to lead to a severe reduction in guanine nucleotide levels, causing replication stress and cell death in glioblastoma cells.

Furthermore, the biochemical assays confirmed that gliocidin selectively disrupted guanine nucleotide synthesis in glioblastoma cells without affecting normal cells. The study demonstrated this specificity across multiple glioblastoma cell lines and patient-derived xenograft models. Additionally, the pharmacokinetic studies revealed that gliocidin successfully crossed the blood-brain barrier and accumulated in the brain, ensuring sustained exposure of the cancer cells to the compound.

Moreover, the in vivo studies in glioblastoma-bearing mice also showed that gliocidin monotherapy significantly suppressed tumor progression. When combined with temozolomide, a standard glioblastoma treatment, gliocidin produced synergistic effects, leading to greater tumor reduction and improved survival outcomes. An analysis of tumor samples from treated mice revealed that the combination therapy enhanced glioblastoma cell death by targeting both proliferative and non-proliferative tumor cells.

The researchers also found that gliocidin’s efficacy depended on nicotinamide nucleotide adenylyltransferase 1 or NMNAT1, an enzyme in the NAD+ salvage pathway. Tumors with higher NMNAT1 expression showed greater sensitivity to gliocidin. Interestingly, combination therapy with temozolomide was found to increase NMNAT1 expression further, amplifying the anti-tumor effects of gliocidin. Conclusions

Overall, the results established that gliocidin could selectively kill glioblastoma cells by disrupting critical nucleotide synthesis pathways. Its ability to penetrate the brain highlights its potential as a promising treatment for glioblastoma.

Furthermore, the enhanced efficacy observed when gliocidin was administered in combination with temozolomide further supports the potential of gliocidin as a future therapeutic approach for glioblastoma patients. Journal reference: Chen, Y.J., Iyer, S. V., Hsieh, D.C.C., Li, B., Elias, H.K., Wang, T., Li, J.,… Parada, L.F. 2024. Gliocidin is a nicotinamide-mimetic prodrug that targets glioblastoma. Nature. doi: 10.1038/s41586-024-08224-z https://www.nature.com/articles/s41586-024-08224-z

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2026 NHL draft prospect watch list: Who joins Gavin McKenna?

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2026 NHL draft prospect watch list: Who joins Gavin McKenna?

With the Hlinka-Gretzky Cup wrapped up, the unofficial start of the 2026 NHL draft scouting season has begun. Junior teams kick off training camp in the next few weeks, NCAA players are settling into campus, and hockey season is right around the corner.

As was the case last year, certain players will dominate the conversation atop the class. Because of rule changes, we’re seeing players make the jump from Canadian major junior play to the NCAA. It will be interesting to track how those players develop — and the impact that older competition has on them.

NHL teams made it clear in the 2025 draft that big defensemen and skilled forwards with bite are valued at a high premium. There is no shortage of right-handed defensemen who will be in the top-10 discussion this season, and a few highly skilled forwards many teams will be tracking closely. These are the players worth familiarizing yourself with, especially if your team is not expected to be a Stanley Cup playoff contender this season.

Note: This list is in alphabetical order with the exception of the odds-on favorite to be the top pick in the 2026 draft in the first spot.

Gavin McKenna
LW, Penn State Nittany Lions (NCAA)

This is the obvious name on the list. The hubbub around his decision to play in the NCAA led “SportsCenter” — a testament to the star quality of this prospect.

McKenna was one of the best players in the Canadian Hockey League last season, and he will be one of the best — if not the best — players in the NCAA this season. Making the jump to Penn State, McKenna is a bring-you-out-of-your-seat offensive dynamo. A playmaker first, McKenna is usually the best player on the ice.

He draws defensive coverage, makes plays at full speed and turns every skater on the ice with him into a threat to score because of his elite puck-distribution skill. Expect him to be among the NCAA’s best players in transition, turning defenders into pretzels and playing in every key situation.

The NCAA will give McKenna the opportunity to add to his lean frame and learn to play against bigger, stronger opponents as he prepares to compete in the NHL next October. You could say he’s one to watch, but the reality is he is the one to watch in this class, and he will be all over the highlight reels.


Ethan Belchetz
LW, Windsor Spitfires (OHL)

A mammoth winger playing for the Spitfires, Belchetz’ 6-foot-5 frame will be impossible to miss. He has developed the ability to physically impose himself to impact the game, which was evident at the recent Hlinka-Gretzky Cup for Canada. He’s learning to use his body along the wall to protect pucks, bump players off balance and bully his way to the dangerous areas of the ice.

Given his physical package and willingness to engage physically, it is easy to understand why teams are excited about him. He’s a powerful winger with above-average puck skill and shooting ability. If he can add speed and bite to his play style, it won’t be surprising to see teams target him with a top-10 pick — the way they did with Brady Martin and Porter Martone in the 2025 class.


Viggo Björck
C/W, Djurgårdens (J20)

It is generally a good sign when you break scoring records and are moved out of your age group (Hlinka) to play in the World Junior Summer Showcase.

Björck fits the bill. He’s a highly skilled center who possesses quality playmaking ability. His creative playstyle showcases elite hockey sense, and he has the ability to control the game with a package of good acceleration, a quick release and above-average puckhandling skill. He’s strong on pucks, defensively sound and a projectable NHL center.

If he grows a couple of inches, there is a real chance he will hear his name called in the top five in June.


Tynan Lawrence
C, Muskegon Lumberjacks (USHL)

Coming off a Clark Cup MVP season in the USHL as a 16-year-old, Lawrence will be a fascinating watch in his final junior season. He’s committed to Boston University for 2026-27.

Having success as a young center in the USHL is no easy task, and Lawrence was more than up to it. He has excellent instincts on both sides of the puck, allowing him to thrive on the penalty kill and power play. I expect he will be in the top units of both for Muskegon this season.

Offensively, he has a smooth catch and release and can let pucks fly once he gets to the middle of the ice. He should be one of the top creators in transition this season with his ability to make plays at speed off the rush. Lawrence will be a key play driver for the Lumberjacks and will be tasked with winning his minutes offensively while playing sound defensive hockey. Scouts like his work rate and instincts, and there’s a path to being a top-10 pick if he dominates the way some believe he can.


Ryan Lin
D, Vancouver Giants (WHL)

He won’t bring you out of your seat with razzle-dazzle the way some players on this list will, but there is arguably not a more well-rounded defenseman in the draft. Lin is the type of player who often goes unnoticed because he doesn’t make mistakes.

He shuts plays down early with proper angles, a good stick and excellent reads. His hockey sense and decision-making are two of his best qualities, allowing him to make the simple play and start his team up the ice with a quality first pass. He plays in every situation, including the penalty kill and power play, and should be the engine of the Giants this season.

His offensive numbers don’t jump off the page, but with some development to his skating he has the potential to be an elite, two-way defender who dictates the game on both sides of the puck. Lin is going to play 30 minutes per game for Vancouver this season and have every opportunity to thrive offensively and defensively. If he grows a few inches — he’s 5-11 — it will only help his draft stock.


Mathis Preston
C/W, Spokane Chiefs (WHL)

One of the most exciting players to watch at the Hlinka-Gretzky Cup, Preston is a crafty playmaker with smooth skating and elite hockey sense.

His offensive instincts constantly have him in the right spot at the right time, drawing defenders toward him before making a play that creates a high-danger chance for a teammate. He’s evasive, makes good decisions with the puck and uses his quick hands to execute with ease.

He’s going to be one the biggest offensive producers this season as a draft-eligible player. If he continues to develop his offensive toolbox, he’ll be a top-10 pick because of his ceiling as a high-end winger in the NHL. Given his late-July birthday, I would expect him to star at the U18 world championship next year if he’s not in the WHL playoffs. Wherever he’s playing, he will catch your eye with his highlight-reel skill.


Chase Reid
D, Sault Ste. Marie Greyhounds (OHL)

Reid’s development curve has been fascinating to watch, and he will have every opportunity to lead the Greyhounds’ blue line this season.

The right-handed defenseman is a good blend of smooth mobility, high-end offensive instincts, quality transition play and enough raw talent to mold into a legitimate top-pairing defender. He will undoubtedly be of the OHL’s best defensemen this season and will be relied upon to play heavy matchups in key situations, producing offense.

It is rare that a defenseman produces a point per game in the Division I season, but Reid did, and it put him on a lot of NHL radars. If his defensive game keeps improving and he becomes elite on both sides of the puck in transition, he will be a hot commodity in the upcoming draft.


Ryan Roobroeck
C/W, Niagara Ice Dogs (OHL)

Roobroeck will be one of the most intriguing prospects to watch this season with many scouts wondering where he will play. He has a late-September birthday, so he’ll be in his third OHL season after leading Niagara in scoring in his D-I year.

The real question is whether Roobroeck will play at center or on the wing as he did in his first two seasons. At 6-4 with good skating, reliable special teams play and an NHL-quality shot, his value will significantly increase if he can prove his capabilities as a play-driving center. If he develops his playmaking in the middle of the ice to become more of a dual threat and more physically engaged, there is every reason to believe he will be a top-10 pick.

There is a lot of potential for Roobroeck, and it will be interesting to track where he is positioned and how that impacts his ability to drive the action.


Daxon Rudolph
D, Prince Albert Raiders (WHL)

Rudolph’s development took off in the back half of last season, and he should be the leader of the Prince Albert blue line this season.

With more opportunities, Rudolph is likely to put up offensive numbers with his ability to beat defenders and find open teammates for high-danger scoring chances. He’s a well-rounded player with good skating that allows him to defend the rush well with gap control. He has thrived when elevated to higher-leverage matchups, and it will be interesting to see how he owns that role for the entire WHL season in his draft year.

Teams will be watching closely to see if he can continue to control play on both sides of the puck and produce offensively as a right-handed blueliner.


Ivar Stenberg
LW/RW, Frölunda HC (SHL)

An ace in transition and with the ability to play both wings, Stenberg has turned heads regardless of the level at which he plays.

He looked like the best player at the world junior showcase as an underaged player after torching the J20 league in his 17-year-old season. He was two weeks from being draft-eligible in 2025 and is on the inside track to be a lottery pick in the upcoming draft.

Playing in the SHL in your draft year is no joke, and Stenberg has the skating, creativity and skill to thrive with Frölunda. His ability to make his teammates better by running a power play, facilitating offense in transition with speed along with elite playmaking and above-average instincts make him an attractive player. At this stage, he projects to be a top-line NHL winger, and he will only improve his value if he continues to develop his play off the puck.


Keaton Verhoeff
D, University of North Dakota Fighting Hawks (NCAA)

A 6-4, minutes-eating, right-handed defenseman with leadership qualities? You know that’s got the attention of the NHL scouting world.

There are some who believe Verhoeff will challenge McKenna for the top spot in the upcoming draft. On skill alone, that’s a tough case to make. But given Verhoeff’s size, ability to impact the game and the fact that he’s a right-handed defenseman, it would not be surprising if some teams felt that way.

He is a go-to player in every situation and should be a key member of the North Dakota blue line this fall. He makes a good first pass to exit the zone, his shot is NHL-caliber, and he has the hockey sense to facilitate offense in the zone.

Defensively, he’s further along than others in this draft class, and that will only improve against tougher competition in the NCAA. If he can improve his skating to match pace, defend in transition and quickly move to offense, he will be drafted in the top three.

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Japan’s finance minister endorses crypto as portfolio diversifier

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Japan’s finance minister endorses crypto as portfolio diversifier

Japan’s finance minister endorses crypto as portfolio diversifier

Japan’s Finance Minister Katsunobu Kato said crypto deserves a spot in portfolios, while pledging to build a sound trading environment for the sector.

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Grayscale seeks SEC approval for Spot Avalanche ETF under AVAX ticker

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Grayscale seeks SEC approval for Spot Avalanche ETF under AVAX ticker

Grayscale seeks SEC approval for Spot Avalanche ETF under AVAX ticker

The Avalanche ETF filing marks another step in Grayscale’s expanding suite of crypto investment products, following XRP and DOGE filings earlier this year.

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