9 ms·
Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy
- ItsHarper 1y agoThis would be incredibly cool if it works in reality and not just simulation. Remarkable that the author is just 17.
- fracus 1y agoShe's also a very talented violinist.
- epcoa 1y agoI’m not going to shit on it, nothing wrong with going into the family business - but it isn’t a complete coincidence that her dad is a PhD biochemist at UT Tyler.
- buckle8017 1y agoIt never is, the winner of this competition is in astral radio telescopes. Something tells me he didn't launch the satellite.
- felineflock 1y agoWith mentorship from Caltech and access to data from NASA’s NEOWISE mission, Matteo created a machine learning algorithm and compiled a groundbreaking database called VarWISE. https://www.societyforscience.org/regeneron-sts/2025-student-finalists/matteo-paz/ https://www.societyforscience.org/regeneron-sts/2025-student...
- qzw 1y agoI knew someone who reached the final stage of one of these science fairs. Project was done at a lab in an Ivy League university over a couple of summers. Relative was a senior scientist at the lab and guided them every step of the way. Not to discount what these kids are doing, but the reality is that these science fairs have largely become a contest about how well your family is connected to science-fair-friendly research facilities and how good your presentation skills are. I mean, do we really think 17 year olds are out there doing human trials on novel cancer therapies? I’m sure there are some projects that are genuinely thought of and done by the students themselves, but looking at a lot of these PhD level research that are supposedly done as after school projects of high school kids, I can’t help but think the whole thing has become a bit of a farce.
- jmcgough 1y agoYeah, it's great to have kids excited about science, but at 17 it's extremely unlikely that she taught herself enough chemistry, organic chemistry and biochemistry to come up with this. She needs years more of college-level coursework. Essentially impossible without a biochemist in the family to guide her.
- hooo 1y agoAnd look at her mother -- https://profiles.unthsc.edu/profile/381 https://profiles.unthsc.edu/profile/381 -- hmmm
- 14 1y agoSeeing articles like this is almost hard to read. My kids are very smart but this girl is 1000 times what they are doing. This girl is 1000 times what I am doing. Maybe it is just imposter syndrome but sometimes I read articles like this and think I fell short in life. But I am also top of my peers at work and I am a health care provider and my clients all request me so I know I am doing good. Sometimes I just wonder what mark I will leave on this world.
- Glyptodon 1y agoMy experience is that stuff like this isn't because someone is wildly smarter than everyone but because there are connections, support, and resources of some form.
- 14 1y agoI understand that and I do know that I am actually very intelligent and smart. Same for my children I mean damn I have already taught my 8 year old how to solder as good as a professional and am working on programming with him. And as a health care worker I can look after even the most difficult complex care clients where other health care workers struggle. That is what I am known for at work. But sometimes seeing literal teens doing things that seem so far ahead of me it
- throwawaymaths 1y agoit's just a four step synthesis. with the help of a phd chemist you could probably learn the steps in three months, and if you put your mind to it you could learn the ochem in a year. this project is the culmination of at least a year-maybe even up to three-of work. whats surprising is that parents let their kids do ochem at 17!! thats some toxic shit :). safety is why chemistry is not a super popular field at high school level science fairs.
- mofunnyman 1y agoC'mon, who doesn't like their kids dusted with methylmercury?
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- Mizza 1y agoShe didn't even break the top 10 in this content: https://www.societyforscience.org/regeneron-sts/2025-student-finalists/ https://www.societyforscience.org/regeneron-sts/2025-student... I'm impressed beyond words by these kids, though I think I'd give her the top prize. Watching my grandfather's final days taken away from him by the effects of morphine has always made me wish so much that we had much more effective non-narcotic painkillers
- irjustin 1y agohttps://www.societyforscience.org/press-release/regeneron-isef-2025-full-awards/ https://www.societyforscience.org/press-release/regeneron-is... She's in top 4, awarded $600? I dunno this is a confusing layout/structure for how the program is conducted seeing as how the headline is $9m awarded.
- ricardobeat 1y agoReversible computing, materials science, genetic research… it’s insane that these kids are doing this level of work in high school.
- deleted 1y ago[deleted]
- timr 1y agoThey aren't doing it on their own. Most of these kids are working with established researchers who give them the shape of the project, as well as the tools and the expertise to accomplish it. More recently the US scientific funding bodies have had summer programs for kids who wouldn't otherwise get that kind of access, but it's still the exception. It takes more than a summer to do this kind of work. Edit: quick search for the father's name brings up this professor of biochemistry at UT Tyler: https://www.uttyler.edu/directory/chemistry/lee-jiyong.php https://www.uttyler.edu/directory/chemistry/lee-jiyong.php and mom's name brings up this professor of pharmaceutical science: https://www.unthsc.edu/college-of-pharmacy/eul-hyun-suh https://www.unthsc.edu/college-of-pharmacy/eul-hyun-suh I don't mean to take anything away from the kid or suggest that they don't work hard, are smart, etc., but these kinds of science fairs are fundamentally about access.
- throwawaymaths 1y agoimpressive for a high schooler but this just adds a protecting group onto tylenol. am i missing something? edit: oh i see. its really blurry but the silyl modified tylenol is predicted to have good trpv1 binding computationally. afaict no in vitro or in vivo studies were done. could be cool. not sure if diethylethynylphenylsilyl group has good Lipinski properties though (i suspect not) edit: s/aspirin/Tylenol
- abrookewood 1y agoIt isn't aspirin - Acetaminophen, also known as N-acetyl-para-aminophenol (APAP) or paracetamol
- throwawaymaths 1y agolol yeah sorry brain too deep into synthetic chemistry bits. thanks.
- gus_massa 1y ago[Very good comment! I'd use the opportunity to add more questions.] How expensive are the steps? They look like advanced steps that can be done in a lab to prepare a few micrograms, but I'm not sure if they can be scaled to industrial production. Why silicon instead of just a carbon? Is it better blocking the docking? Is it better moving the orbital energy levels? Is it as safe as the poster claim?
- throwawaymaths 1y agosilicon is not very successful in drugs. https://www.science.org/content/blog-post/silicon-drug-molecules-revisited https://www.science.org/content/blog-post/silicon-drug-molec... that molecule almost certainly fails the ClogP not greater than five lipinski rule (it's too greasy)
- gus_massa 1y ago[Sorry for the delay.] IIUC from the "In the pipeline" article, drugs with silicon are too similar to their equivalent with carbon, and more difficult to make: "so why bother?" Are they using the silicon to avoid the usual rules of substitutions in benzene cycles? Is it possible to do the same trick with carbon? > that molecule almost certainly fails the ClogP not greater than five lipinski rule (it's too greasy) Is it possible to fix it adding some -NH2 (or -COOH ?) group in the second aromatic cycle? [I understand it's a nice science fair project but the article oversell it.]
- mewse-hn 1y agoso is this already patented by Regeneron?
- throwawaymaths 1y agoregeneron is the sponsor of STS. used to be well known as the Westinghouse STS, then intel took it over in the aughts
- colingauvin 1y agoThey would need to show efficacy to patent it. It seems like this is all computational.
- throwawaymaths 1y agono she did the synthesis and the yields are averaged? over >5 replicates <== just doing that is pretty (spiritually?) impressive, most phd chemists wouldn't do that kind of reproduction of results.
- refurb 1y agoOnly for a utility patent, not for a composition of matter patent.
- Scoundreller 1y agoThey're testing it now against all of their genetic targets they bought from 23andMe
- NortySpock 1y agoThe same website is also for the excellent Science News print magazine, which will ship you top notch science reporting right to your door. My father was a subscriber since, well, whenever blue LEDs were invented, because I recall reading about them in Science News. Strong recommendation for any science-lover.
- shanemhansen 1y agoScience News is a big part of my childhood. My stepdad's dad was a subscriber and every issue was handed down to us gently used. I have thousands of back issues.
- pugworthy 1y agoSame. My highschool library in the 70’s had a subscription and I would read through them with relish.
- bluesounddirect 1y ago[flagged]
- inverted_flag 1y ago[flagged]
- mmooss 1y agoInteresting - how do you see it as 'Boomer'?
- djtango 1y agoThe key synthetic step using Ir was published after I graduated (and left Chemistry...) way to make me feel old :) I'm very impressed by the level of chemistry demonstrated by a 17 year old. During my time as a chemistry student this level of project and synthesis probably could have been included as a chunk of a master's thesis. Did she perform all the synthesis herself? That takes a decent amount of experimental skill and more importantly what lab did she do all of this in? Any uni ought to be delighted to get a precocious talent like this!
- aaron695 1y ago[dead]
- aethrum 1y agoReminds me of this drug company I was pitched a while ago: https://en.wikipedia.org/wiki/Antibe_Therapeutics https://en.wikipedia.org/wiki/Antibe_Therapeutics
- deleted 1y ago[deleted]
- porphyra 1y agoIt's always weird to me that acetaminophen has such a low therapeutic index, like in order to get enough for it to do anything, you're also on the verge of liver failure (especially if you also drink alcohol). Also it just doesn't work super well in my personal experience --- I hardly feel anything when I take it. And yet it's one of the most commonly taken medicines worldwide.
- reedf1 1y agoI take it mostly as an anti-pyretic (fever reducer). For which it is extremely effective. It's my drug of choice for colds, flu, etc.
- MichaelRo 1y agoWell, it doesn't work for high fever (> 39-40 Celsius). For that, I alternate Ibuprofen and sodium metamizole every 4 hours. For pain release, paracetamol it's very modest. Some effect for light head pain, zero for strong pain. Zero effect for strong back pain. Ibuprofen works better in all these cases but comes with stomach damage if taken for long.
- Ey7NFZ3P0nzAe 1y agoParacetamol is nicely synergic with all known painkillers. For example prescribing it with morphine leads to less morphine consumption. Also: it's a terrible rule of thumb to take an NSAID routinely for general infectious symptoms like fever.
- cluckindan 1y agoPrescribing cannabis for pain also leads to less morphine consumption.
- Ey7NFZ3P0nzAe 1y agoThe safety profile of paracetamol is orders of magnitudes higher ghan cannabis though. It is still one of the, if not the, most heavily used and appreciated drug and can be taken at any age
- snibsnib 1y agoI'm not an expert in pharmaceutical chemistry, but this looks like a series of relatively complex and low yield reactions. Would it be likely that this would push the price of this product beyond what is reasonable for a general use drug?
- maxerickson 1y agoThe starting point is ~free (like 2 or 4 cents retail per dose for generic in the US). Given my relatively light usage of pain drugs, I would certainly pay 10x that for reduced toxicity. And then it isn't necessarily the case that the identified reactions are the most cost effective available.
- toast0 1y agoIf you have light usage, do you need reduced toxicity? Acetaminophen's effective dose is pretty close to the dangerous dose, but I would take light use to mean you take something maybe once a month max and only a single dose (or maybe even just one pill when the dose is two pills). At that level of use, I don't think you're at risk of anything. Otoh, if the title is accurate and it can be more effective at pain release and less damaging to the liver, that would be great for people who experience pain frequently.
- w10-1 1y agoIf it makes it to market at a high price, it wouldn't compete directly but be targeted to those at risk of toxicity.
- more_corn 1y agoHow about don’t fucking take it because it’s toxic?
- nandomrumber 1y agoCan acetaminophen be packaged with n-acetyl cysteine to render it not rate limited by same?
- Ey7NFZ3P0nzAe 1y agoAlways wondered that. Maybe too many people would take even more?
- meew0 1y agoThe problem is that N-acetylcysteine tastes and smells awful (like farts/rotten eggs) and often causes nausea and vomiting as a side effect. The vast majority of people use acetaminophen in a safe way, and acetaminophen doesn't really have many side effects by itself, so you'd make life more unpleasant for a large number of people in order to prevent a tiny number of acute poisonings. Probably if this were implemented, most acetaminophen users would switch to e.g. ibuprofen which is less acutely toxic in overdose but has much more chronic toxicity (to the stomach and the kidneys) when used over a long period of time, even at a normal dose. I'd wager this change might even be a net negative on the whole.
- AnthonBerg 1y agoExperiences may vary; I’ve tasted and smelled NAC. The smell is reminescent of a high-potency cannabis strain. (Sulfur-containing molecules.) The taste is very acidic and a bit astringent. Generally the smell and taste of something isn’t a concern with medication. I don’t think acetaminophen tastes great. I’ve never encountered or seen the digestive issues that are often mentioned. I’ve seen other side effects which were noticeable – mast cell and histamine related I believe, kind of weird ones, like psoriasis kind of drying out a bit and the skin on the lips “refreshing” itself. (Really!) Subtle side effects and hard to put into words without making them seem bigger and weirder than they are, but NAC can nonetheless be a sort of histamine and mast cell “flusher”, so to speak and as it seems. Beneficial in the long run imo ime, but tricky to package universally. Still, NAC is also tragically unknown and unused! There’s tons of fascinating literature on it. They fried rats’ brains with methamphetamine and fixed them with NAC; Brutal study, intriguing results on very significant mechanisms.
- foxwolf 1y agoAll my life, I've suffered from frequent (as in daily) headaches. I even have a photo of myself from my 10th birthday (or thereabouts), where you can visibly tell from how I'm holding my head that I had a headache. The nature and intensity of my headaches has changed over time. In my 20's I discovered Excedrin (acetaminophen + caffeine) and, surprisingly, it not only worked, but worked very well. One tablet would kill most of headaches I was having at that time of my life in about 15 minutes. Unfortunately, it stopped working for me by the time I was 30. It no longer has any noticeable effect. Aspirin, Naproxen, Ibuprofin, and Tylenol 3 have no effect, either.
- djmips 1y agoThat is a tragedy. Sounds like you could use some precision medicine but it feels like that revolution is not happening fast though.
- mancerayder 1y agoHave you ruled out head/neck muscle tightness due to jaw clenching? Have you tried muscle Botox injections? or seen a migraine specialist?
- uselesswords 1y agodisclaimer: Not medical advice. Just an exercise in theory. See a real doctor/neurologist or migrane specialist. I would be very suspect of a Medication Overuse Headache (MOH) due what appears to be acute/abortive use of painkiller medication as compared to a prophylactic usage of other drugs. I'll do this exercise mostly ignoring the #1 concern because presumably your doctors would be hyperaware of that. # Pathways 0. Excedrin is combination of aspirin, acetaminophen, & caffeine. 1. Aspirin --> COX-1 (/2) inhibition --> Reduces Prostacyclin/Prostaglandin/Thromboxane Synthesis --> Decreased inflammation, nociceptor sensitization, pain signaling 2. Acetaminophen --> Central COX Inhibition, possible COX-3 inhibition (splice variant of COX-1) --> Reduces Prostacyclin/Prostaglandin/Thromboxane Synthesis --> Decreased inflammation, nociceptor sensitization, pain signaling 3.a. Acetaminophen --> Metabolized to N-Arachidonoylphenolamine (AM404) --> Inhibition of reuptake of Anadamide (endogenous cannabinoid) --> Increased activation of CB1 receptors 3.b. Acetaminophen --> Metabolized to N-Arachidonoylphenolamine (AM404) --> Transient Receptor Potential Vanilloid (TRPV1) agonist --> active? at periaqueductal (central) gray --> opioid receptors that send descending axons to modulate pain at the level of the dorsal horn of the spinal cord 4. Acetaminophen --> Enhancement of serotonergic descending inhibition (5-HT pathways) 5. Caffeine --> Adenosine anatagonist (nonselective A1, A2A, A2B) --> Inhibition of vasodilation --> Cerebral vasoconstriction 6. Caffeine --> Analgesic Adjuvant --> Enhances availability of aspirin and acetaminophen. # Thoughts 1. Selective: -COX, +CB1, +TRPV1, +Opioid, -Serotenergic, -Adenosine, -Inflammation, +Vasoconstriction/-Vasodilation 2. Aspirin doesn't work in isolation. 3. Tylenol-3 (acetaminophen) doesn't work in isolation (surprising!!!). 4. Headaches probably not -COX mechanisms 5. Caffeine is likely needed for -adenosine, vasculature effect implicating cerebral vasodilation 6. Densensitization strongly implicates +CB1/+TRPV1 as well as -adenosine, +Sero, +Opioid. # Concluding Thoughts 0. Need to address MOH, this should be a conversatio with your real doctor. 1. Then for the headache, normal first-line would probably be a TCA prophylaxis such as amitriptyline with bonus target +sero/+opioid. Assuming you've tried this. 2. The failure of your other drugs means you should probably try CGRP Inhibitors to target vascular and pain-signaling effects. Maybe even gepants (acute) 3. Botox could be a consideration in a complex CDH case. 4. Zebras: Ditan/Lasmiditan. I assumed +vasoconstriction, but could be -vasoconstriction which is why non-combination drugs failed. Target 5-HT1F and avoid vasoconstriction for symptomatic relief, but doesn't treat underlying. Probably avoid due to MOH. # Clarifying questions for your doctor, not me 1. Is your headache pulsatile/throbbing (migrane) or dull, tight, & persistent (tension-type)? 2. Onset characterized by stress (tension-type)? 3. Is it unilateral (migrane) or bilateral (tension-type)? # What I would do next 1. Make an appointment with a neurologist 2. Before the appointment, make a detailed headache diary (when your headaches start/end, intensity of the pain, location and quality of the pain, associated symptoms (nausea, light senstivity), any potential triggers, what you did to try to relieve the headache and if it worked)
- gitroom 1y ago[dead]
- neves 1y agoacetaminophen is paracetamol I didn't understand why this post had so many votes
- CommenterPerson 1y agoThis is nothing. My kid discovered dark matter (in middle school).