Bob the Grumpy Med Chemist
@med_chemist
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Jaded. Let me know when one of you figures out how the human body works.
Armchair
Joined May 2021
Have seen this a couple of times recently:. If you are reporting the results of a kinase panel in a paper, please make sure to include not only the concentration of compound used, but also the concentrations of ATP used in said panel.
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I've previously collected similar articles with useful warnings and tips about methods such as scavenger reagents. See them by following the linked threaded tweets.
Glad there is room for papers like this to be published. I hope there will be some follow up on the original ACS Med. Chem. Lett. paper on the supposed probe. Some other references on metal impurities linked below, if useful.
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Wonderful little paper here with many useful warnings inside:.Practical notes:.-Do fresh resynthesis (orthogonal route a +).-Test potentially interfering salts+compounds in assay.-Lots of things bind and give Xray structures at mM . More warnings below. .
pubs.acs.org
Identifying promising chemical starting points for small molecule inhibitors of active, GTP-loaded KRAS “on” remains of great importance to clinical oncology and represents a significant challenge in...
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On the other hand, the efficacy data for antibiotics does mitigate the risk of mischaracterization a bit. Paws up / paws down is a pretty clear endpoint!.
I propose a solution to 2 problems:.- Lack of novel antibiotics.- Abundance of terrible in vivo efficacy studies. Solution:.If you publish a bad efficacy study, you must instead work on antibiotics development, where output of animal model is much clearer. paws up / paws down.
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I'm extremely pleased people are working on novel antibiotics. But it still makes me a bit sad that this is the PK characterization of the key compound in the world's purported premier science journal:
What if there was an antibiotic that doesn't disrupt the gut microbiome?.There is now. A discovery published @Nature today.@PaulHergie and colleagues @UofIllinois @justsaysinmice
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After good data: "May I die if I were to change places with the Persian king!". After bad data: "You know, maybe leaving behind chemistry in exchange for my own kingdom would be a sensible choice if given the option."
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Having just read the article, this was quite apparent:
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If I were the patient, I’d be a bit concerned that the “Amount” field of the label is basically unintelligible.
Me: “So, how’s your pain this morning?”. Patient, pointing to IV: “This stuff is amazing.”. The stuff:
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Forgot to provide the answer: US20220402883 - COMPOUNDS AND METHODS FOR MODULATING RNA FUNCTION.
@dragon38073853: we miss you posting fun patent structures. Can you all guess the target of these compounds?
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Just a reminder to any of you mixing drinks tonight: grapefruit juice is good for masking the taste of alcohol, but beware of juice-drug interactions!.
Bob's Med Chem Fact of the Day:. In the 80s, like many of you tonight, scientists were searching for the best juice to mask the taste of ethanol. They chose grapefruit juice. The eventual study would lead to the surprising discovery of strong grapefruit juice-drug interactions.
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Estimated total $$$ spent making compounds based on misanalyzed SAR — chasing noise rather than true signal…. A Fermi estimate to absolutely no significant figures: WAY TOO MUCH.
Sunday night rant: med chemists and friends, please, in the name of all that is holy, pay attention to significant figures. If I see one more IC50 reported as 10.407 +/- 1.708 uM, I’m going to lose my mind. Y’all learned this in high school ffs. Just stop it.
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Good thread and responses. And before initiating a study always ask:."how will the med chem/discovery strategy change based on the results of this?". Amazing how often people want to spend time+$$$ on studies that will not change anything besides satisfying intellectual curiosity.
Drug Discovery Axiom 6: take measured risks; spend the money, save the time. Folks are often miserly with assays & skimp on study designs. It’s a mistake. All of this pales in comparison to the cost of lost time moving a drug to the clinic & market. Value time correctly.
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The Nobel Prize in Chemistry is awarded for the naming of "fancy-name.". Though no practical use cases have yet been discovered, the creation of "fancy-name" has led to hundreds of papers and reviews noting the promising potential applications of "fancy-name.".
The chemistry Nobel will be announced tomorrow, so it’s that time again! Who will win this year? Wrong answers only.
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I pose the following solution:. - Make med chem (somewhat relevant to physicians) a required course for pre-medical students. - Make organic a prerequisite for med chem. - Organic chem courses are now highly relevant. Now all the students get to be even more angry at chemistry!.
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Now quite annoyed I didn't get at least 10 J. Med. Chem. papers from the last time I was working on a diastereomeric series:.
pubs.acs.org
SARS-CoV-2 is the causative agent behind the COVID-19 pandemic. The main protease (Mpro, 3CLpro) of SARS-CoV-2 is a key enzyme that processes polyproteins translated from the viral RNA. Mpro is...
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5 easy steps to become a modern grumpy med chemist:. - Have a HTS return no useful hits.- Have a virtual screen return no useful hits.- Have a fragment screen return no useful hits.- Have a DEL screen return no useful hits.- Have a literature compound fail to reproduce.
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Perhaps a certain journal and its editors could lead the way in changing this culture, to a world where particularly useful negative results are seen as essential to the main body of the paper. Hint. Hint. Wink. Wink.
As an author, it is hard to put lots of negative examples into a paper because of fear reviewers will not be positive. But what about putting tables of unsuccessful substrates in the SI? #OLAskTheEditor.
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Also this is why all you spring chickens should take up the habit of reading accounts of old, obscure papers :)
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