Ramblings: August 2021

31 August 2021

Here are some collected Twitter ramblings from August 2021.

Keith Hornberger @KRHornberger

Medicinal chemist here 👋. One methyl group does change a substance into a totally new thing, and can make things have radically different pharmacology. Some reading to get things rolling. Plenty more where this came from too. onlinelibrary.wiley.com/doi/abs/10.100…

Dr. Daniel J. Winarick @DrWinarick

@alexophile One methyl group doesn’t change a substance into a totally new thing not resembling the other substance in anyway. At least the tweet arguing for the Rx of crystal meth is intellectually honest, accurate, and coherent. The rest is just garbage.

This poor fellow walked into a minefield when he tried to argue that methyl groups don’t matter. A good number of people stepped up to school him, including yours truly.

Keith Hornberger @KRHornberger

Forget this guy, the people want @levarburton!

Variety @Variety

Mike Richards in Advanced Negotiations to Become Permanent Host of ‘Jeopardy!’ (EXCLUSIVE) https://t.co/N9BkwH5vOM

There aren’t too many things I care about in the entertainment world. Who hosts Jeopardy! is one of them. This was the beginning of the brief Mike Richards affair. I grew up with Reading Rainbow and Star Trek: TNG, and I also love LeVar Burton’s podcast “Levar Burton Reads”. He’s the host that Jeopardy! needs for the 21st century.

Keith Hornberger @KRHornberger

I have anti-vax people in my own family, and I’m ashamed of it. I’ve tried so hard to win hearts and minds, and it’s so disheartening that I’ve largely failed. Opinions and beliefs have trumped science, to our great shame.

Derek Lowe @Dereklowe

I know I'm largely preaching to the choir here. But I cannot find the words to express how angry I am over the vaccine misinformation situation. My emails and messages give me a small window into it, and it's horrifying. (1/3)

Everyone has an idiot cousin. Including me.

Keith Hornberger @KRHornberger

@med_chemist Let’s not forget the truest one of all: “Here’s a thoroughly sanitized version of how this project ran that makes us look like geniuses; all the blind alleys we went down and boneheaded mistakes we made have been removed for clarity, and so nobody thinks we’re dumb.”

We miss so many learning opportunities because papers are written with a deeply scrubbed version of the truth. Mistakes and setbacks are the true teachers.

Keith Hornberger @KRHornberger

Others have made the comparison to this iconic photo of iron workers from NYC working on 30 Rock in 1932. It gives me chills to see us dreaming big and building big. Feels like it’s been a while.

Elon Musk @elonmusk

https://t.co/T6r96fqlPG

One of my other side obsessions is space exploration. I think if I’d been a different kind of scientist, I would have done something in aerospace or something math-y like orbital dynamics. But I’d also mop the floors for SpaceX just to work for them. I’m an enormous fan of what SpaceX (thus Elon Musk) and others are doing to open up the final frontier. What SpaceX is doing in South Texas is not on everyone’s radar, but they are quietly changing everything about space travel.

Keith Hornberger @KRHornberger

Agree with this. I get the temptation to draw “dumbbell” (ends separated) trimers in manuscript figures for visual clarity. But this belies how PROTACs most typically bind: at the “just right” distance that induces PPIs and can give rise to cooperativity.

Andrea Testa @EndriuT

Not the dumbbell again!!!! Please!!!! #PROTAC #TPD https://t.co/bcXyinjFVT

Accuracy matters.

Keith Hornberger @KRHornberger

I won’t stoop to link directly to this deeply scientifically misinformed tweet, but I’m greatly enjoying watching it being ratioed into oblivion.

I try to keep my disdain for all of the anti-science in our society in check. Having helped more than one vaccine hesitant person get over the hump, the one thing they all have in common is that they want to be listened to with compassion — not belittled. I’ll make an exception for Emily Miller. She and her ilk are why we can’t have nice things.

Keith Hornberger @KRHornberger

Happy to lead the crew into the woods once again. This was at Rockhouse Hill Sanctuary in Oxford. We’re now doing some beginner hikes to get more folks involved. Wait until you see where we go next month! Hint: 🏝 #TeamArvinas

Arvinas @ArvinasInc

It’s rare to find a place where you can live, work, AND play, but #Connecticut truly offers it all! #TeamArvinas is partial to all things #NewHaven & the beautiful hiking trails throughout the state – what do you love about #CT? #NationalConnecticutDay https://t.co/y8lfLgwykr

Yet another side project is hiking. I go hiking almost every weekend. It started before the pandemic, but the pandemic kicked the habit into high gear. At a time when there were so few other “normal” things we could do, and when I was trapped working from home, getting outside became a big stress relief valve. Now I take some of the crew from work on an outing once a month.

Keith Hornberger @KRHornberger

Yo @Jeopardy - you misspelled @levarburton 😒

The New York Times @nytimes

Breaking News: "Jeopardy!" announced that it would have two hosts to succeed Alex Trebek: Mike Richards, the show's executive producer, and Mayim Bialik, the actress and neuroscientist known for her roles in "The Big Bang Theory" and “Blossom." https://t.co/EkhDa47mFN

Vide supra.

Keith Hornberger @KRHornberger

Good medicinal chemists know lots of stories and anecdotes and share them to be helpful. Great medicinal chemists know when their story isn’t helpful or relevant to the current situation and pipe down.

Bob the Grumpy Med Chemist @med_chemist

@BagPhos It is very helpful when the other med-chemists provide stories of their old projects throughout the meeting. Lessons from Dave’s CNS project from the 80s are quite pertinent to the current project.

Keith Hornberger @KRHornberger

❗️This right here. Push compounds until they break. Make sure you’re stopping progression based on data, not on biases. (Biases are easy to accumulate!) Screening cascade gates are artificial. Nothing trumps data.

Chris Butler @ButDr31

@BagPhos @med_chemist The whole point of a “tool compound” is to be able to rapidly push as far down your screening funnel as possible and be able to demonstrate where it comes up short. There should be no bias in calling it a tool until you have data that suggests it’s insufficient.

Keith Hornberger @KRHornberger

Strong med chem parallel here to selecting clinical candidates. Rarely is there a drug molecule without blemish. Recognizing the “good enough” molecule is a hard skill to learn. Stories abound of teams having their candidate a long time before realizing they should nominate it.

Jen Heemstra @jenheemstra

One of the more important skills for my job is being able to decide “how good is good enough?” Every manuscript or proposal could always be better with more work, but perfect can also become the enemy of submitted.

Jen Heemstra continues to inspire me with academia-industry parallels.

Keith Hornberger @KRHornberger

My first industry job, the small group I was part of helped the company discover 3 marketed drugs. And still they laid us all off in favor of a bigger group at another site because we didn’t have “critical mass”. Eye opener. Been doing a lot more looking out for me ever since.

Dr Zoë Ayres @ZJAyres

The most important thing for my relationship with my work for me has been understanding I am replaceable. The work will never, ever, love me back. This means I get to prioritise me first. #AcademicMentalHealth

This is a true story. Loyalty is a two-way street. Your company won’t be loyal to you anymore. They’ll feed you to the pigs if they can make more money that way. Never feel pressured to be loyal back. Look out for yourself and your career.

Keith Hornberger @KRHornberger

👇🏽All of this. The fallacy that good scientist = good leader pervades industry as well, although we’re working on doing better on that front. There’s no shame in acknowledging a gap in our skills. Do what humans do best: learn something new!

Jen Heemstra @jenheemstra

Faculty, we have both a research job and a leadership job. And, being a good researcher does not automatically make us a good leader. But, just as we learned research skills, we can also learn leadership skills. The people we work with are counting on us to get this right.

Jen Heemstra inspires. Again.

Keith Hornberger @KRHornberger

This is a leading reason for relatively slow uptake of new synthetic methodology in industrial medicinal chemistry. Reliable and boring trumps elegance. @ me about my Suzuki couplings all day.

Bob the Grumpy Med Chemist @med_chemist

Bob's Med Chem Fact of the Day: Even if you have a total synthesis PhD, it is not below you to do amide couplings + reductive aminations if it gets a drug to patients more quickly. Another reminder that ~0 patients care about or even recognize "chemical elegance" the way you do