Post

How to get URL link on X (Twitter) App

On the Twitter thread, click on or icon on the bottom
Click again on or Share Via icon
Click on Copy Link to Tweet
Paste it above and click "Unroll Thread"!
More info at Twitter Help

Keith Hornberger

Jul 20, 2021 • 9 tweets • 3 min read • Read on X

I support our group with early human dose prediction. Not the fancy, need-tons-of-software and a DMPK pro kind. Just the kind that uses some basic algebra. HDP is a unifying concept for med chemists. It’s the master optimization parameter, and it can’t be easily cheated. 1/

Here’s a wonderful paper from AstraZeneca that speaks to this conceptual framework - this isn’t something I invented. The concept has been around for years. Required reading! 2/
pubs.acs.org/doi/10.1021/mp…

And another. 3/
pubs.acs.org/doi/10.1021/ac…

At my own shop, I’ve built a suite of tools 🛠 in Excel to assist with allometric scaling of Cl/Vss and modeling common HDP scenarios. Playing with input parameters in real time in these sheets is a great way to grasp how they impact dose. 4/

@knime

Beyond the beginnings you can get from Excel, for projects that are in full-on lead optimization, I’ve also built workflows in @knime that can automate this process for many compounds at once. 5/

None of this replaces expert input from your friendly neighborhood DMPK person. But I’m repeatedly astonished how close to the final mark you can get with basic modeling. Medicinal chemists need to claim and own and normalize routine basic HDP. 6/

The biggest barrier is, I think, fear of the math. But you only need some basic algebra to manipulate the equations (and a smidge of calculus if you want to do the derivations). Plus some time invested by one person in a group in learning Excel functions and KNIME pipelining. 7/

Big shoutout to my ex-BI colleague Rob Hughes (also ex-Pfizer) who was WAY ahead of most of us on this stuff. He more than anyone showed me the way and had a huge impact on my own thinking. 8/

Lastly, yes, this is me reclaiming some math after yesterday’s depressing realization that I no longer know quantum chemistry. I make no apologies for boosting my own confidence. 😂 /end

• • •

Missing some Tweet in this thread? You can try to force a refresh

This Thread may be Removed Anytime!

Twitter may remove this content at anytime! Save it as PDF for later use!

More from @KRHornberger

Keith Hornberger

@KRHornberger

Jan 18

Jensen Huang’s comments from JPM24 are now summarized in a Nvidia blog post. He doubles down on exactly the kinds of things that I’ve been cautioning are wildly optimistic. More below. 👇🏽 1/

Usual disclaimer: it’s op-ed time again. My opinions alone, not my employer’s or anyone else’s. 1.5/

For reference, here’s the summary. 2/
blogs.nvidia.com/blog/nvidia-ce…

Read 16 tweets

Keith Hornberger

@KRHornberger

Sep 10, 2023

Time for another pharmacology tweetorial (X-torial?), this time on the subject of receptor occupancy and how it relates to selectivity. 1/

Usual disclaimer: all of this thread is my own thoughts and opinions on the subject, and does not necessarily reflect the views of my employer. Your mileage may vary. Some restrictions may apply. 2/

References first. For an excellent primer on pharmacology in general, which also covers the concept of occupancy extensively, you’ll want to check out this book by my old GSK colleague Terry Kenakin. Chapter X is especially relevant. 3/
sciencedirect.com/book/978032399…

Read 41 tweets

Keith Hornberger

@KRHornberger

Mar 17, 2023

Continuing the occasional Friday pharma #EarlyCareer series. Last time we talked about site interviews. This time let’s talk about negotiating job offers. (Next time we’ll deal with the inevitable rejections.) 🧵 1/

Usual disclaimer: everything in this thread is my observations based on 20+ years of personal experience at pharmas big and small, and should not be construed as reflecting the opinions and practices of, nor an endorsement by, my employer. 1.5/

After a site interview, it’s typical for a job offer or “no thanks” to follow within a few weeks. Allow some time here as more than one person is often being interviewed for a position. If you have time pressure (competing offers), the sooner you tell the company, the better. 2/

Read 26 tweets

Keith Hornberger

@KRHornberger

Feb 24, 2023

Continuing the Friday pharma industry #EarlyCareer tip series. Last time we talked about phone interviews. This time let’s talk about the next step, a really big one: on-site interviews. 🧵 1/

If your phone interview goes well, the hiring manager will usually invite you for a site interview. Pre-pandemic, that almost always meant traveling to the pharma R&D site for the interview. These days, it may also be done virtually on Zoom or Teams instead. 2/

If you require accommodations for any reason, give the hiring manager or HR person a heads-up before the interview. Most companies are happy to work with you on this if they know. If they won’t, that’s a red flag. Consider then whether or not it’s worth going forward. 3/

Read 30 tweets

Keith Hornberger

@KRHornberger

Feb 10, 2023

Since we’re all watching The Last of Us, is it really true that we have nothing (other than bombs) for the coming fungal pandemic? Time to review what we’ve got in the pharmacopeia for fungal infections. Lest we all turn into zombies. 🧵 1/

Broadly, antifungals are woefully under-researched, even among anti-infectives. Fungi are more similar to animals than plants or bacteria. That relative same-ness means finding drugs that target fungi without targeting ourselves is tough. And resistance is ever on the rise. 2/

There are three big main classes of antifungal (or anti-mycotic) agents. Two of those three lean on the fact that fungi make use of ergosterol as the main sterol in their cell membranes rather than the cholesterol typically found in animals. 3/

Read 20 tweets

Keith Hornberger

@KRHornberger

Jan 20, 2023

I’m going to offer some more regular industry #EarlyCareer tips on Fridays. Keeping this focused on chemistry in pharma since that’s what I know about.

Let’s start with applying for the job! 🧵 👇 1/

First off, unlike many other lines of industry work, in pharma chemistry we usually ask for a comprehensive academic-style curriculum vitae (CV) rather than a shorter résumé. Sometimes these terms get used interchangeably in the US, but they’re not the same. 2/

This removes some pressure to compress your professional life into a page or two. A CV typically includes: contact info, work history (most recent first), educational history (most recent first), complete publications & presentations, and possibly other optional sections. 3/