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ShakeNBakeGibson OP t1_j7mcrga wrote

Reply to comment by reddit455 in We’re Recursion and we’re using AI to decode biology and industrialize drug discovery! by ShakeNBakeGibson

Love that we have one of our first questions even before the official start. Honestly, the millions of simulations that fail enable the one that solves the problem. Both matter!

…and yes, Viagra was a drug originally developed for hypertension and angina pectoris, and as the story goes, when the drug didn’t work that well for those indications and they stopped the trials, none of the participants wanted to give back their clinical trial drugs…. because, well, you know…

But counting on serendipity to give us outcomes like that, in diseases of higher unmet need of course, is not a recipe for success. So we’ve created Recursion to systemize serendipity. But we aren’t stopping at known drugs… we’ve built a dataset spanning over a million molecules that could help us find totally new drugs for many diseases. So its alternative uses, new uses, unexpected uses, and more.

My super fun lawyer would want me to also say: this discussion may contain forward looking statements that are based on current day estimates and operations and importantly are subject to a number of risks. For more details please see the "Risk Factors" in our 10-Q and 10-K SEC filings.

EDIT: added link to comment

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EmilyU1F984 t1_j7odx3x wrote

They didn’t stop the trials mate.

Viagra was brought to market first for Pulmobary Hypertension, and is still on the market for that indication.

After release reports showed massive benefit in ED, this approval for that second indication was obtained.

It is still the major treatment option for pulmonary hypertension an otherwise very quickly lethal disease and now progression can be delayed by decades at best.

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ShakeNBakeGibson OP t1_j7qcsog wrote

Please see the following paper with many helpful refs (https://www.nature.com/articles/nrd1468). Since it is behind a paywall, here's the relevant bit...

"Pfizer was seeking a drug for angina when it originally created sildenafil (Viagra) in the 1980s. As an inhibitor of phosphodiesterase-5 (PDE5), sildenafil was intended to relax coronary arteries and therefore allow greater coronary blood flow. The desired cardiovascular effects were not observed on the healthy volunteers tested at the Sandwich, England, R&D facility in 1991–1992. However, several volunteers reported in their questionnaires that they had had unusually strong and persistent erections. Pfizer researchers did not immediately realize that they had a blockbuster on their hands, but when a member of the team read a report that identified PDE5 as a key enzyme in the biochemical pathway mediating erections, a trial in impotent men was quickly set up. A large-scale study carried out on 3,700 men worldwide with erectile dysfunction between 1993 and 1995 confirmed that it was effective in 63% of men tested with the lowest dose level and in 82% of men tested with the highest dose. Of note, in many of these studies, Pfizer’s researchers had difficulties retrieving unused sample of the drug from many subjects in the experimental group as they did not want to give the pills back! By 2003, sildenafil had annual sales of US $1.88 billion and nearly 8 million men were taking sildenafil in the United States alone."

Sildenafil was approved for ED in the US in 1998, but was later approved for pulmonary hypertension in the US 2005.

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Trumpfreeaccount t1_j7q372i wrote

What a surprise a guy who's touting his ai based business is full of shit. Lol.

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JackIsBackWithCrack t1_j7qj9jz wrote

Settle down buddy

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Trumpfreeaccount t1_j7qkzq5 wrote

Pretty settled. Not sure why you're defending a guy who is just making stuff up in an AMA to make himself look knowledgeable. And using phrases like systemize serendipity.

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JackIsBackWithCrack t1_j7qwc6f wrote

Homie 99% of the posts on this god-forsaken subreddit are literally for the express purpose of free advertising. Claiming this guy is unknowledgeable solely because he is planning on using AI is both pointless and obtuse. Pointless because he’s probably just some PR intern and obtuse because AI has the potential to revolutionize the medical field (among others).

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Hipshotopotamus t1_j7mjbiq wrote

Do you start with active sites and conformation and then try to identify a match from ChEMBL? How do you pick where to start?

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IHaque_Recursion t1_j7n0hnm wrote

We actually don’t start our drug discovery efforts from single targets – check out my earlier reply in the AMA for more details. ChEMBL certainly is an excellent source of structural information, but our insights come not from these data, but rather from high-dimensional relationships between cells treated with compounds and genetic knockout. We advance series of compounds using this data prior to having any information about the target itself.

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ShivohumShivohum t1_j7mkdbk wrote

How widely used are GNN based frameworks in your research?

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IHaque_Recursion t1_j7n0rk7 wrote

GNNs are in the suite of methods that we use and evaluate. But it’s useful to recognize that although we often draw molecules as graphs, that is not necessarily the only useful (or best) representation for molecules in machine learning. We recently published (poster and talk, paper) research using DeBERTa-style representations and self-supervision over molecular graphs, achieving SOTA results on 9/22 tasks in the Therapeutic Data Commons ADMET tasks.

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nucleosome t1_j7nfycc wrote

Do you guys need someone who can do CyTOF?

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