Posted by abhishaike 21 hours ago
Pharma companies care very much about off target effects. Molecules get screened against tox targets, and a bad tox readout can be a death sentence for an entire program. And you need to look at the toxicity of major metabolites too.
One of the major value propositions of non small molecule modalities like biologics is specificity, and alternative metabolism pathways; no need to worry about the CYPs.
Another thing they fail to account for is volume of distribution. Does it matter if it hits some receptor only expressed in microglia if it can’t cross the blood brain barrier?
Also the reason why off targets for a lot of FDA approved drugs are unknown is because they were approved in the steampunk industrial era.
To me this whole article reads like an advertisement for a screening assay.
Of course we've thought of all these things. But it's typically fragmented, and oftentimes out of scope. One of the hardest parts of any R&D project is honestly just doing a literature search to the point of exhaustion.
Every attempt to consider the extremely complex dynamics of human biology as a pure state machine, like with Pascal, deterministic of your know all the factors, is simplification and can safely be rejected as hypotheses.
Hormons, age, sex, weight, food, aging, sun, environmental, epigenetic changes, body composition, activity level, infections, medication all play a role, even galenic.
sure! i cover this in the essay, the purpose of this dataset is not just toxicity, but repurposing also
>toxicity of major metabolites
this is planned (and also explicitly mentioned in the article)
>no need to worry about CYP’s
again, this is about more than just toxicity
>volume of distribution
i suppose, but this feels like a strange point to raise. this dataset doesnt account for a lot of things, no biological dataset does
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to some degree: it is! but it is also one that is free for academic usage and the only one of its kind accessible to smaller biopharmas
It also creates physical dependence by suppressing your body’s production, resulting in testicular atrophy. Some people who experiment with testosterone discover that it can take months or years to rebound, if they can at all.
Your body doesn’t become addicted, though. The potential for harm is real if you are not taking it under medical supervision or without proper knowledge of usage, like any other drugs.
This is incorrect. Testosterone can be acutely rewarding and reinforcing, especially at high doses used by people seeking these effects.
Seeking testosterone does not indicate body dysmorphia. People want it (or think they want it) for numerous reasons, from getting stronger to feeling “alpha” to thinking it will give them an edge.
It’s also very dependence inducing because it shuts down physical production, so the person needs to continue taking it just to get back to baseline after using it for a while. At my very first job one of my coworkers got ahold of some testosterone gel and used it for several months until he ran out and couldn’t get any more. I clearly remember how bad he felt while going through withdrawals and rebound for months. I left before he fully recovered.
There's a reason pro body builders generally do not ever recommend them unless somebody is going to compete, where it's a practical necessity. Obviously people can get psychologically addicted to the effects - high energy, easy physique gains, and so on. And when one gets off steroids not only will these generally greatly diminish, but there's a very high probability of one becoming simply fat if they don't dramatically shift their lifestyle. And so that can make it very difficult for people to quit, but they do - because steroids aren't what most people think.
I live in a country where you can legally buy steroids OTC for really cheap - less than $20/month for genuine pharmaceutical steroids. And you can see at the gym a lot of guys have tried this out, and quit, because you wear it for life. They'll be 'huge' but very soft/flabby after quitting the steroids.
No I do not. I am referring to exogenous testosterone. Even dosed within typical replacement ranges it will temporarily stack on top of your already present testosterone and provide a sense of reward and falsely improved well being.
You are trying to redirect the conversation to literal anabolic steroids. Those are also habit-forming, but it’s not what I’m talking about.
Testosterone is a controlled substance because the abuse potential is studied and known.
There's no "falsely improved wellbeing". It's absolutely genuinely improved wellbeing, in the same way that if somebody was significantly deficient of some vitamin or nutrient, then supplementing it would similarly "genuinely" improve their wellbeing. This is why plummeting testosterone levels are a very serious thing. Because a certain minimum level is necessary for reasonable quality of life, and supplementation or increasing it naturally is very non-trivial.
I personally know of several early 20s guys who were between light and heavy cycles all under the supervision of doctors (or at least getting blood tested periodically).
All of them have renal issues, kidney issues, adrenal system issues, thyroid issues. Some have heart problems. Not one of them is unscathed.
It's a steroid, so body builders would use it constantly. It's a sex hormone, so people would use it to masculinize themselves and amp up their sex drive, and it's part of the pubertal cycle so children exposed to it pre-puberty can have masculinizing pubertal side effects before their actual puberty starts.
It's not hard to acquire. Doesn't mean that it's not a controlled substance.
And in fact it is sold over the counter in other countries like Mexico. You get a "prescription" from the "on-site pharmacist" who is actually just some person who works the register.
If the DEA isn't cranky, we go back to pill mills.
In the context of the legally defined controlled substances or "scheduled drugs", no, needing a prescription does not automatically mean it is a controlled drug.
Is a prescription inherently a type of 'control' against who can access certain drugs? Sure, but I don't think anyone was arguing that.
Novartis dataset paper: https://doi.org/10.1038/s41467-023-40064-9