h a l f b a k e r yCompound disinterest.
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I am fully aware that this idea has something of a vibe of a
certain other user's ideas. Where is he incidentally?
Haven't heard from him in ages.
Steroid receptors are inside cells on the nuclear membrane
if I recall correctly. However, when people are given
steroids for various conditions,
their whole bodies are
given them, so they can get side effects. This is
unfortunate, since the action itself only needs to be in a
few tissues.
Clearly they pass through cell membranes into the internal
environment of the cell before reaching the nucleus. In
that environment, there will be certain enzymes which will
act upon particular compounds, such as yanking other
groups off steroid molecules, and will not be present
outside the cell, or at least will be less concentrated.
Consequently, it seems to me that if you added something
to the steroid molecule which made it less active but still
able to pass through the cell membrane, which could then
be removed from the molecule once it was inside the cell,
you would be able to target the steroid to the tissue it
needed to be in. This is all very vague, but say you have a
cell which makes keratin in the skin. That cell will be
doing something enzymy to amino acids to make them into
keratin for the epidermis. If that enzymy thing could be
done to an extra bit tagged onto a steroid molecule, that
steroid could then get to eczema without influencing the
rest of the body as much because that same bit would've
stopped it being steroidy elsewhere in the body.
I feel like I've lost my marbles so this is probably nonsense,
but is it?
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A place to start is some sort of understanding about why existing corticosteroids differ in potency. I thought it was binding affinity but could it be lipophilicity? |
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//I feel like I've lost my marbles so this is probably
nonsense, but is it?// |
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You've invented pro-drug pharmacology. This has,
unfortunately, already been invented. Turns out it's quite
tough. |
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I'm aware of pro-drugs but I'm not aware that it's been
applied to steroids. |
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//Where is he incidentally?// If the person you're thinking about is the person I think you're thinking about then (rather worryingly) I think he tends to live outdoors these days - somewhere kind of Portland(ish). There are occasional YouTube uploads of snippets here and there, but I've not seen anything for maybe 6 months or so. I do hope they're OK. I have considered, in flights of fancy, that if I were ever over that way, I might try and look them up, but I'm not, and I'd probably be too embarrassed/shy/something-else and rationalise a reason not to if I ever were. |
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//pro-drugs but I'm not aware that it's been applied to
steroids// |
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Prednisone is an example. Metabolized to prednisiolone
in the liver. The liver is your best target for pro-drugs, it
has by far the most unique enzymes of any tissue. |
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I should explain my point about your idea better. You
gave the example of the skin. Now, it's true that there
are a train of enzymes used in in the synthesis of
keratin. We don't seem to know much about them, there's
30-ish keratins in skin cells, but then there's a whole lot
of interrelation between that and the cytoskeletal
proteins used in all sorts of cells. Essentially, it' a massive
mess. Your strategy would need you to find a catalytic
enzyme which is unique to your tissue of interest. If you
could use one of them to activate a pro steroid, then
great. But enzymes are relatively specific. If you have an
enzyme that's involved in keratin synthesis, then you
need to design your pro-drug to interact with that. But it
probably won't, because steroids aren't shaped like
keratin. |
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Imagine you solve that problem, and you have a good
skin-specific candidate enzyme which cleaves a group off
a steroid pro drug leaving the active derivative. Say it's
cortisone. Now your drug diffuses out and you barely
achieve any specificity at all. So you design a cortisone
derivative that is functional, but not cell permeable. This
is tricky, this ISN'T cortisone. So now you're in the novel
pharmaceuticals game: you multiply your problem by the
existing problems faced by the pharma industry. |
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1. is it toxic? We know the steroid isn't, but what about
the pro-drug? or the non-permeable derivative? |
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2. is it available? curcumin is quite good at killing
pancreatic cancer cells. Great, we should all eat a ton of
turmeric to head pancreatic cancer off at the pass.
Except that it's not absorbed. It's a fun way to get
fluorescent poo however. |
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3. is it active? too active? not active enough? Does it build
up? Does it absorb UV? |
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And so on. One of the biggest problems is beating existing
drugs. You have to prove it's better, and it's hard to get
better targeting, for the skin at least, than just rubbing it
on. |
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We never really answered [nineteenthly]'s question of
whether or not he's lost his marbles. |
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Does anyone know where thery are now ? if so, technically they're not lost. |
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// it's hard to get better targeting, for the skin at least, than just rubbing it on. // |
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