New drug reverses skin aging and greatly accelerates healing

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PAPoots

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I was really hoping this would turn out to be a peptide that ends up available on the grey market. https://share.google/doHF08V8i2XHXCJtb

Aren't Thymalin and FOX04-dri both involved in clearing out senescent or zombie cells? And do they do that throughout the whole body, rather than only in the skin where this particular drug is meant to be used?
 
I really wish more people had chimed in on what you asked! I'd come across FOX before, but it hadn't clicked that FOX04 and FOX04-DRI work in completely opposite ways — FOX04 shields cells, including senescent ones, whereas FOX04-DRI stops FOX04 from shielding them and actually eliminates them. Looking at one of the factory price sheets I've got, FOX04 goes for $68 per kit, but FOX04-DRI is priced at $400 per kit. My guess is that what we actually want is the elimination of those zombie cells rather than their protection, which would mean the -|DRI variant is the one to go with. Or am I mistaken?
 
from Gemini:

Key Differences​#-key-differences1. Mechanism of Action​#-1-mechanism-of-action
  • ABT-263: Functions as a BH3-mimetic small molecule. Cells that have become senescent depend strongly on anti-apoptotic BCL-2 proteins to remain alive even while carrying internal damage. By binding $\text{BCL-2}$ and $\text{BCL-xL}$, ABT-263 pushes out pro-apoptotic proteins (such as BAX and BAK), which then set off cell death.
  • FOXO4-DRI: Works as a protein-protein interaction inhibitor. Within senescent cells, the transcription factor FOXO4 holds the tumor suppressor protein $\text{p53}$ captive in the nucleus, stopping it from triggering cell death. FOXO4-DRI breaks that interaction, so $\text{p53}$ can move to the mitochondria and induce apoptosis only in senescent cells.
2. Selectivity vs. Off-Target Toxicity​#-2-selectivity-vs-off-target-toxicity
  • ABT-263: Since healthy blood platelets need $\text{BCL-xL}$ to stay alive, giving ABT-263 systemically leads to severe thrombocytopenia (a steep drop in blood platelet count). That toxicity restricts systemic use and has pushed interest toward local/topical formulations (for example, skin wound healing applications).
  • FOXO4-DRI: Healthy tissue shows low FOXO4 expression, whereas senescent cells have markedly higher levels. Consequently, FOXO4-DRI is more selective for senescent cells and does not destroy platelets.
3. Drug Class and Feasibility​#-3-drug-class-and-feasibility
  • ABT-263: As a small molecule, it offers better pharmacokinetic behavior, good cell permeability, and can be given orally or topically.
  • FOXO4-DRI: Being a long 46-amino-acid peptide built with D-amino acids (to withstand enzymatic breakdown), it must be injected, has poor tissue penetration unless linked to cell-penetrating tags (like TAT), and comes with a far higher manufacturing cost.

--- so small molecule with topical functionality vs. long chained one that works only via injection...
 
cheesecake said:

from Gemini:

Key Differences​#-key-differences1. Mechanism of Action​#-1-mechanism-of-action
  • ABT-263: Functions as a BH3-mimetic small molecule. Cells that have become senescent depend strongly on anti-apoptotic BCL-2 proteins to remain alive even while carrying internal damage. By binding $\text{BCL-2}$ and $\text{BCL-xL}$, ABT-263 pushes out pro-apoptotic proteins (such as BAX and BAK), which then set off cell death.
  • FOXO4-DRI: Works as a protein-protein interaction inhibitor. Within senescent cells, the transcription factor FOXO4 holds the tumor suppressor protein $\text{p53}$ captive in the nucleus, stopping it from triggering cell death. FOXO4-DRI breaks that interaction, so $\text{p53}$ can move to the mitochondria and induce apoptosis only in senescent cells.
2. Selectivity vs. Off-Target Toxicity​#-2-selectivity-vs-off-target-toxicity
  • ABT-263: Since healthy blood platelets need $\text{BCL-xL}$ to stay alive, giving ABT-263 systemically leads to severe thrombocytopenia (a steep drop in blood platelet count). That toxicity restricts systemic use and has pushed interest toward local/topical formulations (for example, skin wound healing applications).
  • FOXO4-DRI: Healthy tissue shows low FOXO4 expression, whereas senescent cells have markedly higher levels. Consequently, FOXO4-DRI is more selective for senescent cells and does not destroy platelets.
3. Drug Class and Feasibility​#-3-drug-class-and-feasibility
  • ABT-263: As a small molecule, it offers better pharmacokinetic behavior, good cell permeability, and can be given orally or topically.
  • FOXO4-DRI: Being a long 46-amino-acid peptide built with D-amino acids (to withstand enzymatic breakdown), it must be injected, has poor tissue penetration unless linked to cell-penetrating tags (like TAT), and comes with a far higher manufacturing cost.

--- so small molecule with topical functionality vs. long chained one that works only via injection...
Click to expand...
Hmm, that basically takes ABT-263 off my shopping list!!
 
PAPoots said:

I was really hoping this would turn out to be a peptide that ends up available on the grey market. https://share.google/doHF08V8i2XHXCJtb

Aren't Thymalin and FOX04-dri both involved in clearing out senescent or zombie cells? And do they do that throughout the whole body, rather than only in the skin where this particular drug is meant to be used?
Click to expand...
I have to get my hands on this. Any tiny nick or scratch I pick up (and I live with cats!) stays visible for MONTHS. My thighs are covered in marks that make me look like a cutter (that's where the cats push off when my husband rattles the treat bag) and I absolutely can't stand it
 
reta-stacker said:

cheesecake said:

from Gemini:

Key Differences​#-key-differences1. Mechanism of Action​#-1-mechanism-of-action
  • ABT-263: Functions as a BH3-mimetic small molecule. Cells that have become senescent depend strongly on anti-apoptotic BCL-2 proteins to remain alive even while carrying internal damage. By binding $\text{BCL-2}$ and $\text{BCL-xL}$, ABT-263 pushes out pro-apoptotic proteins (such as BAX and BAK), which then set off cell death.
  • FOXO4-DRI: Works as a protein-protein interaction inhibitor. Within senescent cells, the transcription factor FOXO4 holds the tumor suppressor protein $\text{p53}$ captive in the nucleus, stopping it from triggering cell death. FOXO4-DRI breaks that interaction, so $\text{p53}$ can move to the mitochondria and induce apoptosis only in senescent cells.
2. Selectivity vs. Off-Target Toxicity​#-2-selectivity-vs-off-target-toxicity
  • ABT-263: Since healthy blood platelets need $\text{BCL-xL}$ to stay alive, giving ABT-263 systemically leads to severe thrombocytopenia (a steep drop in blood platelet count). That toxicity restricts systemic use and has pushed interest toward local/topical formulations (for example, skin wound healing applications).
  • FOXO4-DRI: Healthy tissue shows low FOXO4 expression, whereas senescent cells have markedly higher levels. Consequently, FOXO4-DRI is more selective for senescent cells and does not destroy platelets.
3. Drug Class and Feasibility​#-3-drug-class-and-feasibility
  • ABT-263: As a small molecule, it offers better pharmacokinetic behavior, good cell permeability, and can be given orally or topically.
  • FOXO4-DRI: Being a long 46-amino-acid peptide built with D-amino acids (to withstand enzymatic breakdown), it must be injected, has poor tissue penetration unless linked to cell-penetrating tags (like TAT), and comes with a far higher manufacturing cost.

--- so small molecule with topical functionality vs. long chained one that works only via injection...
Click to expand...
Hmm, that basically takes ABT-263 off my shopping list!!
Click to expand...

-- Hold on, don't rush! Check out the second study, or have AI give you a summary. When it was microdosed alongside other compounds, the negative side effects disappeared, but the positive effects stayed!
 
cheesecake said:

reta-stacker said:

cheesecake said:

from Gemini:

Key Differences​#-key-differences1. Mechanism of Action​#-1-mechanism-of-action
  • ABT-263: Functions as a BH3-mimetic small molecule. Cells that have become senescent depend strongly on anti-apoptotic BCL-2 proteins to remain alive even while carrying internal damage. By binding $\text{BCL-2}$ and $\text{BCL-xL}$, ABT-263 pushes out pro-apoptotic proteins (such as BAX and BAK), which then set off cell death.
  • FOXO4-DRI: Works as a protein-protein interaction inhibitor. Within senescent cells, the transcription factor FOXO4 holds the tumor suppressor protein $\text{p53}$ captive in the nucleus, stopping it from triggering cell death. FOXO4-DRI breaks that interaction, so $\text{p53}$ can move to the mitochondria and induce apoptosis only in senescent cells.
2. Selectivity vs. Off-Target Toxicity​#-2-selectivity-vs-off-target-toxicity
  • ABT-263: Since healthy blood platelets need $\text{BCL-xL}$ to stay alive, giving ABT-263 systemically leads to severe thrombocytopenia (a steep drop in blood platelet count). That toxicity restricts systemic use and has pushed interest toward local/topical formulations (for example, skin wound healing applications).
  • FOXO4-DRI: Healthy tissue shows low FOXO4 expression, whereas senescent cells have markedly higher levels. Consequently, FOXO4-DRI is more selective for senescent cells and does not destroy platelets.
3. Drug Class and Feasibility​#-3-drug-class-and-feasibility
  • ABT-263: As a small molecule, it offers better pharmacokinetic behavior, good cell permeability, and can be given orally or topically.
  • FOXO4-DRI: Being a long 46-amino-acid peptide built with D-amino acids (to withstand enzymatic breakdown), it must be injected, has poor tissue penetration unless linked to cell-penetrating tags (like TAT), and comes with a far higher manufacturing cost.

--- so small molecule with topical functionality vs. long chained one that works only via injection...
Click to expand...
Hmm, that basically takes ABT-263 off my shopping list!!
Click to expand...

-- Hold on, don't rush! Check out the second study, or have AI give you a summary. When it was microdosed alongside other compounds, the negative side effects disappeared, but the positive effects stayed!
Click to expand...

That's a fair point. This one does look worth watching.
 
reta-stacker said:

cheesecake said:

from Gemini:

Key Differences​#-key-differences1. Mechanism of Action​#-1-mechanism-of-action
  • ABT-263: Functions as a BH3-mimetic small molecule. Cells that have become senescent depend strongly on anti-apoptotic BCL-2 proteins to remain alive even while carrying internal damage. By binding $\text{BCL-2}$ and $\text{BCL-xL}$, ABT-263 pushes out pro-apoptotic proteins (such as BAX and BAK), which then set off cell death.
  • FOXO4-DRI: Works as a protein-protein interaction inhibitor. Within senescent cells, the transcription factor FOXO4 holds the tumor suppressor protein $\text{p53}$ captive in the nucleus, stopping it from triggering cell death. FOXO4-DRI breaks that interaction, so $\text{p53}$ can move to the mitochondria and induce apoptosis only in senescent cells.
2. Selectivity vs. Off-Target Toxicity​#-2-selectivity-vs-off-target-toxicity
  • ABT-263: Since healthy blood platelets need $\text{BCL-xL}$ to stay alive, giving ABT-263 systemically leads to severe thrombocytopenia (a steep drop in blood platelet count). That toxicity restricts systemic use and has pushed interest toward local/topical formulations (for example, skin wound healing applications).
  • FOXO4-DRI: Healthy tissue shows low FOXO4 expression, whereas senescent cells have markedly higher levels. Consequently, FOXO4-DRI is more selective for senescent cells and does not destroy platelets.
3. Drug Class and Feasibility​#-3-drug-class-and-feasibility
  • ABT-263: As a small molecule, it offers better pharmacokinetic behavior, good cell permeability, and can be given orally or topically.
  • FOXO4-DRI: Being a long 46-amino-acid peptide built with D-amino acids (to withstand enzymatic breakdown), it must be injected, has poor tissue penetration unless linked to cell-penetrating tags (like TAT), and comes with a far higher manufacturing cost.

--- so small molecule with topical functionality vs. long chained one that works only via injection...
Click to expand...
Hmm, that basically takes ABT-263 off my shopping list!!
Click to expand...

PAPoots said:

I was really hoping this would turn out to be a peptide that ends up available on the grey market. https://share.google/doHF08V8i2XHXCJtb

Aren't Thymalin and FOX04-dri both involved in clearing out senescent or zombie cells? And do they do that throughout the whole body, rather than only in the skin where this particular drug is meant to be used?
Click to expand...
If there's a ring structure, there's a route to gray. (Not accurate, but it can seem that way at times.) You can locate this image at https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/navitoclax
 
reta-stacker said:

I really wish more people had chimed in on what you asked! I'd come across FOX before, but it hadn't clicked that FOX04 and FOX04-DRI work in completely opposite ways — FOX04 shields cells, including senescent ones, whereas FOX04-DRI stops FOX04 from shielding them and actually eliminates them. Looking at one of the factory price sheets I've got, FOX04 goes for $68 per kit, but FOX04-DRI is priced at $400 per kit. My guess is that what we actually want is the elimination of those zombie cells rather than their protection, which would mean the -|DRI variant is the one to go with. Or am I mistaken?
Click to expand...
From what I gather, at 63 I'd be interested in giving FOX04-DRI a shot, but my knowledge is still limited, plus there's the cost to consider.
 
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