The Group Buy to End All Group Buys: Twist1 Inhibitor

Nomiea7

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I hope the buy will start in the next day or two. Once it begins I want to get it wrapped up ASAP. I'm anxious to get my hands on this one.
I'm curious, you have such a broad regimen here. Are you going to disregard that entire regimen and just try this? Also, please send me an invite when you do start it. I'd like to get in on this.

Thank you.
 

CTD

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No. This is actually the study I was referring to in the OP which confirms that Twist1 is dispensible in human DPCs. Twist1 is a Wnt target gene, but its effects differ depending on context, whether it forms heterodimers with Tcf12, or homodimers, or interacts with HDAC9 or b-catenin. When it forms more heterodimers it promotes EMT, which is negative for hair growth. (See OP)


Differential Expression between Human Dermal Papilla Cells from Balding and Non-Balding Scalps Reveals New Candidate Genes for Androgenetic Alopecia -

Twist1 is upregulated in Androgenetic Alopecia in this study, and BMP4 is downregulated. BMP4 upregulates Id proteins, which are required for hair growth, and which regulate Twist1 dimer composition.


Ids prevent the emigration of DPCs seen in Androgenetic Alopecia. Their loss results in a progressively shorter hair cycle. In the absence of Id proteins, Twist1 balance shifts to heterodimers and EMT over hair growth promotion.




View attachment 182567
BMP4 was only expressed in non-balding DPCs.


The study you posted shows that Twist1 binds with Tcf4 and activates downstream Tcf4 target genes promoting the release of growth factors, but that Twist1 is not necessary for the promotion of growth factors. B-catenin also binds with Tcf4 and promotes the release of growth factors, but without the activation of negative hair growth regulators.


In other words, Twist1 activates some genes that are positive regulators of hair growth, but it is not necessary for the activation of those genes. What this study didn't explore was the Twist1 gene regulation that negatively regulates hair growth, which is shown in other studies. Since Twist1 is shown here to be dispensible for growth factor secretion, and the deletion of Twist1 keeps hair in anagen indefinitely, the best thing to do is eliminate Twist1 altogether. ADQ comes close to doing that.

Harmine inhibits Wnt signaling through a mechanism unrelated to Twist1, DYRK1A. Also, Twist1 contributes to embryogenesis, creation of new hair follicles in the womb. We already have hair follicles but they are stuck in Anagen II. Twist1 is not helpful in our case.

You're a genius man. I'm assuming you're a scientist or professor.
 

RagnarLothbrok

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Would be pretty epic that the next most successful hairloss drug is found by testing new compounds in an autistic underground hair loss forum. I can already imagine the headline. If it works some scientist or company will try to patent the molecules asap for profit so its only good. Thanks everyone for your service lol
 

losingbattle88

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If this works you wont only grow Long hair on your scalps but all over the Body when it goes systemic. Sounds horrible.
 

RagnarLothbrok

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They using topical so im assuming will work mostly in scalp.

But thats true, the only reason body hair, eyebrows, eyelashes, etc, are shorter lenght is because their anagen phase is shorter, if it worked systemically you would literally grow infinite eyebrows, eyelashes, nose hair, etc, it would be absolutely crazy to mantain a semblance of normal looks lol

> dis a real person with genetic anagen mutation btw
1658259042286.png
 

Roeysdomi

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They using topical so im assuming will work mostly in scalp.

But thats true, the only reason body hair, eyebrows, eyelashes, etc, are shorter lenght is because their anagen phase is shorter, if it worked systemically you would literally grow infinite eyebrows, eyelashes, nose hair, etc, it would be absolutely crazy to mantain a semblance of normal looks lol

> dis a real person with genetic anagen mutation btw
View attachment 182711
far from it
 

Zon Ama

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When does the application start and when you do you expect first results?
 

losingbattle88

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People apply100mg of topical minoxidil and they don't get hypertrichosis whereas they use 5mg orally and get hypertrichosis. Topicals dont go systemic so easily.
It can and will go systemic at least a little bit, but the reason they dont get hair all over the place is because it doesnt go through the liver and activates into sulfotransferase, it just goes straight into the blood.
 

RagnarLothbrok

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Tbh even if I would become a werewolf but recover my whole scalp i'd still go for it, I would laser and kill the follicles of my entire body and problem solved

Only issue would be extremely long eyelashes but just need to learn how to cut them lol
 

InBeforeTheCure

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They using topical so im assuming will work mostly in scalp.

But thats true, the only reason body hair, eyebrows, eyelashes, etc, are shorter lenght is because their anagen phase is shorter, if it worked systemically you would literally grow infinite eyebrows, eyelashes, nose hair, etc, it would be absolutely crazy to mantain a semblance of normal looks lol

People with Saethre-Chotzen syndrome (TWIST1 loss of function) don't have any hypertrichosis whatsoever AFAIK. Compared to mice maybe there's compensation by TWIST2 or other families of transcription factors that pushes the HFs into catagen phase. Judging by the pictures, even the short hairs on the mice's ears didn't grow long, so even there it depends on where on the body the HFs are - DPCs in different regions have different epigenetic profiles.
 

RagnarLothbrok

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idk, the TWIST1 knockout mouse definetely seems to have some werewolf thing going in there, its still a possibility.

1658261585691.png


But is this even bad? You could rock hair that touches your butt like a rockstar :p
 

InBeforeTheCure

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idk, the TWIST1 knockout mouse definetely seems to have some werewolf thing going in there, its still a possibility.

View attachment 182712

But is this even bad? You could rock hair that touches your butt like a rockstar :p

That mop on the right is a Fgfr1/Fgfr2 DP-specific double knockout, not a Twist1 knockout. ;)

 

RagnarLothbrok

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That's not the Twist1 knockout mouse. There is no picture of that. That is an FGFR1/2 knockout mice, showing what happens when RSPO expression is prolonged.
Ohh ok, I thought that was the picture of the TWIST1 knockout mouse, then I guess it might not really cause hypertrichosis in humans since those humans with TWIST1 mutations have full heads of hairs but dont seem hairy anywhere else
 
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