What Can Be A Cxxxc5 Inhibitor? Bosentan!

[Louisa]

Possible cxxxc5 inhibitors.Ethyl5 Benzyloxyindole-2- Carboxylate or Bosentan.Anyone have suggestions?

 

[IdealForehead]

So here's what I know

How Cxxc5 relates to hair
In short, CXXC5 binds to dishevelled, and when this happens, Wnt/B-catenin is inhibited, preventing new hair growth. So we want to either stop CXXC5 from binding to dishevelled or decrease CXXC5 activity in general.

CXXC-type zinc finger protein 5 (CXXC5), which acts as a negative regulator on the Wnt/β-catenin pathway, which is linked to hair regeneration and wound healing.

When CXXC5 binds with a protein called the Dishevelled protein, it prevents follicle development and hair regrowth.

A new biomaterial developed by the team interferes with this binding process. It's called PTD-DBM, and when applied to the bare skin of bald mice for 28 days, new follicles developed.

https://www.sciencealert.com/new-cu...-cxxc5-valproic-acid-wound-induced-neogenesis​

Bosentan and Cxxc5
Bosentan actually seems to be the opposite of what we need.

Mice who have no CXXC5 genes (-/-) have accelerated healing due to increased B-catenin expression.

Adding Bosentan REVERSES THIS and slows back down their healing.

Bosentan reversed the accelerated wound-healing phenotype observed in CXXC5−/− mice and decreased levels of β-catenin, keratin 14, collagen I, and PCNA

http://jem.rupress.org/content/212/7/1061
​

So definitely, Bosentan is not a desirable agent for manipulating this pathway unless I am not understanding something correctly.

 

[Louisa]

So here's what I know

How Cxxc5 relates to hair
In short, CXXC5 binds to dishevelled, and when this happens, Wnt/B-catenin is inhibited, preventing new hair growth. So we want to either stop CXXC5 from binding to dishevelled or decrease CXXC5 activity in general.

CXXC-type zinc finger protein 5 (CXXC5), which acts as a negative regulator on the Wnt/β-catenin pathway, which is linked to hair regeneration and wound healing.​

When CXXC5 binds with a protein called the Dishevelled protein, it prevents follicle development and hair regrowth.

A new biomaterial developed by the team interferes with this binding process. It's called PTD-DBM, and when applied to the bare skin of bald mice for 28 days, new follicles developed.

https://www.sciencealert.com/new-cu...-cxxc5-valproic-acid-wound-induced-neogenesis


Bosentan and Cxxc5
Bosentan actually seems to be the opposite of what we need.

Mice who have no CXXC5 genes (-/-) have accelerated healing due to increased B-catenin expression.

Adding Bosentan REVERSES THIS and slows back down their healing.

Bosentan reversed the accelerated wound-healing phenotype observed in CXXC5−/− mice and decreased levels of β-catenin, keratin 14, collagen I, and PCNA

http://jem.rupress.org/content/212/7/1061
​

So definitely, Bosentan is not a desirable agent for manipulating this pathway unless I am not understanding something correctly.

 

[Louisa]

Thank you thats what I thought.The Ethyl 5 benz does seem to inhibit cxxc5.Just tried as a topicial but gives me a rash.

 

[IdealForehead]

Thank you thats what I thought.The Ethyl 5 benz does seem to inhibit cxxc5.Just tried as a topicial but gives me a rash.

Where did you find the information on Ethyl5 Benzyloxyindole-2-Carboxylate? I can find nothing on it myself.

 

[Louisa]

Type in the name and they actually formulated cxxcc5 for bone growth.

 

[Georgie]

@Louisa are you female?

 

[Louisa]

Type in indole 2-carboxylate blocks cxxc5.This is what the Korean scientist are using.Im a male name is Louis.

 

[HairCook]

Indole-2-carboxylate derivative according to the invention WrU / β - and excellently suppressed CXXC5 catenin involved in the signaling pathway. Since a superior effect for enhancing the activity of osteoblasts, bone diseases. It can be useful in preventing or treating hair loss or injury.

derivative =/= the molecule. Might work, might not. Might just as well exhibit other hair related effects (positive/negative). Patents are also very unreliable, they are more like hints than clear information.

http://www.genecards.org/cgi-bin/carddisp.pl?gene=CXXC5

It is listed as enhancer of schizophrenia, so one might wanna check those meds?

 

[IdealForehead]

Indole-2-carboxylate derivative according to the invention WrU / β - and excellently suppressed CXXC5 catenin involved in the signaling pathway. Since a superior effect for enhancing the activity of osteoblasts, bone diseases. It can be useful in preventing or treating hair loss or injury.

derivative =/= the molecule. Might work, might not. Might just as well exhibit other hair related effects (positive/negative). Patents are also very unreliable.

Yeah looks like it:

From commercially available 5‐benzyloxy indole‐2‐carboxylate ethyl‐ester, KY‐02061 was formally synthesized (Appendix Scheme S1). KY‐02061 is composed of an indole ring with one 4‐methylbenzene sulfonate group at position 5, a carboxylic acid ethylester group at position 2, and ethylacetate group at position 1 (Fig 2A). KY‐02061 decreased Dvl–CXXC5 interaction in a dose‐dependent manner as shown by the in vitro binding assay (Fig 1A) with 50% inhibition concentration (IC50) value of 24 μM (Fig 2B and Appendix Table S1).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4818757/​

So if you wanted to get a Chinese lab to synthesize KY-02061 you could I suppose. But I just have to say this is a level of "experimental science" that I think is going way too far. These compounds work on a biochemical pathway which has never been manipulated in humans before. There is therefore no way of knowing what risks or benefits manipulating it might pose.

General information about CXXC5 is here:

"Ubiquitous expression in brain (RPKM 19.6), kidney (RPKM 19.4) and 24 other tissues"

https://www.ncbi.nlm.nih.gov/gene/51523#gene-expression
​

So we know CXXC5 impairs wound healing and may impair hair neogenesis. But what does it do in the other 25 tissues of the body?

Manipulating a compound where so little is known about it with chemicals that have never even been tested in humans is getting to a stage of recklessness that probably should not be necessary, as there are so many more conventional or even experimental compounds (eg. R-equol) that are much more likely to be safe and useful.

I think you'd really have to be SURE you've exhausted every other option before you start experimenting on yourself like this in any rational way.

 

[HairCook]

Well, it is a peptide, so it is likely to be destroy being taken orally.

Plus taking out a negative feedback mechanism of wnt wouldnt be smart anyways. So you would probably do like wounding + mesogun.

Even if you get it, you dont know the half life, side-effects, dosage (if you overdose it might totally inhibit and possibly retard hair similiar to dkk1 and trpv3 knock-out mice).

I also saw it being induced by Kank. Another Kank was induced by PGJ2. So CXXC5 might just as well be normalizable by Crth2 therapy. Here a random model I made when I looked into everything I could find.

 

[IdealForehead]

Well, it is a peptide, so it is likely to be destroy being taken orally.

Plus taking out a negative feedback mechanism of wnt wouldnt be smart anyways. So you would probably do like wounding + mesogun.

Even if you get it, you dont know the half life, side-effects, dosage (if you overdose it might totally inhibit and possibly retard hair similiar to dkk1 and trpv3 knock-out mice).

I also saw it being induced by Kank. Another Kank was induced by PGJ2. So CXXC5 might just as well be normalizable by Crth2 therapy. Here a random model I made when I looked into everything I could find.

View attachment 84314

That's amazing work. Are you saying ER-alpha stimulation upregulates CXXC5? Can you post the article that suggests so?

If that's the case, this would provide further evidence to support my belief that the estrogen stimulation we want for hair is exclusively ER-beta, and that ER-alpha stimulation is bad for hair.

Edit: Never mind just found it:

We show here that CXXC5 is an E2-ERα responsive gene
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122896/​

Absolutely this is providing further strength to my arguments in favor of estrogens with an ER-beta predominance and AWAY from estrogens with an ER-alpha predominance.

ER-alpha => increased CXXC5, premature catagen, hair falling out, and less new hair coming in

(@Georgie)

 

[Louisa]

Yes I ordered the the 5 Benz from China 20g.Mixed 3gram in acetone dmso appled 2 scalp 2x a day with Sodium valValpor def seemed to work but Got a rash.Currently using Sodium valpValpo for about a month with microneedling seems to be helping.

 

[Louisa]

I read up on Bonestan and seems to block cxxc5 through the endothelial 1.Endothelial 1 meadiates the cxxc5 regenative effects.Buy blocking the Endo 1 receptor you block cxxxc5.I showed my pharmicist the wording and he explained it to me.I think I will order and use with my Sodium Valporate.Will keep you updated.

 

[HairCook]

New study looking for a molecule: https://www.docdroid.net/sOpjTzW/101007-at-s10822-018-0118-x.pdf

 

[jnestor481]

New study looking for a molecule: https://www.docdroid.net/sOpjTzW/101007-at-s10822-018-0118-x.pdf

Way to be on the ball, nice find. Gonna read it now

 

[kingjohn]

New study looking for a molecule: https://www.docdroid.net/sOpjTzW/101007-at-s10822-018-0118-x.pdf

Way to be on the ball, nice find. Gonna read it now

thats not just any study, thats actually the catalyst for the groundbreaking research from ky choi on vpa + ptd-dbm (a cxxc5 inhibitor) which i summed up in this thread https://www.hairlosstalk.com/intera...very-method-from-ky-choi.112804/#post-1638092 and has been covered previously on HairLossTalk.com. definitely an exciting area of research