Winlevi ( Cb 03 01 ) For Acne, Fda Approval

[tomJ]

If you mean Pyrilutamide, their website says they expect to finish enrollment for phase II in 2020, so still quite far from release.
They just said no side effects reported on phase I, but we all know that was the same they were saying with CB.

http://pdf.dfcfw.com/pdf/H3_AP202007241393752560_1.pdf

Correct but are they using the same mode of action as breezula?

 

[Canuto]

Correct but are they using the same mode of action as breezula?

If you mean if they work the same way, yes they do. They are both AR antagonists, but I don't know what's the binding affinity of pyrilutamide. They didn't specify it.
Their other compounds, proxalutamide, which is gonna be targeted to prostate cancer, is even stronger than enzalutamide and downregulate AR receptors over time. It won't pass much time until someone nuts on the forum will trial it on his head.

 

[John Difool]

Enzalutamide already downgraded AR

 

[polishkickbuttowski]

The problem with CB is that it breaks down into steroidal metabolites. That is a huge fail and no idea how they didn't see these kinds of problems coming.

An anti-androgen needs to be designed to break down into completely inert (or as close as possible) components in the bloodstream. Topilutamide had a good approach with that, shame that it's so weak in practice.

Alternatively, we can forget about attempting to compete with androgens for the AR which seems like futile endeavour and instead use SARD's to reduce the amount of AR available to bind to. That seems like a better approach. Of course the rationale above still applies.

Unless this 'Pyrilutamide' magically breaks down into inactive components in the bloodstream and is more effective than CB & RU I wouldn't hold my breath for that.

"In the Pharmacokinetics studies, KX-826 and its metabolite KX-982 could be detected in plasma in a dose-dependent manner, though the concentrations were quite low."

Never mind, lol.

Can you elaborate on SARD's a bit this is the first I'm hearing of them.

 

[whatevr]

Enzalutamide already downgraded AR

Can you elaborate on SARD's a bit this is the first I'm hearing of them.

ARD-69 has the capability to (dose-dependently) achieve nearly complete degradation of the AR in prostate cancer cells. It is over 100 times more potent than Enzalutamide.

https://dl.uswr.ac.ir/bitstream/Han...lChemistry Volume 62 Issue 2 January (34).pdf

As you can see here, in as little as 6h the AR is GONE - there is simply nothing left for androgens to bind to. Comparing this with any other antiandrogen is laughable.

Whether you want to put this stuff on your head is another question...Ah, who am I kidding. I'm sure someone will.

 

[Canuto]

ARD-69 has the capability to (dose-dependently) achieve nearly complete degradation of the AR in prostate cancer cells. It is over 100 times more potent than Enzalutamide.

https://dl.uswr.ac.ir/bitstream/Hannan/67170/1/2019 JournalofMedicalChemistry Volume 62 Issue 2 January (34).pdf

View attachment 147476
As you can see here, in as little as 6h the AR is GONE - there is simply nothing left for androgens to bind to. Comparing this with any other antiandrogen is laughable.

Whether you want to put this stuff on your head is another question...Ah, who am I kidding. I'm sure someone will.

I'm always scared of posting stuff like that, because there are several people who are not fully aware of what they are doing and borderline mentally ill in this forum.

You are basically giving a gun to someone with suicidal thoughts.

 

[whatevr]

I'm always scared of posting stuff like that, because there are several people who are not fully aware of what they are doing and borderline mentally ill in this forum.

You are basically giving a gun to someone with suicidal thoughts.

People here can (and do) gain access to crazy sh*t and use it on themselves. What's one more or less chemical when you have a dude literally dissolving his balls with acid, people going on full blown MTF regimens, using zero-day experimental chemicals from China etc. Those who are that desperate will find out about things like this sooner or later. If someone wants to turn themselves into a chemical eunuch and they would happily live that way, we can't really stop them and those who spread information are not to be held responsible.

I am definitely not advising anyone to use this - merely stating that classical anti-androgens are reaching their limit in regards to efficacy. These PROTAC degraders seem like the next-gen thing - whether any of them can be adapted for hair loss remains to be seen.

 

[constrictedvoid]

The problem with CB is that it breaks down into steroidal metabolites. That is a huge fail and no idea how they didn't see these kinds of problems coming.

An anti-androgen needs to be designed to break down into completely inert (or as close as possible) components in the bloodstream. Topilutamide had a good approach with that, shame that it's so weak in practice.

Alternatively, we can forget about attempting to compete with androgens for the AR which seems like futile endeavour and instead use SARD's to reduce the amount of AR available to bind to. That seems like a better approach. Of course the rationale above still applies.

Unless this 'Pyrilutamide' magically breaks down into inactive components in the bloodstream and is more effective than CB & RU I wouldn't hold my breath for that.

"In the Pharmacokinetics studies, KX-826 and its metabolite KX-982 could be detected in plasma in a dose-dependent manner, though the concentrations were quite low."

Never mind, lol.

Topilutamide gave me testicular and prostate pain for whatever it's worth.

 

[Mustang]

I agree with you and I don't know how they managed to portrait it as "safe" with the FDA and the all the customers, while 10% (!) of their patients got the axis shutdown. Insane.
That's why I'm really curious to see how they will come out of this with phase 3 of Breezula, since on Winlevi they justified it saying not to use it on "a large area" or "for an extended period of time". Tell that to an Androgenetic Alopecia sufferer.

I guess it would be safe on TRT users ... ?

 

[Canuto]

I guess it would be safe on TRT users ... ?

I'm on TRT and didn't have problems with it in 3 months, but I know natural people who reported anti-androgenic sides. I don't know if it was nocebo or real.
I did check my cortisol and DHEA-S levels while on it and found no significant variation, but even on TRT, if they confirm a possible adrenals shutdown on phase 3, then it's a huge problem for everyone.

 

[Mustang]

I was on TRT as well. I had to stop but plan on getting back on it. Why did you stop CB?
Your HPTA is shut down anyways, you can always supplement on Preg and DHEA or Progesterone itself.

 

[Canuto]

I was on TRT as well. I had to stop but plan on getting back on it. Why did you stop CB?
Your HPTA is shut down anyways, you can always supplement on Preg and DHEA or Progesterone itself.

I stopped it for 3 weeks after a hair transplant and get back on it along with other stuff.

Why did you stop TRT?

Just to clarify: we still don't know if Cassiopea meant an HPG shutdown or an adrenals shutdown. In case it's the adrenals to get shut down, neither pregnenolone or progesterone will do anything. You will need corticosteroids and DHEA to carry on.

 

[Mustang]

it's definitely HPA, not HPTA.

I stopped TRT due to massive anxiety and palpitations. I was on 160mg and 175mg a week (TT was 900 and 1050 respectively)
I will try 120mg a week max and might use some HCG as progesterone severely declined after 6 weeks and it might help with that.

Shouldn't people using RU58841 also get adrenals shutdown? It's much more powerful than CB
Cortisol levels remained unchanged in 2 forum members who stay in contact with the company.

CB can't be use as monotherapy, you still need to inhibit DHT. It's got a weak binding affinity compared to DHT but it can potentially compete with Test.

 

[Canuto]

it's definitely HPA, not HPTA.

That's what they wrote, but as I already said many times, you can't isolate the adrenals and expect no feedback on the endocrine system. If the adrenals gets shut down (what someone today calls improperly "adrenal fatigue") both sex hormones and thyroid will slow down.

You need to stay on a dose for 8 to 12 weeks at least in the beginning to reach homeostasis. Vast majority of people on TRT fail because they are impatient and keep moving thing around. They will never get dialed in.
HCG is problematic, but if you want to run it, you need to get dialed in on testosterone only first and then you can introduce it. You don't need HCG to backfill the pathways, it's way easier just using bio-identical hormones.
Some cookie cutter American clinics promote HCG becaue they make money out of it.

RU58841 doesn't gets transformed into cortexolone, a corticosteroid, so there can't be an adrenals shutdown. They are different compounds.

I've already explained why in theory a big dose of CB will outnumber all androgens at the receptor. The binding affinity is for the AR, which means all the androgens, not only testosterone.
Same mechanism with CPA and bicalutamide just to name 2.

 

[Mustang]

That's what they wrote, but as I already said many times, you can't isolate the adrenals and expect no feedback on the endocrine system. If the adrenals gets shut down (what someone today calls improperly "adrenal fatigue") both sex hormones and thyroid will slow down.

You need to stay on a dose for 8 to 12 weeks at least in the beginning to reach homeostasis. Vast majority of people on TRT fail because they are impatient and keep moving thing around. They will never get dialed in.
HCG is problematic, but if you want to run it, you need to get dialed in on testosterone only first and then you can introduce it. You don't need HCG to backfill the pathways, it's way easier just using bio-identical hormones.
Some cookie cutter American clinics promote HCG becaue they make money out of it.

RU58841 doesn't gets transformed into cortexolone, a corticosteroid, so there can't be an adrenals shutdown. They are different compounds.

I've already explained why in theory a big dose of CB will outnumber all androgens at the receptor. The binding affinity is for the AR, which means all the androgens, not only testosterone.
Same mechanism with CPA and bicalutamide just to name 2.

Have you tried RU58841?

It's a shame that 10% of patients got shut down. I wonder if applying it on acne lesions increased penetration causing this. If 1% can cause adrenal shutdown or complete endocrine shutdown then 7.5% will have far worse statistics.

I will test CB-03-01 at 1% to see what happens. If it can prevent seborrheic dermatitis on my scalp (which I suffer from and drastically increases with TRT) then I will be satisfied.

 

[Canuto]

Have you tried RU58841?

No never tried it.

 

[jamesbooker1975]

Have you tried RU58841?

It's a shame that 10% of patients got shut down. I wonder if applying it on acne lesions increased penetration causing this. If 1% can cause adrenal shutdown or complete endocrine shutdown then 7.5% will have far worse statistics.

I will test CB-03-01 at 1% to see what happens. If it can prevent seborrheic dermatitis on my scalp (which I suffer from and drastically increases with TRT) then I will be satisfied.

Yes, could be . But also, keep in mind, that in general , long term scalp that have being or going to be in a chronic topical treatment, are also more permeable than " virgin " skin. The " good thing " is that with a simple blood test you will not if it is shutting down .

 

[Mustang]

That's what they wrote, but as I already said many times, you can't isolate the adrenals and expect no feedback on the endocrine system. If the adrenals gets shut down (what someone today calls improperly "adrenal fatigue") both sex hormones and thyroid will slow down.

You need to stay on a dose for 8 to 12 weeks at least in the beginning to reach homeostasis. Vast majority of people on TRT fail because they are impatient and keep moving thing around. They will never get dialed in.
HCG is problematic, but if you want to run it, you need to get dialed in on testosterone only first and then you can introduce it. You don't need HCG to backfill the pathways, it's way easier just using bio-identical hormones.
Some cookie cutter American clinics promote HCG becaue they make money out of it.

RU58841 doesn't gets transformed into cortexolone, a corticosteroid, so there can't be an adrenals shutdown. They are different compounds.

I've already explained why in theory a big dose of CB will outnumber all androgens at the receptor. The binding affinity is for the AR, which means all the androgens, not only testosterone.
Same mechanism with CPA and bicalutamide just to name 2.

I'd be interested in reading your "theory" on why a big dose of CB could potentially outnumber all circulating androgens.

I have access to a UNI lab that can perform purity tests (2 of them) and enough to apply 7.5% for 6 months with a PG/DMSO solution with no water.

If going back on TRT I will test CB at 1% and gradually increase the dosage with bloodwork weekly (my father has a lab a few blocks away) to asses hormonal panels and any changes.

This could e a fun experiment and hopefully useful to others.

 

[Equal Rights]

Yes, could be . But also, keep in mind, that in general , long term scalp that have being or going to be in a chronic topical treatment, are also more permeable than " virgin " skin. The " good thing " is that with a simple blood test you will not if it is shutting down .

Hey what kind of blood work should i be getting to test if it is shutting down and how often would you recommend i do so? I will be starting cb soon and after reading thr threat and looking at the study i am a little spooked, so want to keep an eye on it.

 

[Canuto]

I'd be interested in reading your "theory" on why a big dose of CB could potentially outnumber all circulating androgens.

It's not my "theory". There are at least 40 years of data on AR antagonist and agonists for the treatment of prostate cancer (which is not trigger by androgens anyway).
If what you claim was true, nilutamide, flutamide, bicalutamide and CPA wouldn't have made it to the market ever.