Darolutamide (odm-201), A Better Topical Than Enzalutamide?

[DavidsDome]

After reading a lot of thread on different forums, a few testimonials from certain persons pop out.
I'm referring to Swiss Temples and his PG protocol for instance.
But last i stumbled upon the story of Xandrus on baldtruthtaIk.
He used topical MDV3100, also known as Enzalutamide or Xtandi.

This substance has a very long half-life.
As far as I have read, this is supposed to be a bad thing.
It can go systemic and continue working for days on places you don't want it having working. (correct me if I'm wrong)
The substance can also cross the blood-brain barrier.

Then I came across Darolutamide (ODM-201).
It works very similar to Enzalutamide but has a shorter half-life.
It also (almost) doesn't cross the blood-brain barrier.

It seems that this would be a better topical than Enzalutamide.
I'm not a scientist nor a chemist so please share your knowledge if you are.
Any thoughts?

 

[whatevr]

We have a thread on enzalutamide here:
https://www.hairlosstalk.com/intera...mide-superstrong-antiandrogen-topical.105093/

MDV-3100 seems to have some unique mechanisms of action though:
http://www.avacor.com/blog/hair-regrowth/the-future-of-hair-regrowth-part-2-–-next-generation-ar-antagonists/
It acts in three different ways upon the AR which makes it extremely powerful.
I don't know if ODM-201 shares all of those properties.

Also, good luck getting ODM-201 anywhere. They don't even sell that on Alibaba yet.

 

[DavidsDome]

more info here:
ncbi.nlm.nih.gov/pmc/articles/PMC4490394/

 

[DavidsDome]

here is Xandrus his (short) story by the way...
baldtruthtaIk.com/threads/23023-My-treatment-works-only-RU58841-5-10-and-MDV3100-2

 

[kawnshawn]

If you're going to buy it off Alibaba make sure you do ALOT of research from the company you're buying it from and try to get it tested. A lot of these company's are extremely shady and you never know what you are getting. My general rule of thumb is that if the rep can't type in proper English then find another source.
Currently trying to buy enza off alibaba

 

[whatevr]

If you're going to buy it off Alibaba make sure you do ALOT of research from the company you're buying it from and try to get it tested. A lot of these company's are extremely shady and you never know what you are getting. My general rule of thumb is that if the rep can't type in proper English then find another source.
Currently trying to buy enza off alibaba

Please let us know if you find a reliable source, I'd be interested in attempting to obtain some of this stuff somewhere down the line.

 

[whatevr]

Thanks for the warning.
I was indeed planning on having it tested.

How do you think penetration would be of ODM-201?
The molar mass is 398.84616 g/mol according to wikipedia.

Under 500 dalton I think even just Ethanol + PG do the job fine.
Xandrus used:

Alcohol 40-45 %
methylidene glycerol 35%
destillated water 25%

I think maybe 96% ethanol, some isopropanol and PG would probably be more than good enough. But I'm no chemist.

 

[Dench57]

maybe in a few years. way too expensive atm

 

[whatevr]

yeah... I found $350 / g
question is a of course how much do you need
because of the shorter half-life, you will need more than enzalutamide

Rather try enzalutamide if you want to mess with these types of things. Won't be a while until we can get ODM-201 reasonably.

 

[kawnshawn]

Please let us know if you find a reliable source, I'd be interested in attempting to obtain some of this stuff somewhere down the line.

Pretty sure I found a good source but I'll know for sure in a few weeks. I'll make sure to post lab results.

 

[chusler]

mdv-3100 is powerfull and i know that it will work (a bit risky even topical), but odm-201 can be a real cure with a right topical vehichle :

Taken from: https://newdrugapprovals.org/2016/03/12/odm-201/

“ODM-201 is a new-generation, potent and selective androgen receptor (AR) inhibitor which is potential useful for treatment of castration-resistant prostate cancer (CRPC). ODM-201 is a full and high-affinity AR antagonist that, similar to second-generation antiandrogens enzalutamide and ARN-509, inhibits testosterone-induced nuclear translocation of AR. Importantly, ODM-201 also blocks the activity of the tested mutant ARs arising in response to antiandrogen therapies, including the F876L mutation that confers resistance to enzalutamide and ARN-509. In addition, ODM-201 reduces the growth of AR-overexpressing VCaP prostate cancer cells both in vitro and in a castration-resistant VCaP xenograft model. ODM-201 overcomes resistance to AR-targeted therapies by antagonizing both overexpressed and mutated ARs. ODM-201 is currently in a phase 3 trial in CRPC”



Relative to enzalutamide (MDV3100 or Xtandi) and apalutamide (ARN-509), two other recent non-steroidal antiandrogens, ODM-201 shows some advantages.

[3] ODM-201 appears to negligibly cross the blood-brain-barrier.[3] This is beneficial due to the reduced risk of seizures and other central side effects from off-target GABAA receptor inhibition that tends to occur in non-steroidal antiandrogens that are structurally similar to enzalutamide.[3]

Moreover, in accordance with its lack of central penetration, ODM-201 does not seem to increase testosterone levels in mice or humans, unlike other non-steroidal antiandrogens.[3]

Another advantage is that ODM-201 has been found to block the activity of all tested/well-known mutant ARs in prostate cancer, including the recently-identified clinically-relevant F876L mutation that produces resistance to enzalutamide and ARN-509.[3] Finally, ODM-201 shows higher affinity and inhibitory efficacy at the AR (Ki = 11 nM relative to 86 nM for enzalutamide and 93 nM for ARN-509; IC50 = 26 nM relative to 219 nM for enzalutamide and 200 nM for ARN-509) and greater potency/efficaciousness in non-clinical models of prostate cancer.

 

[chusler]

i read Fgf-11' s(his firs nickname was : god) comments on hairloscure2020 last year, This dude is right , i believe in his theory, it really makes sense for me. Please read his theory here, even you read it b4. There are xyz123's comments too which are so important to understand fgf-11's theory.

he also is talkin about odm-201 and mdv3100 when he explains his theory

The link: https://www.baldtruthtaIk.com/threads/22187-I-think-I-ve-hacked-it

Thanks to Fgf-11, whatevr, xandurus and JlF...

 

[Kevand]

I believe the increase of testosterone is a good thing to compensate for the systemic anti-androgenetic exposure. Another concern with this compound if wiki is right its a pro-drug, which means it needs to be converted probably in liver to be fully active. However darolutamide as a substance on its own could be comparable to enzalutamide.

 

[Kevand]

mdv-3100 is powerfull and i know that it will work (a bit risky even topical), but odm-201 can be a real cure with a right topical vehichle :

Taken from: https://newdrugapprovals.org/2016/03/12/odm-201/

“ODM-201 is a new-generation, potent and selective androgen receptor (AR) inhibitor which is potential useful for treatment of castration-resistant prostate cancer (CRPC). ODM-201 is a full and high-affinity AR antagonist that, similar to second-generation antiandrogens enzalutamide and ARN-509, inhibits testosterone-induced nuclear translocation of AR. Importantly, ODM-201 also blocks the activity of the tested mutant ARs arising in response to antiandrogen therapies, including the F876L mutation that confers resistance to enzalutamide and ARN-509. In addition, ODM-201 reduces the growth of AR-overexpressing VCaP prostate cancer cells both in vitro and in a castration-resistant VCaP xenograft model. ODM-201 overcomes resistance to AR-targeted therapies by antagonizing both overexpressed and mutated ARs. ODM-201 is currently in a phase 3 trial in CRPC”



Relative to enzalutamide (MDV3100 or Xtandi) and apalutamide (ARN-509), two other recent non-steroidal antiandrogens, ODM-201 shows some advantages.

[3] ODM-201 appears to negligibly cross the blood-brain-barrier.[3] This is beneficial due to the reduced risk of seizures and other central side effects from off-target GABAA receptor inhibition that tends to occur in non-steroidal antiandrogens that are structurally similar to enzalutamide.[3]

Moreover, in accordance with its lack of central penetration, ODM-201 does not seem to increase testosterone levels in mice or humans, unlike other non-steroidal antiandrogens.[3]

Another advantage is that ODM-201 has been found to block the activity of all tested/well-known mutant ARs in prostate cancer, including the recently-identified clinically-relevant F876L mutation that produces resistance to enzalutamide and ARN-509.[3] Finally, ODM-201 shows higher affinity and inhibitory efficacy at the AR (Ki = 11 nM relative to 86 nM for enzalutamide and 93 nM for ARN-509; IC50 = 26 nM relative to 219 nM for enzalutamide and 200 nM for ARN-509) and greater potency/efficaciousness in non-clinical models of prostate cancer.

I wonder if they specifically mean ODM-201 with the results or if it also concerns it's main active metabolite.

 

[whatevr]

i read Fgf-11' s(his firs nickname was : god) comments on hairloscure2020 last year, This dude is right , i believe in his theory, it really makes sense for me. Please read his theory here, even you read it b4. There are xyz123's comments too which are so important to understand fgf-11's theory.

he also is talkin about odm-201 and mdv3100 when he explains his theory

The link: https://www.baldtruthtaIk.com/threads/22187-I-think-I-ve-hacked-it

Thanks to Fgf-11, whatevr, xandurus and JlF...

Yes, it's a shame he was chased away by the illiterate brain-dead retards at BTT with their "omg snake oil give us the cure" mentality.
His post is like a glimpse into the future. The things he writes about will be common in 30 years, and he experimented with them right now.
Everything he wrote makes sense and is very interesting, far ahead of its time, actually. No wonder it went over everyone's head.

 

[chusler]

Oncology Meeting Innovations(Omi)
Next-generation anti-androgen therapy: ARN-509 and ODM-201 - Emmanuel Antonarakis

Link:

at 13:35 odm-201 toxicity and side effects , odm-201 ' s safety is amazing.

 

[Ramsey]

I've been following the enzalutamide thread, very interesting to read through it.

I'm curious, did anyone follow up on darolutamide? In comparison to enzalutamide, it seems that it's hard to buy, expensive, and at least the source I found seems dodgy so I'd also test it for sure (and it's not like enzalutamide is so easy to buy either). But I've been thinking about the darolutamide. I like that it only shows "negligible brain penetrance"; maybe would make it better for long-term, higher-dose use than enzalutamide?

 

[Ramsey]

I'm pretty sure that Daro would be much safer to mess with than Enza.
For Darolutamide (ODM-201), 100g would be FOB203/g.
And if you only need 1-10g, we can give 10% discount as FOB 325/g.

Wow. So let's see, just quick estimating, let's say you want to use a 2% 2ml twice a day. You think that's fair? That's 80 mg per day, so about $800 per month at the <10g price...?!

I'd do $100-150 per month for 6 months on a totally uncharted experiment like this, maybe $200 with all costs including testing, but not $800 per month. If you buy 6 months in advance and can store it, then you can get the lower price per gram and it works out to $500 per month. But that's still a lot; $3,000 for 6-months for an experiment like this... tough call. (Plus, there's the testing fees, and depending on how and where you're getting it, there's risk of customs charging more on top or just blocking it completely).

I'll look around about storage, dose, and supplier, see if I get lucky or the market has gotten better since you were looking a few months ago, but I see now why you went with enza.

 

[IdealForehead]

Darolutamide vs. enzalutamide.

Key points for comparison:
- Both are similarly highly selective androgen receptor antagonists without any agonistic activity.
- Darolutamide is 8.4 times stronger than enzalutamide & around 164 times stronger than RU58841.
- Darolutamide does not cross the blood-brain barrier as easily as enzalutamide. This would reduce risks of anti-androgenism in the brain and seizures.
- Half life of darolutamide is only 16 hours, creating a metabolite which is also highly active and has a half life of another 10 hours. This is not nearly as good as RU58841, but it is WAAAAY better than enzalutamide which has a 6 day half life.

 

[whatevr]

A 2% solution of enzalutamide would be equivalent to around a 0.25% solution of darolutamide in terms of potency. In other words, while you might need 20 mg of enzalutamide a day, we would only need 2.5 mg a day of darolutamide.

A single gram would last you 40 days. At $350/g, that's $8.70 a day, which is not bad at all for a desperate last ditch experimental chemical!

Unless I am missing something, 1000 mg / 2.5 mg a day = 400 days = 0.87$ / day ?