Methyl Estadiol Propanoate (MEP)- ER agonist completely w/o side effects

[FollicleGuardian]

I recently came over a drug called MEP, or Methyl Estradiolpropanoate.

MEP is a part of a drug class called NERA's, short for non hormonal estrogen receptor agonists. It has been shown to be effective in skin conditions. Treating dryness, itching, decreased wound healing and wrinkles.

We know how estrogen is good for Androgenetic Alopecia. Estrogen has for example been shown to transcribe genes that upregulate or regulate pathways essential for reversing androgenic alopecia. We have all seen those insane recoveries with HRT. It also increases the thickness of the cutaneous skin layers such as the epidermis while increasing fibroblasts and proliferation of keratinocytes. These keratinocytes are often used as a stem cell marker in vitro.

If we could do so we would apply HRT like dosages of estrogen. However, it's not possible without adverse effects. Especially for those of us that wants to continue to function as a male.

So what's so special about MEP?

Quite simple, it has shown no systemic activities in humans after topical application. A randomized, placebo controlled study with 60 (placebo= 20) women showed no occurance of MEP or its inactive metabolite in serum. This was after 12 weeks of applying a MEP cream twice daily. (Page 19, http://or-genixtherapeutics.com/wp-...D-presentation-on-Estrogen-Deficient-Skin.pdf)

Unlike estradiol, MEP is not a hormone.



ER expression

The icing on the cake is that MEP was shown to also increase Estrogen Receptor expression in fibroblasts significantly. Check out this comparison:

The catch is that if MEP only agonizes estrogen receptor alpha, it's completely useless. We need it to agonize the ER-beta. I have contacted the manufacturers to get more documentation on selectivity.

 

[FollicleGuardian]

The product is actually available otc:

Emepelle Serum

Powerful, clinically-proven skin serum combatting the affects of menopause. Includes unique MEP technology plus Antioxidants, Niacinamide & Peptides for all-round anti-ageing support

emepelle.co.uk

 

[FollicleGuardian]

I need to go nuclear on my hair loss, my density has basically gone to sh** since microneedling (wtf).

Is this empelle serum gonna do anything for me? Probably not, but it's always good to have options

I'm not sure how strong it is or it's selectivity. I have contacted them to hear.

 

[whatevr]

The binding affinity is not particularly impressive compared to most natural phytoestrogens, but that can be overcome by high-dosing it (which might get expensive).

The real determinator of its potency would be the relative transactivation activity of the receptor compared to estradiol, but I don't see that specified anywhere.

All this assumes that it really does metabolize into inactive metabolites, but where have we heard that before? *cough*CB*cough*...

 

[Dimitri001]

You are such a gem, @FollicleGuardian.

 

[FollicleGuardian]

View attachment 159085

The binding affinity is not particularly impressive compared to most natural phytoestrogens, but that can be overcome by high-dosing it (which might get expensive).

The real determinator of its potency would be the relative transactivation activity of the receptor compared to estradiol, but I don't see that specified anywhere.

All this assumes that it really does metabolize into inactive metabolites, but where have we heard that before? *cough*CB*cough*...

Wait, this isn’t MEP though? I don’t think binding affinity is specified for this. So essentially we have no idea how good it can be.

Regarding the safety. It has been tested with high dosage in humans. Not even the inactive metabolite were found in the blood.

 

[whatevr]

Wait, this isn’t MEP though? I don’t think binding affinity is specified for this. So essentially we have no idea how good it can be.

Regarding the safety. It has been tested with high dosage in humans. Not even the inactive metabolite were found in the blood.

The presentation in your opening post specifies "1% ERß binding affinity of Estradiol" for MEP. I was comparing it to the binding affinities of common phytoestrogens established in another study.

 

[FollicleGuardian]

The presentation in your opening post specifies "1% ERß binding affinity of Estradiol" for MEP. I was comparing it to the binding affinities of common phytoestrogens established in another study.

Damn, I read wrong. I thought it stood ER-a in that picture. If this is the case it seems really weak imo.

 

[FollicleGuardian]

@whatevr Coumestrol seems decent af. Do you know the safety profile?

 

[czecha]

@ChemHead @DogoDiLaurentiis


another catch is that it hasn’t been tested in males though, or has it?

 

[TurboFixer]

keep up the good work cookie man

 

[FollicleGuardian]

@ChemHead @DogoDiLaurentiis


another catch is that it hasn’t been tested in males though, or has it?

It hasn’t but it will def be safe according to the safety studies. Only local effect.

 

[Charger]

Let's not get too excited about this one or Kevin Mann will shoot it down in his next video.

 

[whatevr]

Damn, I read wrong. I thought it stood ER-a in that picture. If this is the case it seems really weak imo.

As I said, it could still be useful if dosed appropriately. The commercial product you linked is very expensive and doesn't specify the % concentration of the synthetic estrogen, so we don't know how much you'd have to use to get a decent effect.

@whatevr Coumestrol seems decent af. Do you know the safety profile?

Well, the deal with all of these plant estrogens is that you have to use enormous amounts to see any good effect on your hair, and by that point you're bathing in them and they will also get into your bloodstream in large enough quantities to cause side effects.

S-Equol in high enough dose probably has the best properties given that it binds DHT and favors ERß greatly, but pretty much everyone who's tried gave up due to sides.

I'd rather use something like in the OP, if we could source it raw that would probably be more affordable.

 

[ChemHead]

I'm not really all that hopeful for topicals of any form to be honest. The best approach would be for pharmaceutical companies to develop a photolabile ligand or cage that can encapsulate drugs (or steroids, in particular). So, then you would cage estradiol, for example, and flood the body with supraphysiological levels of it, but it would be physiologically inactive. This way, you can let natural diffusion occur and you'll have very high levels of physiologically inactive estradiol throughout the entire body, including the skin and hair follicles. Then, you shine a particular wavelength(s) of light from the outside onto the scalp to penetrate to the proper depth with the appropriate energy to photochemically cleave the cage molecule or ligand from the estradiol.

This is desirable over topicals because you can get massive amounts of pharmaceutical or hormones into a cell without causing any side effects (because it's physiologically inactive) and then activate it from the outside where you need it. Little to no side effects compared to how pharmaceuticals currently work.

You could take this idea further in a variety of ways. It doesn't have to be a photolabile cage or ligand. You could, perhaps, exploit some thing that exists in the hair follicle but nowhere else in the body... design a molecule that encapsulates a drug or steroid which, when it meets a unique protein or structure in the hair follicle, unfolds and releases the drug.

Whoever develops an effective photolabile caging molecule or ligand like this that is inert and isn't toxic to the body will easily be a billionaire. Especially, if it can be synthesized around a variety of drugs that already exist. Imagine being able to take twice the amount of estrogens required for MTF transition without actually experiencing side effects or the actual "transition" itself. It's like covertly sneaking these "sleeper" drugs or hormones into all the cells throughout the body and then activating them when they're on the inside. No interruption or collateral damage of other systems in the body.

 

[Tom4362]

S-Equol

Did someone say Brotzu??

 

[Tom4362]

The contrast between my last post and @ChemHead 's is really beautiful

 

[whatevr]

@ChemHead That sounds very sci-fi and I doubt we will have those possibilities soon, but yes, that's the dream.

You don't even need new drugs, you could just load up bicalutamide/CPA+E2 into some kind of vesicle that only releases them in contact with the hair follicle and effectively 'MTF' them... we already have all the tools available, it's the delivery methods that suck. We have no way to contain the action to the hair follicles.

@Tom4362 I am talking doses of 30 mg/mL and above, not the homeopathic levels that abomination of a lotion had.

 

[FollicleGuardian]

I'm not really all that hopeful for topicals of any form to be honest. The best approach would be for pharmaceutical companies to develop a photolabile ligand or cage that can encapsulate drugs (or steroids, in particular). So, then you would cage estradiol, for example, and flood the body with supraphysiological levels of it, but it would be physiologically inactive. This way, you can let natural diffusion occur and you'll have very high levels of physiologically inactive estradiol throughout the entire body, including the skin and hair follicles. Then, you shine a particular wavelength(s) of light from the outside onto the scalp to penetrate to the proper depth with the appropriate energy to photochemically cleave the cage molecule or ligand from the estradiol.

This is desirable over topicals because you can get massive amounts of pharmaceutical or hormones into a cell without causing any side effects (because it's physiologically inactive) and then activate it from the outside where you need it. Little to no side effects compared to how pharmaceuticals currently work.

You could take this idea further in a variety of ways. It doesn't have to be a photolabile cage or ligand. You could, perhaps, exploit some thing that exists in the hair follicle but nowhere else in the body... design a molecule that encapsulates a drug or steroid which, when it meets a unique protein or structure in the hair follicle, unfolds and releases the drug.

Whoever develops an effective photolabile caging molecule or ligand like this that is inert and isn't toxic to the body will easily be a billionaire. Especially, if it can be synthesized around a variety of drugs that already exist. Imagine being able to take twice the amount of estrogens required for MTF transition without actually experiencing side effects or the actual "transition" itself. It's like covertly sneaking these "sleeper" drugs or hormones into all the cells throughout the body and then activating them when they're on the inside. No interruption or collateral damage of other systems in the body.

I shared this photocaged idea a while ago. I think this would only be viable with an AR degrader though? Because you can’t shine a light 24/7 for the estrogen to be active on your scalp? Maybe sleep with a light helmet lmao.

 

[FollicleGuardian]

I'm not really all that hopeful for topicals of any form to be honest. The best approach would be for pharmaceutical companies to develop a photolabile ligand or cage that can encapsulate drugs (or steroids, in particular). So, then you would cage estradiol, for example, and flood the body with supraphysiological levels of it, but it would be physiologically inactive. This way, you can let natural diffusion occur and you'll have very high levels of physiologically inactive estradiol throughout the entire body, including the skin and hair follicles. Then, you shine a particular wavelength(s) of light from the outside onto the scalp to penetrate to the proper depth with the appropriate energy to photochemically cleave the cage molecule or ligand from the estradiol.

This is desirable over topicals because you can get massive amounts of pharmaceutical or hormones into a cell without causing any side effects (because it's physiologically inactive) and then activate it from the outside where you need it. Little to no side effects compared to how pharmaceuticals currently work.

You could take this idea further in a variety of ways. It doesn't have to be a photolabile cage or ligand. You could, perhaps, exploit some thing that exists in the hair follicle but nowhere else in the body... design a molecule that encapsulates a drug or steroid which, when it meets a unique protein or structure in the hair follicle, unfolds and releases the drug.

Whoever develops an effective photolabile caging molecule or ligand like this that is inert and isn't toxic to the body will easily be a billionaire. Especially, if it can be synthesized around a variety of drugs that already exist. Imagine being able to take twice the amount of estrogens required for MTF transition without actually experiencing side effects or the actual "transition" itself. It's like covertly sneaking these "sleeper" drugs or hormones into all the cells throughout the body and then activating them when they're on the inside. No interruption or collateral damage of other systems in the body.

Also there is a LACE system, Crispr-Cas9 that is activated by light. Would be interesting to test out.