Sm04554

[charlie76761]

They must have a lot of hope for this drug as they are only recruiting severely bald males. "Males between 18 and 60 years of age, inclusive
Diagnosed with androgenetic (AGA) alopecia with a Norwood-Hamilton Classification score of 4, 5, 6 or 7."

Most trials would never consider recruiting a nw7.

Good spot - v interesting. Not sure what to conclude bar think they have something very powerful although impossible to say bar speculation. One hopes..

Very keen to understand the compound being used... can some ping Desmond and ask for this thoughts?

I've believe i've found the patent (or at least several candidates)

http://www.faqs.org/patents/app/20140005228

i think this is the compound being used in Samumed's SM trials in San Diegeo - one the lead inventors listed on the patent works for Samumed as per https://www.linkedin.com/pub/sunil-kumar-kc/3/934/149 and the his patents listed seems v relevant, e.g. one states

"..The method of the present invention is useful in the treatment of alopecia in mammals, and as such may be used to promote, increase, or assist in the growth of hair. Subjects may be male or female"

it is also around WNT signalling


Sunil also has these patents... http://www.faqs.org/patents/inventor...an-diego-us-1/ - i think one of these is SM04554.. just need an expert to understand the difference between them and which is likely to be the compound... can then get out to Kane for synthesis

Thoughts?

[FearTheLoss]

I don't think this is something that we should be trying to replicate and experiment with. WNT pathways and signaling can potentially be dangerous. Granted, they already passed safety trials, I wouldn't trust a random chemist to make this for me.

[Justinian]

I don't think this is something that we should be trying to replicate and experiment with. WNT pathways and signaling can potentially be dangerous. Granted, they already passed safety trials, I wouldn't trust a random chemist to make this for me.

I think phase 2 serves as safety too.

Could this product be why histogen is having problems getting funding? It appears to work via a similar mechanism and is already in the middle of phase 2. If it is similar, that's good news because I remember seeing really good results from a histogen trial.

[burtandernie]

between this, bim and CB I have faith atleast one of them will make through to the finish line. I think in the next 5 years will actually turn out to be true this time. I hope all of them make it and work better than expected

[It's2014ComeOnAlready]

I think a lot sooner than 5 years, hair loss treatments will change big time. For the better.

[Kudu]

I think a lot sooner than 5 years, hair loss treatments will change big time. For the better.

This. People really need to quit saying that things aren't going to get better. Things may not be better yet, but they will be.

[FearTheLoss]

This. People really need to quit saying that things aren't going to get better. Things may not be better yet, but they will be.

I agree, there are so many advancements in the pipeline.

We have Dr. Wesley bringing a scarless transplant with regeneration, how much? we will see.

We have this, bim, CB, histogen (maybe), and replicel all in the pipeline. Further, there are many docs experimenting with various forms of PRP therapy that will eventually be a viable treatment. I have seen some great PRP results, and it's a matter of time before the optimal formula is found.

Next, we still have Dr. Cole experimenting with various ways to improve donor regeneration. I know he's working hard to improve the field and I wouldn't be surprised if we eventually see him offering regeneration with his hair transplants.

Then we have the cellular advancements being made, sure it could be 30 years before they figure it out, but at the rate they've been increasing their knowledge in the field and making advancements lately, I'd bet it will be before 2020 that they've figured it out, then they go through FDA hell though.

[It's2014ComeOnAlready]

I agree, there are so many advancements in the pipeline.

We have Dr. Wesley bringing a scarless transplant with regeneration, how much? we will see.

We have this, bim, CB, histogen (maybe), and replicel all in the pipeline. Further, there are many docs experimenting with various forms of PRP therapy that will eventually be a viable treatment. I have seen some great PRP results, and it's a matter of time before the optimal formula is found.

Next, we still have Dr. Cole experimenting with various ways to improve donor regeneration. I know he's working hard to improve the field and I wouldn't be surprised if we eventually see him offering regeneration with his hair transplants.

Then we have the cellular advancements being made, sure it could be 30 years before they figure it out, but at the rate they've been increasing their knowledge in the field and making advancements lately, I'd bet it will be before 2020 that they've figured it out, then they go through FDA hell though.

I also have faith in follica, at least for a new treatment. If bim turns out to be successful, it could prove a lot with regards to hair loss and prostaglandins. If a pharmaceutical company hasn't been working with them already on a new treatment, then they will jump at the chance if they see that bimatoprost is successful. We know they are at most, one clinical trial away from releasing a hair loss product, so either way I think we should see something.

Being quiet doesn't necessarily mean "dead." That's not how their company operates, and while it's frustrating, I've been following follica closely, and based on every bit of evidence, it's quite hard to believe that a pgd2 inhibitor product won't be available soon. They even mention in their patent that it would be used with a pgf2 analog, and the potential for billions is just too great to pass up on. Plus as we can see, there are a number of other companies working on treatments. It's open season since minoxidil and propecia's patents have run out.

[Hicks]

Next, we still have Dr. Cole experimenting with various ways to improve donor regeneration. I know he's working hard to improve the field and I wouldn't be surprised if we eventually see him offering regeneration with his hair transplants.

He already does if you look at his website. I have no earthly idea if regeneration is really 50% on average, but why would he advertise that on this forum with all the Interent Rangers set to blast him or anyone that says something. IMO it gives him or anyone no strategic advantage in business. Dr. Wesley is throwing us a bone and we eat it and him in the process. There are some impressive photos of PRP treatment yet some blast it and mention Min to others on a seperate thread. Best of luck everyone! I hope we get something that makes the big 3 look like M&Ms this year.

[FearTheLoss]

He already does if you look at his website. I have no earthly idea if regeneration is really 50% on average, but why would he advertise that on this forum with all the Interent Rangers set to blast him or anyone that says something. IMO it gives him or anyone no strategic advantage in business. Dr. Wesley is throwing us a bone and we eat it and him in the process. There are some impressive photos of PRP treatment yet some blast it and mention Min to others on a seperate thread. Best of luck everyone! I hope we get something that makes the big 3 look like M&Ms this year.

Yeah, Dr. Wesley hasn't been posting about it lately. It's tragic how poorly he was treated by some members here. We get doctors working to improve our lives, like him and Dr. Gardner, and then some of the crazy people on the forum scare them away so we no longer get the communication they were taking time out of their busy lives to give us.

[hellouser]

Yeah, Dr. Wesley hasn't been posting about it lately. It's tragic how poorly he was treated by some members here. We get doctors working to improve our lives, like him and Dr. Gardner, and then some of the crazy people on the forum scare them away so we no longer get the communication they were taking time out of their busy lives to give us.

You'd think his absence would be a good thing if he really was working on pilofocus...

[Halo26]

Hello all, new to the board here.

Start this trial today (USA). The doctor is extremely encouraged by the potential of this treatment, although the clinical research nurse with whom I spoke said she hasn't witnessed much growth in the patients she has seen thus far.

We shall see.

SM04554 patient, how many patients had the nurse seen already? Which site are you at? I'm at the Encinitas site--really hoping this is going to work...

[sdsurfin]

Sm patent

Here is the patent for the compounds that Samumed is testing. Somewhere in here is the formula for SM04554. This contains some more info on how this works, basically it promotes wnt signaling, which I know nothing about, but which seems to be pretty central to hair loss and a whole lot of other things. I have some hope for this drug especially as a maintenance drug, but really who know what side effects it could have. At least it prob won't kill your dick. hormonally based treatments are garbage, this seems more to the point. It's possible that kane or someone could make this if they study the patents enough, there are diagrams of the molecules, but some guesswork to do for sure.
--------------------------



One embodiment of a Wnt/β-catenin signaling pathway activator disclosed herein includes a compound having the structure of Formula I:


Figure US20120046320A1-20120223-C00001
R1 is selected from the group consisting of substituted or unsubstituted heteroaryl and substituted or unsubstituted heterocyclyl, with the proviso that a carbon atom is attached to the carbonyl;

R2 is selected from the group consisting of substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl and substituted or unsubstituted heterocyclyl, with the proviso that a carbon atom is attached to the carbonyl; and

R3, R4, R5 and R6 are independently selected from a group consisting of H, —C1-9alkyl, —C1-9alkylaryl and —C1-9alkylheteroaryl.

Another embodiment of a Wnt/β-catenin signaling pathway activator disclosed herein includes a compound having the structure of Formula II:


Figure US20120046320A1-20120223-C00002
R1 is selected from the group consisting of substituted or unsubstituted heteroaryl and substituted or unsubstituted heterocyclyl, with the proviso that a carbon atom is attached to the carbonyl;

R2 is selected from the group consisting of substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl and substituted or unsubstituted heterocyclyl, with the proviso that a carbon atom is attached to the carbonyl; and

R3 and R4 are independently selected from a group consisting of H, —C1-9alkyl, —C1-9alkylaryl and —C1-9alkylheteroaryl.

Another embodiment of a Wnt/β-catenin signaling pathway activator disclosed herein includes a compound having the structure of Formula III:


Figure US20120046320A1-20120223-C00003
R1 is selected from the group consisting of substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl and substituted or unsubstituted heterocyclyl, with the proviso that a carbon atom is attached to the carbonyl;

R2 is selected from the group consisting of substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl and substituted or unsubstituted heterocyclyl, with the proviso that a carbon atom is attached to the carbonyl; and

R3 and R4 are independently selected from a group consisting of H, —C1-9alkyl, —C1-9alkylaryl and —C1-9alkylheteroaryl.

Some embodiments include stereoisomers and pharmaceutically acceptable salts of a compound of Formulas I, II or III.

Some embodiments include pro-drugs of a compound of Formulas I, II and III.

Some embodiments of the present invention include pharmaceutical compositions comprising a compound of Formulas I, II or III and a pharmaceutically acceptable carrier.

Another embodiment disclosed herein includes a pharmaceutical composition comprising a compound according to any of the above formulas and a pharmaceutically acceptable carrier, diluent, or excipient.

Some embodiments of the present invention include methods to prepare compounds of Formulas I, II or III.

It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed.

DETAILED DESCRIPTION OF THE INVENTION
It has been discovered that β-diketones, γ-diketones and γ-hydroxyketones are capable of activating the Wnt/β-catenin signaling pathway. The Wnt/β-catenin signaling pathway has been found to play a crucial role in the differentiation and development of nerve cells for the central nervous system, bone formation, hair follicle development and regeneration, and stimulation of stem cell growth, maintenance and differentiation.

The present invention relates a method for increasing cell or tissue regeneration in a vertebrate subject. The invention relates to methods for increasing the successful activity of embryonic and/or adult stem cells, progenitor cells, mesenchymal progenitor/stem cells, or differentiated cells in vivo in a vertebrate subject. The invention further relates to methods for increasing cell or tissue regeneration in a vertebrate subject by administering a compound according to Formulas I, II or III to the vertebrate subject in need thereof, and increasing in vivo a stem cell, progenitor cell population, or differentiated cell in the vertebrate subject compared to the stem cell or progenitor cell, or differentiated cell population in the vertebrate subject before treatment, to increase cell or tissue regeneration in the vertebrate subject. A method for increasing stem cell or progenitor cell population is provided to repair or replace damaged tissue in a vertebrate subject, wherein the cell or tissue regeneration occurs in bone, chondrocytes/cartilage, muscle, skeletal muscle, cardiac muscle, pancreatic cells, endothelial cells, vascular endothelial cells, adipose cells, liver, skin, connective tissue, hematopoietic stem cells, neonatal cells, umbilical cord blood cells, fetal liver cells, adult cells, bone marrow cells, peripheral blood cells, erythroid cells, granulocyte cells, macrophage cells, granulocyte-macrophage cells, B cells, T cells, multipotent mixed lineage colony types, embryonic stem cells, mesenchymal progenitor/stem cells, mesodermal progenitor/stem cells, neural progenitor/stem cells, or nerve cells.

Hair Growth

Compositions comprising compounds according to Formulas I, II or III can be used to promote hair growth.

“Promoting hair growth” refers to maintaining, inducing, stimulating, accelerating, or revitalizing the germination of hair.

The method of the present invention is useful in the treatment of alopecia in mammals, and as such may be used to promote, increase, or assist in the growth of hair. Subjects may be male or female. The term alopecia refers to both the complete absence of hair in skin which typically exhibits hair growth, as well as to a loss or diminution in the amount of hair. Multiple types and causes of alopecia are recognized in humans, including male pattern baldness, chemotherapy induced hair loss, congenital alopecia, and alopecia areata. The term treating alopecia refers to both the treatment of skin with a total absence of hair growth as well as the treatment of skin having reduced or patchy hair growth. Successful treatment results in an increased number of hairs.

Subjects to be treated according to the invention include human subjects as well as other mammalian subjects, such as dogs, cats, mice, rats, goats, llamas, minks, seals, beavers, ermines, and sheep. These can be treated for hair loss due or simply for enhancing wool or pelt production.

“Treating alopecia” refers to (i) preventing alopecia in an animal which may be predisposed to alopecia, (ii) inhibiting, retarding or reducing alopecia, (iii) promoting hair growth and/or (iv) prolonging the anagen phase of the hair cycle.

A method for promoting hair growth in accordance with the present invention is characterized by applying an effective amount of a compound according to Formulas I, II or III, or a pharmacologically acceptable salt thereof on the skin of mammals and in particular, on human scalp.

[sdsurfin]

Interestingly, curcumin (main ingredient in turmeric) is a b-dyketone, which is what Sm is too I think. Curcumin has been touted for hair loss, but i don't think there's been much success. However, I think it would have to be applied topically, and it is yellow. I hope Sm is more useful than curcumin, the Wnt thing seems tricky because you need a very powerful agent, and this pathway is implicated in a lot of things, so messing with it in drastic ways is probably dangerous. I'm really curious to get more inside info from the people in the trial. or if anyone is in touch with researchers or dermatologists, especially in san diego, you should look into it and see what people say.

[charlie76761]

Hi sdsurfin, sounds like you have some knowledge, but why do you think that is the patent? Be good to understand. Thanks