Category Archives: Wnt/Beta-Catenin

Samumed, SM04554, Wnt/Beta-Catenin

Samumed’s Compound Structure

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I have covered Samumed and its SM04554 compound to treat hair loss dozens of times in the past. Phase 3 Trials ending in 2020. Please use the categories menu of this blog to find my past posts on this company.

Samumed is aiming to treat numerous medical and cosmetic conditions via activating and/or modulating the Wnt signaling pathway. Of all those targeted conditions, androgenic alopecia is the furthest ahead and the only one that is currently in Phase 3 Trials:

Samumed Pipeline 2019
Samumed Pipeline: https://www.samumed.com/pipeline/default.aspx

Samumed Compound Structure

A few days ago, a reader named “Thomas” emailed me about a new Samumed patent (Publication date = November 22, 2018; Filing date = December 27, 2017).

Thomas pointed out something very interesting. For the first time ever, Samumed has published the chemical structure of its main Wnt/ß-catenin signaling compound. Right under the section titled “Abstract” in the above linked new patent.

Samumed Compound Molecule
Samumed’s Compound Chemical Structure.

Samumed has a decade-long online trail of numerous filed patents, with the vast majority of them including the names of their key scientists John Hood and Sunil Kumar. I have not tried to go through all of these online patent documents, especially those not focused on androgenetic alopecia (male pattern hair loss).

So I am not certain if the above chemical compound structure image is the first time that it has ever been released. It is also not clear if all of  Samumed’s products will be very close in structure to the above compound image. The company has published compound images in the past that look very different from the above (e.g., the one in here for cancer treatments; another in here for Indazole-3-carboxamides and their use as Wnt/β-catenin inhibitors and more).

It would be useful if readers (especially the Chemistry experts on here) provide relevant feedback to this post. For example:

  • What does this compound’s molecular structure mean and how is it unique from other compounds (Samumed ones and non-Samumed ones) that modulate Wnt/ß -catenin signaling?
  • How does this latest compound image differ from other related compound images that Samumed has published in the past?
  • If this really is the first time that this particular image has been released by Samumed, why so late in the process?
DKK2, Sarah Millar, Wnt/Beta-Catenin

DKK2 and Hairless vs. Hairy Skin

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Last week, researchers and scientists led by University of Pennsylvania’s Dr. Sarah Millar published a fascinating new open-access journal article titled:

“Regional Control of Hairless versus Hair-Bearing Skin by Dkk2.”

It seems like the researchers were trying to find an answer to an age old question: why don’t humans have hair on their palms and soles?

I always assumed that human beings and most other animals have no hair follicles and dermal papilla cells on their palms and feet/soles.

However, it seems like this is not true. You can get hairy palms and hairy feet based on just one slight genetic alteration (the removal of Dkk2). In fact, some animals such as rabbits and polar bears do have hairy feet/paws due to this very reason.

Dkk2: Remove it if you want Hairy Palms

Dickkopf-related protein 2 (Dkk2) is a protein that is encoded by the Dkk2 gene. This gene, when expressed in the palms and feet, works to inhibit Wnt/β-catenin signaling. This in turn results in totally hairless skin in those regions. The authors term Dkk2 as a Wnt inhibitor.

The Penn Medicine research team that led this latest research found that when they genetically removed Dkk2 expression from the plantar skin of mice, the animals began to sprout hair in this previously hairless area. This was due to the removal of Wnt signal inhibition.

Wnt/β-catenin signaling is crucial for hair growth in any area of the human body, and is the most researched subject area when it comes to the search for a hair loss cure. Not surprisingly, by now I must have written at least 50 posts on this blog in which I at least briefly mention Wnt/β-catenin or Wnt signaling.

Dkk2 Hairy Skin
Song et al., Regional Control of Hairless versus Hair-Bearing Skin by Dkk2, Cell Reports (2018), https://doi.org/
10.1016/j.celrep.2018.11.017

Dkk2 and Baldness

According to this article, Some studies have found correlations between baldness and DKK2 levels, but it is unclear whether this relationship is causal in nature.

According to Dr. Millar:

“We’re interested in taking a look at the precise nature in the difference in DKK2 in balding scalps versus normally-haired scalps,” Millar said. “We don’t know the answer yet.”

It is interesting that several companies over the years have worked on products that could both reduce body hair and increase head hair. The most famous of these is Follicum, although the company no longer seems to be working on a body hair reduction product.

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