Androgenetic alopecia, commonly known as male-pattern baldness, has been a challenge to treat effectively. While options like Finasteride and Dutasteride target systemic hormone levels, a Pyrilutamide (KX-826) a topical antiandrogen offers a more targeted approach – a class of drugs referred to as a ‘golden bullet’ in treating androgenic alopecia.

RU58841 & Pyrilutamide (KX-826)

Pyrilutamide (Kx-826) is a non-steroidal antiandrogen, and silent antagonist of the Androgen Receptor, being developed as a potential treatment for androgenic alopecia (male-pattern baldness). Unlike Finasteride or Dutasteride, Pyrilutamide works by inhibiting DHT from binding to the androgen receptor locally at the scalp. It is classified as a silent antagonist, because after binding to the androgen receptor it has 0 activity that it transcribes, and leads to no downstream effects. It essentially acts as a shield, preventing DHT from binding to scalp androgen receptors when applied topically to the scalp. 

RU58841 is also a non-steroidal antiandrogen, researched for its potential use in treating androgenetic alopecia and acne. It works the same way as Pyrilutamide – by preventing DHT from binding to the androgen receptor locally at the scalp (acting as a shield). 

The promise of these compounds is that they are non-steroidal, so even if they are absorbed systemically they are highly unlikely to interfere with the HPA axis or the endocrine feedback loops. Ultimately, they offer a way to halt androgenic alopecia without having any altered hormone profiles.

The Comparison

An advantage Pyrilutamide has over Ru58841 is its affinity for the androgen receptor. It has an affinity of 0.28nM, whereas Ru58841 has a binding affinity of 1.1nM. Although there is some controversy about whether this binding affinity is accurate, I think disregarding it is foolish. Kintor Pharmaceuticals likely invested multi millions into its development and used a concentration lower than that seen at other trials of topical antiandrogens, reflecting they believe it to be a more potent antiandrogen – meaning it had a greater binding affinity than other antiandrogens. To think we know better based on conflictory information on the patent filed is not a good idea. Pyrilutamide also surely has a more favorable IC50 and Ki value then RU58841.

For those who dont know, the lower the number the higher the binding affinity. Something to note is DHT has a binding affinity of 0.25-0.5nM, so Pyrilutamide essentially has the same binding affinity as DHT. This means Pyrilutamide will more easily outcompete DHT for the androgen receptor relative to Ru58841. This process is called competitive inhibition. This also means less Pyrilutamide will need to be applied to effectively outcompete DHT for the androgen receptor, meaning there is less chance it will be absorbed systemically compared to Ru58841. 

To give you an idea on how high Pyrilutamide’s binding affinity is for the androgen receptor, at the time of its development RU58841 was considering the most promising for the treatment of androgenic alopecia because it had the highest binding affinity compared to the class of antiandrogens developed at the time. 

Its high binding affinities caused researchers at the time to state that it was “destined to be used topically for the treatment of acne, alopecia and hirsutism”.

Compared to Ru58841, Pyrilutamide literally has a 4x greater binding affinity for the androgen receptor. As said before, it has a binding affinity equal to that of DHT, the most potent hormone in the entire body. 

Another advantage Pyrilutamide holds to Ru58841 is it has more research data in humans. Ru58841 has been studied extensively in preclinical animal models, however there is more pyrilutamide information publicly available. All three phases in human clinical trials of Pyrilutamide noted no side effects were absorbed except for contact dermatitis which is extremely mild. No anti-androgenic systemic side effects were noted.

There were also two human clinical trials conducted on Ru58841. Unfortunately neither one of them were published, however there is a lot of information about them available online.

For those who don’t know, Ru58841 was renamed PSK-3841 after a series of pharmaceutical mergers and acquisitions. The company that studied Ru58841 (PSK-3841) mentioned no systemic anti-androgenic effects were observed in clinical trials, in a statement release on their old website in an attempt to license the product.

Additionally, in a statement released about the efficacy of Ru58841 (PSK 3841) after it completed its 6 month phase IIa human clinical trial, the company described it to have achieved better net hair growth than finasteride. 

Pyrilutamide (KX-826) is the most promising advancement in the treatment of androgenetic alopecia since the development of Finasteride over 20 years ago. Its mechanism as a highly selective, non-steroidal antiandrogen allows it to effectively block DHT at the scalp without causing antiandrogenic effects on systemic hormone profiles. While the infamous phase 3 trial didn’t demonstrate a significant increase in hair count, in my opinion this does not diminish its potential. The goal of halting DHT-induced miniaturization, and Pyrilutamide has the potential for gradual regrowth becoming apparent only over extended timelines. Its high binding affinity, comparable to that of DHT, gives it an edge over RU58841, ensuring effective receptor competition with lower required concentrations and reduced systemic absorption risks. Combined with extensive safety data from human trials and the absence of systemic anti-androgenic side effects, its likely ongoing studies will keep highlighting its safety, and its efficacy will become even more evident in the years to come.

One of the biggest disadvantages of Pyrilutamide is we have a limited understanding of its pharmacodynamics. Almost everything we know about it comes from press releases made by Kintor Pharmaceuticals and a patent filed a few years back. In contrast we understand how RU58841 and its metabolites interact in our body surprisingly well, it’s just that we lack human trials. Overall Pyrilutamide is the safer option.

Another small disadvantage of Pyrilutamide is its price. Ru58841 has been used recreationally for over 20 years so obviously it has a lower price, however Pyrilutamide’s price will likely begin to drop over time.

Lets Address *THAT* Pyrilutamide Study

Pyrilutamide can still be considered effective for treating androgenetic alopecia, even without a significant increase in hair count during a shorter study period (e.g., less than a year), for several reasons. 

Stopping Further Miniaturization is Key: The primary goal of treating androgenetic alopecia is to prevent DHT-induced hair miniaturization, not necessarily to produce immediate regrowth. Miniaturization is a slow process that occurs over years, and stabilizing hair loss is a major success in managing the condition. Pyrilutamide may already be achieving this effect, even if hair count hasn’t visibly increased within the study’s timeframe. Many researchers have acknowledged DHT-induced miniaturization takes years, the reversal would logically also, and thats why there are some studies that show finasteride becoming more effective after 5 years.

Reversal Takes Time: Since miniaturization develops gradually over years, reversing it is also a slow process. Treatments like Finasteride or topical antiandrogens work by halting the progression of miniaturization first, which can then gradually allow thicker, healthier hair to replace miniaturized hairs over time. Research suggests this regrowth may take 5+ years for substantial changes to be noticeable.

Study Duration Matters: A trial lasting less than a year is not long enough to fully evaluate a treatment’s long-term benefits for reversing miniaturization and stimulating regrowth. Hair cycles are slow, with each phase lasting months or years, and regrowth from treatments addressing the root cause (DHT) may only become evident over a longer period.

The last reason is only a 0.5% solution was used. For reference Ru58841 was tested in clinical trials using a 5% solution. Researchers in Kintor Pharmaceuticals (the producer of Pyrilutamide) may have realised this which is why they relaunched a new Phase III trial using a 1% solution instead.

Ultimately I believe Pyrilutamide to be the more efficacious and safe choice.