Kintor new AR degrader w/o side effects

[scientist_0005]

Their doses tested in mice were 0.4, 0.8, 1.6 and 3.2%. It performed equal to minoxidil 5%.

For acne (sebum/gland reduction) it was actually outperformed by Breezula on hamsters xD

"Both indications of androgenetic alopecia and acne vulgaris have huge unmet clinical needs. According to animal experiments, the efficacy of GT20029 is superior to other small molecule AR inhibitors"

liars

Kintor Pharmaceutical Limited

Kintor Pharmaceutical Limited

en.kintor.com.cn

but if it is not superior to pyrilutamide y woukd they, even trial it and spend money on it?

also the only reason for this to not completely outperform anything else must be absorption. if all the ARs were degraded, it is virtually impossible for any androgenic action to take place. it seems that this compound fails to do so even thoifh they claimes it stays in tissue long after application, yad yada.

it is not the time to be hopeful about anything tbh.

thankfully by 2029 Dr nagasaki from Tokio will start his trial on white mice with an-al finasteride. that is something to look forward to. go Dr nagasaki, go a-nal finasteride

 

[scientist_0005]

New topical antiandrogenic formulations can stimulate hair growth in human bald scalp grafted onto mice - PubMed

The purpose of this study was to test the ability of topical formulations of finasteride and flutamide to re-enlarge hair follicles in male-pattern baldness. This was evaluated by an experimental model of human scalp skin graft transplanted onto SCID mice. A comparison was made between...

pubmed.ncbi.nlm.nih.gov

maybe animal studiea are kind of non indicative and garbage for gauging potency and merely offer an idea for proof of concept. in the above study they took human hair and planted it on mice and flutamid was more effective than finasteride even tho topical flutamide does not work for AA. but still it is quite concerning that a drug that is literally supposed to degrade rhe entire target protein is weaker than a comical experiment from an italian pharma company fhat will not so phase 3 trials bc their product is total garbage

 

[scientist_0005]

So GT20029, which is supposed to be more advanced and superior to pyrilutamide, was only as effective as standard minoxidil?

and even worse, less potent than CB in the hamster model which is an even bigger deal because for all we know mice mighr respond very well to minoxidil you cant compare it and they dont have AA naturally. but worse than CB is completely ridiculous, a degrader should be unmatched as an anti androgen if it gets absorbed properly

 

[Ralph Wiggum]

And Pyrilutamide will therefore be even worse than this, right?

 

[nick123]

I think it's a bit too early to judge on GT20029s efficacy...

Yes CB-03-01 performed the best for Sebaceous gland growth inhibition according to the table:

Although this is a test on the sebaceous gland which they did to test it's efficacy against acne, I don't think it's safe to assume that this will also be the case for dermal papilla when testing against hair loss..

In another experiment designed for treating hair loss when head to head with 5% minoxidil, 1% and 3% GT20029 performed just as well at 5% Minoxidil on day 17. Let's also not forget mice are good responders to minoxidil.

"In this experiment, 6 groups were used, namely, a Vehicle group, a DHT (30mg/kg) concentration group, a DHT (30mg/kg) + minoxidil 5% concentration group, a DHT (30mg/kg) + A460.5% concentration group, a DHT (30mg/kg) + A461% concentration group and a DHT (30mg/kg) + A463% concentration group. The results of hair regrowth in the androgen alopecia model in C57 mice are shown in table 9 below: table 9 hair regrowth effect on C57 mouse androgen alopecia model (AVER, n ═ 6) As can be seen from the results, the DHT (30mg/kg) concentration group scored 0.5 for hair development 17 days after the administration, and had almost no hair development, which was significantly lower than that of the Vehicle group, indicating successful molding. The average value of the score of the DHT (30mg/kg) + minoxidil 5% concentration group is 2.33, which is obviously higher than that of the DHT (30mg/kg) model group, and the DHT/minoxidil composition shows good hair growth effect. The DHT (30mg/kg) + A460.5% concentration group scored slightly higher than the building block DHT (dihydrotestosterone) group, but there was no statistical difference. The scores at Day17 for the A461% and 3% concentration dose groups were approximately equivalent to the 5% minoxidil group, and the scores were significantly different from the DHT (dihydrotestosterone) group (p < 0.05; p < 0.01)."

Patent Source: https://patents.google.com/patent/CN113387930A/en?assignee=Suzhou+Kintor+Pharmaceuticals,+Inc.&sort=new

There still could be adjustments needed for the vehicle since the molecule size for GT20029 is quite large.

Finally if you are comparing it to CB-03-01, let's not forget that CB-03-01 massively drops after the 6 month mark (maybe due to the upregulation of receptors when using an an AR antagonists), this might not happen with AR degraders.

 

[Kagaho]

Yeah, rodent models can be quite contradictory sometimes and CB outperformed finasteride and a bunch of other antiandrogens on hamsters.

Also this drug already started clinical trials in China.

Dont freak out just yet.

 

[scientist_0005]

we also do not know whether the dosage used with the degrader is the best one. for all we inow they used CB in much larger quantities than breezula contains. if you use 20% breezula then you sure has hell will have better results. remember the first study of CB with the iotophoresis where CB produced better results than flutamide, finasteride or even cyproterone acetate, it is all a question of delivery and if you can get the CB to the follicle it is in fact a very potent AA with better IC50 value than RU. but with the degrader yiu cannot twlk about affinity since it is not an antagonist, we can talk about IC50 though. but for all we know q much higher dosage would be required for human usage and that could be just fine. it would have been more interesting if they did histological tissue dissection to see how many ARs where actually degraded like olix did ij their animal model.

if it was not more promising than their pyralutamide why would they even trial it, to spent money developing it only for it to then cut away their own pyralutamide profits a drug they also spent time developing?

furthermore a synergystic mechanism between the two is very likely as they have very different modes of action. degrade some of the AR with the degrader and use the antagonist(CB or pyralutamide or even finasteride) to block activity on the remaining ones. for those that can tolerate finasteride you can even combine the three to achieve tripple anti adrogenic action. and the iRNA method of olix has yet another method of action that also leads to interruption of AR synthesis so thats a lot of anti androgenic sh*t

 

[Diffused_confidence]

we also do not know whether the dosage used with the degrader is the best one. for all we inow they used CB in much larger quantities than breezula contains. if you use 20% breezula then you sure has hell will have better results. remember the first study of CB with the iotophoresis where CB produced better results than flutamide, finasteride or even cyproterone acetate, it is all a question of delivery and if you can get the CB to the follicle it is in fact a very potent AA with better IC50 value than RU. but with the degrader yiu cannot twlk about affinity since it is not an antagonist, we can talk about IC50 though. but for all we know q much higher dosage would be required for human usage and that could be just fine. it would have been more interesting if they did histological tissue dissection to see how many ARs where actually degraded like olix did ij their animal model.

if it was not more promising than their pyralutamide why would they even trial it, to spent money developing it only for it to then cut away their own pyralutamide profits a drug they also spent time developing?

furthermore a synergystic mechanism between the two is very likely as they have very different modes of action. degrade some of the AR with the degrader and use the antagonist(CB or pyralutamide or even finasteride) to block activity on the remaining ones. for those that can tolerate finasteride you can even combine the three to achieve tripple anti adrogenic action. and the iRNA method of olix has yet another method of action that also leads to interruption of AR synthesis so thats a lot of anti androgenic sh*t

I've wondered why they made an antagonist and a degrader. Maybe hedging against itself?

If it is just as effective as 5% minoxidil wouldn't that be an added bonus? I only expected an AR degrader to be purely an effective prevention treatment and not yield any regrowth. I'm not expecting any regrowth cures during my lifetime.

 

[scientist_0005]

I've wondered why they made an antagonist and a degrader. Maybe hedging against itself?

If it is just as effective as 5% minoxidil wouldn't that be an added bonus? I only expected an AR degrader to be purely an effective prevention treatment and not yield any regrowth. I'm not expecting any regrowth cures during my lifetime.

this is not about regrowth. in this mouse model the gave the mice who were not balding dht to suppress the growth of hair. this is very different from regrowth as the hair is not minaturized yet, mice do not have AA but this is the cheapest animal model to get at least some proof of concept. even though mice do not have AA massive amounts of dht still suppress the growth of the hair of mice after you shave them. when you shave a mouse all hair cycles reset and they all grow together apparently. very different to humans. regrowth is also losely defined, but if this should compete against finasteride regrowth should be expected bc finasteride contrary to popukar opinion actually recovers quite a bit in most men. but you cant reqlly talk about regrowth in this mouse model, you talk about "less suppressed growth"

 

[trialAcc]

extremely discouraging as CB is hot garbage and so is minoxidil

Seriously? This and minoxidil are polar opposite treatments. If you get legitimate growth from an AR degrader, it's permanent and will probably last decades with 90%+ of the AR degraded.

This doesn't even factor in that every other growth treatment including minoxidil (and future ones) will work significantly better with almost 0 androgens attacking the follicle.

 

[scientist_0005]

Seriously? This and minoxidil are polar opposite treatments. If you get legitimate growth from an AR degrader, it's permanent and will probably last decades with 90%+ of the AR degraded.

This doesn't even factor in that every other growth treatment including minoxidil (and future ones) will work significantly better with almost 0 androgens attacking the follicle.

but CB gave regrowth and then it declined to baseline. finasteride gives better regrowth than minoxidil as well

 

[trialAcc]

but CB gave regrowth and then it declined to baseline. finasteride gives better regrowth than minoxidil as well

CB doesn't even have enough strength to compete with DHT. If it had decent results and lost them it's because whatever temporary boost your hair gets from removing a slight amount of DHT and T isn't sustainable.

This compound degrades/removes the AR completely, it's not the same thing, and you are wasting everyone's time by scoping in on one line about sebaceous glands on hamsters.

 

[Diffused_confidence]

but CB gave regrowth and then it declined to baseline. finasteride gives better regrowth than minoxidil as well

Finasteride doesn't give regrowth. All it does is prevent miniaturization and may extend the anagen phase which would give the appearance of regrowth. Minoxidil is a growth stimulant that also extends the anagen phase but isn't effective alone long term. There are literally 0 treatments for regrowth. Once an area is bald, it's basically game over.

 

[froggy7]

will I have to take these drugs continuously? will it help people who are already bald to grow back at least part of their hair?

 

[Johnson40]

You are happy too soon , we seen in the past plenty of data on things that works on mice but barely on human.
This drug is our last chance to stop male pattern baldness for good .. if this dosent work every other drug will be temporery solution like its always been

Why? From what i understood AR degrader do not completely destroy the AR forever, the human body regenerate that sh*t better than it regenerates hair lmao, still need continued use.

The only thing that could allow you to buy some years before having to obsess over your scalp again is HMI, and the fact that people from the GB reports shedding after cessation of SMI treatment doesn't look particularly good for that part, tho it's hard to tell with that.

 

[Johnson40]

Yeah i have seen that too sad . Its like every drug that work on paper dosent work for us

Androgenetic Alopecia is just that complex, Gods of hair are just that fickle.

Though for SMI, we have to take a step back, we barely know the role of prolactin, which seems to be rather indirect mediating various signals and proteins.
The competitive SMI might just be too weak to shutdown the PRLR enough, it is possible that those terminal hair might stay if one used SMI with a sufficient concentration for a long enough period of time.

Also we must not forget that this is not a controlled and rigorous study.
The shed might also be placebo, probably not, but still, people are not always rigorous in their evaluation of shedding.

 

[scientist_0005]

Finasteride doesn't give regrowth. All it does is prevent miniaturization and may extend the anagen phase which would give the appearance of regrowth. Minoxidil is a growth stimulant that also extends the anagen phase but isn't effective alone long term. There are literally 0 treatments for regrowth. Once an area is bald, it's basically game over.

this is not true studies have shown that while the DP degenerates it is always there even in full bald areas. despite various estrogen regimens have shown they can be reactivated. finasteride does increase hair count and hair weight, the latter is what i count as regrowth and even more signifcant than hair count. you can grow more hairs but if the existing ones get thicker that is an even bigger win cosmetically. thats why hair weight is a primary outcome in most studies, that IS regrowth in my book

 

[scientist_0005]

You are happy too soon , we seen in the past plenty of data on things that works on mice but barely on human.
This drug is our last chance to stop male pattern baldness for good .. if this dosent work every other drug will be temporery solution like its always been

i dont understand your conclusion why would it be the last chance? you think biology is done with inventions lol? its only began

 

[scientist_0005]

Why? From what i understood AR degrader do not completely destroy the AR forever, the human body regenerate that sh*t better than it regenerates hair lmao, still need continued use.

The only thing that could allow you to buy some years before having to obsess over your scalp again is HMI, and the fact that people from the GB reports shedding after cessation of SMI treatment doesn't look particularly good for that part, tho it's hard to tell with that.

of course you have to apply it every couply of days but what exactly is the problem? do yiu give up on oral hygiene because you have to brush your teeth everyday? the body makes new AR just as it makes new 5AR thats how its always been but i dont see why this is a problem. people expect a gene editing solution that simply cannot exist yet with modern technology, its unrealistic. of course in some decades that will be possible but not now, its too new

 

[scientist_0005]

I think it's a bit too early to judge on GT20029s efficacy...

Yes CB-03-01 performed the best for Sebaceous gland growth inhibition according to the table:

View attachment 170679

Although this is a test on the sebaceous gland which they did to test it's efficacy against acne, I don't think it's safe to assume that this will also be the case for dermal papilla when testing against hair loss..

In another experiment designed for treating hair loss when head to head with 5% minoxidil, 1% and 3% GT20029 performed just as well at 5% Minoxidil on day 17. Let's also not forget mice are good responders to minoxidil.

"In this experiment, 6 groups were used, namely, a Vehicle group, a DHT (30mg/kg) concentration group, a DHT (30mg/kg) + minoxidil 5% concentration group, a DHT (30mg/kg) + A460.5% concentration group, a DHT (30mg/kg) + A461% concentration group and a DHT (30mg/kg) + A463% concentration group. The results of hair regrowth in the androgen alopecia model in C57 mice are shown in table 9 below: table 9 hair regrowth effect on C57 mouse androgen alopecia model (AVER, n ═ 6) As can be seen from the results, the DHT (30mg/kg) concentration group scored 0.5 for hair development 17 days after the administration, and had almost no hair development, which was significantly lower than that of the Vehicle group, indicating successful molding. The average value of the score of the DHT (30mg/kg) + minoxidil 5% concentration group is 2.33, which is obviously higher than that of the DHT (30mg/kg) model group, and the DHT/minoxidil composition shows good hair growth effect. The DHT (30mg/kg) + A460.5% concentration group scored slightly higher than the building block DHT (dihydrotestosterone) group, but there was no statistical difference. The scores at Day17 for the A461% and 3% concentration dose groups were approximately equivalent to the 5% minoxidil group, and the scores were significantly different from the DHT (dihydrotestosterone) group (p < 0.05; p < 0.01)."

Patent Source: https://patents.google.com/patent/CN113387930A/en?assignee=Suzhou+Kintor+Pharmaceuticals,+Inc.&sort=new

There still could be adjustments needed for the vehicle since the molecule size for GT20029 is quite large.

Finally if you are comparing it to CB-03-01, let's not forget that CB-03-01 massively drops after the 6 month mark (maybe due to the upregulation of receptors when using an an AR antagonists), this might not happen with AR degraders.

View attachment 170681

i think the drop in CB is simply bc its not strong of an anti androgen. upregulation of AR is not common with anti androgens, if it was thrn this mechanism would have been discovered becsuse it would be VERY bad for conditions like prostate cancer where sou rely on continuous suppression of androgenic activity. no literature would suggest this kind of reaction. however that poses the questioj if it was strong enough to give better results than finasteride its clearly getting to the follicle so why would it suddenly drop? it is quite strange and unusual for anti androgens in hair loss