Kintor new AR degrader w/o side effects

[5minutesbeforemiracle]

It is suspicious but at the same time the Reddit user hasn’t plugged where he got the chemical from or the lab where it was tested so what are they gaining?

It could be advanced advertising for one of those groups that sell on grey market. After all, the redditor is a new account yet somehow already participates in group buys? Why is he sharing to reddit then?
Pay attention, if a *new*account says "I did some research, did you buy pyrilutamide from x?" and the OP redditor says "yeah that's the one" then it would raise some flags.

 

[Ollie]

There is no way it is real. How the hell did they get the compound off the Grey market?

Any half decent chemist can decipher the patents / chemical structures. China will make and sell anything

 

[scientist_0005]

It could be advanced advertising for one of those groups that sell on grey market. After all, the redditor is a new account yet somehow already participates in group buys? Why is he sharing to reddit then?
Pay attention, if a *new*account says "I did some research, did you buy pyrilutamide from x?" and the OP redditor says "yeah that's the one" then it would raise some flags.

lol you are all so f*****g delusional if you think this is some kind of conspiracy. why would it raise some flags, maybe that was the actual distributer? like, kintor is developing a compound that works for hair loss through an obvious pqthway, they have not found side effects in their phase 2 trials and have reported statistically significant increase in hair count although thwy have not published the results entirely yet this already shows that it probably does something and is quite safe. the chemical structure is in the patent and in contrast to HMI for examppe not that hard and expensive to make. so why would this even be hard to believe or good to be true? this tells us jothing about hoe effective the drug is anyway as this is not q study but merely a report of some dude on the internet. but to suggest it is hard to believe is ridiculous, why would it be

 

[froggy7]

every drug is suspect, even Tsuji: D it must be in 5 years

 

[scientist_0005]

No point in using pyralutamide if you are on gt20029. 6 weeks with no results is pretty bad honestly.

based on the retardation of your comments i assume you are also a redditor?

 

[Seuxin]

Hi people, i asked HDD pharma about kx-826, they answered me a lot of people askem them but since there isn't public structure of it, they cannot produce it.....

HDD pharma is a reliabler producer. Be warned about this reddit thread. Yeah there is patent, but there is a lot of fake/false informations in patent to avoid "full" duplication....

 

[5minutesbeforemiracle]

lol you are all so f*****g delusional if you think this is some kind of conspiracy. why would it raise some flags, maybe that was the actual distributer? like, kintor is developing a compound that works for hair loss through an obvious pqthway, they have not found side effects in their phase 2 trials and have reported statistically significant increase in hair count although thwy have not published the results entirely yet this already shows that it probably does something and is quite safe. the chemical structure is in the patent and in contrast to HMI for examppe not that hard and expensive to make. so why would this even be hard to believe or good to be true? this tells us jothing about hoe effective the drug is anyway as this is not q study but merely a report of some dude on the internet. but to suggest it is hard to believe is ridiculous, why would it be

I don't think it's a conspiracy, however I am open-minded about it possibly beong a scam. The post's existence is at least a little bit suspicious.

 

[BigBadBaldie]

It could be advanced advertising for one of those groups that sell on grey market. After all, the redditor is a new account yet somehow already participates in group buys? Why is he sharing to reddit then?
Pay attention, if a *new*account says "I did some research, did you buy pyrilutamide from x?" and the OP redditor says "yeah that's the one" then it would raise some flags.

So far he hasn’t so I’m inclined to believe it but it’s good to be sceptical. Especially since there are no photos.

 

[trialAcc]

So far he hasn’t so I’m inclined to believe it but it’s good to be sceptical. Especially since there are no photos.

What photos would you want? A picture of white powder or the before/after's of 6 weeks of a topical AA?

 

[BigBadBaldie]

What photos would you want? A picture of white powder or the before/after's of 6 weeks of a topical AA?

Photos of results, pictures of white powder could be anything.

 

[badnewsbearer]

i think since they have this platform what prevents them from also targeting 5AR with their PROTAC? I mean if you look at prostate cancer studies these drugs can often not degrade all the AR proteins and since this is for hair loss and not cancer it will be a topical with again the apsorption and localisation problem. i think it would be smart to also degrwde the 5AR and the technology should literally be the same, i think it should be in fact quite easy for them to have this two way product? why not?

 

[Micky_007]

i think since they have this platform what prevents them from also targeting 5AR with their PROTAC? I mean if you look at prostate cancer studies these drugs can often not degrade all the AR proteins and since this is for hair loss and not cancer it will be a topical with again the apsorption and localisation problem. i think it would be smart to also degrwde the 5AR and the technology should literally be the same, i think it should be in fact quite easy for them to have this two way product? why not?

Topical absorbtion problems have solutions. One of them is Microneedling.

 

[badnewsbearer]

Topical absorbtion problems have solutions. One of them is Microneedling.

I should reformulate, not absorption but deliver to the target cells. sure you can absorb more by doing various things, using warm water on the skin before to provide better vascularisation, needling etc. but what happens when you have an androgen receptor degrader and then you needle and open the micro vasculature, it goes directly into the blood stream, then the androgen receptors in your brain, heart or penis will also get degraded which is pretty problematic, more so than finasteride even. in their description they talk about localized deliver and that it stays in tissue for many days and that in animal models systemic activity was very low but they never talk about the technique that assures this. after all Kintor has been in attention recently for exaggerating effects of drugs without proper evidence. but I guess we will see as it is in phase 1 clinical trials rn and if it does have systemic action we will most certainly find out except if chines men are not reliant on androgens

 

[badnewsbearer]

Different Levels of 5α-Reductase Type I and II, Aromatase, and Androgen Receptor in Hair Follicles of Women and Men with Androgenetic Alopecia

In this study, 12 women and 12 men, ages 18-33 year, with androgenetic alopecia were selected for biopsies from frontal and occipital scalp sites. The…

reader.elsevier.com

study about receptor density of frontal vs occiputal scalp. the density in frontal scalp is about twice as high on frontal scalp than in occiputal scalp for cytoplams and a little less for nuclear receptors. i assume they mean receptors that still linger around in the cytoplams or those that have entered the nucleus bound to an androgen for transcription. if this treatment could degrade just a good 50% of the AR(unrealistic in my opinion due to absoprtion) that would normalize this. however then there would still be the even greater problem that is higher 5AR expression in frontal scalp. dht is extremely potent and it will just bind up all the left over AR.

people seem to think degaders get rid off all receptors however this is just not realistic for AA. it is more realistic for prostate canced with oral dosing where 95%+ of receptors get degraded in prpstates(not even sure if this is in vitro or vivo)

 

[badnewsbearer]

"each PROTAC molecule can degrade multiple AR proteins, drugs based on PROTAC can achieve efficacy with a low dosage. In addition, as long as there are a small amount of PROTAC molecules in the cells, the efficacy of the drugs can be maintained"


"will not cause excessive drug accumulation and notable side effects. While achieving efficacy, GT20029 can effectively avoid systemic exposure to mitigate or avoid the side effects ofthe oral androgen signaling pathway inhibitors."

so they state that accumulation is kot anproblem but they also state rhat that is not needed because a small number of molecules can do the job. thats good for hair but if this goes systemic a tiny bit it WILL cause accumulation as in a tiny number of molecules will be in penile or neural, bone tissue etc and degrade AR there. much worse than reducing dht is reducin ability of T and DHT to excert action.

either kintor is full of very secretive geniuses or its another chines scam project of so many

 

[trialAcc]

eh we're a few years away from worrying about whether it works locally without going systemic in anyone

Kintor's current PR disaster w.r.t. the Proxalutamide covid trial on the other hand could really hurt them, whether any wrongdoing even happened

their PROTAC just entered phase I and is the first clinical attempt at a topical approach...
will be very interesting to see whether it progresses to phase II and what challenges are revealed in a couple years from such a novel application

Considering they are testing for this in the current phase (which is over btw, results should be Q1), I'd say it's a little sooner then a few years away. They will be looking for evidence of systematic absorption at the tested levels and if it's going systemic they will have a difficult time ever progressing in trials.

 

[trialAcc]

yeah phase I dosing in humans is likely almost, if not already, finished if they started in July

and they'll obviously find some range of phase I doses that don't go systemic, without worrying yet if it works

then they'll very carefully analyze all the tissue and blood samples from every subject to avoid any surprises in phase II...
and to package it into a clean report for regulators in both China and US

so IMO only reason phase II doesn't get greenlit is if:
1. there's a surprise off-target effect
2. the dose turns out to be much lower than expected and they don't want to risk cost of advancing it to larger trials

edit:
so not personally expecting phase I results report by Q1 2021, when they can focus on delivering their Pyrilutamide phase II report as a PR win
GT phase II results will be where it gets interesting for me, which is years away

I almost guarantee you that they will have a GT phase 2 report next year around this time, assuming it gets greenlit for phase 2. Pyralutamide was in phase 1 in 2020 and its entering phase 3 now. Kintor is going to push GT forward as fast as it can.

 

[fashy]

Yeah, Kintor forecasts GT to be out by 2024 in China and looking at how fast (and most importantly on schedule) they move with Pyrilutamide, it will not take years for them to release phase II results for GT unless the drug fails. We should have them by the end of next year.

 

[John Difool]

I agree with the faster deadlines. We are talking about China here, not some San Diego or Israel company more interested to scam investors short term than to deliver a product with good ROI. The only exception is Bayer with.HOPE and again it's China.

 

[trialAcc]

You could be right

but IMO the pace of pushing forward a relatively cookie cutter flutamide derivative doesn’t have the unknown unknowns that could pop up dealing a whole new modality for PROTACs

Unless it gets held back for safety concerns I'm not sure why that would matter. They have a release estimate that's only 1 year after Pyralutamide, and in order to achieve that it will need to be in phase 2 in 2022.