How come people are more interested in cox-inhibitors and OC000459 than Ramatroban? There must be something wrong with Ramatroban because nobody is talking about it or interested in it but I have no idea what’s wrong with it.
If anyone knows what’s wrong with the idea of topicalizing Ramatrobam please share that information with us.
» How come people are more interested in cox-inhibitors and OC000459 than
» Ramatroban? There must be something wrong with Ramatroban because nobody
» is talking about it or interested in it but I have no idea what’s wrong
» with it.
» If anyone knows what’s wrong with the idea of topicalizing Ramatrobam
» please share that information with us.
i read it has an anti-platlet aggregatory effect (i.e. bleeding) because it does not bind as selectively as OC000459 does. Apart from binding to CRT2 ramatroban also binds to the Thromboxane receptor.
also, supposedly TM300089 is an analogue of Ramatroban but higher receptor selectivity (“source”: GangsterBoy)
» also, supposedly TM300089 is an analogue of Ramatroban but higher receptor
» selectivity (“source”: GangsterBoy)
here is an actual source confirming what GangsterBoy claimed, namely that TM300089 and Ramatroban are closely related and that TM300089 is highly selective, compared to Ramatroban.
background:
The present study involving mice explores the specificity of CRTH2 antagonism of TM30089, which is structurally closely related to the dual TP/CRTH2 antagonist ramatroban, and compares the ability of ramatroban and TM30089 to inhibit asthma-like pathology.
conclusion:
TM30089, displayed high selectivity for and antagonistic potency on mouse CRTH2 but lacked affinity to TP and many other receptors including the related anaphylatoxin C3a and C5a receptors, selected chemokine receptors and the cyclooxygenase isoforms 1 and 2 which are all recognized players in allergic diseases. Furthermore, TM30089 and ramatroban, the latter used as a reference herein, similarly inhibited asthma pathology in vivo by reducing peribronchial eosinophilia and mucus cell hyperplasia.
» How come people are more interested in cox-inhibitors and OC000459 than
» Ramatroban? There must be something wrong with Ramatroban because nobody
» is talking about it or interested in it but I have no idea what’s wrong
» with it.
» If anyone knows what’s wrong with the idea of topicalizing Ramatrobam
» please share that information with us.
I found this on google, but when you click on the link the page seems to have been modified
BAY u3405 an antagonist of thromboxane A2- and prostaglandin D2 …
www.researchgate.net/…/21359285_BAY_u340… - Diese Seite übersetzen
Although BAY u3405 appears to have a half life of less than 1 h in man, it exhibits inhibitory activity, as assessed by ex vivo inhibition of U-46619-induced …
btw: bay u3405 = ramatroban
a half life of less than 1 hour would mean that at 2 hours only approximately 25% of all receptors are still being blocked. That doesn’t sound very promising… we should try to find out more abt the halflife of OC000459
another thing i found out is that:
PGD2 is rapidly metabolized (half-life in blood is about 6 seconds) to 13,14-dihydro-15-keto PGD2 or …
Rama molecular mass: 416.46 g/mol
one thing that worries me about the whole PGD2 approach is that, according to http://scholar.google.com Dr. Cotsarelis’ study has only be cited 5 times and mostly quite out of context and seemingly by not very serious journal publications.
If this was the breakthrough that the media makes it out to be, then I wonder why other institutes are not pouncing on it and conducting research of their own. In physics at least if there is a break through discovery then labs all over the world would conduct research of their own to confirm or to dispute the data presented in the publication. Why is this not happening? 
» I found this on google, but when you click on the link the page seems to
» have been modified
»
» BAY u3405 an antagonist of thromboxane A2- and prostaglandin D2 …
» www.researchgate.net/…/21359285_BAY_u340…
» - Diese Seite übersetzen
»
» Although BAY u3405 appears to have a half life of less than 1 h in man, it
» exhibits inhibitory activity, as assessed by ex vivo inhibition of
» U-46619-induced …
»
» btw: bay u3405 = ramatroban
»
» a half life of less than 1 hour would mean that at 2 hours only
» approximately 25% of all receptors are still being blocked. That doesn’t
» sound very promising… we should try to find out more abt the halflife of
» OC000459
»
»
» another thing i found out is that:
»
» PGD2 is rapidly metabolized (half-life in blood is about 6 seconds) to
» 13,14-dihydro-15-keto PGD2 or …
»
» source:
» https://www.caymanchem.com/app/template/Article.vm/article/2140;jsessionid=EEAEFB409423347FDE326280AABDD091
»
»
» Rama molecular mass: 416.46 g/mol
» one thing that worries me about the whole PGD2 approach is that, according
» to http://scholar.google.com Dr. Cotsarelis’ study has only be cited 5
» times and mostly quite out of context and seemingly by not very serious
» journal publications.
»
» If this was the breakthrough that the media makes it out to be, then I
» wonder why other institutes are not pouncing on it and conducting research
» of their own. In physics at least if there is a break through discovery
» then labs all over the world would conduct research of their own to confirm
» or to dispute the data presented in the publication. Why is this not
» happening?
This!! This is what i have an issue with aswel. If this was such a huge breakthrough why are companies not starting trials dedicated for hairloss. yes there are trials going for asthma but why are companies not jumping on this and making a dedicated hairloss treatment making themselfs a shed load of cash. yes it costs money but im sure they can get funding with the study to help investors.
also i dont feel its quite as simple as what some people are making it out to be, block this all goes back to normal, add this hair grows. companies would of jumped on this approach.
i would love to be wrong, i really would.
well… actually, according to some of the news articles Cotsarelis IS in fact in talks with companies to market drugs directed for hairloss. The whole PGD2 is supposedly still under investigation and I presume that more preliminary information needs to be gathered before they will conduct fullscale, expensive trials.
Also, Cotsarelis holds patents on using PGD2 for hair growth and hair growth inhibition. I could imagine it is not so easy for big pharma to just step over him and market PGD2 drugs on their own.
» This!! This is what i have an issue with aswel. If this was such a huge
» breakthrough why are companies not starting trials dedicated for hairloss.
» yes there are trials going for asthma but why are companies not jumping on
» this and making a dedicated hairloss treatment making themselfs a shed load
» of cash. yes it costs money but im sure they can get funding with the study
» to help investors.
»
» also i dont feel its quite as simple as what some people are making it out
» to be, block this all goes back to normal, add this hair grows. companies
» would of jumped on this approach.
»
» i would love to be wrong, i really would.
» PGD2 is rapidly metabolized (half-life in blood is about 6 seconds) to
» 13,14-dihydro-15-keto PGD2 or …
If PGD2 is metabolized within 6 seconds, then it makes me wonder how PGD2 concentrations could be measured accurately with ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Wouldn’t the same preparation take a lot longer than 6 seconds?
Hello Men, I am still doing fine for almst 1 month on the PDG2 blockers. Still havent lost any hair, but no regrowth, no side effects. I do find it interesting that I need a haircut in the area where I still have hair (it has continued to grow at normal pace). So, with that being said, the PDG2 blockers did not discourage of my normal healthy hairs from growing. Also thank you guys for your research and input into finding the formula to regrow hair and think we are close. Alec
» Hello Men, I am still doing fine for almst 1 month on the PDG2 blockers.
» Still havent lost any hair, but no regrowth, no side effects. I do find it
» interesting that I need a haircut in the area where I still have hair (it
» has continued to grow at normal pace). So, with that being said, the PDG2
» blockers did not discourage of my normal healthy hairs from growing. Also
» thank you guys for your research and input into finding the formula to
» regrow hair and think we are close. Alec
hey alec,
i have literally spent the last few days intensifying my “laymans research” on the topic and reading the publications and the references found therein.
I found a few interesting references to a few publications which I am having trouble obtaining since I am not a university student and am bared from access to most journals. Two interesting articles are references found in (20) and (29). These articles show the postive effects of PGE2 and PGF2a in mice hair growth models. What I am hoping to get from these publications is information as to the concentration, vehicle and substances used to penetrate the mouse skin. We will need such information when attempting to make our own formula to increase PGE2 in the balding scalp.
I am afraid however that even balancing out PGD2 and PGE2 only exhibit slight improvement and not regrow cosmetically significant amounts of hair, but merely maintain what we already have.
Cots states something similar in his publication:
“Inhibiting PGD2 may prevent miniaturization and provide benefit to those in the process of balding; however, it is unclear whether men who are already bald will regrow hair.”
I believe that in order to reverse follicle miniaturization, it will probably be necessary to do some kind of WNT stem cell activation or skin wounding to push the sleeping follicles back in to an active state.
However for me at least, I would be quite content in maintaining my current status and maybe freshening up the crown and the temples a bit with a HT procedure.
anyway back to the point:
does anyone here have access to journals and could obtain the two publications 20 and 29 referred to in Cots paper?
Another interesting reference is 40, a list of at least 10 existing GPR44 antagonists.
-
Sasaki S, Hozumi Y, Kondo S. Influence of prostaglandin F2α and its analogues on hair regrowth and follicular melanogenesis in a murine model. Exp Dermatol. 2005; 14:323 328. [PubMed: 15854125]
-
Geng L, Hanson WR, Malkinson FD. Topical or systemic 16,16 Dm prostaglandin E2 or WR-2721 (WR-1065) protects mice from alopecia after fractionated irradiation. Int J Radiat Biol. 1992; 61:533–537. [PubMed: 1349335]
-
Roman RJ. P-450 metabolites of arachidonic acid in the control of cardiovascular function. Physiol
Rev. 2002; 82:131–185. [PubMed: 11773611]
if someone can get those pubs please drop me a mail at ursulaslover at gmail dot com
» » PGD2 is rapidly metabolized (half-life in blood is about 6 seconds) to
» » 13,14-dihydro-15-keto PGD2 or …
»
» If PGD2 is metabolized within 6 seconds, then it makes me wonder how PGD2
» concentrations could be measured accurately with ultra-high-performance
» liquid chromatography-mass spectrometry (UHPLC-MS). Wouldn’t the same
» preparation take a lot longer than 6 seconds?
the answer to this is found on page 10 Ultra-high-performance liquid chomatography. Basically the tissue samples were “snap-frozen”
» » Hello Men, I am still doing fine for almst 1 month on the PDG2 blockers.
» » Still havent lost any hair, but no regrowth, no side effects. I do find
» it
» » interesting that I need a haircut in the area where I still have hair
» (it
» » has continued to grow at normal pace). So, with that being said, the
» PDG2
» » blockers did not discourage of my normal healthy hairs from growing.
» Also
» » thank you guys for your research and input into finding the formula to
» » regrow hair and think we are close. Alec
»
» hey alec,
»
» i have literally spent the last few days intensifying my “laymans research”
» on the topic and reading the publications and the references found
» therein.
»
» I found a few interesting references to a few publications which I am
» having trouble obtaining since I am not a university student and am bared
» from access to most journals. Two interesting articles are references found
» in (20) and (29). These articles show the postive effects of PGE2 and PGF2a
» in mice hair growth models. What I am hoping to get from these publications
» is information as to the concentration, vehicle and substances used to
» penetrate the mouse skin. We will need such information when attempting to
» make our own formula to increase PGE2 in the balding scalp.
»
» I am afraid however that even balancing out PGD2 and PGE2 only exhibit
» slight improvement and not regrow cosmetically significant amounts of hair,
» but merely maintain what we already have.
»
» Cots states something similar in his publication:
» “Inhibiting PGD2 may prevent miniaturization and provide benefit to those
» in the process of balding; however, it is unclear whether men who are
» already bald will regrow hair.”
»
»
» However for me at least, I would be quite content in maintaining my current
» status and maybe freshening up the crown and the temples a bit with a HT
» procedure.
»
» anyway back to the point:
»
» does anyone here have access to journals and could obtain the two
» publications 20 and 29 referred to in Cots paper?
»
» Another interesting reference is 40, a list of at least 10 existing GPR44
» antagonists.
»
» 20. Sasaki S, Hozumi Y, Kondo S. Influence of prostaglandin F2α and
» its analogues on hair regrowth and follicular melanogenesis in a murine
» model. Exp Dermatol. 2005; 14:323 328. [PubMed: 15854125]
»
» 29. Geng L, Hanson WR, Malkinson FD. Topical or systemic 16,16 Dm
» prostaglandin E2 or WR-2721 (WR-1065) protects mice from alopecia after
» fractionated irradiation. Int J Radiat Biol. 1992; 61:533–537. [PubMed:
» 1349335]
»
» 40. Roman RJ. P-450 metabolites of arachidonic acid in the control of
» cardiovascular function. Physiol
» Rev. 2002; 82:131–185. [PubMed: 11773611]
»
»
» if someone can get those pubs please drop me a mail at ursulaslover at
» gmail dot com
If someone gets these articles then I would like a copy too so that I can turn them over to IronDragon. The more info we get to IronDragon, and the quicker we do it, the better.
jarjar? arent you a university student? doesn’t your university subscribe to journals? Usually these are available when using the university library internet or some kind of student intranet facility (i.e. intranet). At least thats how it is in germany.
» If someone gets these articles then I would like a copy too so that I can
» turn them over to IronDragon. The more info we get to IronDragon, and the
» quicker we do it, the better.
Good point.
I was waiting for new information about PGD2 and hair loss to come out at the Caribbean hair researcher get-together but nothing new came out. I don’t get it either. It seems like hair researchers would be all over this.
On the other hand, there is proof beyond a reasonable doubt that prostaglandins play a mediating role in hair growth. We know that for fact because:
-
Minoxidil has been proven to grow some hair (likely via it’s affectation on PGE2).
-
Allergan’s latisse grows eyelash hair and other hairs.
-
Allergan has released a PR recently stating that their scalp version of latisse is growing scalp hair.
-
Numerous studies involving latanoprost or bimatoprost have established that both grow hair.
Does this prove that negating PGD2 can arrest hair loss? No. However, it does prove that prostaglandins can mediate hair growth.
That aside, I have no idea why researchers are not all over Cotseralis’s study. It’s really surprising. You would think that given Cotseralis’s stature and his study results other researchers would be interested but the fact that other researchers are not paying attention may say something negative about the other resarchers rather than Cotseralis’s conclusions.
Remember, like I told everyone before, when I told Histogen about Cotseralis’s PGD2 theories they kind of snickered and called it an “old theory.”
Meanwhile, as the world turns, more and more people using PGD2 blockers are saying that their hair loss has stopped and more and more evidence is piling up that stimulating PGE2 (and possibly PGF2a) stimulates hair growth. So maybe it’s the other researchers who are wrong and maybe Cotseralis is right.
» one thing that worries me about the whole PGD2 approach is that, according
» to http://scholar.google.com Dr. Cotsarelis’ study has only be cited 5
» times and mostly quite out of context and seemingly by not very serious
» journal publications.
»
» If this was the breakthrough that the media makes it out to be, then I
» wonder why other institutes are not pouncing on it and conducting research
» of their own. In physics at least if there is a break through discovery
» then labs all over the world would conduct research of their own to confirm
» or to dispute the data presented in the publication. Why is this not
» happening?
»
»
»
» » I found this on google, but when you click on the link the page seems to
» » have been modified
» »
» » BAY u3405 an antagonist of thromboxane A2- and prostaglandin D2 …
» »
» www.researchgate.net/…/21359285_BAY_u340…
» » - Diese Seite übersetzen
» »
» » Although BAY u3405 appears to have a half life of less than 1 h in man,
» it
» » exhibits inhibitory activity, as assessed by ex vivo inhibition of
» » U-46619-induced …
» »
» » btw: bay u3405 = ramatroban
» »
» » a half life of less than 1 hour would mean that at 2 hours only
» » approximately 25% of all receptors are still being blocked. That doesn’t
» » sound very promising… we should try to find out more abt the halflife
» of
» » OC000459
» »
» »
» » another thing i found out is that:
» »
» » PGD2 is rapidly metabolized (half-life in blood is about 6 seconds) to
» » 13,14-dihydro-15-keto PGD2 or …
» »
» » source:
» »
» https://www.caymanchem.com/app/template/Article.vm/article/2140;jsessionid=EEAEFB409423347FDE326280AABDD091
» »
» »
» » Rama molecular mass: 416.46 g/mol
No, I’m not a student. I don’t work for a university either. Sorry. I wish I could get this info but I can’t. I do believe that Iron Dragon could find the info useful though. Ultimately, we may have to count on IronDragon because Kain is kind of iffy.
» jarjar? arent you a university student? doesn’t your university subscribe
» to journals? Usually these are available when using the university library
» internet or some kind of student intranet facility (i.e. intranet). At
» least thats how it is in germany.
»
»
» » If someone gets these articles then I would like a copy too so that I
» can
» » turn them over to IronDragon. The more info we get to IronDragon, and
» the
» » quicker we do it, the better.
» well… actually, according to some of the news articles Cotsarelis IS in
» fact in talks with companies to market drugs directed for hairloss. The
» whole PGD2 is supposedly still under investigation and I presume that more
» preliminary information needs to be gathered before they will conduct
» fullscale, expensive trials.
»
» Also, Cotsarelis holds patents on using PGD2 for hair growth and hair
» growth inhibition. I could imagine it is not so easy for big pharma to just
» step over him and market PGD2 drugs on their own.
the news articles also stated we would have this cure within 2 years. did we have any statement from Dr C actually stating he is in talks? or are we to believe these news articles?
» » well… actually, according to some of the news articles Cotsarelis IS
» in
» » fact in talks with companies to market drugs directed for hairloss. The
» » whole PGD2 is supposedly still under investigation and I presume that
» more
» » preliminary information needs to be gathered before they will conduct
» » fullscale, expensive trials.
» »
» » Also, Cotsarelis holds patents on using PGD2 for hair growth and hair
» » growth inhibition. I could imagine it is not so easy for big pharma to
» just
» » step over him and market PGD2 drugs on their own.
»
» the news articles also stated we would have this cure within 2 years. did
» we have any statement from Dr C actually stating he is in talks? or are we
» to believe these news articles?
You are raising stupid issues that have obvious answers.
» You are raising stupid issues that have obvious answers.
as stated before im fairly new to all this. while these “stupid questions and issues” may not be to your taste, im trying to find either answers or get some clarity on whats going on. i was asking a question about if he has actually made a statement wether he is in talks or not. you say the answer is obvious so please share…
also why the hell would i be trying to troll you guys when im in exactly the same boat as you… i have nothing to gain from “trolling” nor would i waste my time trying to “troll” random people on the net…
»
» also why the hell would i be trying to troll you guys when im in exactly
» the same boat as you… i have nothing to gain from “trolling” nor would i
» waste my time trying to “troll” random people on the net…
You’re getting flak because there isn’t much benefit-of-the-doubt left for noobs around here.
There are a few longtime members who are chronic trolls. They have a habit of re-registering under new screen names every time the moderators kick them off again.
JarJarbinx also does not have much patience for people who aren’t already up to speed with his train of thought. He’s a bit rough sometimes.
» the news articles also stated we would have this cure within 2 years. did
» we have any statement from Dr C actually stating he is in talks? or are we
» to believe these news articles?
to answer your question:
yes dr Cots actually made a corrective announcement after he felt that the media had misinterpreted his words. After an interview with cots, the media wrote a statement claiming that Dr. Cots was in talks to market a drug within the next 2 years. I believe Cots then wrote corrected this statement, saying that the media misinterpreted things and that clinical trails could start within two years and a marketed drug would not be out for the next 5 years.