Curis, P&g, And The Lost Baldness Cure
- Thread starter pegasus2
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What were users trying this treatment using for drug?
HH-AG, but I don't know if it was the same one we are using, 1.5, or another one? I doubt they got 1.8.
While not essential for hair follicle initiation during embryonic development, SHh is required for controlling growth and morphogenesis of the follicle past the hair germ stage.[35, 36] SHh-/- mice exhibit normal levels of hair placodes; however, dermal papillae do not form properly and follicular epithelium proliferation is impaired. The reduction in hair follicle papillae correlated with decreased expression of both Gli1 and Ptch1. In adults, SHh mediates the transition from the resting (telogen) to the growth stage (anagen) during the normal follicle cycle and anti-SHh antibodies prevented hair growth in adult mice.[37, 38] Taken together, these studies suggest activation of Hh signaling holds therapeutic potential in diseases characterized by decreased follicular proliferation and altered cycling (such as androgenetic alopecia).
Competitive binding experiments demonstrated that all three GCs[glucocorticoids] displaced BODIPY-Cyc from Smo; however, maximal displacement was modest (20–25 %) in comparison to the small-molecule SMO agonist (SAG, 100% displacement) at the highest concentrations evaluated (10 uM).
The most promising class of agonists, the biaryl benzothiophenes under development at Curis, was licensed by Wyeth in early 2004 for extensive preclinical development in models of stroke and cardiovascular injury and by Proctor & Gamble for hair-loss treatment. Both collaborations ended prior to an Hh agonist entering clinical trials, reportedly for safety concerns. While the exact issues encountered for these compounds has not been reported, as many of the disorders targeted by the Hh agonists require chronic administration, long-term safety is a key concern. In addition, as noted above and extensively reviewed elsewhere,[91, 92] constitutive activation of Hh signaling has been implicated in the development of numerous forms of cancer. It is unclear whether the therapeutic effects of prolonged Hh agonism can be separated from the detrimental effects commonly linked to tumor formation; however, the ability to decouple these activities is crucial to moving this class of compounds forward.
https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/cmdc.201300358
In the presence of an shh inhibitor it takes large doses to activate shh.
Ec50 is given as 3nM here with a Kd of 59nM. It is still a potent agonist up to 1uM, with an ic50 of 3uM, and loses most of its effect by 10uM.
SAG Activity Provides Evidence for a Downstream Effector. One interesting aspect of SAG activity is its diminished potency at concentrations above 1uM (see Fig. 2B). This loss of pathway activity is not caused by cytotoxicity, as indicated by measurements of control reporter constructs (not shown), which suggests that SAG not only binds to Smo but can also inhibit a cellular component required for Hh signaling.
https://pdfs.semanticscholar.org/04ef/b5044cabe130bff5bc3d73338f823e7ed248.pdf
This is interesting reading on the history of hedgehog drugs.
Competitive binding experiments demonstrated that all three GCs[glucocorticoids] displaced BODIPY-Cyc from Smo; however, maximal displacement was modest (20–25 %) in comparison to the small-molecule SMO agonist (SAG, 100% displacement) at the highest concentrations evaluated (10 uM).
The most promising class of agonists, the biaryl benzothiophenes under development at Curis, was licensed by Wyeth in early 2004 for extensive preclinical development in models of stroke and cardiovascular injury and by Proctor & Gamble for hair-loss treatment. Both collaborations ended prior to an Hh agonist entering clinical trials, reportedly for safety concerns. While the exact issues encountered for these compounds has not been reported, as many of the disorders targeted by the Hh agonists require chronic administration, long-term safety is a key concern. In addition, as noted above and extensively reviewed elsewhere,[91, 92] constitutive activation of Hh signaling has been implicated in the development of numerous forms of cancer. It is unclear whether the therapeutic effects of prolonged Hh agonism can be separated from the detrimental effects commonly linked to tumor formation; however, the ability to decouple these activities is crucial to moving this class of compounds forward.
https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/cmdc.201300358
In the presence of an shh inhibitor it takes large doses to activate shh.
Ec50 is given as 3nM here with a Kd of 59nM. It is still a potent agonist up to 1uM, with an ic50 of 3uM, and loses most of its effect by 10uM.
SAG Activity Provides Evidence for a Downstream Effector. One interesting aspect of SAG activity is its diminished potency at concentrations above 1uM (see Fig. 2B). This loss of pathway activity is not caused by cytotoxicity, as indicated by measurements of control reporter constructs (not shown), which suggests that SAG not only binds to Smo but can also inhibit a cellular component required for Hh signaling.
https://pdfs.semanticscholar.org/04ef/b5044cabe130bff5bc3d73338f823e7ed248.pdf
This is interesting reading on the history of hedgehog drugs.
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I have hair growing on my hairline and temples, even where i have never had terminal hair before.
PS: Don't try this at home, kids!
PS: Don't try this at home, kids!
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REGROWTH PICS
If privacy is not a problem, would you mind posting Before/After pics of your temples?
If you want to keep them more anonymous, a small area BW pic would do -
just to get an idea of this treatment's potential.
Thanks
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Sorry I won't post pics on a public forum.
Wow, that's exciting stuff guys. I'm so glad you guys are seeing results so quick. It's not surprising considering that's what the studies say but it's always nice to actually see it happen. Pegasus, are you going to be posting before and after pics? I don't see any issue with posting anonymous pictures.
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Posting pics when some idiots are talking about Nazism as a good thing? Yeah right...
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How about sending your pics in private messages?
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are you guys seeing new growth on some previously slick bald area if you don't mind me asking? Thanks for trying this and taking such risks good luck on your progress
I think that's what john difool meant. I am just seeing more new hairs coming in on my temples and vellus hairs going terminal. I already had some vellus hairs coming in around my juvenile hairline. I don't think there's been any acceleration there, but the temples have picked up steam in the NW2 area the last couple weeks. It's filling in in what most people here would call NW1, but I know my original hairline was a half inch lower, and that's just vellus hairs still.
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Congratulations.
I understand that "vellus hairs going terminal" need a new hair cycle, Is it right?
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These things take time. But when hair grow back you usually notice quickly
This attitude is exactly why I'm not posting pictures. People like you and hair cook can do your own experiments if you want pictures. It's not my job to help people who only post their experiments on their private Nazi forum, and come on here just to attack people. Maybe I'll create my own private forum and share pictures.
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That may depend on your definition of "vellus", "intermediate", and "terminal". Hairs can definitely start growing longer and thicker without shedding.
this doesn’t make any sense to me, if you looked through my post I’m the least Nazi person on this site, I’m always calling out their bullshit on here to no avail. I just think posting pics is good protocol.