again just gonna be a quick thread like the last one on combining ghrfs + gh
https://looksmax.gg/threads/combination-of-ghrfs-and-gh-high-iq-negros-gtfih.17726/
ky19382 is a small molecule indirubin analogue which acts primarily as an inhibitor of the protein-protein interaction between CXXC5 and Dishevelled (dvl), while simultaneously acting as a Glycogen Synthase Kinase 3 Beta(gsk3b) inhibitor. Through these actions, it acts as a potent canonical Wnt/Beta catenin upregulator. Originally used to treat alopecia through upregulation of the Wnt/B catenin pathway, it was found to also promote wound healing, and most importantly longitudinal growth in adolescent mice.
Hair growth: ky19382 was shown to be more effective than minoxidil in rats in one study, and was able to promote de novo follicle formation, as in the growth of completely new hair follicles in adult tissue, thought to have been impossible until the discovery of this and other Wnt and HH modulators/upregulators.
Wound Healing: ky19382 accelerates wound healing by around 30%-50%, and was significantly faster than using endothelial growth factor (EGF) and PTD-DBM, which is a peptide that targets the same pathway as ky19382 itself. PTD-DBM is most likely inferior to ky19382 due to not affecting gsk3b, a factor which when inhibited, promotes the accumulation of nuclear beta catenin, which is beneficial for all of ky19382's desired effects.
Longitudinal growth:
This is the real important part on why ky19382 is such a mogger compound.
I'm sure that basically everyone on here knows that estrogen fuses the plates. It does this through both genomic and non genomic signalling pathways, which I'm not going to get deep into. When estrogen binds to the estrogen receptor alpha (ErA), it dimerises into hetero or homo dimers and moves within the nucleus of the cell. These dimers bind to estrogen response elements (ERE) in the cxxc5 promoter region of the dna, leading to increased cxxc5 expression which acts as the direct tool to upregulate growth plate fusion. CXXC5 causes a decrease in nuclear beta catenin levels, which are necessary to promote proliferative genes such as Sox9. We know a lack of CXXC5 can prevent estrogen from inducing senescence, because in mice models where the gene of CXXC5 is knocked out, the plates can't close even in high estrogen environments.
From this, I'm sure you've gathered that CXXC5 inhibition is very downstream and likely smarter compared to the relatively caveman-brained method of just inhibiting aromatase to slow bone age. But, does this mean its enough?
Is aromatase inhibition still needed?
From the studies with CXXC5 knockout models, we know that even if CXXC5 is missing and the plates cant fuse, estrogen genomic signalling still occurs as the receptor can bind to other genes. This means that even though your chondrocytes will keep proliferating and hypertrophying, your chondrocytes will still "age", in the sense that as they continue to multiply, they will retain the genomic changes made by estrogen, maturing and dying faster than they would have otherwise. Using ky19382 would likely allow for estrogen levels to be higher than actually needed to delay fusion, but you might still need to use low dose aromatase inhibitors (i recommend arimidex). I genuinely believe that aromatase inhibition combined with cxxc5 - dvl inhibition could potentially add 3+ years of active growth plate chondrocyte proliferation, hypertrophy, and thus growth.
Can more be done?
I'm sure most of you have heard of HDACi to promote longitudinal growth, unfortunately the reasoning behind it is pretty shit and pan-hdaci such as vorinostat are known to have a detrimental impact on growth. A lot of hdacs are necessary for longitudinal growth to occur, and one of high interest is HDAC4. HDAC4 is a crucial downstream factor to prevent chondrocytes from beginning to hypertrophy. Theoretically, if HDAC4 was upregulated, aromatase was inhibited, and cxxc5 - dvl interaction was inhibited, the growth plate may never fuse, allowing us to use androgens and hgh for pretty much as long as we need. I'm not going to get into how HDAC4 could be increased in the growth plate (likely gonna gatekeep further information on exact compounds needed), but the potential is there.
How would KY19382 actually be used?
A benefit of using small molecules over most other compounds is oral bioavailability, which ky19382 favourably exhibits. From some studies ive read (and just asking google's ai
) the best easily available solvent for it is peg400 at around a 60%-80% mix with water (probably distilled or purified or whatever). Buying it from a mainstream source is genuinely expensive as fuck, on medchem express 100mg costs like 2k usd. Comparatively, from my source ky19382 costs around the same but for 10 grams, which lasts way way longer. To convert rat oral dosing to human dosing you have to determine human equivalent dose, which im not fucked explaining. Just ask ai to do it
sorry for the giga low effort thread i wasnt bothered finding pictures, if i got anything wrong please correct me cus this is all from memory
tagging every nigga i remember
Biomaxx
C
cp_
oldfag
BastiHgH
https://looksmax.gg/threads/combination-of-ghrfs-and-gh-high-iq-negros-gtfih.17726/
ky19382 is a small molecule indirubin analogue which acts primarily as an inhibitor of the protein-protein interaction between CXXC5 and Dishevelled (dvl), while simultaneously acting as a Glycogen Synthase Kinase 3 Beta(gsk3b) inhibitor. Through these actions, it acts as a potent canonical Wnt/Beta catenin upregulator. Originally used to treat alopecia through upregulation of the Wnt/B catenin pathway, it was found to also promote wound healing, and most importantly longitudinal growth in adolescent mice.
Hair growth: ky19382 was shown to be more effective than minoxidil in rats in one study, and was able to promote de novo follicle formation, as in the growth of completely new hair follicles in adult tissue, thought to have been impossible until the discovery of this and other Wnt and HH modulators/upregulators.
Wound Healing: ky19382 accelerates wound healing by around 30%-50%, and was significantly faster than using endothelial growth factor (EGF) and PTD-DBM, which is a peptide that targets the same pathway as ky19382 itself. PTD-DBM is most likely inferior to ky19382 due to not affecting gsk3b, a factor which when inhibited, promotes the accumulation of nuclear beta catenin, which is beneficial for all of ky19382's desired effects.
Longitudinal growth:
This is the real important part on why ky19382 is such a mogger compound.
I'm sure that basically everyone on here knows that estrogen fuses the plates. It does this through both genomic and non genomic signalling pathways, which I'm not going to get deep into. When estrogen binds to the estrogen receptor alpha (ErA), it dimerises into hetero or homo dimers and moves within the nucleus of the cell. These dimers bind to estrogen response elements (ERE) in the cxxc5 promoter region of the dna, leading to increased cxxc5 expression which acts as the direct tool to upregulate growth plate fusion. CXXC5 causes a decrease in nuclear beta catenin levels, which are necessary to promote proliferative genes such as Sox9. We know a lack of CXXC5 can prevent estrogen from inducing senescence, because in mice models where the gene of CXXC5 is knocked out, the plates can't close even in high estrogen environments.
From this, I'm sure you've gathered that CXXC5 inhibition is very downstream and likely smarter compared to the relatively caveman-brained method of just inhibiting aromatase to slow bone age. But, does this mean its enough?
Is aromatase inhibition still needed?
From the studies with CXXC5 knockout models, we know that even if CXXC5 is missing and the plates cant fuse, estrogen genomic signalling still occurs as the receptor can bind to other genes. This means that even though your chondrocytes will keep proliferating and hypertrophying, your chondrocytes will still "age", in the sense that as they continue to multiply, they will retain the genomic changes made by estrogen, maturing and dying faster than they would have otherwise. Using ky19382 would likely allow for estrogen levels to be higher than actually needed to delay fusion, but you might still need to use low dose aromatase inhibitors (i recommend arimidex). I genuinely believe that aromatase inhibition combined with cxxc5 - dvl inhibition could potentially add 3+ years of active growth plate chondrocyte proliferation, hypertrophy, and thus growth.
Can more be done?
I'm sure most of you have heard of HDACi to promote longitudinal growth, unfortunately the reasoning behind it is pretty shit and pan-hdaci such as vorinostat are known to have a detrimental impact on growth. A lot of hdacs are necessary for longitudinal growth to occur, and one of high interest is HDAC4. HDAC4 is a crucial downstream factor to prevent chondrocytes from beginning to hypertrophy. Theoretically, if HDAC4 was upregulated, aromatase was inhibited, and cxxc5 - dvl interaction was inhibited, the growth plate may never fuse, allowing us to use androgens and hgh for pretty much as long as we need. I'm not going to get into how HDAC4 could be increased in the growth plate (likely gonna gatekeep further information on exact compounds needed), but the potential is there.
How would KY19382 actually be used?
A benefit of using small molecules over most other compounds is oral bioavailability, which ky19382 favourably exhibits. From some studies ive read (and just asking google's ai
) the best easily available solvent for it is peg400 at around a 60%-80% mix with water (probably distilled or purified or whatever). Buying it from a mainstream source is genuinely expensive as fuck, on medchem express 100mg costs like 2k usd. Comparatively, from my source ky19382 costs around the same but for 10 grams, which lasts way way longer. To convert rat oral dosing to human dosing you have to determine human equivalent dose, which im not fucked explaining. Just ask ai to do itsorry for the giga low effort thread i wasnt bothered finding pictures, if i got anything wrong please correct me cus this is all from memory
tagging every nigga i remember
Biomaxx
C
cp_
oldfag
BastiHgH
