FreakyLoser
Huh
- Joined
- Aug 10, 2026
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I decided to right this randomly while revising someone elses take on AKT upregulation for increased FAH. Their take was hot garbage but after looking into it myself I saw the general concept did actually have quite a bit of potential, so here is everything I found.
Upregulate AKT through inhibiting PTEN.
Increase AKT signaling through PI3K-mediated conversion of PIP2 to PIP3, which promotes AKT recruitment and activation.
TSC1/TSC2 works as a break on Rheb-GTP which lowers mTORC1. AKT phosphorylates TSC2 and inhibits the TSC complex. AKT phosphorylates TSC2 and inhibits the TSC complex, in turn, upregulating mTORC1.
-AKT upregulates mTORC1 which activates S6K1 which promotes various aspects of translation and ribosome function, in turn, upregulating protein synthesis as well.
AKT phosphorylates members of the FOXO transcription-factor family. When FOXO is active in the nucleus, it can promote expression of genes involved in things like stress resistance, cell-cycle inhibition, and apoptosis. AKT phosphorylation causes FOXO to associate with 14-3-3 proteins and move out of the nucleus, reducing its transcriptional activity, in turn putting the cells in a pro-survival state.
AKT is an important downstream mediator of insulin signaling and promotes glucose uptake, which can be helpful to have alongside things like Retatrutide, Berberine, or Metformin while on high doses of exogenous hGH.
Chronic pharmacologic or genetic activation of the PI3K/AKT/mTOR axis can promote cellular growth and survival and may increase oncogenic risk, particularly when tumor-suppressive restraints such as PTEN or TSC signaling are impaired.
We may be able to use things like FOXO4-DRI or PNC-27 to defend ourself from the possible increased cancer risks that come from removing the breaks on these growth pathways possibly feeding additional growth to not just good cells, but also bad and cancerous cells.
-FOXO4-DRI leads to FOXO4/p53 interaction disruptuon, upregulated p53 activity, apoptosis of susceptible senescent cells. You can think of FOXO4-DRI as taking a different route to counteract some of the consequences of reduced FOXO activity from upregulated AKT, instead of restoring FOXO transcriptional activity, it disrupts FOXO4–p53 binding and promote the clearance of susceptible senescent cells. Which should hypothetically help reduce cancer risk. FOXO4-DRI can be helpful for increasing FAH aswell since it causes the removal of certain senescent cells, which creates a healthier growth-plate environment, better preservation of growth-plate function, potentially more longitudinal growth.
-PNC-27 binds MDM2 associated with cancer-cell membranes, activates membrane pore formation, increases membrane disruption, increases necrotic cell death. MDM2 normally binds p53 and regulates its stability, including promoting p53 degradation, which can also be helpful for the goal of increasing FAH despite the fact that I just said that upregulated p53 activity is good. Well, P53 is a protein expressed in chondrocytes activated by cellular stress signals. Initially, P53 is partially activated in response to cellular stress and induces cell cycle arrest through downstream effectors to repair DNA damage. However, severe damage results in sustained activation which either caused chondrocyte senescence or activates pro-apoptotic genes and proteins to induce apoptosis. This results in many negative effects to the growth plates. When P53 was deleted in mice, chondrocyte proliferation and proliferation zone size increased significantly. So the side effect of promoting p53 degradation can also be a beneficial way to increase FAH.
Finally, compounds and medications we can use to increase AKT.
-SC79, it is a small-molecule AKT activator. It binds the PH domain of AKT and promotes its phosphorylation/activation. Interestingly, it can activate AKT even though it interferes with AKT's normal membrane translocation.
-Insulin, exogenous hGH, and GHS activate its receptor and can stimulate the PI3K→PIP3→AKT pathway.
-bpV(phen), bpV(pic), bpV(HOpic) are all extremely potent PTEN inhibitors, but they are not very PTEN specific and also inhibit other phosphatases.
-VO-OHpic and SF1670 have both been used to inhibit PTEN in different ways, but VO-OHpic is much much more potent and extremely selective, while SF1670 is reversable and less potent, but it attacks PTEN at the very base. Both of these compounds end up also upregulating the following growth pathways; JAK/STAT, TIE2→ERK/AKT, and ERK/MAPK very strongly. JAK/STAT is a major intracellular pathway for growth hormone signaling. While ERK/MAPK is one of the major cellular signaling systems controlling cell proliferation, differentiation, migration, gene expression, and developmental responses to growth factors. And TIE2→ERK/AKT is in charge of regulating blood-vessel development and stability, endothelial-cell survival, vascular remodeling, PI3K/AKT signaling, and ERK/MAPK signaling. All synergising EXTREMELY well for the ultimate goal of this theory and its main components.
-740Y-P is the clearest commonly used compound to increase PI3K. It is a cell-permeable phosphopeptide that binds the SH2 domain of the p85 regulatory subunit of PI3K, this promotes PI3K activity. Consequently, it increases PIP3 → AKT phosphorylation. It is widely used as a PI3K/AKT pathway activator in cell and animal research.
In conclusion, I'd personally say that using this general theory of upregulating AKT through inhibiting PTEN and upregulating PI3K and upregulating the non-intentional growth pathways from these compounds is an extremely synergenic concept that could definitely work, just not as well as other things and this whole theory would fit more in a place of an additional stack to add onto an already large heightmaxxing stack if you have plently of money to through around. And of course none of this is legitimate medical advice, talk to your doctor before doing anything. Dnr dnr dnr.
So for this theory in specific if you'd like to ever attempt this I'd say the most likely bet is to use 740Y-P, VO-OHpic, SF1670, SC79, PNC27, and some other compound that helps inhibit p53. But if you'd like to go down the more cancer-safe route I'd recommend taking out the p53 inhibiting compound and adding in FOXO4-DRI.
Upregulate AKT through inhibiting PTEN.
Increase AKT signaling through PI3K-mediated conversion of PIP2 to PIP3, which promotes AKT recruitment and activation.
TSC1/TSC2 works as a break on Rheb-GTP which lowers mTORC1. AKT phosphorylates TSC2 and inhibits the TSC complex. AKT phosphorylates TSC2 and inhibits the TSC complex, in turn, upregulating mTORC1.
mTORC1 activates 4E-BP1 and S6K1.
-AKT upregulates mTORC1 which activates 4E-BP1 phosphorylation, 4E-BP1 lets go of eIF4E which initiates translating, in turn, upregulating protein synthesis. -AKT upregulates mTORC1 which activates S6K1 which promotes various aspects of translation and ribosome function, in turn, upregulating protein synthesis as well.
AKT phosphorylates members of the FOXO transcription-factor family. When FOXO is active in the nucleus, it can promote expression of genes involved in things like stress resistance, cell-cycle inhibition, and apoptosis. AKT phosphorylation causes FOXO to associate with 14-3-3 proteins and move out of the nucleus, reducing its transcriptional activity, in turn putting the cells in a pro-survival state.
AKT is an important downstream mediator of insulin signaling and promotes glucose uptake, which can be helpful to have alongside things like Retatrutide, Berberine, or Metformin while on high doses of exogenous hGH.
Chronic pharmacologic or genetic activation of the PI3K/AKT/mTOR axis can promote cellular growth and survival and may increase oncogenic risk, particularly when tumor-suppressive restraints such as PTEN or TSC signaling are impaired.
We may be able to use things like FOXO4-DRI or PNC-27 to defend ourself from the possible increased cancer risks that come from removing the breaks on these growth pathways possibly feeding additional growth to not just good cells, but also bad and cancerous cells.
-FOXO4-DRI leads to FOXO4/p53 interaction disruptuon, upregulated p53 activity, apoptosis of susceptible senescent cells. You can think of FOXO4-DRI as taking a different route to counteract some of the consequences of reduced FOXO activity from upregulated AKT, instead of restoring FOXO transcriptional activity, it disrupts FOXO4–p53 binding and promote the clearance of susceptible senescent cells. Which should hypothetically help reduce cancer risk. FOXO4-DRI can be helpful for increasing FAH aswell since it causes the removal of certain senescent cells, which creates a healthier growth-plate environment, better preservation of growth-plate function, potentially more longitudinal growth.
-PNC-27 binds MDM2 associated with cancer-cell membranes, activates membrane pore formation, increases membrane disruption, increases necrotic cell death. MDM2 normally binds p53 and regulates its stability, including promoting p53 degradation, which can also be helpful for the goal of increasing FAH despite the fact that I just said that upregulated p53 activity is good. Well, P53 is a protein expressed in chondrocytes activated by cellular stress signals. Initially, P53 is partially activated in response to cellular stress and induces cell cycle arrest through downstream effectors to repair DNA damage. However, severe damage results in sustained activation which either caused chondrocyte senescence or activates pro-apoptotic genes and proteins to induce apoptosis. This results in many negative effects to the growth plates. When P53 was deleted in mice, chondrocyte proliferation and proliferation zone size increased significantly. So the side effect of promoting p53 degradation can also be a beneficial way to increase FAH.
Finally, compounds and medications we can use to increase AKT.
-SC79, it is a small-molecule AKT activator. It binds the PH domain of AKT and promotes its phosphorylation/activation. Interestingly, it can activate AKT even though it interferes with AKT's normal membrane translocation.
-Insulin, exogenous hGH, and GHS activate its receptor and can stimulate the PI3K→PIP3→AKT pathway.
-bpV(phen), bpV(pic), bpV(HOpic) are all extremely potent PTEN inhibitors, but they are not very PTEN specific and also inhibit other phosphatases.
-VO-OHpic and SF1670 have both been used to inhibit PTEN in different ways, but VO-OHpic is much much more potent and extremely selective, while SF1670 is reversable and less potent, but it attacks PTEN at the very base. Both of these compounds end up also upregulating the following growth pathways; JAK/STAT, TIE2→ERK/AKT, and ERK/MAPK very strongly. JAK/STAT is a major intracellular pathway for growth hormone signaling. While ERK/MAPK is one of the major cellular signaling systems controlling cell proliferation, differentiation, migration, gene expression, and developmental responses to growth factors. And TIE2→ERK/AKT is in charge of regulating blood-vessel development and stability, endothelial-cell survival, vascular remodeling, PI3K/AKT signaling, and ERK/MAPK signaling. All synergising EXTREMELY well for the ultimate goal of this theory and its main components.
-740Y-P is the clearest commonly used compound to increase PI3K. It is a cell-permeable phosphopeptide that binds the SH2 domain of the p85 regulatory subunit of PI3K, this promotes PI3K activity. Consequently, it increases PIP3 → AKT phosphorylation. It is widely used as a PI3K/AKT pathway activator in cell and animal research.
In conclusion, I'd personally say that using this general theory of upregulating AKT through inhibiting PTEN and upregulating PI3K and upregulating the non-intentional growth pathways from these compounds is an extremely synergenic concept that could definitely work, just not as well as other things and this whole theory would fit more in a place of an additional stack to add onto an already large heightmaxxing stack if you have plently of money to through around. And of course none of this is legitimate medical advice, talk to your doctor before doing anything. Dnr dnr dnr.
So for this theory in specific if you'd like to ever attempt this I'd say the most likely bet is to use 740Y-P, VO-OHpic, SF1670, SC79, PNC27, and some other compound that helps inhibit p53. But if you'd like to go down the more cancer-safe route I'd recommend taking out the p53 inhibiting compound and adding in FOXO4-DRI.
