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SAG21K GUIDE: A COMPLETE GUIDE TO SAG21K
1 what is sag21k
2 Smoothened receptor
3 What is the HH pathway
4 how can it be used for growth
5 risks and potential side effects
1 ๐พ๐ฏ๐จ๐ป ๐ฐ๐บ ๐บ๐จ๐ฎ21๐ฒ? SAG21K is a synthetic small molecule agonist (a molecule that binds to a receptor, that triggers a biological response) of the Hedgehog signalling pathway. SAG21K is designed to activate the Smoothened (smo) receptor. The โSAGโ stands for Smoothened agonist, while the โ21Kโ labels the brain-permeable derivative (a chemical that can pass the blood-brain barrier).
The Indian Hedgehog (IHH) pathway controls bone growth and cartilage development, driven by the IHH protein. Research also found that โIHH acts as an essential mediator of mechanotransduction in cartilageโ.
The sonic Hedgehog (SHH) pathway is a cell-signaling system which controls embryonic development and how cells grow. Researchers also found โClosely spaced eyes can indicate holoprosencephaly, a condition linked to the loss of the Shh geneโ.
The Dessert Hedgehog (DHH) pathway is a biological communication system involving the DHH ligand and Patched receptors. Researchers also found โmechanism wherein Desert hedgehog (Dhh), secreted from epithelial neuroendocrine cells, elicits a regenerative/ protective response from mesenchymal cellsโ.
SAG21k could (theoretically) cause bone growth by binding directly to the Smoothened (SMO) receptor, bypassing upstream ligands to activate the canonical Hedgehog (HH) pathway and simulate the effects of Indian Hedgehog (Ihh) and Sonic Hedgehog (Shh) pathways. This stops the degradation of Gli1 and Gli2 transcription factors. Then initiating two-phases: first, inducing chondrogenesis by upregulating Sox9 and Collagen II to create a cartilaginous callus scaffold; second, Inducing ossification by promoting chondrocyte hypertrophy, vascular invasion, osteoblast differentiation, and Alkaline Phosphatase (ALP) upregulation, leading to mineralization and the replacement of the cartilaginous scaffold with mature bone tissue.
1 what is sag21k
2 Smoothened receptor
3 What is the HH pathway
4 how can it be used for growth
5 risks and potential side effects
Written by
MNR
@MNR
1 ๐พ๐ฏ๐จ๐ป ๐ฐ๐บ ๐บ๐จ๐ฎ21๐ฒ?
2 ๐บ๐ด๐ถ๐ถ๐ป๐ฏ๐ฌ๐ต๐ฌ๐ซ ๐น๐ฌ๐ช๐ฌ๐ท๐ป๐ถ๐น
The smoothened receptor (also called SMO) cell membrane protein that controls the hedgehog signaling pathway. The smoothened receptor in theory could affect height through the Hedgehog signaling pathway, more specifically the Indian Hedgehog, which activates Smoothened through the Hedgehog pathway.3 ๐พ๐ฏ๐จ๐ป ๐ฐ๐บ ๐ป๐ฏ๐ฌ ๐ฏ๐ฏ ๐ท๐จ๐ป๐ฏ๐พ๐จ๐?
There are three different individual Hedgehog pathways.The Indian Hedgehog (IHH) pathway controls bone growth and cartilage development, driven by the IHH protein. Research also found that โIHH acts as an essential mediator of mechanotransduction in cartilageโ.
The sonic Hedgehog (SHH) pathway is a cell-signaling system which controls embryonic development and how cells grow. Researchers also found โClosely spaced eyes can indicate holoprosencephaly, a condition linked to the loss of the Shh geneโ.
The Dessert Hedgehog (DHH) pathway is a biological communication system involving the DHH ligand and Patched receptors. Researchers also found โmechanism wherein Desert hedgehog (Dhh), secreted from epithelial neuroendocrine cells, elicits a regenerative/ protective response from mesenchymal cellsโ.
4 ๐ฏ๐ถ๐พ ๐ช๐จ๐ต ๐บ๐จ๐ฎ21๐ฒ ๐ฉ๐ฌ ๐ผ๐บ๐ฌ๐ซ ๐ญ๐ถ๐น ๐ฎ๐น๐ถ๐พ๐ป๐ฏ
(this is all hypothetical, in reality there is no guarantee that SAG21K will work in this exact order or for height).SAG21k could (theoretically) cause bone growth by binding directly to the Smoothened (SMO) receptor, bypassing upstream ligands to activate the canonical Hedgehog (HH) pathway and simulate the effects of Indian Hedgehog (Ihh) and Sonic Hedgehog (Shh) pathways. This stops the degradation of Gli1 and Gli2 transcription factors. Then initiating two-phases: first, inducing chondrogenesis by upregulating Sox9 and Collagen II to create a cartilaginous callus scaffold; second, Inducing ossification by promoting chondrocyte hypertrophy, vascular invasion, osteoblast differentiation, and Alkaline Phosphatase (ALP) upregulation, leading to mineralization and the replacement of the cartilaginous scaffold with mature bone tissue.
We see here that in mice (murine) who had large femur defects, were given a cycle of 2 compounds (SAG21K and IOX2). It was found that SAG21K activated cartilage-related genes (PTCH1, GLI1, SOX9) in response to the treatment.
5 ๐น๐ฐ๐บ๐ฒ๐บ ๐จ๐ต๐ซ ๐บ๐ฐ๐ซ๐ฌ ๐ฌ๐ญ๐ญ๐ฌ๐ช๐ป๐บ
Potential risks and side effects may include; cancer risks, abnormal formation of bone, effects on the nervous system, and potentially developmental problems.