Mechanism and Growth Plate
MIV-711 is a potent, highly selective inhibitor of cathepsin K (CTSK), the primary lysosomal cysteine protease responsible for degrading type I and type II collagen in bone and cartilage. Pathway inhibition: By inhibiting cathepsin K, MIV-711 significantly suppresses osteoclast-mediated bone resorption and breakdown of the extracellular matrix within the growth plate. Impact on chondrogenesis: In the epiphyseal plate, blocking cathepsin K activity slows down the enzymatic degradation of the hypertrophic chondrocyte System. This can theoretically protect cartilage integrity, delay premature growth plate mineralization/senescence, and preserve the active proliferative zone longer for sustained linear elongation.
Dosing
Looking at data from preclinical models and phase 2 clinical trials (such as NCT02558582): Human Trial Dosing: Oral administration in clinical trials evaluated doses of 10 mg to 200 mg daily, with 100 mg to 200 mg daily showing
substantial reductions in bone and cartilage degradation biomarkers.
Animal/Preclinical Dosing: Preclinical rodent and non-human primate studies typically used doses around 1 mg/kg to 10 mg/kg daily, demonstrating strong dose-dependent suppression of collagen degradation products (CTX-I and CTX-II).
Tissue accumulation: MIV-711 features solid oral bioavailability and once-daily dosing kinetics, accumulating effectively in subchondral bone and cartilage tissue.
Theoretical Growth Potential
Assuming open growth plates and sufficient growth hormone / IGF-1 levels, reducing matrix breakdown via targeted cathepsin K inhibition could theoretically preserve the active chondrocyte pool longer, yielding an additional 2 to 3 cm (it depends that's just a spculation )of longitudinal growth over an extended cycle.
What do you think about it?
Studies:
PMID: 29743078
PMID: 31887087
PMCID: PMC7265882
NCT02558582
MIV-711 is a potent, highly selective inhibitor of cathepsin K (CTSK), the primary lysosomal cysteine protease responsible for degrading type I and type II collagen in bone and cartilage. Pathway inhibition: By inhibiting cathepsin K, MIV-711 significantly suppresses osteoclast-mediated bone resorption and breakdown of the extracellular matrix within the growth plate. Impact on chondrogenesis: In the epiphyseal plate, blocking cathepsin K activity slows down the enzymatic degradation of the hypertrophic chondrocyte System. This can theoretically protect cartilage integrity, delay premature growth plate mineralization/senescence, and preserve the active proliferative zone longer for sustained linear elongation.
Dosing
Looking at data from preclinical models and phase 2 clinical trials (such as NCT02558582): Human Trial Dosing: Oral administration in clinical trials evaluated doses of 10 mg to 200 mg daily, with 100 mg to 200 mg daily showing
substantial reductions in bone and cartilage degradation biomarkers.
Animal/Preclinical Dosing: Preclinical rodent and non-human primate studies typically used doses around 1 mg/kg to 10 mg/kg daily, demonstrating strong dose-dependent suppression of collagen degradation products (CTX-I and CTX-II).
Tissue accumulation: MIV-711 features solid oral bioavailability and once-daily dosing kinetics, accumulating effectively in subchondral bone and cartilage tissue.
Theoretical Growth Potential
Assuming open growth plates and sufficient growth hormone / IGF-1 levels, reducing matrix breakdown via targeted cathepsin K inhibition could theoretically preserve the active chondrocyte pool longer, yielding an additional 2 to 3 cm (it depends that's just a spculation )of longitudinal growth over an extended cycle.
What do you think about it?
Studies:
PMID: 29743078
PMID: 31887087
PMCID: PMC7265882
NCT02558582