https://share.google/E8cxRzoSKU3evgmNM
https://share.google/FhE2LNiYpt5iUFls8
From Gemini:
What is the name of the small molecule inhibitor of PDGH that has passed a phase 1 clinical trial for the treatment of muscle weakness?
The small molecule inhibitor of 15-PGDH (15-hydroxyprostaglandin dehydrogenase) that has successfully passed Phase 1 clinical trials for treating muscle weakness is MF-300.
Developed by Epirium Bio, MF-300 is designed to treat sarcopenia (age-related muscle wasting and weakness) and potentially other neuromuscular diseases. In September 2025, the company announced positive results from its Phase 1 trial in healthy volunteers, confirming the drug’s safety, tolerability, and “proof of mechanism.”
Key Details of MF-300
- Mechanism of Action: MF-300 reversibly inhibits the 15-PGDH enzyme. This enzyme is responsible for breaking down Prostaglandin E2 (PGE2), a molecule essential for muscle repair and mitochondrial function. By blocking the enzyme, MF-300 increases PGE2 levels in the muscle.
- The “Gerozyme” Connection: 15-PGDH is often referred to as a “gerozyme” because its levels increase as people age, leading to a depletion of PGE2 and subsequent muscle atrophy.
- Clinical Findings: * Phase 1 Success: The trial showed that MF-300 was safe for human use and demonstrated significant target engagement (measured via increased urinary PGE2 and decreased metabolites).
- Preclinical Promise: In mice, inhibiting 15-PGDH not only prevented muscle loss but actually increased muscle mass, strength, and exercise endurance in aged subjects.
Other Notable Inhibitors
While MF-300 is the lead candidate in clinical trials, you may also encounter the following in scientific literature:
- Preclinical Promise: In mice, inhibiting 15-PGDH not only prevented muscle loss but actually increased muscle mass, strength, and exercise endurance in aged subjects.
- SW033291: A highly potent small molecule inhibitor used extensively in preclinical research (developed by the same team that identified 15-PGDH as a target). It served as the chemical “parent” or proof-of-concept molecule that led to the development of clinical-grade versions like MF-300.
- Swiss-15-PGDH: Another nomenclature sometimes used for optimized versions of these inhibitors.
Would you like more information on the specific Phase 1 data or how this treatment differs from current exercise-based approaches for sarcopenia?