THR-123
Also known as: BMP-7 Mimetic Peptide, ALK3 Agonist THR-123, Cyclized BMP-7 Peptide
Key Facts: THR-123
- Category
- Metabolic
- FDA Status
- Not FDA Approved
- Clinical Status
- Preclinical - Animal studies only. Structural analog THR-184 in Phase 2 for cardiac surgery-associated AKI
- Administration
- Oral (cyclized peptide is GI-stable, which is unusual for a peptide). Some animal studies use intraperitoneal injection.
- Typical Dose
- 2-5 mg orally per day (community starter, extrapolated from animal data)
- Frequency
- Once daily
- Duration
- 2-8 weeks in animal model studies; community protocols mirror this with 4-8 week cycles
Mechanism of Action
THR-123 is a cyclized peptide derived from BMP-7 that selectively binds and activates ALK3 (also called BMPR1A), a BMP type I receptor. ALK3 activation triggers SMAD-mediated signaling that suppresses inflammation, apoptosis, and the epithelial-to-mesenchymal transition (EMT) that drives organ fibrosis. Unlike full-length BMP-7, THR-123 does not induce osteogenic activity, sidestepping one of the main translational challenges of BMP-7 therapy. In the pancreas, THR-123 reactivates dormant progenitor cells residing in the pancreatic ducts and induces nongenetic conversion of pancreatic exocrine cells into functional, glucose-responsive insulin-producing endocrine cells. The peptide is small and stable enough to remain active when given orally, which is uncommon for peptide therapeutics.
Research Summary
Foundational publication: Sugimoto et al, Nature Medicine 2012 demonstrated that oral THR-123 reverses established kidney fibrosis in mouse models of acute and chronic renal injury, with restoration of normal kidney function and no osteogenic side effects. Subsequent work characterized the ALK3-dependent mechanism and downstream SMAD pathway. Diabetes Research Institute (University of Miami) published in Nature Communications, July 2025: THR-123 induced nongenetic conversion of human pancreatic exocrine cells into insulin-expressing functional endocrine cells in vitro, with rapid reversal of diabetes in animal models in vivo. A structural analog, THR-184, has progressed to Phase 2 clinical trials for cardiac surgery-associated acute kidney injury, providing some early human safety signal for the molecular family, though THR-184 is a distinct molecule. No human trials for THR-123 itself in any indication as of 2026.
Dosing Information
Note: Animal study doses may not translate directly to humans.
Typical Dosingⓘ
Community experience
2-5 mg orally per day (community starter, extrapolated from animal data)
2-10 mg per day, oral
Once daily
There are no human clinical trials for THR-123. Community-reported ranges so far are extrapolated from the mouse data (0.5-2 mg/kg orally daily, Nature Medicine 2012 + Nature Communications 2025) using standard FDA allometric scaling (mouse to human: divide mg/kg by 12.3). For a 70 kg adult that lands at roughly 2-10 mg orally per day. The handful of community protocols circulating start at the low end (2-5 mg/day) and titrate based on tolerance. THR-123 is unusual in that it is genuinely orally bioavailable thanks to its cyclized structure, so injection is not necessary. Cycles typically run 4-8 weeks, matching the animal model durations.
Research Dosingⓘ
Scientific studies
All published dosing is preclinical (mouse). The community-extrapolated human range below is based on standard FDA allometric scaling from mouse to human (divide mg/kg by 12.3), not on any human clinical trial.
Doses from Studies
0.5-2 mg/kg orally daily (mouse)
Pancreatic regeneration mouse protocol
Duration
2-8 weeks in animal model studies; community protocols mirror this with 4-8 week cycles
Administration
Oral (cyclized peptide is GI-stable, which is unusual for a peptide). Some animal studies use intraperitoneal injection.
Timing & Administration
Best Time to Take
Morning, on an empty stomach (preclinical protocols)
Once daily in most animal model studies
Food Recommendation
With or without food
Why This Timing?
Oral peptides typically have better absorption on an empty stomach. Animal model protocols dosed in the morning to align with natural circadian regenerative cycles.
Possible Side Effects
Not everyone experiences these effects. Individual responses vary based on dosage, duration, and personal factors.
- ●No human safety data exists
- ●No osteogenic side effects observed in animal studies (unlike full-length BMP-7)
- ●Long-term safety profile unknown
- ●BMP signaling has broad tissue effects; off-target signaling possible at higher doses
- ●Research chemical quality and purity vary widely between suppliers
- ●Not FDA approved for any indication
References
- https://pubmed.ncbi.nlm.nih.gov/22426421/
- https://pubmed.ncbi.nlm.nih.gov/35873578/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC6748948/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC5031890/
- https://diabetesresearch.org/regenerating-the-pancreas-dri-scientists-demonstrate-diabetes-reversal-in-preclinical-model-using-small-peptide/
Research This Peptide Further
Frequently Asked Questions
What does THR-123 do?
An orally administered cyclized small peptide that mimics bone morphogenetic protein 7 (BMP-7) signaling through the ALK3 receptor. Originally developed for kidney fibrosis where it reversed established fibrosis in animal models. A 2025 Nature Communications study from the Diabetes Research Institute showed THR-123 regenerated insulin-producing pancreatic beta cells and reversed diabetes in preclinical models. No human clinical trials yet.
How does THR-123 work?
THR-123 is a cyclized peptide derived from BMP-7 that selectively binds and activates ALK3 (also called BMPR1A), a BMP type I receptor. ALK3 activation triggers SMAD-mediated signaling that suppresses inflammation, apoptosis, and the epithelial-to-mesenchymal transition (EMT) that drives organ fibrosis. Unlike full-length BMP-7, THR-123 does not induce osteogenic activity, sidestepping one of the main translational challenges of BMP-7 therapy. In the pancreas, THR-123 reactivates dormant progenitor cells residing in the pancreatic ducts and induces nongenetic conversion of pancreatic exocrine cells into functional, glucose-responsive insulin-producing endocrine cells. The peptide is small and stable enough to remain active when given orally, which is uncommon for peptide therapeutics.
Is THR-123 FDA approved?
No, THR-123 is not currently FDA approved. Current status: Preclinical - Animal studies only. Structural analog THR-184 in Phase 2 for cardiac surgery-associated AKI
What are the side effects of THR-123?
Reported side effects include: No human safety data exists, No osteogenic side effects observed in animal studies (unlike full-length BMP-7), Long-term safety profile unknown, BMP signaling has broad tissue effects; off-target signaling possible at higher doses, Research chemical quality and purity vary widely between suppliers. Individual responses vary based on dosage, duration, and personal health factors.
What is the typical dose of THR-123?
Community-reported common dose: 2-5 mg orally per day (community starter, extrapolated from animal data) (Once daily). Range: 2-10 mg per day, oral. Administration: Oral (cyclized peptide is GI-stable, which is unusual for a peptide). Some animal studies use intraperitoneal injection.. Extrapolated from animal data, NOT validated by human clinical trials. The structural analog THR-184 is in Phase 2 for cardiac surgery acute kidney injury but is a different molecule. Use of THR-123 in humans has no clinical evidence base. Not FDA approved. For research use only.
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