Metabolic

THR-123

Also known as: BMP-7 Mimetic Peptide, ALK3 Agonist THR-123, Cyclized BMP-7 Peptide

Preclinical
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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
Also Known As
BMP-7 Mimetic Peptide, ALK3 Agonist THR-123, Cyclized BMP-7 Peptide

Mechanism of Action

BMP7 is a natural kidney-protective signal, and TGF-beta is the master driver of scarring (fibrosis) - the two roughly oppose each other. THR-123 is cyclized via a disulfide bond between its first and eleventh residues to hold a 3D shape resembling the finger-2 loop of BMP7, which lets it bind the BMP receptor ALK3 (and weakly ALK2, but not ALK6). When THR-123 activates ALK3, it triggers Smad1/5 signaling, which in the published mouse work suppressed inflammation, cell death (apoptosis), and the epithelial-to-mesenchymal transition that turns kidney tubule cells into scar-producing cells. The proposed payoff is that nudging this pathway can both block new scarring and let damaged tubules regenerate, but that mechanism is established in rodents, not validated in humans.

Research Summary

The core evidence comes from Sugimoto and colleagues in Nature Medicine (2012), from Raghu Kalluri's group, which identified ALK3 as a key co-receptor for BMP7 and reported that orally administered THR-123 localized to the kidney cortex within hours and reversed established fibrosis across five mouse models, including ischemia-reperfusion injury, unilateral ureteral obstruction, nephrotoxic nephritis, Alport (Col4a3 knockout) mice, and streptozotocin diabetic nephropathy. Combining THR-123 with an ACE inhibitor (captopril) added benefit in the diabetic model, hinting at complementary mechanisms. More recently a 2025 Nature Communications paper reported the ALK3 agonist THR-123 promoting pancreatic beta-cell regeneration, extending interest beyond the kidney. The crucial honesty point: there are no published human clinical trials of THR-123 itself - all efficacy data are animal-only. The related intravenous compound THR-184 was studied in a multicenter Phase 2 trial for acute kidney injury around cardiac surgery (completed around 2015), but the program did not lead to an approved drug. So THR-123 is a scientifically interesting proof of concept, not a validated therapy.

Trial Progress:Phase II
Pre
I
II
III
IV
FDA

Dosing Information

Animal Studies·Multiple preclinical studies including foundational 2012 Nature Medicine paper and 2025 Nature Communications paper; no human trials

Note: Animal study doses may not translate directly to humans.

Typical Dosing

Community experience

Common Dose

2-5 mg orally per day (community starter, extrapolated from animal data)

Range

2-10 mg per day, oral

Frequency

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.

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

Research This Peptide Further

Frequently Asked Questions

What does THR-123 do?

THR-123 is a small synthetic 16-residue cyclic peptide designed to mimic part of the protein BMP7 (bone morphogenetic protein 7) and switch on its receptor, ALK3, in the kidney. It was developed by Thrasos Therapeutics and made famous by a 2012 Nature Medicine paper showing that, taken orally, it could reverse kidney fibrosis and trigger kidney regeneration in mice. It is a preclinical research compound with no human trials of its own, though its intravenous sibling THR-184 reached Phase 2 for acute kidney injury.

How does THR-123 work?

BMP7 is a natural kidney-protective signal, and TGF-beta is the master driver of scarring (fibrosis) - the two roughly oppose each other. THR-123 is cyclized via a disulfide bond between its first and eleventh residues to hold a 3D shape resembling the finger-2 loop of BMP7, which lets it bind the BMP receptor ALK3 (and weakly ALK2, but not ALK6). When THR-123 activates ALK3, it triggers Smad1/5 signaling, which in the published mouse work suppressed inflammation, cell death (apoptosis), and the epithelial-to-mesenchymal transition that turns kidney tubule cells into scar-producing cells. The proposed payoff is that nudging this pathway can both block new scarring and let damaged tubules regenerate, but that mechanism is established in rodents, not validated in humans.

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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Bioregulators

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