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Org 34517 targeted a different piece of the depression puzzle entirely, the glucocorticoid receptor, on the theory that chronically elevated cortisol signaling drives depressive symptoms, especially in psychotic and melancholic depression where HPA-axis dysregulation is most pronounced. Organon (later folded into Merck/Schering-Plough) took it into Phase III, and an early paroxetine-controlled trial in 142 patients showed comparable antidepressant effects with a notable edge in patients who ran hypercortisolaemic. Despite that promising signal, the program stalled inside the corporate mergers that consumed Organon in the late 2000s, and the compound resurfaced years later, rebranded as PT-150, in the hands of a small biotech pursuing it for entirely different indications. It is one of the clearer cases of a molecule losing momentum not to failed science, but to a failed company.
- significantly reduced HAM-D scores versus baseline in early trials
- comparable antidepressant effect to paroxetine in a controlled trial
- particularly effective signal in hypercortisolaemic (high-cortisol) patients
- Org 34517 was designed as a cleaner alternative to mifepristone (RU-486), the abortion drug that also happens to be a glucocorticoid receptor antagonist studied for psychotic depression.
Mechanism
Selective, competitive at the glucocorticoid receptor (GR) without the partial activity seen in mifepristone (RU-486); designed to normalize HPA-axis hyperactivity and signaling implicated in depression.
Safetyrisks and cautions, not medical advice
Blocking the glucocorticoid receptor does not stop at mood, and the protocols show it. A follow-on safety study at 900 mg excluded anyone who had experienced severe breakthrough bleeding, been diagnosed with prostatitis or shown abnormal testosterone during the earlier trial, and required a normal PSA before re-dosing, which is a plain admission that the hormonal effects were real enough to screen for. A 273-patient study in psychotic depression followed. Later Phase 1 work on the same molecule, renamed PT150 and given at 900 mg daily with and without alcohol, found no clinically significant ECG changes and no serious adverse events.
History
Developed by Organon (N.V. Organon) in the 2000s; a paroxetine-controlled Phase II/III trial in 142 depressed patients showed comparable efficacy, with a particular signal in hypercortisolaemic patients. Development stalled amid Organon's absorption into Schering-Plough and then Merck; the compound later resurfaced as PT-150 under Pop Test Cortisol LLC for unrelated indications.
Subjective profileweighing the evidence above
A promising mechanism that got lost in a corporate merger rather than killed by a failed trial.
Resources
This entry is here for reference.
Research
1 listed here; entry last updated July 2026
Reviews
My notesprivate to this device
FAQ
Why did Org 34517 disappear if it worked in trials?
It did not fail on efficacy; the program lost momentum as Organon was absorbed into Schering-Plough and then Merck through mergers in the late 2000s.
Is Org 34517 still being developed?
A version of it resurfaced as PT-150 under a different company, but for indications outside its original antidepressant use.
Notes and cautions
- reduced HPA-axis and ethanol-withdrawal severity in preclinical models, suggesting a favorable stress-reactivity profile
- no major published human safety signal from the completed trial