PT150 (Org 34517)

Mechanism of action#

Competitive antagonist of the glucocorticoid receptor (GR, NR3C1), a ligand-activated nuclear receptor. In AtT20 pituitary cells Org 34517 blocked corticosterone-induced GR nuclear translocation without inducing translocation itself (unlike mifepristone), and was described as a true competitive GR antagonist without partial agonist activity. In rats it occupied GR in the anterior pituitary and brain without occupying the mineralocorticoid receptor, and did not cause episodic HPA-axis activation on chronic dosing. The current sponsor describes PT150 as a modulator of both GR and the androgen receptor (AR): predominantly systemic GR antagonism in vivo, with direct AR down-regulation and minor GR agonism at the cellular level. In patients with psychotic depression it produced a dose-dependent rise in salivary cortisol, consistent with central GR blockade. The clinical hypothesis in PTSD and alcohol use disorder is that blocking GR signalling normalizes stress (HPA-axis) responses that drive symptoms, craving and stress-induced drinking.

Formulations#

PT150 (Org 34517) for Post-traumatic stress disorder#

Phase 2ActivePost-traumatic stress disorder indication →

PT150, an oral glucocorticoid receptor antagonist, for post-traumatic stress disorder in U.S. veterans. On 2026-02-19 Pop Test Oncology (dba Palisades Therapeutics) announced that the FDA had granted permission to proceed with a Phase 2a trial, 'Efficacy and Safety of PT150 in U.S. Veterans with Post Traumatic Stress Disorder (PTSD)': a dual-site, double-blind, placebo-controlled study funded by the Department of Defense Congressionally Directed Medical Research Programs, enrolling 120 veterans at VA medical centers in San Diego and Houston, with a primary endpoint of change in PTSD symptoms from baseline to 4 weeks post-treatment. The registered study (NCT07187011, sponsored by San Diego Veterans Healthcare System) titrates PT150 150-900 mg over 7 days against placebo. As of its last registry update (2025-12-23) it was not yet recruiting, with an estimated start of April 2026 and estimated primary completion in March 2029. This is PT150's most advanced active indication.

PT150 (Org 34517) for Major depressive disorder#

DiscontinuedDiscontinuedMajor depressive disorder indication →

Org 34517 (now PT150), a glucocorticoid receptor antagonist, as adjunctive treatment for psychotic major depression, developed by Organon N.V. In the Phase 2 dose-finding trial (Protocol 28130, October 2004 to July 2006; 274 patients dosed in Belgium, Czech Republic, Germany, India, the UK and the US), 300 mg or 900 mg once daily for 2 weeks on top of usual treatment failed to beat placebo on the primary endpoint of sustained 50% response on the PANSS positive scale (900 mg vs placebo p=0.14), and missed the key secondary HAMD-17 and 300 mg comparisons. The 900 mg dose was numerically better than placebo on PANSS total and positive scores, reaching significance only at some visits. It was well tolerated and raised salivary cortisol dose-dependently. A Phase 2 re-exposure safety study (28133) and a Weill Cornell Phase 2 safety study also completed by 2006. No later depression trial has been registered, and the molecule's current developer is pursuing PTSD and alcohol use disorder instead.

PT150 (Org 34517) for Alcohol use disorder#

Phase 1ActiveAlcohol use disorder indication →

PT150, an oral glucocorticoid receptor antagonist, for alcohol use disorder, on the hypothesis that blocking stress-hormone (GR) signalling reduces stress-induced drinking and the behavioural effects of alcohol. Clinical work so far is Phase 1. Two ethanol-interaction studies in healthy, alcohol-experienced volunteers at the Michael E. DeBakey VA Medical Center (NCT03548714, completed 2019; NCT04331288, completed 2023) found no significant pharmacokinetic interaction between PT150 900 mg/day and ethanol in either direction, and no serious adverse events or clinically significant ECG abnormalities (J Addict Med 2025). A Phase 1 human laboratory study in people with AUD (NCT06712602), started February 2025 and recruiting, tests 225 mg and 450 mg twice daily before alcohol-administration and cold-pressor stress sessions. Estimated primary completion is July 2028.

Clinical trials#