CORT108297 / Corcept Therap - LARVOL DELTA

Trial of CORT108297 to Attenuate the Effects of Acute Stress in the Allocortex (CORT-X) (clinicaltrials.gov) - P2 | N=52 | Recruiting | Sponsor: Johns Hopkins University | Trial primary completion date: Jun 2025 ➔ Jun 2026

Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • APOE

Phase IIa Trial of a Selective Glucocorticoid Receptor Antagonist in the Treatment of Veterans With Posttraumatic Stress Disorder (PTSD) (Seven Study) (clinicaltrials.gov) - P2 | N=88 | Recruiting | Sponsor: VA Office of Research and Development | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

Super-enhancer Activates Master Transcription Factor NR3C1 Expression and Promotes 5-FU Resistance in Gastric Cancer. (PubMed, Adv Sci (Weinh)) - "Poor response to 5-fluorouracil (5-FU) remains an obstacle in the treatment of gastric cancer (GC)...JQ1 and Cort108297 both improve 5-FU efficacy in PDOs and patient-derived xenografts (PDXs) by destroying SEs or inhibiting NR3C1. In conclusion, SE-driven NR3C1 promotes 5-FU resistance in GC. SE destruction and NR3C1 inhibition lead to enhancer reconstruction and reduce 5-FU-related gene transcription, providing alternative therapeutic strategies for improving 5-FU sensitivity."

Journal • Gastric Cancer • Oncology • Solid Tumor • NR3C1

Phase IIa Trial of a Selective Glucocorticoid Receptor Antagonist in the Treatment of Veterans With Posttraumatic Stress Disorder (PTSD) (Seven Study) (clinicaltrials.gov) - P2 | N=88 | Recruiting | Sponsor: VA Office of Research and Development | Phase classification: P2a ➔ P2

Phase classification • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

Trial of CORT108297 to Attenuate the Effects of Acute Stress in the Allocortex (CORT-X) (clinicaltrials.gov) - P2 | N=52 | Recruiting | Sponsor: Johns Hopkins University | Trial completion date: Jan 2024 ➔ Jan 2027 | Trial primary completion date: Jun 2023 ➔ Jun 2025

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • APOE

Glucocorticoid Receptor and β-Catenin Interact in Prostate Cancer Cells and Their Co-Inhibition Attenuates Tumorsphere Formation, Stemness, and Docetaxel Resistance. (PubMed, Int J Mol Sci) - "As expected, we observed that treatment with the glucocorticoid dexamethasone promotednuclear accumulation of GR and active β-catenin in PCa cells...Pharmacological co-inhibition of GR and β-catenin, using the GR modulator CORT-108297 and the selective β-catenin inhibitor MSAB, enhanced cytotoxicity in DTX-resistant PCa cells grown in adherent and spheroid cultures and decreased CD44+/CD24- cell populations in tumorspheres. These results indicate that GR and β-catenin influence cell survival, stemness, and tumorsphere formation in DTX-resistant cells. Their co-inhibition could be a promising therapeutic strategy to overcome PCa therapy cross-resistance."

Journal • Genito-urinary Cancer • Immune Modulation • Oncology • Prostate Cancer • Solid Tumor • CD24 • CTNNB1

Psychological stress induces an increase in cholinergic enteric neuromuscular pathways mediated by glucocorticoid receptors. (PubMed, Front Neurosci) - "Finally, we showed that a GR-specific antagonist (CORT108297) prevented the increase of acetylcholine colonic tissue level and in vivo colonic motility. Our study suggests that RASt-induced functional changes in motility are, at least partly, due to a GR-dependent enhanced cholinergic component in the ENS."

Journal • Gastrointestinal Disorder • NR3C1

Phase IIa Trial of a Selective Glucocorticoid Receptor Antagonist in the Treatment of Veterans With Posttraumatic Stress Disorder (PTSD) (clinicaltrials.gov) - P2a | N=88 | Recruiting | Sponsor: VA Office of Research and Development | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

Application of a pharmacological transcriptome filter identifies a shortlist of mouse glucocorticoid receptor target genes associated with memory consolidation. (PubMed, Neuropharmacology) - "Therefore, we utilized in an explorative study the properties of selective GR modulators (CORT108297 and CORT118335), alongside the endogenous agonist corticosterone and the classical GR antagonist RU486, to pinpoint GR-dependent transcriptional changes. This identified a manageable shortlist of eight genes by which glucocorticoids may modulate memory consolidation, warranting in-depth follow-up. Overall, we showcase the strength of the concept of pharmacological transcriptome filtering, which can be readily applied to other research topics with an established role of glucocorticoids."

Journal • Preclinical

Phase IIa Trial of a Selective Glucocorticoid Receptor Antagonist in the Treatment of Veterans With Posttraumatic Stress Disorder (PTSD) (clinicaltrials.gov) - P2a; N=88; Not yet recruiting; Sponsor: VA Office of Research and Development; Trial completion date: Dec 2023 ➔ Dec 2024; Trial primary completion date: Dec 2023 ➔ Dec 2024

Trial completion date • Trial primary completion date • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

Trial of CORT108297 to Attenuate the Effects of Acute Stress in the Allocortex (CORT-X) (clinicaltrials.gov) - P2; N=52; Recruiting; Sponsor: Johns Hopkins University; Trial completion date: Jun 2024 ➔ Jan 2024; Trial primary completion date: Feb 2023 ➔ Jun 2023

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • APOE

The glucocorticoid receptor specific modulator CORT108297 reduces brain pathology following status epilepticus. (PubMed, Exp Neurol) - "Results demonstrate that baseline corticosterone levels can be normalized with C108297, and implicate glucocorticoid signaling in the development of structural changes following status epilepticus. These findings support the further development of glucocorticoid receptor modulators as novel therapeutics for the prevention of brain pathology following status epilepticus."

Journal • CNS Disorders • Epilepsy

Trial of CORT108297 to Attenuate the Effects of Acute Stress in the Allocortex (CORT-X) (clinicaltrials.gov) - P2; N=52; Recruiting; Sponsor: Johns Hopkins University; Trial completion date: Dec 2023 ➔ Jun 2024

Trial completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • APOE

Glucocorticoid receptor modulators decrease alcohol self-administration in male rats. (PubMed, Neuropharmacology) - "The mixed glucocorticoid/progesterone receptor antagonist mifepristone and selective GR antagonist CORT113176 have been shown to selectively reduce alcohol consumption in alcohol-dependent rats...The present study tested the effects of the GR modulators CORT118335, CORT122928, CORT108297, and CORT125134 on alcohol self-administration in nondependent (air-exposed) and alcohol-dependent (alcohol vapor-exposed) adult male rats...The present results support the potential of GR modulators for the development of treatments for AUD. Future studies that characterize genomic and nongenomic effects of these GR modulators will elucidate potential molecular mechanisms that underlie alcohol drinking in alcohol-dependent and nondependent states."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Psychiatry

Phase IIa Trial of a Selective Glucocorticoid Receptor Antagonist in the Treatment of Veterans With Posttraumatic Stress Disorder (PTSD) (clinicaltrials.gov) - P2a; N=88; Not yet recruiting; Sponsor: VA Office of Research and Development; Trial completion date: Mar 2023 ➔ Dec 2023; Initiation date: Jan 2021 ➔ Sep 2021; Trial primary completion date: Mar 2023 ➔ Dec 2023

Trial completion date • Trial initiation date • Trial primary completion date • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

Trial of CORT108297 to Attenuate the Effects of Acute Stress in the Allocortex (CORT-X) (clinicaltrials.gov) - P2; N=52; Recruiting; Sponsor: Johns Hopkins University; Trial completion date: Jul 2023 ➔ Dec 2023; Initiation date: Nov 2020 ➔ Feb 2021; Trial primary completion date: Jul 2022 ➔ Dec 2022

Trial completion date • Trial initiation date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Trial of CORT108297 to Attenuate the Effects of Acute Stress in the Allocortex (CORT-X) (clinicaltrials.gov) - P2; N=52; Recruiting; Sponsor: Johns Hopkins University

New P2 trial • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Phase IIa Trial of a Selective Glucocorticoid Receptor Antagonist in the Treatment of Veterans With Posttraumatic Stress Disorder (PTSD) (clinicaltrials.gov) - P2a; N=88; Not yet recruiting; Sponsor: VA Office of Research and Development

New P2a trial • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder