Relacorilant
[CAS# 1496510-51-0]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound
• Name: Relacorilant
• Synonyms: [(4aR)-1-(4-fluorophenyl)-6-(1-methylpyrazol-4-yl)sulfonyl-4,5,7,8-tetrahydropyrazolo[3,4-g]isoquinolin-4a-yl]-[4-(trifluoromethyl)pyridin-2-yl]methanone
• Molecular Formula: C₂₇H₂₂F₄N₆O₃S
• Molecular Weight: 586.56
• CAS Registry Number: 1496510-51-0
• SMILES: CN1C=C(C=N1)S(=O)(=O)N2CCC3=CC4=C(C[C@@]3(C2)C(=O)C5=NC=CC(=C5)C(F)(F)F)C=NN4C6=CC=C(C=C6)F

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P280-P301+P312-P302+P352-P305+P351+P338

Discovory and Applicatios

Relacorilant is a selective glucocorticoid receptor modulator (SGRM) developed to address conditions associated with excessive glucocorticoid activity, particularly endogenous Cushing’s syndrome and other disorders linked to cortisol overproduction. Its discovery was driven by the need for a compound that could effectively block the glucocorticoid receptor without the side effects commonly associated with earlier glucocorticoid receptor antagonists.

Relacorilant functions by selectively binding to the glucocorticoid receptor, inhibiting the effects of cortisol while sparing the mineralocorticoid receptor and other steroid hormone receptors. This selective mechanism reduces the likelihood of adverse effects such as hypokalemia, edema, and hypertension, which are often seen with non-selective receptor antagonists.

The clinical development of Relacorilant focused on its potential to improve metabolic and clinical symptoms in patients with Cushing’s syndrome, a condition characterized by chronic exposure to high cortisol levels leading to obesity, diabetes, hypertension, muscle weakness, and osteoporosis. By modulating the glucocorticoid receptor, Relacorilant aims to alleviate these symptoms by blocking the pathological actions of cortisol.

In addition to Cushing’s syndrome, Relacorilant has been investigated for its applications in other diseases involving glucocorticoid dysregulation, including certain cancers and psychiatric disorders, where glucocorticoid receptor modulation may provide therapeutic benefits. The compound’s oral bioavailability and favorable safety profile make it a promising candidate for long-term treatment.

Relacorilant’s discovery and development represent significant advances in selective receptor modulation, offering an alternative to traditional therapies that either broadly suppress cortisol production or non-selectively block glucocorticoid receptors. This selectivity is crucial for minimizing side effects and improving patient outcomes.

Overall, Relacorilant is a selective glucocorticoid receptor modulator developed to treat conditions of cortisol excess, especially endogenous Cushing’s syndrome. Its targeted mechanism of action and improved safety profile distinguish it from earlier glucocorticoid receptor antagonists, highlighting its potential in managing glucocorticoid-related disorders.

References

2017. Identification of the Clinical Candidate (R)-(1-(4-Fluorophenyl)-6-((1-methyl-1H-pyrazol-4-yl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(4-(trifluoromethyl)pyridin-2-yl)methanone (CORT125134): A Selective Glucocorticoid Receptor (GR) Antagonist. Journal of Medicinal Chemistry, 60(8).
DOI: 10.1021/acs.jmedchem.7b00162

2021. Relacorilant, a Selective Glucocorticoid Receptor Modulator, Induces Clinical Improvements in Patients With Cushing Syndrome: Results From A Prospective, Open-Label Phase 2 Study. Frontiers in Endocrinology, 12.
DOI: 10.3389/fendo.2021.662865

2024. Relacorilant plus nab-paclitaxel for the treatment of metastatic pancreatic ductal adenocarcinoma: results from the open-label RELIANT study. The Oncologist, 29(10).
DOI: 10.1093/oncolo/oyae210