CORT-108297 (Cat.No:I006191), also known as ADS-108297 and C-108927, is a cortisol receptor (GR-II) antagonist potentially for the mitigation of antipsychotic induced obesity.
| Catalog Number | I006191 |
| CAS Number | 1018679-79-2 |
| Synonyms | CORT-108297; ADS-108297; C-108927; CORT 108297; ADS 108297; C 108927; CORT108297; ADS108297; C108927;(R)-4a-(ethoxymethyl)-1-(4-fluorophenyl)-6-((4-(trifluoromethyl)phenyl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinoline |
| Molecular Formula | C26H25F4N3O3S |
| Purity | 95% |
| Target | cortisol receptor antagonist |
| Solubility | Soluble in DMSO |
| Storage | 0 - 4°C for short term ,or -20 °C for long term |
| IUPAC Name | (4aR)-4a-(ethoxymethyl)-1-(4-fluorophenyl)-6-[4-(trifluoromethyl)phenyl]sulfonyl-4,5,7,8-tetrahydropyrazolo[3,4-g]isoquinoline |
| InChI | InChI=1S/C26H25F4N3O3S/c1-2-36-17-25-14-18-15-31-33(22-7-5-21(27)6-8-22)24(18)13-20(25)11-12-32(16-25)37(34,35)23-9-3-19(4-10-23)26(28,29)30/h3-10,13,15H,2,11-12,14,16-17H2,1H3/t25-/m1/s1 |
| InChIKey | SLKURXRZHJOZOD-RUZDIDTESA-N |
| SMILES | CCOCC12CC3=C(C=C1CCN(C2)S(=O)(=O)C4=CC=C(C=C4)C(F)(F)F)N(N=C3)C5=CC=C(C=C5)F |
| Reference | 1:Horm Behav. 2014 Apr;65(4):363-71. doi: 10.1016/j.yhbeh.2014.02.002. Epub 2014 Feb 11. The selective glucocorticoid receptor antagonist CORT 108297 decreases neuroendocrine stress responses and immobility in the forced swim test.Solomon MB,Wulsin AC,Rice T,Wick D,Myers B,McKlveen J,Flak JN,Ulrich-Lai Y,Herman JP, PMID: 24530653 PMCID: PMC4074011 DOI: 10.1016/j.yhbeh.2014.02.002 </br><span>Abstract:</span> Pre-clinical and clinical studies have employed treatment with glucocorticoid receptor (GR) antagonists in an attempt to limit the deleterious behavioral and physiological effects of excess glucocorticoids. Here, we examined the effects of GR antagonists on neuroendocrine and behavioral stress responses, using two compounds: mifepristone, a GR antagonist that is also a progesterone receptor antagonist, and CORT 108297, a specific GR antagonist lacking anti-progestin activity. Given its well-documented impact on neuroendocrine and behavioral stress responses, imipramine (tricyclic antidepressant) served as a positive control. Male rats were treated for five days with mifepristone (10mg/kg), CORT 108297 (30mg/kg and 60mg/kg), imipramine (10mg/kg) or vehicle and exposed to forced swim test (FST) or restraint stress. Relative to vehicle, imipramine potently suppressed adrenocorticotropin hormone (ACTH) responses to FST and restraint exposure. Imipramine also decreased immobility in the FST, consistent with antidepressant actions. Both doses of CORT 108297 potently suppressed peak corticosterone responses to FST and restraint stress. However, only the higher dose of CORT 108297 (60mg/kg) significantly decreased immobility in the FST. In contrast, mifepristone induced protracted secretion of corticosterone in response to both stressors, and modestly decreased immobility in the FST. Taken together, the data indicate distinct effects of each compound on neuroendocrine stress responses and also highlight dissociation between corticosterone responses and immobility in the FST. Within the context of the present study, our data suggest that CORT 108297 may be an attractive alternative for mitigating neuroendocrine and behavioral states associated with excess glucocorticoid secretion. Copyright © 2014 Elsevier Inc. All rights reserved. |
