Relacorilant (CORT 125134) is a potent and selective glucocorticoid receptor (GR) antagonist[1-2]. Relacorilant can increase the abundance and function of NK and other immune cells in the tumor microenvironment, while promoting immune responses in malignancies characterized by excessive glucocorticoid production (GC+). Relacorilant is used in research related to Cushing's syndrome (CS) and tumors, such as adrenocortical carcinoma and platinum-resistant ovarian cancer[3-4].
In vitro, Relacorilant (300nM) was co-administered with paclitaxel to OVCAR5 ovarian cancer cells. Relacorilant restored the potency (IC50) of paclitaxel, and enhanced the activity of various cytotoxic agents, including paclitaxel, carboplatin, and gemcitabine[5]. Relacorilant (1-10µM) was co-administered with docetaxel to docetaxel-resistant PC3-DR prostate cancer cells. Relacorilant significantly reduced the IC50 of docetaxel in a concentration-dependent manner and enhanced docetaxel-induced apoptosis[6].
In vivo, in an aged female mouse skin experiment, Relacorilant (60mg/kg/day) was administered to 18-month-old C57BL/6J female mice via oral chow for 8 weeks. Relacorilant significantly inhibited the gene expression of Scnn1g in the skin[7]. Relacorilant (60mg/kg/day) was administered to 8-week-old C57BL/6J male mice via gavage for 5 days. Relacorilant improved sustained corticosterone exposure-induced hyperinsulinemia and immunosuppression (e.g., reductions in leukocytes and lymphocytes) and exhibited antagonistic effects on glucocorticoid receptor (GR) target gene expression in peripheral tissues (liver, adrenal glands, pituitary)[8].
References:
[1] Greenstein AE, Habra MA, Wadekar SA, et al. Adrenal tumors provide insight into the role of cortisol in NK cell activity. Endocr Relat Cancer. 2021 Jun 29;28(8):583-592.
[2] Dua VK, Verma G, Singh B, et al. Anti-malarial property of steroidal alkaloid conessine isolated from the bark of Holarrhena antidysenterica. Malar J. 2013 Jun 10;12:194.
[3] Colombo N, Van Gorp T, Matulonis UA, et al. Relacorilant + Nab-Paclitaxel in Patients With Recurrent, Platinum-Resistant Ovarian Cancer: A Three-Arm, Randomized, Controlled, Open-Label Phase II Study. J Clin Oncol. 2023 Oct 20;41(30):4779-4789.
[4] Pivonello R, Bancos I, Feelders RA, et al. Relacorilant, a Selective Glucocorticoid Receptor Modulator, Induces Clinical Improvements in Patients With Cushing Syndrome: Results From A Prospective, Open-Label Phase 2 Study. Front Endocrinol (Lausanne). 2021 Jul 14;12:66286.
[5] Greenstein AE, Hunt HJ. Glucocorticoid receptor antagonism promotes apoptosis in solid tumor cells. Oncotarget. 2021 Jun 22;12(13):1243-1255.
[6] Sanchez-Hernandez ES, Ochoa PT, Suzuki T, et al. Glucocorticoid Receptor Regulates and Interacts with LEDGF/p75 to Promote Docetaxel Resistance in Prostate Cancer Cells. Cells. 2023 Aug 11;12(16):2046.
[7] Ali A, Fossas De Mello N, et al. The Effect of Glucocorticoid and Mineralocorticoid Receptor Antagonists in the Skin of Aged Female Mice. Int J Mol Sci. 2025 Aug 28;26(17):8346.
[8] Viho EMG, Kroon J, Feelders RA, et al. Peripheral glucocorticoid receptor antagonism by relacorilant with modest HPA axis disinhibition. J Endocrinol. 2022 Dec 22;256(2):e220263.
Relacorilant (CORT 125134)是一种有效的糖皮质激素受体（GR）拮抗剂[1-2]。Relacorilant可以增加肿瘤微环境中NK和其他免疫细胞的丰度和功能，同时能促进具有糖皮质激素过量产生（GC+）情况的恶性肿瘤中的免疫反应。Relacorilant可用于库欣综合征（CS）和肿瘤（如肾上腺皮质癌、铂耐药卵巢癌）的相关研究[3-4]。
在体外，Relacorilant（300nM）与紫杉醇联合处理OVCAR5卵巢癌细胞，Relacorilant可恢复紫杉醇的效力（IC50），并能改善紫杉醇、卡铂、吉西他滨等多种细胞毒性药物的活性[5]。Relacorilant（1-10μM）与多西他赛联合处理对多西他赛耐药的PC3-DR前列腺癌细胞，Relacorilant以浓度依赖的方式显著降低PC3-DR对多西他赛的IC50值，并增强多西他赛诱导的细胞凋亡[6]。
在体内，在老龄雌性小鼠皮肤实验中，Relacorilant（60mg/kg/day）通过口服饲料给药处理18月龄C57BL/6J雌性小鼠8周，Relacorilant显著抑制了皮肤中Scnn1g的基因表达[7]。Relacorilant（60mg/kg/天）通过灌胃给药处理8周龄C57BL/6J雄性小鼠5天，Relacorilant可改善由持续皮质酮暴露诱导的高胰岛素血症和免疫抑制（如白细胞、淋巴细胞减少），可抑制外周组织（肝脏、肾上腺、垂体）中的糖皮质激素受体（GR）靶基因表达表现出拮抗作用[8]。