Jetten AM, Ueda E. Retinoid-related orphan receptors (RORs): roles in cell survival, differentiation and disease. Cell Death Differ. 2002;9:1167–71.
Article CAS PubMed Google Scholar
Zhang Y, Luo XY, Wu DH, Xu Y. ROR nuclear receptors: structures, related diseases, and drug discovery. Acta Pharmacol Sin. 2015;36:71–87.
Fauber BP, Magnuson S. Modulators of the nuclear receptor retinoic acid receptor-related orphan receptor-γ (RORγ or RORc). J Med Chem. 2014;57:5871–92.
Article CAS PubMed Google Scholar
Huang M, Bolin S, Miller H, Ng HL. RORγ structural plasticity and druggability. Int J Mol Sci. 2020;21:5329.
Article CAS PubMed PubMed Central Google Scholar
Ivanov I, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, et al. The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006;126:1121–33.
Article CAS PubMed Google Scholar
Huang ZF, Xie HM, Wang RQ, Sun ZM. Retinoid-related orphan receptor γt is a potential therapeutic target for controlling inflammatory autoimmunity. Expert Opin Ther Tar. 2007;11:737–43.
Codarri L, Gyulveszi G, Tosevski V, Hesske L, Fontana A, Magnenat L, et al. RORγt drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nat Immunol. 2011;12:560–67.
Article CAS PubMed Google Scholar
Wang JJ, Zou JX, Xue XQ, Cai D, Zhang Y, Duan ZJ, et al. ROR-γ drives androgen receptor expression and represents a therapeutic target in castration-resistant prostate cancer. Nat Med. 2016;22:488–96.
Article CAS PubMed PubMed Central Google Scholar
Cai D, Wang JJ, Gao B, Li J, Wu F, Zou JX, et al. RORγ is a targetable master regulator of cholesterol biosynthesis in a cancer subtype. Nat Commun. 2019;10:4621.
Article PubMed PubMed Central Google Scholar
Dong Y, Chen CC, Chen C, Zhang CX, Zhang L, Zhang Y, et al. Stigmasterol inhibits the progression of lung cancer by regulating retinoic acid-related orphan receptor C. Histol Histopathol. 2021;36:1285–99.
Zhang X, Huang ZH, Wang JJ, Ma Z, Yang J, Corey E, et al. Targeting feedforward loops formed by nuclear receptor RORγ and kinase PBK in mCRPC with hyperactive AR signaling. Cancers. 2021;13:1672.
Article CAS PubMed PubMed Central Google Scholar
Yang N, Yang Y, Huang Z, Chen HW. Deregulation of cholesterol homeostasis by a nuclear hormone receptor crosstalk in advanced prostate cancer. Cancers. 2022;14:3110.
Article CAS PubMed PubMed Central Google Scholar
Chen JH, Hu YW, Zhang J, Wang QY, Wu XZ, Huang WY, et al. Therapeutic targeting RORγ with natural product N-hydroxyapiosporamide for small cell lung cancer by reprogramming neuroendocrine fate. Pharmacol Res. 2022;178:106160.
Article CAS PubMed Google Scholar
Pan XF, Li B, Zhang G, Gong YY, Liu R, Chen BX, et al. Identification of RORγ as a favorable biomarker for colon cancer. J Int Med Res. 2022;49:1–12.
Kamenecka TM, Lyda B, Chang MR, Griffin PR. Synthetic modulators of the retinoic acid receptor-related orphan receptors. Med Chem Comm. 2013;4:764–76.
Kojetin DJ, Burris TP. REV-ERB and ROR nuclear receptors as drug targets. Nat Rev Drug Discov. 2014;13:197–216.
Article CAS PubMed PubMed Central Google Scholar
Cyr P, Bronner SM, Crawford JJ. Recent progress on nuclear receptor RORγ modulators. Bioorg Med Chem Lett. 2016;26:4387–93.
Article CAS PubMed Google Scholar
Bronner SM, Zbieg JR, Crawford JJ. RORγ antagonists and inverse agonists: a patent review. Expert Opin Ther Pat. 2017;27:101–12.
Article CAS PubMed Google Scholar
Pandya VB, Kumar S, Sachchidanand, Sharma R, Desai RC. Combating autoimmune diseases with retinoic acid receptor-related orphan receptor-γ (RORγ or RORc) inhibitors: hits and misses. J Med Chem. 2018;61:10976–95.
Article CAS PubMed Google Scholar
Jetten AM, Cook DN. (Inverse) agonists of retinoic acid-related orphan receptor γ: regulation of immune responses, inflammation, and autoimmune disease. Annu Rev Pharmacol Toxicol. 2020;60:371–90.
Article CAS PubMed Google Scholar
Fauber BP, Gobbi A, Savy P, Burton B, Deng YZ, Everett C, et al. Identification of N-sulfonyl-tetrahydroquinolines as RORc inverse agonists. Bioorg Med Chem Lett. 2015;25:4109–13.
Article CAS PubMed Google Scholar
Kumar N, Lyda B, Chang MR, Lauer JL, Solt LA, Burris TP, et al. Identification of SR2211: a potent synthetic RORγ-selective modulator. ACS Chem Biol. 2012;7:672–77.
Article CAS PubMed PubMed Central Google Scholar
Wang YH, Cai W, Cheng YB, Yang T, Liu Q, Zhang GF, et al. Discovery of biaryl amides as potent, orally bioavailable, and CNS penetrant RORγt inhibitors. ACS Med Chem Lett. 2015;6:787–92.
Article CAS PubMed PubMed Central Google Scholar
2016. https://www.clinicaltrials.gov/study/NCT03237832?term=ARN-6039&rank=1 A phase 1 study of ARN-6039. Clinical Trials May 16, 2016 Accessed 16 Jan 2024.
A study to test how well patients with plaque psoriasis tolerate BI 730357 over a longer period and how effective it is. Clinical Trials Mar 18, 2019: https://www.clinicaltrials.gov/study/NCT03835481?term=BI%20730357&rank=9 (2019). Accessed 16 Jan 2024.
An Ascending Multiple Dose Study With VTP-43742 in Healthy Volunteers. Clinical Trials Aug 1, 2015: https://clinicaltrials.gov/study/NCT03724292?cond=VTP-43742&rank=1 (2015). Accessed 16 Jan 2024.
Safety and PK/PD of RTA 1701 in healthy adults. Clinical Trials Jun 20, 2018: https://www.clinicaltrials.gov/study/NCT03579030?term=1701%20&rank=1 (2018). Accessed 16 Jan 2024.
Study to evaluate the efficacy and safety of JTE-451 in subjects with moderate to severe plaque psoriasis (IMPACT-PS). Clinical Trials Jan 17, 2019: https://clinicaltrials.gov/study/NCT03832738?term=JTE-451%20&rank=2 (2019). Accessed 16 Jan 2024.
Polasek TM, Leelasena I, Betscheider I, Marolt M, Kohlhof H, Vitt D, et al. Safety, tolerability, and pharmacokinetics of IMU-935, a novel inverse agonist of retinoic acid receptor-related orphan nuclear receptor gammat: results from a double-blind, placebo-controlled, first-in-human phase 1 study. Clin Pharmacol Drug Dev. 2023;12:525–34.
Article CAS PubMed Google Scholar
Butler W, Huang J. Glycosylation changes in prostate cancer progression. Front Oncol. 2021;11:809170.
Article CAS PubMed PubMed Central Google Scholar
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72:7–33.
Huggins C, Hodges CV. Studies on prostatic cancer. I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. 1941. J Urol. 2002;168:9–12.
Stein MN, Goodin S, Dipaola RS. Abiraterone in prostate cancer: a new angle to an old problem. Clin Cancer Res. 2012;18:1848–54.
Article CAS PubMed PubMed Central Google Scholar
Mukherji D, Pezaro CJ, De-Bono JS. MDV3100 for the treatment of prostate cancer. Expert Opin Inv Drug. 2012;21:227–33.
Chowdhury S, Oudard S, Uemura H, Joniau S, Dearden L, Capone C, et al. Apalutamide compared with darolutamide for the treatment of non-metastatic castration-resistant prostate cancer: efficacy and tolerability in a matching-adjusted indirect comparison. Adv Ther. 2022;39:518–31.
Article CAS PubMed Google Scholar
Feng Q, He B. Androgen receptor signaling in the development of castration-resistant prostate cancer. Front Oncol. 2019;9:858.
Article PubMed PubMed Central Google Scholar
Quigley DA, Dang HX, Zhao SG, Lloyd P, Aggarwal R, Alumkal JJ, et al. Genomic hallmarks and structural variation in metastatic prostate cancer. Cell. 2018;174:758–69.
Article CAS PubMed PubMed Central Google Scholar
Grasso CS, Wu YM, Robinson DR, Cao XH, Dhanasekaran SM, Khan AP, et al. The mutational landscape of lethal castration-resistant prostate cancer. Nature. 2012;487:239–43.
Article CAS PubMed PubMed Central Google Scholar
Zhang Y, Wu XS, Xue XQ, Li CC, Wang JJ, Wang R, et al. Discovery and characterization of XY101, a potent, selective, and orally bioavailable RORγ inverse agonist for treatment of castration-resistant prostate cancer. J Med Chem. 2019;62:4716–30.
Article CAS PubMed Google Scholar
Wu XS, Shen H, Zhang Y, Wang C, Li Q, Zhang C, et al. Discovery and characterization of benzimidazole derivative XY123 as a potent, selective, and orally available RORγ inverse agonist. J Med Chem. 2021;64:8775–97.
Comments (0)