Miricorilant

Miricorilant
Clinical data
Other names	CORT 118335
Legal status
Legal status	Investigational;
Identifiers
	IUPAC name trans-6-(4-phenylcyclohexyl)-5-[[3-(trifluoromethyl)phenyl]methyl]-1H-pyrimidine-2,4-dione;
CAS Number	1400902-13-7;
PubChem CID	66550324;
IUPHAR/BPS	10059;
DrugBank	DB16234;
ChemSpider	76826991;
KEGG	D11667;
ChEMBL	ChEMBL4297602;
Chemical and physical data
Formula	C24H23F3N2O2
Molar mass	428.455 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1CC(CCC1C2=CC=CC=C2)C3=C(C(=O)NC(=O)N3)CC4=CC(=CC=C4)C(F)(F)F;
	InChI InChI=1/C24H23F3N2O2/c25-24(26,27)19-8-4-5-15(13-19)14-20-21(28-23(31)29-22(20)30)18-11-9-17(10-12-18)16-6-2-1-3-7-16/h1-8,13,17-18H,9-12,14H2,(H2,28,29,30,31)/t17-,18-; Key:GVVUZBSCYAVFTI-IYARVYRRNA-N;

Miricorilant (CORT 118335) is a small molecule that works as a selective glucocorticoid receptor modulator and mineralcorticoid receptor antagonist.^[1]^[2]^[3]^[4] It was developed by Corcept Therapeutics for nonalcoholic steatohepatitis^[5] and weight gain associated with atypical antipsychotics.^[6]

References

^ Hunt, Hazel J.; Ray, Nicholas C.; Hynd, George; Sutton, Jon; Sajad, Mohammed; o'Connor, Elizabeth; Ahmed, Shahadat; Lockey, Peter; Daly, Steve; Buckley, Gerry; Clark, Robin D.; Roe, Robert; Blasey, Christine; Belanoff, Joe (2012). "Discovery of a novel non-steroidal GR antagonist with in vivo efficacy in the olanzapine-induced weight gain model in the rat". Bioorganic & Medicinal Chemistry Letters. 22 (24): 7376–7380. doi:10.1016/j.bmcl.2012.10.074. PMID 23131342.
^ Mammi, C.; Marzolla, V.; Armani, A.; Feraco, A.; Antelmi, A.; Maslak, E.; Chlopicki, S.; Cinti, F.; Hunt, H.; Fabbri, A.; Caprio, M. (June 2016). "A novel combined glucocorticoid-mineralocorticoid receptor selective modulator markedly prevents weight gain and fat mass expansion in mice fed a high-fat diet". International Journal of Obesity. 40 (6): 964–972. doi:10.1038/ijo.2016.13. ISSN 1476-5497. PMID 26830012. S2CID 19751493.
^ Nguyen, Elizabeth T.; Berman, Sarah; Streicher, Joshua; Estrada, Christina M.; Caldwell, Jody L.; Ghisays, Valentina; Ulrich-Lai, Yvonne; Solomon, Matia B. (1 August 2019). "Effects of combined glucocorticoid/mineralocorticoid receptor modulation (CORT118335) on energy balance, adiposity, and lipid metabolism in male rats". American Journal of Physiology. Endocrinology and Metabolism. 317 (2): E337–E349. doi:10.1152/ajpendo.00018.2019. PMID 31112405. S2CID 162170330.
^ Nguyen, Elizabeth T.; Caldwell, Jody L.; Streicher, Joshua; Ghisays, Valentina; Balmer, Nikolaus J.; Estrada, Christina M.; Solomon, Matia B. (January 2018). "Differential effects of imipramine and CORT118335 (Glucocorticoid receptor modulator/mineralocorticoid receptor antagonist) on brain-endocrine stress responses and depression-like behavior in female rats". Behavioural Brain Research. 336: 99–110. doi:10.1016/j.bbr.2017.08.045. PMID 28866130. S2CID 5511661.
^ Koorneef, Lisa L; van den Heuvel, José K; Kroon, Jan; Boon, Mariëtte R; ’t Hoen, Peter A C; Hettne, Kristina M; van de Velde, Nienke M; Kolenbrander, Kelsey B; Streefland, Trea C M; Mol, Isabel M; Sips, Hetty C M; Kielbasa, Szymon M; Mei, Hailiang; Belanoff, Joseph K; Pereira, Alberto M; Oosterveer, Maaike H; Hunt, Hazel; Rensen, Patrick C N; Meijer, Onno C (12 October 2018). "Selective glucocorticoid receptor modulation prevents and reverses non-alcoholic fatty liver disease in male mice". Endocrinology. 159 (12): 3925–3936. doi:10.1210/en.2018-00671. hdl:1887/79939. PMID 30321321. S2CID 53501584.
^ Hunt, Hazel J.; Donaldson, Kirsteen; Strem, Mark; Tudor, Iulia Cristina; Sweet-Smith, Suzanne; Sidhu, Sharan (November–December 2021). "Effect of Miricorilant, a Selective Glucocorticoid Receptor Modulator, on Olanzapine-Associated Weight Gain in Healthy Subjects: A Proof-of-Concept Study". Journal of Clinical Psychopharmacology. 41 (6): 632–637. doi:10.1097/JCP.0000000000001470. ISSN 1533-712X. PMC 8575171. PMID 34369902.

[1] Hunt, Hazel J.; Ray, Nicholas C.; Hynd, George; Sutton, Jon; Sajad, Mohammed; o'Connor, Elizabeth; Ahmed, Shahadat; Lockey, Peter; Daly, Steve; Buckley, Gerry; Clark, Robin D.; Roe, Robert; Blasey, Christine; Belanoff, Joe (2012). "Discovery of a novel non-steroidal GR antagonist with in vivo efficacy in the olanzapine-induced weight gain model in the rat". Bioorganic & Medicinal Chemistry Letters. 22 (24): 7376–7380. doi:10.1016/j.bmcl.2012.10.074. PMID 23131342.

[2] Mammi, C.; Marzolla, V.; Armani, A.; Feraco, A.; Antelmi, A.; Maslak, E.; Chlopicki, S.; Cinti, F.; Hunt, H.; Fabbri, A.; Caprio, M. (June 2016). "A novel combined glucocorticoid-mineralocorticoid receptor selective modulator markedly prevents weight gain and fat mass expansion in mice fed a high-fat diet". International Journal of Obesity. 40 (6): 964–972. doi:10.1038/ijo.2016.13. ISSN 1476-5497. PMID 26830012. S2CID 19751493.

[3] Nguyen, Elizabeth T.; Berman, Sarah; Streicher, Joshua; Estrada, Christina M.; Caldwell, Jody L.; Ghisays, Valentina; Ulrich-Lai, Yvonne; Solomon, Matia B. (1 August 2019). "Effects of combined glucocorticoid/mineralocorticoid receptor modulation (CORT118335) on energy balance, adiposity, and lipid metabolism in male rats". American Journal of Physiology. Endocrinology and Metabolism. 317 (2): E337–E349. doi:10.1152/ajpendo.00018.2019. PMID 31112405. S2CID 162170330.

[4] Nguyen, Elizabeth T.; Caldwell, Jody L.; Streicher, Joshua; Ghisays, Valentina; Balmer, Nikolaus J.; Estrada, Christina M.; Solomon, Matia B. (January 2018). "Differential effects of imipramine and CORT118335 (Glucocorticoid receptor modulator/mineralocorticoid receptor antagonist) on brain-endocrine stress responses and depression-like behavior in female rats". Behavioural Brain Research. 336: 99–110. doi:10.1016/j.bbr.2017.08.045. PMID 28866130. S2CID 5511661.

[5] Koorneef, Lisa L; van den Heuvel, José K; Kroon, Jan; Boon, Mariëtte R; ’t Hoen, Peter A C; Hettne, Kristina M; van de Velde, Nienke M; Kolenbrander, Kelsey B; Streefland, Trea C M; Mol, Isabel M; Sips, Hetty C M; Kielbasa, Szymon M; Mei, Hailiang; Belanoff, Joseph K; Pereira, Alberto M; Oosterveer, Maaike H; Hunt, Hazel; Rensen, Patrick C N; Meijer, Onno C (12 October 2018). "Selective glucocorticoid receptor modulation prevents and reverses non-alcoholic fatty liver disease in male mice". Endocrinology. 159 (12): 3925–3936. doi:10.1210/en.2018-00671. hdl:1887/79939. PMID 30321321. S2CID 53501584.

[6] Hunt, Hazel J.; Donaldson, Kirsteen; Strem, Mark; Tudor, Iulia Cristina; Sweet-Smith, Suzanne; Sidhu, Sharan (November–December 2021). "Effect of Miricorilant, a Selective Glucocorticoid Receptor Modulator, on Olanzapine-Associated Weight Gain in Healthy Subjects: A Proof-of-Concept Study". Journal of Clinical Psychopharmacology. 41 (6): 632–637. doi:10.1097/JCP.0000000000001470. ISSN 1533-712X. PMC 8575171. PMID 34369902.

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