Mizacorat

Mizacorat
Clinical data
Other names	AZD9567
Legal status
Legal status	Investigational;
Identifiers
	IUPAC name 2,2-Difluoro-N-[(1R,2S)-3-methyl-1-[1-(1-methyl-6-oxopyridin-3-yl)indazol-5-yl]oxy-1-phenylbutan-2-yl]propanamide;
CAS Number	1893415-00-3;
PubChem CID	121248172;
IUPHAR/BPS	9812;
ChemSpider	57617761;
UNII	GGK40O1O85;
ChEMBL	ChEMBL4207852;
Chemical and physical data
Formula	C27H28F2N4O3
Molar mass	494.543 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC(C)[C@@H]([C@@H](C1=CC=CC=C1)OC2=CC3=C(C=C2)N(N=C3)C4=CN(C(=O)C=C4)C)NC(=O)C(C)(F)F;
	InChI InChI=1S/C27H28F2N4O3/c1-17(2)24(31-26(35)27(3,28)29)25(18-8-6-5-7-9-18)36-21-11-12-22-19(14-21)15-30-33(22)20-10-13-23(34)32(4)16-20/h5-17,24-25H,1-4H3,(H,31,35)/t24-,25+/m0/s1; Key:ZQFNDBISEYQVRR-LOSJGSFVSA-N;

Mizacorat (AZD9567) is an investigational selective glucocorticoid receptor modulator that has a better ratio of therapeutic effect to adverse effects compared to prednisolone according to preliminary studies. It is developed by AstraZeneca for rheumatoid arthritis.^[1]^[2]^[3]^[4]^[5]^[6]

References

^ van Laar, Jacob M.; Lei, Alejhandra; Safy-Khan, Mary; Almquist, Joachim; Belfield, Graham; Edman, Karl; Öberg, Lisa; Angermann, Bastian R.; Dillmann, Inken; Berntsson, Pia; E., Damla; Dainty, Ian; Astbury, Carol; Belvisi, Maria G.; Nemes, Szilárd; Platt, Adam; Prothon, Susanne; Samuelsson, Sara; Svanberg, Petter; Keen, Christina (23 October 2023). "AZD9567 versus prednisolone in patients with active rheumatoid arthritis: A phase IIa , randomized, double-blind, efficacy, and safety study". Clinical and Translational Science. 16 (12): 2494–2506. doi:10.1111/cts.13624. ISSN 1752-8054. PMC 10719483. PMID 37873558. S2CID 264437480.
^ Putra, Okky Dwichandra; Ottosson, Jenny; Nilsson Lill, Sten O.; Pettersen, Anna (5 January 2022). "Understanding Crystal Structures to Guide Form Selection of Active Pharmaceutical Ingredients: A Case Study of AZD9567". Crystal Growth & Design. 22 (1): 535–546. doi:10.1021/acs.cgd.1c01124. S2CID 245412213.
^ Ripa, Lena; Edman, Karl; Dearman, Matthew; Edenro, Goran; Hendrickx, Ramon; Ullah, Victoria; Chang, Hui-Fang; Lepistö, Matti; Chapman, Dave; Geschwindner, Stefan; Wissler, Lisa; Svanberg, Petter; Lawitz, Karolina; Malmberg, Jesper; Nikitidis, Antonios; Olsson, Roine I.; Bird, James; Llinas, Antoni; Hegelund-Myrbäck, Tove; Berger, Markus; Thorne, Philip; Harrison, Richard; Köhler, Christian; Drmota, Tomas (8 March 2018). "Discovery of a Novel Oral Glucocorticoid Receptor Modulator (AZD9567) with Improved Side Effect Profile". Journal of Medicinal Chemistry. 61 (5): 1785–1799. doi:10.1021/acs.jmedchem.7b01690. PMID 29424542.
^ Hegelund Myrbäck, Tove; Prothon, Susanne; Edman, Karl; Leander, Jacob; Hashemi, Mahdi; Dearman, Matthew; Edenro, Goran; Svanberg, Petter; Andersson, Eva-Marie; Almquist, Joachim; Ämmälä, Carina; Hendrickx, Ramon; Taib, Ziad; Johansson, Kicki A; Berggren, Anders R; Keen, Christina M; Eriksson, Ulf G; Fuhr, Rainard; Carlsson, Björn C L (January 2020). "Effects of a selective glucocorticoid receptor modulator (AZD9567) versus prednisolone in healthy volunteers: two phase 1, single-blind, randomised controlled trials". The Lancet Rheumatology. 2 (1): e31–e41. doi:10.1016/S2665-9913(19)30103-1. PMID 38258274. S2CID 214447281.
^ Hendrickx, R.; Hegelund-Myrbäck, T.; Dearman, M.; Prothon, S.; Edenro, G.; Leander, J.; Fuhr, R.; Körnicke, T.; Svanberg, P.; Berggren, A. R.; Drmota, T.; Keen, C.; Eriksson, U. G. (1 June 2018). "SAT0245 Azd9567: a novel oral selective glucocorticoid receptor modulator, demonstrated to have an improved therapeutic ratio compared to prednisolone in pre-clinical studies, is safe and well tolerated in first clinical study". Annals of the Rheumatic Diseases. 77 (Suppl 2): 984–985. doi:10.1136/annrheumdis-2018-eular.6360. ISSN 0003-4967. S2CID 58137270.
^ Almquist, Joachim; Sadiq, Muhammad Waqas; Eriksson, Ulf G.; Hegelund Myrbäck, Tove; Prothon, Susanne; Leander, Jacob (August 2020). "Estimation of Equipotent Doses for Anti-Inflammatory Effects of Prednisolone and AZD9567, an Oral Selective Nonsteroidal Glucocorticoid Receptor Modulator". CPT: Pharmacometrics & Systems Pharmacology. 9 (8): 444–455. doi:10.1002/psp4.12536. ISSN 2163-8306. PMC 7438818. PMID 32501650.

[1] van Laar, Jacob M.; Lei, Alejhandra; Safy-Khan, Mary; Almquist, Joachim; Belfield, Graham; Edman, Karl; Öberg, Lisa; Angermann, Bastian R.; Dillmann, Inken; Berntsson, Pia; E., Damla; Dainty, Ian; Astbury, Carol; Belvisi, Maria G.; Nemes, Szilárd; Platt, Adam; Prothon, Susanne; Samuelsson, Sara; Svanberg, Petter; Keen, Christina (23 October 2023). "AZD9567 versus prednisolone in patients with active rheumatoid arthritis: A phase IIa , randomized, double-blind, efficacy, and safety study". Clinical and Translational Science. 16 (12): 2494–2506. doi:10.1111/cts.13624. ISSN 1752-8054. PMC 10719483. PMID 37873558. S2CID 264437480.

[2] Putra, Okky Dwichandra; Ottosson, Jenny; Nilsson Lill, Sten O.; Pettersen, Anna (5 January 2022). "Understanding Crystal Structures to Guide Form Selection of Active Pharmaceutical Ingredients: A Case Study of AZD9567". Crystal Growth & Design. 22 (1): 535–546. doi:10.1021/acs.cgd.1c01124. S2CID 245412213.

[3] Ripa, Lena; Edman, Karl; Dearman, Matthew; Edenro, Goran; Hendrickx, Ramon; Ullah, Victoria; Chang, Hui-Fang; Lepistö, Matti; Chapman, Dave; Geschwindner, Stefan; Wissler, Lisa; Svanberg, Petter; Lawitz, Karolina; Malmberg, Jesper; Nikitidis, Antonios; Olsson, Roine I.; Bird, James; Llinas, Antoni; Hegelund-Myrbäck, Tove; Berger, Markus; Thorne, Philip; Harrison, Richard; Köhler, Christian; Drmota, Tomas (8 March 2018). "Discovery of a Novel Oral Glucocorticoid Receptor Modulator (AZD9567) with Improved Side Effect Profile". Journal of Medicinal Chemistry. 61 (5): 1785–1799. doi:10.1021/acs.jmedchem.7b01690. PMID 29424542.

[4] Hegelund Myrbäck, Tove; Prothon, Susanne; Edman, Karl; Leander, Jacob; Hashemi, Mahdi; Dearman, Matthew; Edenro, Goran; Svanberg, Petter; Andersson, Eva-Marie; Almquist, Joachim; Ämmälä, Carina; Hendrickx, Ramon; Taib, Ziad; Johansson, Kicki A; Berggren, Anders R; Keen, Christina M; Eriksson, Ulf G; Fuhr, Rainard; Carlsson, Björn C L (January 2020). "Effects of a selective glucocorticoid receptor modulator (AZD9567) versus prednisolone in healthy volunteers: two phase 1, single-blind, randomised controlled trials". The Lancet Rheumatology. 2 (1): e31–e41. doi:10.1016/S2665-9913(19)30103-1. PMID 38258274. S2CID 214447281.

[5] Hendrickx, R.; Hegelund-Myrbäck, T.; Dearman, M.; Prothon, S.; Edenro, G.; Leander, J.; Fuhr, R.; Körnicke, T.; Svanberg, P.; Berggren, A. R.; Drmota, T.; Keen, C.; Eriksson, U. G. (1 June 2018). "SAT0245 Azd9567: a novel oral selective glucocorticoid receptor modulator, demonstrated to have an improved therapeutic ratio compared to prednisolone in pre-clinical studies, is safe and well tolerated in first clinical study". Annals of the Rheumatic Diseases. 77 (Suppl 2): 984–985. doi:10.1136/annrheumdis-2018-eular.6360. ISSN 0003-4967. S2CID 58137270.

[6] Almquist, Joachim; Sadiq, Muhammad Waqas; Eriksson, Ulf G.; Hegelund Myrbäck, Tove; Prothon, Susanne; Leander, Jacob (August 2020). "Estimation of Equipotent Doses for Anti-Inflammatory Effects of Prednisolone and AZD9567, an Oral Selective Nonsteroidal Glucocorticoid Receptor Modulator". CPT: Pharmacometrics & Systems Pharmacology. 9 (8): 444–455. doi:10.1002/psp4.12536. ISSN 2163-8306. PMC 7438818. PMID 32501650.

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