Mitiperstat

Mitiperstat
Legal status
Legal status	Investigational;
Identifiers
	IUPAC name 1-[[2-[(1R)-1-Aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one;
CAS Number	1933460-19-5;
PubChem CID	121362450;
ChemSpider	114711423;
UNII	S6GYK3X4QQ;
ChEMBL	ChEMBL5095218;
Chemical and physical data
Formula	C15H15ClN4OS
Molar mass	334.82 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C[C@H](C1=C(C=CC(=C1)Cl)CN2C3=C(C(=O)NC2=S)NC=C3)N;
	InChI InChI=1S/C15H15ClN4OS/c1-8(17)11-6-10(16)3-2-9(11)7-20-12-4-5-18-13(12)14(21)19-15(20)22/h2-6,8,18H,7,17H2,1H3,(H,19,21,22)/t8-/m1/s1; Key:BHKKSKOHRFHHIN-MRVPVSSYSA-N;

Mitiperstat (AZD4831) is an irreversible inhibitor of myeloperoxidase and experimental drug in development for heart failure with preserved ejection fraction.^[1]^[2]^[3]^[4]^[5]^[6]^[7] It is being developed by AstraZeneca.^[8]

References

^ Michaëlsson, Erik; Lund, Lars H.; Hage, Camilla; Shah, Sanjiv J.; Voors, Adriaan A.; Saraste, Antti; Redfors, Björn; Grove, Erik L.; Barasa, Anders; Richards, A. Mark; Svedlund, Sara; Lagerström-Fermér, Maria; Gabrielsen, Anders; Garkaviy, Pavlo; Gan, Li-Ming; Lam, Carolyn S.P. (July 2023). "Myeloperoxidase Inhibition Reverses Biomarker Profiles Associated With Clinical Outcomes in HFpEF". JACC: Heart Failure. 11 (7): 775–787. doi:10.1016/j.jchf.2023.03.002. PMID 37140510. S2CID 258485391.
^ Lam, Carolyn S.P.; Lund, Lars H.; Shah, Sanjiv J.; Voors, Adriaan A.; Erlinge, David; Saraste, Antti; Pirazzi, Carlo; Grove, Erik L.; Barasa, Anders; Schou, Morten; Aziz, Ahmed; Svedlund, Sara; Wijngaarden, Jan Van; Lindstedt, Eva-Lotte; Gustavsson, Andreas; Nelander, Karin; Garkaviy, Pavlo; Gan, Li-Ming; Gabrielsen, Anders (April 2023). "Myeloperoxidase Inhibition in Heart Failure With Preserved or Mildly Reduced Ejection Fraction: SATELLITE Trial Results". Journal of Cardiac Failure. doi:10.1016/j.cardfail.2023.04.003. PMID 37072105. S2CID 258184680.
^ Bhattacharya, Chandrali; Sandinge, Ann-Sofie; Bragg, Ryan A.; Heijer, Maria; Yan, Jingjing; Andersson, Linda C.; Jurva, Ulrik; Pelay-Gimeno, Marta; Vaes, Wouter H.J.; de Ligt, Rianne A.F.; Gränfors, Malin; Amilon, Carl; Lindstedt, Eva-Lotte; Menakuru, Somasekhara R.; Garkaviy, Pavlo; Weidolf, Lars; Gopaul, V. Sashi (April 2023). "Application of Accelerator Mass Spectrometry to Characterize the Mass Balance Recovery and Disposition of AZD4831, a Novel Myeloperoxidase Inhibitor, following Administration of an Oral Radiolabeled Microtracer Dose in Humans". Drug Metabolism and Disposition. 51 (4): 451–463. doi:10.1124/dmd.122.001100. PMID 36639243. S2CID 255800825.
^ Jurva, Ulrik; Weidolf, Lars; Sandinge, Ann-Sofie; Leandersson, Carina; Ekdahl, Anja; Li, Xue-Qing; Antonsson, Thomas; Sundell, Johan; Westerlund, Kristina; Amilon, Carl; Inghardt, Tord; Gopaul, V. Sashi (April 2023). "Biotransformation of the Novel Myeloperoxidase Inhibitor AZD4831 in Preclinical Species and Humans". Drug Metabolism and Disposition. 51 (4): 464–479. doi:10.1124/dmd.122.001099. PMC 11022936. PMID 36653117. S2CID 255972963.
^ Nelander, Karin; Lagerstrom‐Fermer, Maria; Amilon, Carl; Michaëlsson, Erik; Heijer, Maria; Kjaer, Magnus; Russell, Muir; Han, David; Lindstedt, Eva‐Lotte; Whatling, Carl; Gan, Li‐Ming; Ericsson, Hans (May 2021). "Early Clinical Experience With AZD4831, A Novel Myeloperoxidase Inhibitor, Developed for Patients With Heart Failure With Preserved Ejection Fraction". Clinical and Translational Science. 14 (3): 812–819. doi:10.1111/cts.12859. PMC 8212712. PMID 32770730.
^ Gan, Li‐Ming; Lagerström‐Fermér, Maria; Ericsson, Hans; Nelander, Karin; Lindstedt, Eva‐Lotte; Michaëlsson, Erik; Kjaer, Magnus; Heijer, Maria; Whatling, Carl; Fuhr, Rainard (April 2019). "Safety, tolerability, pharmacokinetics and effect on serum uric acid of the myeloperoxidase inhibitor AZD4831 in a randomized, placebo‐controlled, phase I study in healthy volunteers". British Journal of Clinical Pharmacology. 85 (4): 762–770. doi:10.1111/bcp.13855. PMC 6422671. PMID 30618054.
^ Inghardt, Tord; Antonsson, Thomas; Ericsson, Cecilia; Hovdal, Daniel; Johannesson, Petra; Johansson, Carina; Jurva, Ulrik; Kajanus, Johan; Kull, Bengt; Michaëlsson, Erik; Pettersen, Anna; Sjögren, Tove; Sörensen, Henrik; Westerlund, Kristina; Lindstedt, Eva-Lotte (8 September 2022). "Discovery of AZD4831, a Mechanism-Based Irreversible Inhibitor of Myeloperoxidase, As a Potential Treatment for Heart Failure with Preserved Ejection Fraction". Journal of Medicinal Chemistry. 65 (17): 11485–11496. doi:10.1021/acs.jmedchem.1c02141. PMC 9469207. PMID 36005476.
^ "AstraZeneca's investigational MPO inhibitor AZD4831 shows promise in patients with heart failure and a preserved ejection fraction". AstraZeneca. July 2021. Retrieved 11 November 2023.

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[1] Michaëlsson, Erik; Lund, Lars H.; Hage, Camilla; Shah, Sanjiv J.; Voors, Adriaan A.; Saraste, Antti; Redfors, Björn; Grove, Erik L.; Barasa, Anders; Richards, A. Mark; Svedlund, Sara; Lagerström-Fermér, Maria; Gabrielsen, Anders; Garkaviy, Pavlo; Gan, Li-Ming; Lam, Carolyn S.P. (July 2023). "Myeloperoxidase Inhibition Reverses Biomarker Profiles Associated With Clinical Outcomes in HFpEF". JACC: Heart Failure. 11 (7): 775–787. doi:10.1016/j.jchf.2023.03.002. PMID 37140510. S2CID 258485391.

[2] Lam, Carolyn S.P.; Lund, Lars H.; Shah, Sanjiv J.; Voors, Adriaan A.; Erlinge, David; Saraste, Antti; Pirazzi, Carlo; Grove, Erik L.; Barasa, Anders; Schou, Morten; Aziz, Ahmed; Svedlund, Sara; Wijngaarden, Jan Van; Lindstedt, Eva-Lotte; Gustavsson, Andreas; Nelander, Karin; Garkaviy, Pavlo; Gan, Li-Ming; Gabrielsen, Anders (April 2023). "Myeloperoxidase Inhibition in Heart Failure With Preserved or Mildly Reduced Ejection Fraction: SATELLITE Trial Results". Journal of Cardiac Failure. doi:10.1016/j.cardfail.2023.04.003. PMID 37072105. S2CID 258184680.

[3] Bhattacharya, Chandrali; Sandinge, Ann-Sofie; Bragg, Ryan A.; Heijer, Maria; Yan, Jingjing; Andersson, Linda C.; Jurva, Ulrik; Pelay-Gimeno, Marta; Vaes, Wouter H.J.; de Ligt, Rianne A.F.; Gränfors, Malin; Amilon, Carl; Lindstedt, Eva-Lotte; Menakuru, Somasekhara R.; Garkaviy, Pavlo; Weidolf, Lars; Gopaul, V. Sashi (April 2023). "Application of Accelerator Mass Spectrometry to Characterize the Mass Balance Recovery and Disposition of AZD4831, a Novel Myeloperoxidase Inhibitor, following Administration of an Oral Radiolabeled Microtracer Dose in Humans". Drug Metabolism and Disposition. 51 (4): 451–463. doi:10.1124/dmd.122.001100. PMID 36639243. S2CID 255800825.

[4] Jurva, Ulrik; Weidolf, Lars; Sandinge, Ann-Sofie; Leandersson, Carina; Ekdahl, Anja; Li, Xue-Qing; Antonsson, Thomas; Sundell, Johan; Westerlund, Kristina; Amilon, Carl; Inghardt, Tord; Gopaul, V. Sashi (April 2023). "Biotransformation of the Novel Myeloperoxidase Inhibitor AZD4831 in Preclinical Species and Humans". Drug Metabolism and Disposition. 51 (4): 464–479. doi:10.1124/dmd.122.001099. PMC 11022936. PMID 36653117. S2CID 255972963.

[5] Nelander, Karin; Lagerstrom‐Fermer, Maria; Amilon, Carl; Michaëlsson, Erik; Heijer, Maria; Kjaer, Magnus; Russell, Muir; Han, David; Lindstedt, Eva‐Lotte; Whatling, Carl; Gan, Li‐Ming; Ericsson, Hans (May 2021). "Early Clinical Experience With AZD4831, A Novel Myeloperoxidase Inhibitor, Developed for Patients With Heart Failure With Preserved Ejection Fraction". Clinical and Translational Science. 14 (3): 812–819. doi:10.1111/cts.12859. PMC 8212712. PMID 32770730.

[6] Gan, Li‐Ming; Lagerström‐Fermér, Maria; Ericsson, Hans; Nelander, Karin; Lindstedt, Eva‐Lotte; Michaëlsson, Erik; Kjaer, Magnus; Heijer, Maria; Whatling, Carl; Fuhr, Rainard (April 2019). "Safety, tolerability, pharmacokinetics and effect on serum uric acid of the myeloperoxidase inhibitor AZD4831 in a randomized, placebo‐controlled, phase I study in healthy volunteers". British Journal of Clinical Pharmacology. 85 (4): 762–770. doi:10.1111/bcp.13855. PMC 6422671. PMID 30618054.

[7] Inghardt, Tord; Antonsson, Thomas; Ericsson, Cecilia; Hovdal, Daniel; Johannesson, Petra; Johansson, Carina; Jurva, Ulrik; Kajanus, Johan; Kull, Bengt; Michaëlsson, Erik; Pettersen, Anna; Sjögren, Tove; Sörensen, Henrik; Westerlund, Kristina; Lindstedt, Eva-Lotte (8 September 2022). "Discovery of AZD4831, a Mechanism-Based Irreversible Inhibitor of Myeloperoxidase, As a Potential Treatment for Heart Failure with Preserved Ejection Fraction". Journal of Medicinal Chemistry. 65 (17): 11485–11496. doi:10.1021/acs.jmedchem.1c02141. PMC 9469207. PMID 36005476.

[8] "AstraZeneca's investigational MPO inhibitor AZD4831 shows promise in patients with heart failure and a preserved ejection fraction". AstraZeneca. July 2021. Retrieved 11 November 2023.

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