Oxidative metabolism of razuprotafib (AKB-9778), a sulfamic acid phosphatase inhibitor, in human microsomes and recombinant human CYP2C8 enzyme

References

• Asai F, Jakubowski JA, Naganuma H, Brandt JT, Matsushima N, Hirota T, Freestone S, Winters KJ. 2006. Platetlet inhibitory activity and pharmacokinetics of prasugel (CS-747) a novel thienopyridine P2Y12 inhibitor: a single ascending dose study in healthy humans. Platelets. 17(4):209–217.
   PubMed Web of Science ®Google Scholar
• Benson GA, Spillane WJ. 1980. Sulfamic acid and its N-substituted derivatives. Chem Rev. 80(2):151–186.
   Web of Science ®Google Scholar
• Campochiaro PA, Khanani A, Singer M, Patel S, Boyer D, Dugel P, Kherani S, Withers B, Gambino L, Peters K, et al. 2016. Enhanced benefit in diabetic macular edema from AKB-9778 Tie2 activation combined with vascular endothelial growth factor suppression. Ophthalmology. 123(8):1722–1730.
   PubMed Web of Science ®Google Scholar
• Campochiaro P, Peters K. 2016. Targeting Tie2 for treatment of diabetic retinopathy and diabetic macular edema. Curr Diab Rep. 16(12):126.
   PubMed Web of Science ®Google Scholar
• Collings AJ. 1989. Metabolism of Cyclamate and its conversion to cyclohexylamine. Diabetes Care. 12(1):50–55.
   PubMed Web of Science ®Google Scholar
• Dalvie DK, Kalgutkar AS, Khojasteh-Bakht SC, Obach RS, O'Donnell JP. 2002. Biotransformation reactions of five-membered aromatic heterocyclic rings. Chem Res Toxicol. 15(3):269–299.
   PubMed Web of Science ®Google Scholar
• Dansette PM, Bertho G, Mansuy D. 2005. First evidence that cytochrome P450 may catalyze both S-oxidation and epoxidation of thiophene derivatives. Biochem Biophys Res Commun. 338(1):450–455.
   PubMed Web of Science ®Google Scholar
• Dansette PM, Levent D, Hessani A, Bertho G, Mansuy D. 2013. Thiolactone sulfoxides as new reactive metabolites acting as bis-electrophiles: implication in clopidogrel and prasugrel bioactivation. Chem Res Toxicol. 26(5):794–802.
   PubMed Web of Science ®Google Scholar
• Dansette PM, Libraire J, Bertho G, Mansuy D. 2009. Metabolic oxidative cleavage of thioesters: evidence for the formation of sulfenic acid intermediates in the bioactivation of the antithrombotic prodrugs ticlopidine and clopidogrel. Chem Res Toxicol. 22(2):369–373.
   PubMed Web of Science ®Google Scholar
• Dansette PM, Rosi J, Bertho G, Mansuy D. 2012a. Cytochromes P450 catalyze both steps of the major pathway of clopidogrel bioactivation, whereas paraoxonase catalyzes the formation of a minor thiol metabolite isomer. Chem Res Toxicol. 25(2):348–356.
   PubMed Web of Science ®Google Scholar
• Dansette PM, Rosi J, Debernardi J, Bertho G, Mansuy D. 2012b. Metabolic activation of prasugrel: nature of the two competitive pathways resulting in the opening of its thiophene ring. Chem Res Toxicol. 25(5):1058–1065.
   PubMed Web of Science ®Google Scholar
• Dansette PM, Thebault S, Bertho G, Mansuy D. 2010. Formation and fate of a sulfenic acid intermediate in the metabolic activation of the antithrombotic prodrug prasugrel. Chem Res Toxicol. 23(7):1268–1274.
   PubMed Web of Science ®Google Scholar
• Donat F, Duret JP, Santoni A, Cariou R, Necciari J, Magnani H, de Grief R. 2002. The pharmacokinetics of fondaparinux sodium in healthy volunteers. Clin Pharmacokinet. 41(Supp2):1–9.
   PubMed Web of Science ®Google Scholar
• Farid N, Kurihara A, Wrighton SA. 2010. Metabolism and disposition of the thienopyridine antiplatelet drugs Ticlopidine, clopidogrel, and prasugrel in humans. J Clin Pharmacol. 50(2):126–142.
   PubMed Web of Science ®Google Scholar
• Farid NA, McIntosh M, Garofolo F, Wong E, Shwajch A, Kennedy M, Young M, Sarkar P, Kawabata K, Takahashi M, et al. 2007a. Determination of the active and inactive metabolites of prasugrel in human plasma by liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom. 21(2):169–179.
   PubMed Web of Science ®Google Scholar
• Farid NA, Smith RL, Gillespie TA, Rash TJ, Blair PE, Kurihara A, Goldberg MJ. 2007b. The disposition of Prasugrel, a novel thienopyridine, in humans. Drug Metab Dispos. 35(7):1096–1104.
   PubMed Web of Science ®Google Scholar
• Gramec D, Masic LP, Dolenc MS. 2014. Bioactivation potential of thiophene-containing drugs. Chem Res Toxicol. 27(8):1344–1358.
   PubMed Web of Science ®Google Scholar
• Hagihara K, Kazui M, Kurihara A, Iwabuchi H, Ishikawa M, Kobayashi H, Tanaka N, Okazaki O, Farid NA, Ikeda T. 2010. Biotransformation of prasugrel, a novel thienopyridine antiplatelet agent, to the pharmacologically active metabolite. Drug Metab Dispos. 38(6):898–904.
   PubMed Web of Science ®Google Scholar
• Kazui M, Hagihara K, Izumi T, Ikeda T, Kurihara A. 2014. Hepatic microsomal thiol methyltransferase is involved in stereoselective methylation of pharmacologically active metabolite of prasugrel. Drug Metab Dispos. 42(7):1138–1145.
   PubMed Web of Science ®Google Scholar
• Kim M, Jeong ES, Park J, Lee S, Ghim JL, Choi C, Shin J, Kim D. 2014. Multiple cytochrome P450 isoforms are involved in the generation of a pharmacologically active thiol metabolite, whereas paraoxonase 1 and carboxylesterase 1 catalyze the formation of a thiol metabolite isomer from ticlopidines. Drug Metab Dispos. 42(1):141–152.
   PubMed Web of Science ®Google Scholar
• Liu C, Chen Z, Zhong K, Li L, Zhu W, Chen X, Zhong D. 2015. Human liver cytochrome P450 enzymes and microsomal thiol methyltransferase are involved in the stereoselective formation and methylation of the pharmacologically active metabolite of clopidogrel. Drug Metab Dispos. 43(10):1632–1641.
   PubMed Web of Science ®Google Scholar
• McNulty CAM, Garden GMF, Ashby GJ, Wise R. 1985. Pharmacokinetics and tissue penetration of carumonam, a new synthetic monobactam. Antimicrob Agents Chemother. 28(3):425–427.
   PubMed Web of Science ®Google Scholar
• NCT04405425. Study to assess the efficacy, safety and tolerability of AKB-9778 ophthalmic solution as an adjunct to latanoprost in patients with ocular hypertension or open angle glaucoma. https://clinicaltrials.gov/ct2/show/NCT04405245.
   Google Scholar
• Parkinson A, Mudra DR, Johnson C, Dwyer A, Carroll KM. 2004. The effects of gender, age, ethnicity, and liver cirrhosis on cytochrome P450 enzyme activity in human liver microsomes and inducibility in cultured human hepatocytes. Toxicol Appl Pharmacol. 199(3):193–209.
   PubMed Web of Science ®Google Scholar
• Pearce RE, McIntyre CJ, Madan A, Sanzgiri U, Draper AJ, Bullock PL, Cook DC, Burton LA, Latham J, Nevins C, et al. 1996. Effects of freezing, thawing, and storing human liver microsomes on cytochrome P450 activity. Arch Biochem Biophys. 331(2):145–169.
   PubMed Web of Science ®Google Scholar
• Saharinen P, Eklund L, Alitalo K. 2017. Therapeutic targeting of the angiopoietin-TIE Pathway. Nat Rev Drug Discov. 16(9):635–661.
   PubMed Web of Science ®Google Scholar
• Savi P, Pereillo JM, Uzabiaga MF, Combalbert J, Picard C, Maffrand JP, Pascal M, Herbert JM. 2000. Identification and Biological Activity of the Active Metabolite of Clopidogrel. Thromb Haemost. 84(5):891–896.
   PubMed Web of Science ®Google Scholar
• Shen J, Frye M, Lee BL, Reinardy JL, McClung JM, Ding K, Kojima M, Xia H, Seidel C, Lima e Silva R, et al. 2014. Targeting VE-PTP activates Tie2 and stabilizes the ocular vasculature. J Clin Invest. 124(10):4564–4576.
   PubMed Web of Science ®Google Scholar
• Soldo B, Camilleri P, Buch A, Janusz JM. 2021. The in vivo disposition of subcutaneous injected 14C-razuprotafib (14C-AKB-9778), a sulfamic acid phosphatase inhibitor, in nonclinical species and human. Xenobiotica.
   Google Scholar
• Sugidachi A, Asai F, Ogawa T, Inoue T, Koike H. 2000. The in vivo pharmacological profile of CS-747, a novel antiplatelet agent with platelet ADP receptor antagonist properties. Br J Pharmacol. 129(7):1439–1446.
   PubMed Web of Science ®Google Scholar
• Swabb EA, Singhvi SM, Leitz MA, Frantz M, Sugerman AA. 1983. Metabolism and pharmacokinetics of aztreonam in healthy subjects. Antimicrob Agents Chemother. 24(3):394–400.
   PubMed Web of Science ®Google Scholar
• Takahashi M, Pang H, Kawabata K, Farid NA, Kurihara A. 2008. Quantitative determination of clopidogrel active metabolite in human plasma by LC-MS/MS. J Pharm Biomed Anal. 48(4):1219–1224.
   PubMed Web of Science ®Google Scholar
• Vestweber D. 2021. Vascular endothelial protein tyrosine phosphatase regulates endothelial function. Physiology. 36(2):84–93.
   PubMed Web of Science ®Google Scholar
• Yoneda K, Iwamura R, Kishi H, Mizukami Y, Mogami K, Kobayashi S. 2004. Identification of the active metabolite of ticlopidine from rat in vitro metabolites. Br J Pharmacol. 142(3):551–557.
   PubMed Web of Science ®Google Scholar
• Zhang H, Lau WC, Hollenberg PF. 2012. Formation of the thiol conjugates and active metabolite of clopidogrel by human liver microsomes. Mol Pharmacol. 82(2):302–309.
   PubMed Web of Science ®Google Scholar