Identification and characterization of metabolites of ASP015K, a novel oral Janus kinase inhibitor, in rats, chimeric mice with humanized liver, and humans

Xenobiotica

Volumn 45, Issue 9, 2015, Pages 757-765

  Nakada, Naoyuki ^a   Oda, Kazuo ^a  

^a ASTELLAS PHARMA INC   (Japan)

Author keywords

ASP015K; chimeric mice; humanized; metabolite

Indexed keywords

(4'S) 4' HYDROXY ASP015K 4' O GLUCURONIDE; 6' HYDROXY ASP015K; 6' HYDROXY ASP015K 5' O GLUCURONIDE; 7 N METHYL ASP015K; 7 N METHYL ASP015K 5' O SULFATE; 7' HYDROXY ASP015K; 7' HYDROXY ASP015K 7 N GLUCURONIDE; ASP015K 2 GLUTATHIONE CONJUGATE; ASP015K 3 GLUTATHIONE CONJUGATE; ASP015K 5' O GLUCURONIDE; ASP015K 5' O SULFATE; ASP015K 7 N OXIDE; DIHYDROHYDROXY ASP015K GLUTATHIONE CONJUGATE; DRUG METABOLITE; GLUCURONIDE; PEFICITINIB; UNCLASSIFIED DRUG; 4-((5-HYDROXY-2-ADAMANTYL)AMINO)-1H-PYRROLO(2,3-B)PYRIDINE-5-CARBOXAMIDE; ADAMANTANE; CARBON; ION; JANUS KINASE; NICOTINAMIDE; PROTEIN KINASE INHIBITOR;

ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; DRUG CONJUGATION; DRUG HYDROXYLATION; DRUG IDENTIFICATION; DRUG METABOLISM; FAST ATOM BOMBARDMENT MASS SPECTROMETRY; GLUTATHIONE METABOLISM; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN TISSUE; LIQUID CHROMATOGRAPHY; LIVER CELL; MALE; MASS SPECTROMETRY; MAXIMUM PLASMA CONCENTRATION; MOLECULAR WEIGHT; MOUSE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PROTON NUCLEAR MAGNETIC RESONANCE; RAT; URINALYSIS; ANALOGS AND DERIVATIVES; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; CHIMERA; DRUG EFFECTS; LIVER; METABOLISM; METABOLOME; METABOLOMICS; ORAL DRUG ADMINISTRATION; SPRAGUE DAWLEY RAT;

MUS; RATTUS;

ADAMANTANE; ADMINISTRATION, ORAL; ANIMALS; CARBON RADIOISOTOPES; CARBON-13 MAGNETIC RESONANCE SPECTROSCOPY; CHIMERA; CHROMATOGRAPHY, LIQUID; HUMANS; IONS; JANUS KINASES; LIVER; MALE; MASS SPECTROMETRY; METABOLIC NETWORKS AND PATHWAYS; METABOLOME; METABOLOMICS; MICE; NIACINAMIDE; PROTEIN KINASE INHIBITORS; PROTON MAGNETIC RESONANCE SPECTROSCOPY; RATS, SPRAGUE-DAWLEY;

EID: 84940033203     PISSN: 00498254     EISSN: 13665928     Source Type: Journal    
DOI: 10.3109/00498254.2015.1019594     Document Type: Article

References (28)

1. Bateman TJ, Reddy VG, Kakuni M, et al. (2014). Application of chimeric mice with humanized liver for study of human-specific drug metabolism. Drug Metab Dispos 42: 1055-65
2. Dalvie D, Obach RS, Kang P, et al. (2009). Assessment of three human in vitro systems in the generation of major human excretory and circulating metabolites. Chem Res Toxicol 22: 357-68
3. De Serres M, Bowers G, Boyle G, et al. (2011). Evaluation of a chimeric (uPA+/+)/SCID mouse model with a humanized liver for prediction of human metabolism. Xenobiotica 41: 464-75
4. FDA. 2008). Safety testing of drug metabolites. Rockville, MD: Food and Drug Administration
5. Higashi Y, Inami M, Ito M, et al. (2012). ASP015K: a novel JAK inhibitor demonstrated potent efficacy in a chronic oxazolone-induced dermatitis model in rats. Abstracts (P093) of the 3rd World Psoriasis & Psoriatic Arthritis Conference (2012): "Psoriasis-a global health challenge"; Stockholm, Sweden
6. Hop CE, Wang Z, Chen Q, Kwei G. (1998). Plasma-pooling methods to increase throughput for in vivo pharmacokinetic screening. J Pharm Sci 87: 901-3
7. Hussaini SH, Farrington EA. (2014). Idiosyncratic drug-induced liver injury: an update on the 2007 overview. Expert Opin Drug Saf 13: 67-81
8. ICH. 2009. ICH Guideline M3 (R2): Guidance on Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals. International Conference on Harmonisation, Geneva, Switzerland
9. Ihle JN. (1994). The Janus kinase family and signaling through members of the cytokine receptor superfamily. Proc Soc Exp Biol Med 206: 268-72
10. Imada K, Leonard WJ. (2000). The Jak-STAT pathway. Mol Immunol 37: 1-11
11. Inoue T, Sugihara K, Ohshita H, et al. (2009). Prediction of human disposition toward S-3H-warfarin using chimeric mice with humanized liver. Drug Metab Pharmacokinet 24: 153-60
12. Johnston JA, Kawamura M, Kirken RA, et al. (1994). Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2. Nature 370: 151-3
13. Kalasz H, Petroianu G, Hosztafi S, et al. (2013). Medicinal chemistry of drugs with active metabolites following conjugation. Mini Rev Med Chem 13: 1550-63
14. Kamimura H, Nakada N, Suzuki K, et al. (2010). Assessment of chimeric mice with humanized liver as a tool for predicting circulating human metabolites. Drug Metab Pharmacokinet 25: 223-35
15. Katoh M, Matsui T, Nakajima M, et al. (2004). Expression of human cytochromes P450 in chimeric mice with humanized liver. Drug Metab Dispos 32: 1402-10
16. Katoh M, Matsui T, Okumura H, et al. (2005). Expression of human phase II enzymes in chimeric mice with humanized liver. Drug Metab Dispos 33: 1333-40
17. Klimas R, Mikus G. (2014). Morphine-6-glucuronide is responsible for the analgesic effect after morphine administration: a quantitative review of morphine, morphine-6-glucuronide, and morphine-3-glucuronide. Br J Anaesth 113: 935-44
18. Leonard WJ. (2001). Role of Jak kinases and STATs in cytokine signal transduction. Int J Hematol 73: 271-7
19. Linnekin D, Mou S, Deberry CS, et al. (1997). Stem cell factor, the JAK-STAT pathway and signal transduction. Leuk Lymphoma 27: 439-44
20. Oda K, Nakada N, Nagasaka Y. (2014). Sex differences in the metabolism of ASP015K, an novel oral Janus kinase (JAK) inhibitor, and its sulfuric metabolite M2 in rats. Xenobiotica. (in press)
21. Papp K, Pariser D, Wierz G, et al. (2012). Phase IIa randomized, double-blind, placebo-controlled, sequential dose-escalation study to evaluate the efficacy and safety of ASP015K, a novel Janus kinase (JAK) inhibitor, in patients with moderate to severe psoriasis. 3rd World Psoriasis & Psoriatic Arthritis Conference; 2012 Jun 27-Jul 1; Stockholm, Sweden
22. Ram N, Kalasz H, Adeghate E, et al. (2012). Medicinal chemistry of drugs with active metabolites (N-, O-, and S-desalkylation and some specific oxidative alterations). Curr Med Chem 19: 5683-704
23. Smith DA, Dalvie D. (2012). Why do metabolites circulate? Xenobiotica 42: 107-26
24. Tateno C, Yoshizane Y, Saito N, et al. (2004). Near completely humanized liver in mice shows human-type metabolic responses to drugs. Am J Pathol 165: 901-12
25. Testa B, Pedretti A, Vistoli G. (2012). Reactions and enzymes in the metabolism of drugs and other xenobiotics. Drug Discov Today 17: 549-60
26. Wang Q, Jia R, Ye C, et al. (2005). Glucuronidation and sulfation of 7-hydroxycoumarin in liver matrices from human, dog, monkey, rat, and mouse. In Vitro Cell Dev Biol Anim 41: 97-103
27. Yamazaki H, Kuribayashi S, Inoue T, et al. (2010). Approach for in vivo protein binding of 5-n-butyl-pyrazolo[1,5-a]pyrimidine bioactivated in chimeric mice with humanized liver by two-dimensional electrophoresis with accelerator mass spectrometry. Chem Res Toxicol 23: 152-8
28. Zhu T. (2012). Pharmacodynamics of ASP015K, a novel Janus kinase inhibitor, in healthy volunteers. San Diego (CA): American College of Clinical Pharmacology