Prolyl hydroxylase inhibition corrects functional iron deficiency and inflammation-induced anaemia in rats

British Journal of Pharmacology

Volumn 172, Issue 16, 2015, Pages 4078-4088

  Barrett, Terrance D ^a   Palomino, Heather L ^b   Brondstetter, Theresa I ^c   Kanelakis, Kimon C ^d   Wu, Xiaodong ^a   Yan, Wen ^e   Merton, Katherine P ^a   Schoetens, Freddy ^a   Ma, Jing Ying ^a   Skaptason, Judy ^a   Gao, Jingjin ^a   Tran, Da Thao ^a   Venkatesan, Hariharan ^a   Rosen, Mark D ^d   Shankley, Nigel P ^f   Rabinowitz, Michael H ^d  

^a JOHNSON AND JOHNSON PHARMACEUTICAL RESEARCH AND DEVELOPMENT   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c Covenant Care ^*  (United States)

^d CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

^e Arcturus   (United States)

^f Higher Todsworthy Farm   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

1 [6 (2,6 DIMETHYLPHENOXY) 7 FLUORO 4 OXO 3,4 DIHYDROQUINAZOLIN 2 YL] 1H PYRAZOLE 4 CARBOXYLIC ACID; ANTIANEMIC AGENT; CYTOCHROME B; ERYTHROPOIETIN; GAMMA INTERFERON; HYPOXIA INDUCIBLE FACTOR 1ALPHA; INTERLEUKIN 6; IRON; PROCOLLAGEN PROLINE 2 OXOGLUTARATE 4 DIOXYGENASE; PROLYL HYDROXYLASE 1; PROLYL HYDROXYLASE 2; PROLYL HYDROXYLASE 3; PROLYL HYDROXYLASE INHIBITOR; RECOMBINANT ERYTHROPOIETIN; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; CATION TRANSPORT PROTEIN; HEMOGLOBIN; JNJ-42905343; PEPTIDOGLYCAN; PYRAZOLE DERIVATIVE; QUINAZOLINONE DERIVATIVE; SOLUTE CARRIER FAMILY 11- (PROTON-COUPLED DIVALENT METAL ION TRANSPORTERS), MEMBER 2;

ANEMIA; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DCYTB GENE; DMT1 GENE; DOSE TIME EFFECT RELATION; DRUG EFFICACY; DRUG MECHANISM; DRUG MEGADOSE; DRUG POTENCY; DRUG STRUCTURE; ENZYME INHIBITION; FEMALE; FUNCTIONAL IRON DEFICIENCY; GENE EXPRESSION REGULATION; HEMOGLOBIN BLOOD LEVEL; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION INDUCED ANEMIA; IRON ABSORPTION; IRON BLOOD LEVEL; IRON DEFICIENCY; IRON METABOLISM; LEUKOCYTE COUNT; LOW DRUG DOSE; MEAN CORPUSCULAR HEMOGLOBIN; MEAN CORPUSCULAR VOLUME; NONHUMAN; OUTCOME ASSESSMENT; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; TREATMENT DURATION; UPREGULATION; ANIMAL; BLOOD; CHEMICALLY INDUCED; COMPLICATION; DRUG EFFECTS; DUODENUM; GENE EXPRESSION; GENETICS; INFLAMMATION; KIDNEY; LEWIS RAT; LIVER; METABOLISM;

ANEMIA; ANIMALS; CATION TRANSPORT PROTEINS; CYTOCHROMES B; DUODENUM; ERYTHROCYTE INDICES; ERYTHROPOIETIN; FEMALE; GENE EXPRESSION; HEMOGLOBINS; INFLAMMATION; IRON; KIDNEY; LIVER; PEPTIDOGLYCAN; PROLYL-HYDROXYLASE INHIBITORS; PYRAZOLES; QUINAZOLINONES; RATS, INBRED LEW;

EID: 84937516446     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.13188     Document Type: Article

References (28)

1. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, et al. (2013a). The Concise Guide to PHARMACOLOGY 2013/14: transporters. Br J Pharmacol 170: 1706-1796.
2. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, et al. (2013b). The Concise Guide to PHARMACOLOGY 2013/14: enzymes. Br J Pharmacol. 170: 1797-1867.
3. Barrett TD, Palomino HL, Brondstetter TI, Kanelakis KC, Wu X, Haug PV, et al. (2011). Pharmacological characterization of 1-(5-chloro-6-(trifluoromethoxy)-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid (JNJ-42041935), a potent and selective hypoxia-inducible factor prolyl hydroxylase inhibitor. Mol Pharmacol 79: 910-920.
4. Besarab A, Hulter HN, Klaus S, Lee TT, Lilienfeld DE, Neff T, et al. (2010). FG-4592, a novel oral HIF prolyl hydroxylase inhibitor (HIF-PHI), elevates haemoglobin in anemic stage 3-4 CKD patients. J Am Soc Nephrol 21: 95A. (Abstract #SA-FC416).
5. Bruick RK, McKnight SL, (2001). A conserved family of prolyl-4-hydroxylases that modify HIF. Science 294: 1337-1340.
6. Coccia MA, Cooke K, Stoney G, Pistillo J, Del Castillo J, Duryea D, et al. (2001). Novel erythropoiesis stimulating protein (darbepoetin alfa) alleviates anemia associated with chronic inflammatory disease in a rodent model. Exp Hematol 29: 1201-1209.
7. Elliott J1, Mishler D, Agarwal R, (2009). Hyporesponsiveness to erythropoietin: causes and management. Adv Chronic Kidney Dis 2: 94-100.
8. Epstein AC, Gleadle JM, McNeill LA, Hewitson KS, O'Rourke J, Mole DR, et al. (2001). C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 107: 43-54.
9. Flamme I, Oehme F, Ellinghaus P, Jeske M, Keldenich J, Thuss U, (2014). Mimicking hypoxia to treat anemia: HIF-stabilizer BAY 85-3934 (molidustat) stimulates erythropoietin production without hypertensive effects. PLoS ONE 11: e111838.
10. Guideline on the Humane Care & Use of Animals (2013). Available at: http://www.jnj.com/sites/default/files/pdf/guideline-on-humane-care-and-use-of-animals-20130322.pdf (accessed 10/6/2015).
11. 2 sensing. Science 292: 464-468.
12. 2-regulated prolyl hydroxylation. Science 292: 468-472.
13. Johnson DW, Pollock CA, Macdougall IC, (2007). Erythropoiesis-stimulating agent hyporesponsiveness. Nephrology (Carlton) 12: 321-330.
14. Kanelakis KC, Palomino HL, Li L, Wu J, Yan W, Rosen MD, et al. (2009). Characterization of a robust enzymatic assay for inhibitors of 2-oxoglutarate-dependent hydroxylases. J Biomol Screen 14: 627-635.
15. Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG, (2010). Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol 8: e1000412.
16. Lando D, Peet DJ, Gorman JJ, Whelan DA, Whitelaw ML, Bruick RK, (2002). FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes Dev 16: 1466-1471.
17. Mastrogiannaki M, Matak P, Keith B, Simon MC, Vaulont S, Peyssonnaux C, (2009). HIF-2alpha, but not HIF-1 alpha, promotes iron absorption in mice. J Clin Invest 119: 1159-1166.
18. McGrath JC, Drummond GB, McLachlan EM, Kilkenny C, Wainwright CL, (2010). Guidelines for reporting experiments involving animals: the ARRIVE guidelines. Br J Pharmacol 160: 1573-1576.
19. McMullin MF, (2010). HIF pathway mutations and erythrocytosis. Expert Rev Hematol 3: 93-101.
20. Minamishima YA, Kaelin KG, (2010). Reactivation of hepatic EPO synthesis in mice after PHD loss. Science 329: 407.
21. Mittman N, Sreedhara R, Mushnick R, Chattopadhyay J, Zelmanovic D, Vaseghi M, et al. (1997). Reticulocyte haemoglobin content predicts functional iron deficiency in hemodialysis patients receiving rHuEPO. Am J Kidney Dis 30: 912-922.
22. Pawson AJ, Sharman JL, Benson HE, Faccenda E, Alexander SP, Buneman OP, et al.; NC-IUPHAR (2014). The IUPHAR/BPS Guide to PHARMACOLOGY: an expert-driven knowledgebase of drug targets and their ligands. Nucl. Acids Res 42 (Database Issue): D1098-D1106.
23. Rosen MD, Venkatesan H, Peltier HM, Bembenek SD, Kanelakis KC, Zhao LX, et al. (2010). Benzimidazole-2-pyrazole HIF prolyl 4-hydroxylase inhibitors as oral erythropoietin secretagogues. ACS Med Chem Lett 1: 526-529.
24. Sartor RB, Anderle SK, Rifai N, Goo DA, Cromartie WJ, Schwab JH, (1989). Protracted anemia associated with chronic, relapsing systemic inflammation induced by arthropathic peptidoglycan-polysaccharide polymers in rats. Infect Immun 57: 1177-1185.
25. Semenza GL, (2011). Oxygen sensing, homeostasis, and disease. N Engl J Med 365: 537-547.
26. Shah YM, Matsubara T, Ito S, Yim SH, Gonzalez FJ, (2009). Intestinal hypoxia-inducible transcription factors are essential for iron absorption following iron deficiency. Cell Metab 9: 152-164.
27. Thomas DW, Hinchliffe RH, Briggs C, Macdougall IC, Littlewood T, Cavill I, (2013). Guideline for the laboratory diagnosis of functional iron deficiency. Br J Haematol 161: 639-648.
28. Weiss G, (2009). Iron metabolism in the anemia of chronic disease. Biochim Biophys Acta 1790: 682-693