Clinical and preclinical characterization of the Histamine H4 receptor Antagonist JNJ-39758979s

Journal of Pharmacology and Experimental Therapeutics

Volumn 349, Issue 2, 2014, Pages 176-184

  Thurmond, Robin L ^a   Chen, Bin ^a   Dunford, Paul J ^a   Greenspan, Andrew J ^a   Karlsson, Lars ^a,b   La, David ^a   Ward, Peter ^a   Xu, Xie L ^a  

^a JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

^b NOVO NORDISK A S   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

4 (3 AMINO PYRROLIDIN 1 YL) 6 ISOPROPYL PYRIMIDIN 2 YLAMINE; ANTIHISTAMINIC AGENT; HISTAMINE H4 RECEPTOR; JNJ 39758979; PLACEBO; UNCLASSIFIED DRUG;

ABDOMINAL PAIN; ABNORMAL FECES; ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DIARRHEA; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG DETERMINATION; DRUG DISTRIBUTION; DRUG DOSE ESCALATION; DRUG ELIMINATION; DRUG HALF LIFE; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SAFETY; DRUG SCREENING; DRUG STRUCTURE; DRUG TISSUE LEVEL; DRUG TOLERABILITY; EAR EDEMA; EPISTAXIS; FEMALE; FLU LIKE SYNDROME; GASTROINTESTINAL SYMPTOM; HEADACHE; HERPETIC STOMATITIS; HUMAN; HUMAN EXPERIMENT; IN VITRO STUDY; IN VIVO STUDY; MACACA FASCICULARIS; MALAISE; MALE; MAXIMUM PLASMA CONCENTRATION; NAUSEA; NONHUMAN; OROPHARYNX PAIN; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RASH; RAT; TIME TO MAXIMUM PLASMA CONCENTRATION; TOXICITY TESTING; VOMITING;

ANIMALS; ANTI-INFLAMMATORY AGENTS; ASTHMA; CELL SHAPE; DERMATITIS, CONTACT; DOUBLE-BLIND METHOD; EOSINOPHILS; FEMALE; HUMANS; ISOTHIOCYANATES; MACACA FASCICULARIS; MALE; OVALBUMIN; PYRIMIDINES; RATS; RECEPTORS, G-PROTEIN-COUPLED; RECEPTORS, HISTAMINE; THIAZOLES;

EID: 84897437498     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.113.211714     Document Type: Article

References (24)

1. Ballerini C, Aldinucci A, Luccarini I, Galante A, Manuelli C, Blandina P, Katebe M, Chazot PL, Masini E, and Passani MB (2013) Antagonism of histamine H4 receptors exacerbates clinical and pathological signs of experimental autoimmune encephalomyelitis. Br J Pharmacol 170:67-77
2. Cowden JM, Riley JP, Ma JY, Thurmond RL, and Dunford PJ (2010a) Histamine H4 receptor antagonism diminishes existing airway inflammation and dysfunction via modulation of Th2 cytokines. Respir Res 11:86
3. Cowden JM, Yu F, Banie H, Farahani M, Ling P, Nguyen S, Riley JP, Zhang M, Zhu J, and Dunford PJ, et al. (2014) The histamine H4 receptor mediates inflammation and Th17 responses in preclinical models of arthritis. Ann Rheum Dis 73:600-608
4. Cowden JM, Zhang M, Dunford PJ, and Thurmond RL (2010b) The histamine H4 receptor mediates inflammation and pruritus in Th2-dependent dermal inflammation. J Invest Dermatol 130:1023-1033
5. del Rio R, Noubade R, Saligrama N, Wall EH, Krementsov DN, Poynter ME, Zachary JF, Thurmond RL, and Teuscher C (2012) Histamine H4 receptor optimizes T regulatory cell frequency and facilitates anti-inflammatory responses within the central nervous system. J Immunol 188:541-547
6. Dunford PJ, O'Donnell N, Riley JP, Williams KN, Karlsson L, and Thurmond RL (2006) The histamine H4 receptor mediates allergic airway inflammation by regulating the activation of CD41 T cells. J Immunol 176:7062-7070
7. Dunford PJ, Williams KN, Desai PJ, Karlsson L,McQueen D, and Thurmond RL (2007) Histamine H4 receptor antagonists are superior to traditional antihistamines in the attenuation of experimental pruritus. J Allergy Clin Immunol 119: 176-183
8. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, and Harvey KJ (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem J 451:313-328
9. Ling P, Ngo K, Nguyen S, Thurmond RL, Edwards JP, Karlsson L, and Fung-Leung W-P (2004) Histamine H4 receptor mediates eosinophil chemotaxis with cell shape change and adhesion molecule upregulation. Br J Pharmacol 142:161-171
10. Matsushita A, Seike M, Okawa H, Kadawaki Y, and Ohtsu H (2012) Advantages of histamine H4 receptor antagonist usage with H1 receptor antagonist for the treatment of murine allergic contact dermatitis. Exp Dermatol 21: 714-715
11. Mowbray CE, Bell AS, Clarke NP, Collins M, Jones RM, Lane CAL, Liu WL, Newman SD, Paradowski M, and Schenck EJ, et al. (2011) Challenges of drug discovery in novel target space. The discovery and evaluation of PF-3893787: a novel histamine H4 receptor antagonist. Bioorg Med Chem Lett 21:6596-6602
12. Nent E, Frommholz D, Gajda M, Bräuer R, and Illges H (2013) Histamine 4 receptor plays an important role in auto-Antibody-induced arthritis. Int Immunol 25: 437-443
13. Ohsawa Y and Hirasawa N (2012) The antagonism of histamine H1 and H4 receptors ameliorates chronic allergic dermatitis via anti-pruritic and anti-inflammatory effects in NC/Nga mice. Allergy 67:1014-1022
14. Reasor MJ, Hastings KL, and Ulrich RG (2006) Drug induced phospholipidosis: issues and future directions. Expert Opin Drug Saf 5:567-583
15. Rossbach K, Nassenstein C, Gschwandtner M, Schnell D, Sander K, Seifert R, Stark H, Kietzmann M, and Bäumer W (2011) Histamine H1, H3 and H4 receptors are involved in pruritus. Neuroscience 190:89-102
16. Salcedo C, Pontes C, and Merlos M (2013) Is the H4 receptor a new drug target for allergies and asthma? Front. Biosci. Elite Ed. E5:178-187
17. Savall BM, Chavez F, Tays K, Dunford PJ, Cowden J, Hack MD, Wolin RL, Thurmond RL, and Edwards JP (2014) Discovery and SAR of 6-Alkyl-2,4- diaminopyrimidines as histamine H4 receptor antagonists. J Med Chem DOI:10.1021/jm401727m [published ahead of print]
18. Shin N, Covington M, Bian D, Zhuo J, Bowman K, Li Y, Soloviev M, Qian D-Q, Feldman P, and Leffet L, et al. (2012) INCB38579, a novel and potent histamine H4 receptor small molecule antagonist with anti-inflammatory pain and anti-pruritic functions. Eur J Pharmacol 675:47-56
19. Somma T, Cinci L, Formicola G, Pini A, Thurmond R, Ennis M, Bani D, and Masini E (2013) A selective antagonist of histamine H4 receptors prevents antigen-induced airway inflammation and bronchoconstriction in guinea pigs: involvement of lipocortin-1. Br J Pharmacol 170:200-213
20. Suwa E, Yamaura K, Oda M, Namiki T, and Ueno K (2011) Histamine H(4) receptor antagonist reduces dermal inflammation and pruritus in a hapten-induced experimental model. Eur J Pharmacol 667:383-388
21. Thurmond RL, Desai PJ, Dunford PJ, Fung-Leung W-P, Hofstra CL, Jiang W, Nguyen S, Riley JP, Sun S, and Williams KN, et al. (2004) A potent and selective histamine H4 receptor antagonist with anti-inflammatory properties. J Pharmacol Exp Ther 309:404-413
22. Varga C, Horvath K, Berko A, Thurmond RL, Dunford PJ, and Whittle BJR (2005) Inhibitory effects of histamine H4 receptor antagonists on experimental colitis in the rat. Eur J Pharmacol 522:130-138
23. Yamaura K, Oda M, Suwa E, Suzuki M, Sato H, and Ueno K (2009) Expression of histamine H4 receptor in human epidermal tissues and attenuation of experimental pruritus using H4 receptor antagonist. J Toxicol Sci 34:427-431
24. Yu F, Wolin RL, Wei J, Desai PJ, McGovern PM, Dunford PJ, Karlsson L, and Thurmond RL (2010) Pharmacological characterization of oxime agonists of the histamine H4 receptor. J Receptor Ligand Channel Res 3:37-49.