PMID- 28259713
OWN - NLM
STAT- MEDLINE
DCOM- 20170417
LR  - 20170417
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 801
DP  - 2017 Apr 15
TI  - JTE-852, a novel spleen tyrosine kinase inhibitor, blocks mediator secretion from 
      mast cells with immunoglobulin E crosslinking.
PG  - 1-8
LID - S0014-2999(17)30136-X [pii]
LID - 10.1016/j.ejphar.2017.02.048 [doi]
AB  - Mast cells stimulated by immunoglobulin E (IgE)-crosslinking secrete mediators, 
      which are mainly categorized into three groups: granule contents, arachidonate 
      metabolites, and cytokines. These mediators play important roles in pathogenesis 
      of allergic diseases; indeed, some conventional drugs which target the mediators 
      are used in clinical practices. However, these drugs are not yet sufficient 
      enough in their efficacy. That is because most of them are blockers of single 
      mediators and are unable to prevent simultaneously various reactions caused by 
      the three group mediators. Spleen tyrosine kinase (Syk) is a non-receptor protein 
      tyrosine kinase. In mast cells, Syk locates at almost top of the signal cascades 
      induced by IgE-crosslinking and plays pivotal roles in secretion of the three 
      groups of mediators. Therefore, inhibition of Syk would suppress the secretion of 
      all the mediators from mast cells and be a promising-treatment strategy for 
      allergic diseases. In the present study, we characterized pharmacological 
      profiles of JTE-852, which was identified as a novel Syk inhibitor. JTE-852 
      inhibited kinase activity of Syk in an adenosine 5'-triphosphate 
      (ATP)-competitive fashion. JTE-852 also blocked the secretion of granule 
      contents, arachidonate metabolites, and cytokines from mast cells stimulated by 
      IgE-crosslinking, with similar potencies. The results suggest that JTE-852 is 
      supposed to prevent various allergic reactions caused by the three group 
      mediators in vivo. In fact, oral gavage of JTE-852 attenuated an allergic 
      reaction mediated by histamine, which is a representative of the three groups of 
      mediators. JTE-852 is expected to be a novel, highly-efficacious, and orally 
      available anti-allergic drug.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Kato, Toshinobu
AU  - Kato T
AD  - Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research 
      Institute, Japan Tobacco Inc., Osaka, Japan. Electronic address: 
      toshinobu.kato@jt.com.
FAU - Iwasaki, Hidenori
AU  - Iwasaki H
AD  - Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research 
      Institute, Japan Tobacco Inc., Osaka, Japan.
FAU - Kobayashi, Hatsue
AU  - Kobayashi H
AD  - Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research 
      Institute, Japan Tobacco Inc., Osaka, Japan.
FAU - Miyagawa, Naoki
AU  - Miyagawa N
AD  - Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research 
      Institute, Japan Tobacco Inc., Osaka, Japan.
FAU - Matsuo, Akira
AU  - Matsuo A
AD  - Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research 
      Institute, Japan Tobacco Inc., Osaka, Japan.
FAU - Hata, Takahiro
AU  - Hata T
AD  - Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research 
      Institute, Japan Tobacco Inc., Osaka, Japan.
FAU - Matsushita, Mutsuyoshi
AU  - Matsushita M
AD  - Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research 
      Institute, Japan Tobacco Inc., Osaka, Japan.
LA  - eng
PT  - Journal Article
DEP - 20170301
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Aminopyridines)
RN  - 0 (JTE-852)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Thiazoles)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - EC 2.7.10.2 (Syk Kinase)
SB  - IM
MH  - Aminopyridines/*pharmacology
MH  - Animals
MH  - Cell Line, Tumor
MH  - Immunoglobulin E/*immunology
MH  - Intracellular Space/drug effects/metabolism
MH  - Mast Cells/cytology/*drug effects/*immunology/metabolism
MH  - Passive Cutaneous Anaphylaxis/drug effects
MH  - Protein Kinase Inhibitors/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Syk Kinase/*antagonists & inhibitors/metabolism
MH  - Thiazoles/*pharmacology
OTO - NOTNLM
OT  - Allergy
OT  - IgE-crosslinking
OT  - JTE-852
OT  - Mast cell
OT  - Mediator
OT  - Spleen tyrosine kinase
EDAT- 2017/03/06 06:00
MHDA- 2017/04/18 06:00
CRDT- 2017/03/06 06:00
PHST- 2017/01/25 00:00 [received]
PHST- 2017/02/28 00:00 [revised]
PHST- 2017/02/28 00:00 [accepted]
PHST- 2017/03/06 06:00 [pubmed]
PHST- 2017/04/18 06:00 [medline]
PHST- 2017/03/06 06:00 [entrez]
AID - S0014-2999(17)30136-X [pii]
AID - 10.1016/j.ejphar.2017.02.048 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2017 Apr 15;801:1-8. doi: 10.1016/j.ejphar.2017.02.048. Epub 
      2017 Mar 1.