PMID- 17669674
OWN - NLM
STAT- MEDLINE
DCOM- 20081027
LR  - 20161124
IS  - 1094-5539 (Print)
IS  - 1094-5539 (Linking)
VI  - 21
IP  - 3
DP  - 2008
TI  - Syk inhibitors as treatment for allergic rhinitis.
PG  - 461-7
AB  - Allergic rhinitis is characterized by a hypersensitive immune response in the 
      upper airways to seasonal or perennial allergens leading to episodes of sneezing, 
      itching, runny nose and nasal congestion. These symptoms are mainly the 
      manifestations of a large number of mediators released by mast cells and 
      basophils localized in the nasal mucosa, following their activation via 
      allergen-specific immunoglobulin E (IgE) receptors. Current medications 
      antagonize the action of distinct mediators such as histamine and leukotrienes 
      for symptom relief, or block the production of pro-inflammatory cytokines to 
      suppress allergic inflammation. Notably, rather than neutralizing individual 
      mediators, Syk kinase inhibitors can block the allergen-induced release of all 
      mast cell mediators and the production of most eicosanoids and cytokines. Thus, 
      Syk kinase represents an attractive therapeutic target for acute and chronic 
      allergic inflammation. Syk kinase inhibitors are now entering clinical trials. 
      Using cell-based structure-activity relationships with primary human mast cells, 
      a series of 2,4-diaminopyrimidine Syk kinase inhibitors was developed. One of 
      these compounds, referred to as R112, exhibited suitable characteristics for 
      intranasal delivery and was tested for safety and efficacy in allergic rhinitis 
      patients. In a park environment, R112 showed remarkable amelioration of acute 
      allergic rhinitis symptoms with rapid onset of action. These results demonstrate 
      the clinical significance of inhibiting Syk in allergic upper airway disorders.
FAU - Masuda, Esteban S
AU  - Masuda ES
AD  - Rigel Inc., 1180 Veterans Boulevard, South San Francisco, CA 94080, USA. 
      emasuda@rigel.com <emasuda@rigel.com>
FAU - Schmitz, Jochen
AU  - Schmitz J
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20070628
PL  - England
TA  - Pulm Pharmacol Ther
JT  - Pulmonary pharmacology & therapeutics
JID - 9715279
RN  - 0 (Anti-Allergic Agents)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Receptors, IgE)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (SYK protein, human)
RN  - EC 2.7.10.2 (Syk Kinase)
SB  - IM
MH  - Animals
MH  - Anti-Allergic Agents/pharmacology/*therapeutic use
MH  - Enzyme Inhibitors/pharmacology/*therapeutic use
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Immunoglobulin E/drug effects/physiology
MH  - Intracellular Signaling Peptides and Proteins/*antagonists & inhibitors/genetics
MH  - Protein-Tyrosine Kinases/*antagonists & inhibitors/genetics
MH  - Receptors, IgE/drug effects/physiology
MH  - Rhinitis, Allergic, Perennial/*drug therapy/immunology/physiopathology
MH  - Rhinitis, Allergic, Seasonal/*drug therapy/immunology/physiopathology
MH  - Signal Transduction/drug effects
MH  - Syk Kinase
RF  - 54
EDAT- 2007/08/03 09:00
MHDA- 2008/10/28 09:00
CRDT- 2007/08/03 09:00
PHST- 2007/08/03 09:00 [pubmed]
PHST- 2008/10/28 09:00 [medline]
PHST- 2007/08/03 09:00 [entrez]
AID - S1094-5539(07)00050-8 [pii]
AID - 10.1016/j.pupt.2007.06.002 [doi]
PST - ppublish
SO  - Pulm Pharmacol Ther. 2008;21(3):461-7. doi: 10.1016/j.pupt.2007.06.002. Epub 2007 
      Jun 28.