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Table 3 Interference with Th2 signal transduction pathway and their inhibitors

From: Treatment of allergic asthma: Modulation of Th2 cells and their responses

Class

Examples of inhibitor(s)

Effect

Reference*

EGF receptor inhibitor

Gefitinib

Reduces the cell counts and Th2 cytokine levels in an OVA-challenged mouse model of allergic asthma

[200]

Syk inhibitors

BAY 61-3606

Inhibits disease signs in a mouse model of asthma

[201]

 

R112

Reduces allergic rhinitis upon intranasal administration

[202]

JAK3 inhibitors

CP690550

Blocks expression and signalling of IL-2, IL-4 and IL-13

[203]

 

WHI-P131 and WHI-P97

Interferes with inflammatory mediators and mast cell degranulation in animal models of asthma

[204, 205]

p38 MAPK/ERK inhibitor

U0126

Inhibits airway and lung inflammation in mouses model of asthma

Role of p38 in steroid resistant asthma patients is investigated in a clinical trial

[206]

NCT00676572

Inhaled p38 MAPK antisense oligonucleotide

ISIS101757

Inhibits allergic immunity in mice

[207]

p38α inhibitors

BIRB796, SB203580 and RWJ67657

Inhibits airway and lung inflammation in mouse models of asthma

[208–210]

JNK inhibitor

SP600125

Inhibits T cell cytokine production and lung inflammation in mouse models of asthma

[211, 212]

Inhibitor of adenosine A1, A2b and A3 receptors, p38 MAPK and PDE4D

CGH2466

Inhibits allergic asthma in mice

[213]

PI3K inhibitors

Wortmannin and Ly294002

Inhibits allergic asthma in mice

[214, 215]

Inhibitor of IkappaB kinase-2 (IKK-2)

N/A

Reduces allergen-induced airway inflammation and AHR in animal models of asthma

[216, 217]

IkappaB ubiquitination inhibitor

GS143

Represses Th2, but not Th1 differentiation after allergen challenge in a mouse model of allergic asthma

[218]

Selective PDE4 inhibitors

GSK256066, MK-0359

Inhibits the fall in lung function in patients with asthma caused by inhaled allergen challenge

[219, 220]

PDE3 and PDE4 inhibitors

RPL554

Inhibits eosinophil recruitment following antigen challenge in guinea pigs

[221]

  1. * Numbers starting with NTC represent clinical study code from http://clinicaltrials.gov/