The progress in molecular targeting
therapy includes two tides, namely, small molecule compounds and large molecule
biological agents. Although the latter prevails in the field of clinical immunology, the former attracts more and more attention in these few years. Most of molecular targeting small compounds are the inhibitors of
tyrosine kinases, including pioneering
imatinib which inhibits the receptor for
platelet-derived growth factor (
PDGF), c-Abl, etc. The therapeutic concentrations of
imatinib almost completely abrogated the morphological alteration and proliferation of fibroblastic cells induced by PDGF stimulation in 3-dimensional culture system in vitro. Indeed,
imatinib has been shown to be effective in various
animal disease models for
arthritis,
interstitial pneumonia,
glomerulonephritis, and
pulmonary hypertension. Furthermore, its efficacy in patients with
systemic sclerosis has been recently reported from several institutes. Since established treatments had not been found for fibrotic lesion before,
imatinib, a dual inhibitor of both
transforming growth factor beta-, and PDGF-signaling, is likely to be a potent
drug against
fibrosis. Its efficacy and safety in fibrotic and immune-mediated diseases, such as
systemic sclerosis, are currently under investigation throughout the world.