Dermatology; pulmonary

Cell culture and mouse studies suggest inhibiting SHP-2 could help treat dermal and pulmonary fibrosis. In primary human dermal fibroblasts stimulated with the fibrosis mediator transforming growth factor β 1(TGFB1), levels of SHP-2 activity were higher than in unstimulated fibroblasts. In two genetic mouse models of dermal fibrosis and one mouse model of chemical-induced dermal fibrosis, fibroblast-specific knockout of SHP-2 decreased dermal thickness, myofibroblast numbers and hydroxyproline levels in the skin compared with normal SHP-2 expression. In one of the genetic models of dermal fibrosis and in a mouse model of chemical-induced pulmonary fibrosis, three tool compound SHP-2 inhibitors decreased myofibroblast numbers and hydroxyproline levels in fibrotic tissues compared with vehicle. Also in the model of dermal fibrosis, the compounds decreased dermal thickness, and in the model of pulmonary fibrosis, the compounds decreased fibrotic area in the lung. Next steps could include testing SHP-2 inhibition in animal models of other types of fibrosis.

Novartis AG has the SHP-2 inhibitor TNO155 in Phase I testing for non-small cell lung cancer (NSCLC) and solid tumors...