Notch-signaling activity determines uptake and biological effect of imatinib in systemic sclerosis dermal fibroblasts.

Tyrosine kinase inhibitors (TKI) have emerged as therapeutic option for rheumatic diseases such as systemic sclerosis (SSc). Since TKs like c-Abl kinase are important for fibroblast activation and fibrosis development in SSc, the c-Abl inhibitor imatinib was proposed for SSc treatment. Transporters for organic cations have become increasingly recognized as an important determinant for uptake and efficacy of TKI. Therefore, we investigated the role of organic cation transporters in the uptake of imatinib.