ausblenden:
Schlagwörter:
RECEPTOR TYROSINE KINASE; MYELOID-LEUKEMIA CELLS; BREAST-CANCER;
SURVIVAL ACTIVITIES; TUMOR; GAS6; FIBROBLASTS; METASTASIS; ACTIVATION;
RESISTANCEPharmacology & Pharmacy;
Zusammenfassung:
The overexpression of AXL kinase has been described in many types of cancer. Due to its role in proliferation, survival, migration, and resistance, AXL represents a promising target in the treatment of the disease. In this study we present a novel compound family that successfully targets the AXL kinase. Through optimization and detailed SAR studies we developed low nanomolar inhibitors, and after further biological characterization we identified a potent AXL kinase inhibitor with favorable pharmacokinetic profile. The antitumor activity was determined in xenograft models, and the lead compounds reduced the tumor size by 40% with no observed toxicity as well as lung metastasis formation by 66% when compared to vehicle control.
