Structure-Guided Strategy for the Development of Potent Bivalent ERK Inhibitors.

ABSTRACT: ERK is the effector kinase of the RAS-RAF-MEK-ERK signaling cascade, which promotes cell transformation and malignancy in many cancers and is thus a major drug target in oncology. Kinase inhibitors targeting RAF or MEK are already used for the treatment of certain cancers, such as melanoma. Although the initial response to these drugs can be dramatic, development of drug resistance is a major challenge, even with combination therapies targeting both RAF and MEK. Importantly, most resistance mechanisms still rely on activation of the downstream effector kinase ERK, making it a promising target for drug development efforts. Here, we report the design and structural/functional characterization of a set of bivalent ERK inhibitors that combine a small molecule inhibitor that binds to the ATP-bi

SUBMITTER: Lechtenberg BC 

PROVIDER: S-EPMC5512124 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature