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MEK signaling inhibitor

Dysregulated MAPK signaling is implicated in a wide range of cancers and occurs via multiple mechanisms.² Abnormal expression or activating mutations in receptors, such as EGFR, may lead to overactive MAPK signaling.¹ Additionally, activating K-Ras and B-Raf mutations that are exhibited in
a large number of solid tumors lead to overactive MAPK signaling and may confer resistance to chemotherapeutic and targeted agents.^1,2

The inhibition of MAPK signaling with agents targeted toward critical proteins in the pathway, such as MEK, has the potential to inhibit growth in a variety of tumor types.⁶ GDC-0973 is a potent, selective, orally bioavailable small molecule inhibitor of MEK being developed in collaboration with Exelixis, that is designed to bind to MEK in a non-ATP site, resulting in high specificity.^6,7 Inhibiting MEK may overcome activating mutations that occur upstream in the MAPK cascade.⁶

1. GDC-0973 is a small molecule being developed in collaboration with Exelixis, that, in preclinical studies, potently and selectively inhibits MEK, a key mediator of cell proliferation and survival.^6,7

   

2. GDC-0973 binds to MEK, resulting in inhibition of its kinase activity. As a consequence, the oncogenic signal from cell surface, Ras and Raf, to ERK is interrupted.^6,7

   

3. Sustained inhibition of ERK activation translates into decreased proliferation and induction of apoptosis. In multiple preclinical studies, GDC-0973 has been shown to inhibit cell growth and induce tumor regression.⁷

   

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