GDC-0879 has been researched along with Neoplasms* in 2 studies
1 review(s) available for GDC-0879 and Neoplasms
| Article | Year |
|---|---|
Current Insights of BRAF Inhibitors in Cancer.
Oncogenic BRAF kinase deregulates the ERK signaling pathway in a large number of human tumors. FDA-approved BRAF inhibitors for BRAFV600E/K tumors have provided impressive clinical responses extending survival of melanoma patients. However, these drugs display paradoxical activation in normal tissue with BRAFWT due to RAF transactivation and priming, acquired drug resistance, and limited clinical effectiveness in non-V600 BRAF-dependent tumors, underscoring the urgent need to develop improved BRAF inhibitors. This review provides an overview of recent structural and biochemical insights into the mechanisms of BRAF regulation by BRAF inhibitors that are linked to their clinical activity, clinical liabilities, and medicinal chemistry properties. The effectiveness and challenges of structurally diverse next generation RAF inhibitors currently in preclinical and clinical development are discussed, along with mechanistic insights for developing more effective RAF inhibitors targeting different oncogenic BRAF conformations. Topics: Animals; Drug Discovery; Humans; Mutation; Neoplasms; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf | 2018 |
1 other study(ies) available for GDC-0879 and Neoplasms
| Article | Year |
|---|---|
Design, synthesis and biological evaluation of novel 5-phenyl-1H-pyrazole derivatives as potential BRAF(V600E) inhibitors.
A series of novel 5-phenyl-1H-pyrazole derivatives (5 a-5 u) containing niacinamide moiety were synthesized and evaluated for biological activity as potential BRAF(V600E) inhibitors. Among them, compound 5h exhibited the most potent inhibitory activity with an IC50 value of 0.33 μM for BRAF(V600E). Antiproliferative assay results indicated that compound 5h has better antiproliferative activity against WM266.4 and A375 in vitro with IC50 value of 2.63 and 3.16 μM, respectively, being comparable with the positive control vemurafenib. Molecular docking of 5h into the BRAF(V600E) active site was performed to determine the probable binding mode. Furthermore, molecular docking and 3D QSAR study by means of DS 3.5 (Discovery Studio 3.5, Accelrys, Co. Ltd) explored the binding modes and the structure and activity relationship (SAR) of these derivatives. Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Humans; Molecular Docking Simulation; Neoplasms; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Pyrazoles; Quantitative Structure-Activity Relationship; Structure-Activity Relationship | 2014 |