Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 29, Issue 4, Pages 534-538Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2019.01.003
Keywords
Melanoma; BRAF(v600E); BRAF(wt) CRAF; Selectivity
Categories
Funding
- National Research Foundation of Korea [NRF-2017R1A2B4006447]
Ask authors/readers for more resources
Notorious oncogenic BRAF V600E plays a significant role in the signal transduction of the MAPK pathway, which is involved in tumor growth, especially in melanoma. Much effort has been made to suppress BRAF V600E through small molecules like vemurafenib and dabrafenib, but the MAPK pathway remains active through paradoxical activation, where CRAF transmits the signal of the MAPK pathway either alone or along with BRAF V600E. Therefore, we designed and synthesized a new series of N-(3-(3-alkyl-1H-pyrazol-5-yl) phenyl)-aryl amide/urea analogues that showed potent inhibitory activities against BRAF V600E and CRAF. Compound 7c exhibited particularly superior selectivity toward BRAF V600E and CRAF over 30 other protein kinases, implying that this chemotype could be investigated as a BRAF paradox breaker. (C) 2019 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available