PLX4032, a potent inhibitor of the B-Raf V600E oncogene, selectively inhibits V600E-positive melanomas

Lee, John T., Li, Ling, Brafford, Patricia A., Van Den Eijnden, Marcia, Halloran, Molly B., Sproesser, Katrin, Haass, Nikolas K., Smalley, Keiran S. M., Tsai, James, Bollag, Gideon and Herlyn, Meenhard (2010) PLX4032, a potent inhibitor of the B-Raf V600E oncogene, selectively inhibits V600E-positive melanomas. Pigment Cell and Melanoma Research, 23 6: 820-827. doi:10.1111/j.1755-148X.2010.00763.x


Author Lee, John T.
Li, Ling
Brafford, Patricia A.
Van Den Eijnden, Marcia
Halloran, Molly B.
Sproesser, Katrin
Haass, Nikolas K.
Smalley, Keiran S. M.
Tsai, James
Bollag, Gideon
Herlyn, Meenhard
Title PLX4032, a potent inhibitor of the B-Raf V600E oncogene, selectively inhibits V600E-positive melanomas
Journal name Pigment Cell and Melanoma Research   Check publisher's open access policy
ISSN 1755-1471
1755-148X
Publication date 2010
Year available 2010
Sub-type Article (original research)
DOI 10.1111/j.1755-148X.2010.00763.x
Open Access Status
Volume 23
Issue 6
Start page 820
End page 827
Total pages 8
Place of publication Malden, MA United States
Publisher Wiley-Blackwell Publishing, Inc.
Collection year 2011
Language eng
Subject 2708 Dermatology
2730 Oncology
1300 Biochemistry, Genetics and Molecular Biology
Abstract Targeted intervention of the B-Raf V600E gene product that is prominent in melanoma has been met with modest success. Here, we characterize the pharmacological properties of PLX4032, a next-generation inhibitor with exquisite specificity against the V600E oncogene and striking anti-melanoma activity. PLX4032 induces potent cell cycle arrest, inhibits proliferation, and initiates apoptosis exclusively in V600E-positive cells in a variety of in vitro experimental systems; follow-up xenograft studies demonstrate extreme selectivity and efficacy against melanoma tumors bearing the V600E oncoproduct. The collective data support further exploration of PLX4032 as a candidate drug for patients with metastatic melanoma; accordingly, validation of PLX4032 as a therapeutic tool for patients with melanoma is now underway in advanced human (Phase III) clinical trials.
Keyword Melanoma
Therapy
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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Created: Fri, 30 May 2014, 17:51:36 EST by Nikolas Haass on behalf of UQ Diamantina Institute