Dabrafenib, Methanesulfonate Salt (Dabrafenib Mesylate, GSK-2118436, Tafinlar, CAS 1195768-06-9), >99%

LC Laboratories' Product Number D-5699 - Dabrafenib, Methanesulfonate Salt (Dabrafenib Mesylate, GSK-2118436, Tafinlar, CAS 1195768-06-9), >99% - for research use only. Dabrafenib, also known as GSK2118436, is a potent and selective BRAF inhibitor. It inhibited human wtBRAF, BRAF(V600E) and BRAF(V600K) kinase activities with IC50 values of 3.2, 0.6, and 0.5 nM, respectively, decreased MEK and ERK phosphorylation, and blocked cell proliferation. In a BRAF(V600E)-containing xenograft model of human melanoma, dabrafenib inhibited ERK activation and tumor growth. However, dabrafenib caused MAPK pathway activation in wild-type BRAF cells through CRAF (RAF1) signalling. This research compound is the methanesulfonate salt form of dabrafenib. We also offer the free base form; please see Dabrafenib, Free Base, Cat. No. D-5678. Dabrafenib inhibited B-RafV600E kinase with an IC50 of 0.7 nM, inhibited pERK in SKMEL28 cells with an IC50 of 4 nM, and blocked SKMEL28 cell proliferation with an IC50 of 3 nM. It also dramatically inhibited tumor growth in mice bearing B-RafV600E human melanoma tumors. Dabrafenib inhibited cell proliferation and MAPK pathway in melanoma cell lines carrying BRAFV600D and BRAFV600R mutations but had no significant anti-proliferative effect in a melanoma cell line carrying wild type BRAF. The acquired resistance to the BRAF inhibitor dabrafenib in the A375 BRAFV600E and the YUSIT1 BRAFV600K melanoma cell lines was overcome by combinations of BRAF, MEK, and PI3K/mTOR inhibitors. A phase I clinical study showed that dabrafenib was tolerable, had activity against BRAFV600E and BRAFV600K melanoma, and had activity against melanoma metastases in the brain. A phase 2 clinical trial demonstrated that dabrafenib had activity and an acceptable safety profile in patients with BRAFV600E melanoma and brain metastases. A phase 3 trial in patients with BRAF(V600E)-mutated metastatic melanoma demonstrated dabrafenib significantly improved progression-free survival compared with dacarbazine. Dabrafenib is the active ingredient in the drug product sold under the trade name Tafinlar®. This drug is currently approved in at least one country for use in patients with melanoma. NOTE: THE DABRAFENIB, FREE BASE RESEARCH COMPOUND SOLD BY LC LABORATORIES IS NOT TAFINLAR®, AND IS NOT FOR HUMAN USE. This dabrafenib product is the methanesulfonate salt, whose CAS number is given above. The CAS number of the free base form is 1195765-45-7.

• Supplier: LC Laboratories
• Product #: D-5699
• Sku #: D-5699_500mg