Vemurafenib, Free Base **
產品名稱：Vemurafenib, Free Base
產品貨號：LC V-2800
產品規(guī)格：1 G
NOTE: As of September 2011 the current correct CAS number for vemurafenib, also known as PLX4032, is given above. Chemical Abstracts Service recently canceled another CAS number, 1029872-54-5, that had previously been used for vemurafenib under its older name, PLX4032. However, this canceled number remains in wide use and receives the vast majority of hits on Google.
Vemurafenib inhibited ERK1/2 in the highly sensitive BRAF(V600E/K) cells, while it activated the pathway in the (resistant) BRAF(WT) cells. Halaban, R., et al. "PLX4032, a selective BRAF(V600E) kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAF melanoma cells." Pigment Cell Melanoma Res. 23: 190-200 (2010).
Using an IC50g cutoff of 1 µM, 13 of 35 cell lines tested showed sensitivity to vemurafenib, 16 were resistant, and 6 were intermediate in sensitivity. Vemurafenib caused growth inhibition, G0/G1 arrest, and apoptosis in the sensitive cell lines. A BRAF mutation favored but did not guarantee a sensitive response, while cells bearing a neuroblastoma RAS viral oncogene homolog mutation or wild-type BRAF were resistant. Tap, W.D., et al. "Pharmacodynamic characterization of the efficacy signals due to selective BRAF inhibition with PLX4032 in malignant melanoma." Neoplasia 12: 637-649 (2010).
Vemurafenib inhibited the growth of B-Raf V600E-positive melanomas in vitro and in vivo. Lee, J.T., et al. "PLX4032, a potent inhibitor of the B-Raf V600E oncogene, selectively inhibits V600E-positive melanomas." Pigment Cell Melanoma Res. 23: 820-827 (2010).
Vemurafenib selectively inhibited the RAF/MEK/ERK pathway in BRAF mutant cells and induced regression of BRAF mutant xenografts. However, no tumor regression occurred in patients until greater than 80% inhibition of ERK phosphorylation in the tumors was reached. Bollag, G., et al. "Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma." Nature 467: 596-599 (2010).
Treatment of patients with metastatic melanoma that carry the V600E BRAF mutation with vemurafenib resulted in complete or partial tumor regression in the majority of patients. Flaherty, K.T., et al. "Inhibition of mutated, activated BRAF in metastatic melanoma." N. Engl. J. Med. 363: 809-819 (2010).
Vemurafenib is the active ingredient in the drug product sold under the trade name Zelboraf®. This drug is currently approved in at least one country for use in patients with late-stage melanoma. NOTE: THE VEMURAFENIB, FREE BASE RESEARCH COMPOUND SOLD BY LC LABORATORIES IS NOT ZELBORAF®, AND IS NOT FOR HUMAN USE.
Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 100 mg/mL; very poorly soluble in ethanol; very poorly soluble in water; maximum solubility in plain water is estimated to be about 25-50 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A
