PLX-4720 is a potent and selective inhibitor of B-RafV600E with IC50 of 13 nM in a cell-free assay, equally potent to c-Raf-1(Y340D and Y341D mutations), and 10-fold selectivity for B-RafV600E than wild-type B-Raf.
PLX-4720 is a potent and selective inhibitor of B-RafV600E with IC50 of 13 nM in a cell-free assay, equally potent to c-Raf-1(Y340D and Y341D mutations), and 10-fold selectivity for B-RafV600E than wild-type B-Raf.
Targets
Target
Value
Cell Research
Cell Line
Type
Value
Description
References
In Vitro
Kinase Selectivity: PLX-4720 exhibits high selectivity for the oncogenic B-Raf^V600E^ kinase, displaying >10 times selectivity against wild-type B-Raf and >100 times selectivity over other kinases, such as Frk, Src, Fak, FGFR, and Aurora A, with IC50 values ranging from 1.3 to 3.4 μM. [1]
ERK Phosphorylation Inhibition: PLX-4720 significantly inhibits ERK phosphorylation in cell lines bearing the B-Raf^V600E^ mutation, with IC50 values ranging from 14 to 46 nM, while showing minimal effect on cells with wild-type B-Raf. [1]
Tumor Cell Growth Inhibition: PLX-4720 potently inhibits the growth of tumor cell lines harboring the B-Raf^V600E^ oncogene. For example, it shows GI50 values of 0.31 μM in COLO205, 0.50 μM in A375, 1.5 μM in WM2664, and 1.7 μM in COLO829 cells. [1]
Induction of Apoptosis and Cell Cycle Arrest: PLX-4720 treatment at 1 μM induces cell cycle arrest and apoptosis exclusively in B-Raf^V600E^ mutant cell lines, such as 1205Lu cells, but has no effect on B-Raf wild-type cells, such as C8161. [1]
PTEN Status and BIM Expression: PLX-4720 treatment (10 μM) significantly increases BIM expression (>14-fold) in PTEN+ melanoma cells, whereas PTEN- cell lines exhibit only a 4-fold increase in BIM expression. This difference explains the resistance of PTEN- cells to PLX-4720-induced apoptosis. [2]
References
Tsai J, et al. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc Natl Acad Sci U S A, 2008, 105(8), 3041-3046. PMID: 18287029
Paraiso KH, et al. PTEN loss confers BRAF inhibitor resistance to melanoma cells through the suppression of BIM expression. Cancer Res, 2011, 71(7), 2750-2760. PMID: 21317224
Store lyophilized at -20ºC, keep desiccated. In lyophilized form, the chemical is stable for 36 months. In solution, store at -20ºC and use within 1 months to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.
Solubility
In vitro (25°C)
DMSO
81 mg/mL (195.73 mM)
Water
Insoluble
Ethanol
Insoluble
In vivo
2% DMSO+50% PEG 300+5% Tween 80+ddH2O
4 mg/mL
* <1 mg/ml means slightly soluble or insoluble. * Please note that Adooq tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
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