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Formula | C17H14ClF2N3O3S |
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Molecular Weight | 413.83 | CAS No. | 918505-84-7 | |
Solubility (25°C)* | In vitro | DMSO | 82 mg/mL (198.14 mM) | |
Water | Insoluble | |||
Ethanol | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck 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. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.) |
Description | PLX4720 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), 10-fold selectivity for B-RafV600E than wild-type B-Raf. | ||||||||
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In vitro | PLX-4720 displays >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 of 1.3-3.4 μM. PLX-4720 significantly inhibits the ERK phosphorylation in cell lines bearing B-RafV600E with IC50 of 14-46 nM, but not the cells with wild-type B-Raf. PLX-4720 significantly inhibits the growth of tumor cell lines bearing the B-RafV600E oncogene, such as COLO205, A375, WM2664, and COLO829 with GI50 of 0.31 μM, 0.50 μM, 1.5 μM, and 1.7 μM, respectively. In addition, PLX-4720 treatment at 1 μM induces cell cycle arrest and apoptosis exclusively in the B-RafV600E-positive 1205Lu cells, but not in the B-Raf wild-type C8161 cells. [1] PLX-4720 treatment (10 μM) significantly induces >14-fold expression of BIM in the PTEN+ cells, compared with the PTEN- cell lines (4-fold), giving an explanation of the resistance of PTEN- cells to PLX-4720-induced apoptosis. [2] | ||||||||
In vivo | Oral administration of PLX-4720 at 20 mg/kg/day induces significant tumor growth delays and regressions in B-RafV600E-dependent COLO205 tumor xenografts, without obvious adverse effects in mice even at dose of 1 g/kg. PLX-4720 at 100 mg/kg twice daily almost completely eliminates the 1205Lu xenografts bearing B-RafV600E, while has no activity against C8161 xenografts bearing wild-type B-Raf. The anti-tumor effects of PLX-4720 correlate with the blockade of MAPK pathway in those cells harboring the V600E mutation. [1] PLX-4720 treatment at 30 mg/kg/day significant inhibits the tumor growth of 8505c xenografts by >90%, and dramatically decreases distant lung metastases. [3] |
Kinase Assay:[1] |
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Cell Assay:[1] |
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Animal Study:[1] |
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Data from [Data independently produced by Cancer Discov, 2013, 3, 350-62]
Data from [Data independently produced by Genes Dev, 2012, 26, 1055-69]
Data from [Proc Natl Acad Sci USA, 2011, 108, 6067-6072]
Data from [Cancer Res, 2011, 71, 2750-2760]
The ribotoxic stress response drives UV-mediated cell death [ Cell, 2024, 187(14):3652-3670.e40] | PubMed: 38843833 |
Tracking the EMT-like phenotype switching during targeted therapy in melanoma by analyzing extracellular vesicle phenotypes [ Biosens Bioelectron, 2024, 10.1016/j.bios.2023.115819] | PubMed: 37952322 |
Mcl-1 mediates intrinsic resistance to RAF inhibitors in mutant BRAF papillary thyroid carcinoma [ Cell Death Discov, 2024, 10(1):175] | PubMed: 38622136 |
The ERK5 pathway in BRAFV600E melanoma cells plays a role in development of acquired resistance to dabrafenib but not vemurafenib [ FEBS Lett, 2024, 10.1002/1873-3468.14960] | PubMed: 38977937 |
Executioner caspases restrict mitochondrial RNA-driven Type I IFN induction during chemotherapy-induced apoptosis [ Nat Commun, 2023, 14(1):1399] | PubMed: 36918588 |
Executioner caspases restrict mitochondrial RNA-driven Type I IFN induction during chemotherapy-induced apoptosis [ Nat Commun, 2023, 14(1):1399] | PubMed: 36918588 |
TFEB inhibition induces melanoma shut-down by blocking the cell cycle and rewiring metabolism [ Cell Death Dis, 2023, 14(5):314] | PubMed: 37160873 |
Inhibition of TGF-β signaling, invasion, and growth of cutaneous squamous cell carcinoma by PLX8394 [ Oncogene, 2023, 10.1038/s41388-023-02863-8] | PubMed: 37864034 |
WNT5A-ROR2 axis mediates VEGF dependence of BRAF mutant melanoma [ Cell Oncol (Dordr), 2023, 46(2):391-407] | PubMed: 36539575 |
Dual VEGFA/BRAF targeting boosts PD-1 blockade in melanoma through GM-CSF-mediated infiltration of M1 macrophages [ Mol Oncol, 2023, 10.1002/1878-0261.13450] | PubMed: 37183363 |
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