[CAS NO. 918505-84-7] PLX-4720
PRODUCTS SPECIFICATIONS [918505-84-7]
DESCRIPTION [918505-84-7]
Overview
| MDL | MFCD14635203 |
|---|---|
| Molecular Weight | 413.83 |
| Molecular Formula | C17H14ClF2N3O3S |
| SMILES | O=S(NC1=CC=C(C(C(C2=CNC3=NC=C(C=C23)Cl)=O)=C1F)F)(CCC)=O |
6 Publications Citing Use of MCE
Summary
PLX-4720 is a potent and selective inhibitor of B-Raf V600E with IC 50 of 13 nM in a cell-free assay, equally potent to c-Raf-1(Y340D and Y341D mutations), and 10-fold selectivity for B-Raf V600E than wild-type B-Raf.
IC50 & Target
|
B-Raf V600E 13 nM (IC 50 ) |
B-Raf 160 nM (IC 50 ) |
BRK 130 nM (IC 50 ) |
FRK 1300 nM (IC 50 ) |
Csk 1500 nM (IC 50 ) |
Src 1700 nM (IC 50 ) |
FAK 1700 nM (IC 50 ) |
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|
FGFR 1900 nM (IC 50 ) |
KDR 2300 nM (IC 50 ) |
HGK 2800 nM (IC 50 ) |
CSF1R 3300 nM (IC 50 ) |
Aurora A 3400 nM (IC 50 ) |
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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 IC 50 of 1.3-3.4 μM. PLX-4720 significantly inhibits the ERK phosphorylation in cell lines bearing B-Raf V600E with IC 50 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-Raf V600E oncogene, such as COLO205, A375, WM2664, and COLO829 with GI 50 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-Raf V600E -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] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Oral administration of PLX-4720 at 20 mg/kg/day induces significant tumor growth delays and regressions in B-Raf V600E -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-Raf V600E , 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] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 100 mg/mL ( 241.65 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.4165 mL | 12.0823 mL | 24.1645 mL |
| 5 mM | 0.4833 mL | 2.4165 mL | 4.8329 mL |
| 10 mM | 0.2416 mL | 1.2082 mL | 2.4165 mL |
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Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.08 mg/mL (5.03 mM); Clear solution
References
- [1] 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.
- [2] 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.
- [3] Nucera C, et al. B-Raf(V600E) and thrombospondin-1 promote thyroid cancer progression. Proc Natl Acad Sci U S A, 2010, 107(23), 10649-10654.
- [4] Rizzolio S, et al. Neuropilin-1 upregulation elicits adaptive resistance to oncogene-targeted therapies. J Clin Invest. 2018 Aug 31;128(9):3976-3990.
Synonyms