PLX-4720BRAF kinase inhibitor CAS# 918505-84-7 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 918505-84-7 | SDF | Download SDF |
PubChem ID | 24180719 | Appearance | Powder |
Formula | C17H14ClF2N3O3S | M.Wt | 413.83 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Solubility | DMSO : ≥ 50 mg/mL (120.82 mM) *"≥" means soluble, but saturation unknown. | ||
Chemical Name | N-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl]propane-1-sulfonamide | ||
SMILES | CCCS(=O)(=O)NC1=C(C(=C(C=C1)F)C(=O)C2=CNC3=NC=C(C=C23)Cl)F | ||
Standard InChIKey | YZDJQTHVDDOVHR-UHFFFAOYSA-N | ||
Standard InChI | InChI=1S/C17H14ClF2N3O3S/c1-2-5-27(25,26)23-13-4-3-12(19)14(15(13)20)16(24)11-8-22-17-10(11)6-9(18)7-21-17/h3-4,6-8,23H,2,5H2,1H3,(H,21,22) | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | PLX4720 is a potent and selective inhibitor of B-RafV600E with IC50 of 13 nM, equally potent to c-Raf-1(Y340D and Y341D mutations), 10-fold selectivity for B-RafV600E than wild-type B-Raf. | |||||
Targets | B-RafV600E | c-Raf-1Y340D/Y341D | ||||
IC50 | 13 nM | 6.7 nM |
Cell experiment: [1] | |
Cell lines | WM793 cells |
Preparation method | The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
Reacting condition | 0.5 μM, 96 hours |
Applications | Viable cells were identified following 96 h incubation with PLX-4720. Cell viability was further evaluated after re-plating onto non-fibrillar collagen gels, in the continued presence of the drug. Viable cells were identified in ~63% of PLX-4720 treated cultures. These data indicate that melanoma cells harboring a BRAFV600E mutation can survive despite reductions in BRAF activation of the MEK-ERK signaling cascade. |
Animal experiment: [2] | |
Animal models | Athymic nude mice injected with melanoma A375 cells |
Dosage form | Intraperitoneal injection, 25–50mg/kg daily |
Application | PLX-4720 decreased tumor growth as single therapy. When combined with the CRM1 inhibitor KPT-276 (75 mg/kg every day), the two inhibitors induced complete tumor regression per RECIST criteria. The difference between both single therapy and the combination therapy was statistically significant. The effect on apoptosis was believed to be the greatest contribution of the combination since it was significantly increased by the drug combination. |
Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
References: [1] Klein R M, Higgins P J. A switch in RND3-RHOA signaling is critical for melanoma cell invasion following mutant-BRAF inhibition. Mol Cancer, 2011, 10: 114. [2] Fragomeni R A S, Chung H W, Landesman Y, et al. CRM1 and BRAF inhibition synergize and induce tumor regression in BRAF-mutant melanoma. Molecular cancer therapeutics, 2013, 12(7): 1171-1179. |
PLX-4720 Dilution Calculator
PLX-4720 Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.4165 mL | 12.0823 mL | 24.1645 mL | 48.329 mL | 60.4113 mL |
5 mM | 0.4833 mL | 2.4165 mL | 4.8329 mL | 9.6658 mL | 12.0823 mL |
10 mM | 0.2416 mL | 1.2082 mL | 2.4165 mL | 4.8329 mL | 6.0411 mL |
50 mM | 0.0483 mL | 0.2416 mL | 0.4833 mL | 0.9666 mL | 1.2082 mL |
100 mM | 0.0242 mL | 0.1208 mL | 0.2416 mL | 0.4833 mL | 0.6041 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
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PLX-4720, a 7-azaindole derivative discovered by a structure-guided discovery approach, is a potent inhibitor of B-RafV600E, the most frequent oncogenic protein kinase mutation, with the value of 50% inhibition concentration IC50 of 13 nM. PLX-4720 exhibits selective inhibition against B-RafV600E rather than wild type B-Raf (IC50 = 160 nM) as well as a wide range of other kinases, such as FRK, CSK, SRC, FAK, FGFR, and Aurora A (IC50 > 1000 nM for all). PLX-4720 potently inhibits ERK phosphorylation in tumor cell lines harboring B-RafV600E, induces cell cycle arrest and apoptosis in B-RafV600E-positive melanoma cells and causes tumor growth delays in B-RafV600E-dependent tumor xenograft models through oral administration.
Reference
Tsai J, Lee JT, Wang W, Zhang J, Cho H, Mamo S, Bremer R, Gillette S, Kong J, Haass NK, Sproesser K, Li L, Smalley KS, Fong D, Zhu YL, Marimuthu A, Nguyen H, Lam B, Liu J, Cheung I, Rice J, Suzuki Y, Luu C, Settachatgul C, Shellooe R, Cantwell J, Kim SH, Schlessinger J, Zhang KY, West BL, Powell B, Habets G, Zhang C, Ibrahim PN, Hirth P, Artis DR, Herlyn M, Bollag G. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3041-3046
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B-Raf inhibition in conjunctival melanoma cell lines with PLX 4720.[Pubmed:26347528]
Br J Ophthalmol. 2015 Dec;99(12):1739-45.
PURPOSE: Mutations in the gene coding for the kinase B-Raf are associated with tumour growth in conjunctival melanoma. The purpose of this study is to explore effects of pharmacological B-Raf inhibition in conjunctival melanoma cell lines. METHODS: The B-Raf genotypes were assessed by PCR and subsequent sequencing. Cytotoxicity, cell viability, proliferation, apoptosis rate and phosphorylation rate of ERK and Akt were analysed in three different conjunctival melanoma cell lines under the influence of the B-Raf inhibitor PLX 4720 at various concentrations. RESULTS: The cell lines CRMM-1 and CM2005.1 showed the B-Raf V600E mutation, whereas CRMM-2 expressed a B-Raf wild type. CM2005.1 was highly sensitive to PLX 4720, showing a complete cytotoxic effect for >1 microM, as well as a significant concentration-dependent reduction of the proliferation rate and viability rate. Even though CRMM-1 also carries the B-Raf V600E mutation, it did not react as sensitive to PLX 4720 inhibition as CM2005.1, but showed a significant concentration-dependent reduction regarding proliferation and viability. PLX 4720 had only slight impact on CRMM-2 in high concentrations (10 microM) regarding cytotoxicity, proliferation and viability. Fluorescence-activated cell sorting analysis revealed that PLX 4720 acted predominantly antiproliferative and not via an induction of apoptosis. The phosphorylation rate of ERK was significantly reduced in CRMM-1 and CM2005.1, while it remained unchanged in CRMM-2. The phosphorylation rate of Akt was significantly elevated in CRMM-2. CONCLUSIONS: Proliferation inhibition of conjunctival melanoma cells by PLX 4720 depends on their B-Raf genotype. Therefore, therapeutic application of B-Raf inhibitors should take into account the specific B-Raf genotype.