PLX-4720 (Synonyms: Raf Kinase Inhibitor V) |
| Catalog No.GC14732 |
An orally-available inhibitor of the B-raf mutant B-RafV600E
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 918505-84-7
Sample solution is provided at 25 µL, 10mM.
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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
[1].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
| Cell experiment: [1] | |
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Cell lines |
WM793 cells |
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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. |
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Reaction Conditions |
0.5 μM, 96 hours |
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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] | |
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Animal models |
Athymic nude mice injected with melanoma A375 cells |
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Dosage form |
Intraperitoneal injection, 25–50mg/kg daily |
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Applications |
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. |
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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. |
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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. | |
| Cas No. | 918505-84-7 | SDF | |
| Sinónimos | Raf Kinase Inhibitor V | ||
| Chemical Name | N-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl]propane-1-sulfonamide | ||
| Canonical SMILES | CCCS(=O)(=O)NC1=C(C(=C(C=C1)F)C(=O)C2=CNC3=NC=C(C=C23)Cl)F | ||
| Formula | C17H14ClF2N3O3S | M.Wt | 413.83 |
| Solubility | ≥ 20.69mg/mL in DMSO | Storage | Store at 4°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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