PLX7904
Based on 3 publication(s) in Google Scholar
PLX7904 is a potent and selective BRAF inhibitor, with IC50 of appr 5 nM against BRAFV600E in mutant RAS expressing cells.
For research use only. We do not sell to patients.
- Purity: 98.72%
- CAS No.: 1393465-84-3
- Formula: C24H22F2N6O3S
- Molecular Weight:512.53
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocol
- Purity & Documentation
- References
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Help & FAQs
Publications Citing Use of MedChemExpress (MCE) PLX7904
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Biological Activity
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BRafV600E 5 nM (IC50, in mutant RAS expressing cells) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A-375 | IC50 |
170 nM
Compound: 20; PLX7904
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Cytotoxicity against human A375 cells harboring BRAF V600E mutant
Cytotoxicity against human A375 cells harboring BRAF V600E mutant
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[PMID: 29461827] |
PLX7904 inhibits the in vitro growth of two melanoma cell lines (A375 and COLO829) and an additional human colorectal cancer cell line COLO205 that expresses BRAFV600E with IC50 values of 0.17 μM, 0.53 μM, and 0.16 μM, respectively, on a par with vemurafenib IC50 values in the same assays (0.33 μM, 0.69 μM, and 0.25 μM, respectively)[1]. PLX7904 and PLX8394 potently inhibit ERK1/2-driven GAL4-Elk1 reporter activity in PRT cells as well as parental cells. PLX7904 and PLX8394 treatment at 1 μM concentration reduce colony formation and viability in parental cells to a similar level as PLX4720[2]. PPLX7904 potently inhibits phosphorylation of ERK1/2 in mutant BRAF melanoma cells without eliciting paradoxical activation in wild-type BRAF, mutant NRAS melanoma cells. PPLX7904 inhibits ERK1/2 in PLX470-resistant cell lines. PPLX7904 treatment promotes apoptosis and inhibits anchorage-independent growth of vemurafenib resistant cells[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 1393465-84-3
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Appearance Solid
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Molecular Weight 512.53
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Formula C24H22F2N6O3S
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Color White to light brown
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SMILES
O=S(NC1=CC=C(F)C(C(C2=CNC3=NC=C(C4=CN=C(C5CC5)N=C4)C=C32)=O)=C1F)(N(CC)C)=O
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Synonyms
PB04
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Publications (3)
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Journal Impact Factor
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Most Recent
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Nat Commun
Sustained activation of the Aryl hydrocarbon Receptor transcription factor promotes resistance to BRAF-inhibitors in melanoma. [Abstract]2018 Nov 14;9(1):4775. PMID: 30429474 -
Mol Cell Biol
2016 Sep 26;36(20):2612-25. PMID: 27503857 -
Solvent & Solubility
DMSO : ≥ 30 mg/mL (58.53 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (4.88 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocol
For MTT assays, 2×103 cells are seeded in triplicate in 96 wells in their regular culture medium (containing PLX4720 for PRT lines). Next day, cells are washed twice with PBS and then the medium is replenished containing the indicated RAF inhibitor. Medium is changed 48 hours later and after a further 48 hours, 10 μL of 5 mg/mL MTT reagent is added to wells, and incubated for three hours. Formazan crystals are then solubilized overnight with a 1:10 dilution of 0.1 M glycine (pH 10.5) in DMSO. Wells are then analyzed at 450 nM in a Multiskan® Spectrum spectrophotometer. Results depicted are normalized to DMSO conditions and are a composite of three independent experiments. Error bars shown are representative of the standard error of mean (SEM).
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
COLO205 tumour cells are cultured in DMEM 10% FBS 1% penicillin/streptomycin supplemented with bovine insulin, at 37°C. Balb/C nude mice, female, 6-8 weeks old, weighing approximately 18-22 g, are inoculated subcutaneously at the right flank with COLO205 tumour cells (5×106) in 0.1 mL of PBS mixed with matrigel (50:50) for tumour development. The treatment is started when mean tumour size reach approximately 100 mm3, with eight mice in each treatment group randomized to balance the average weight and tumour size. B9 cells are expanded in DMEM 10% FBS 1% penicillin/streptomycin. Upon trypsinization the cells are washed three times with 20 mL RPMI, and after the final centrifugation are re-suspended, counted, and adjusted by volume to a final concentration of 5×107 cells per millilitre. B9 xenografts are started by injection of 5×106 cells subcutaneously in 6- to 7-week-old female nude Balb/c mice. Compound dosing starts when the average size of tumours reach 50-70 mm3. Animals are equally distributed over treatment groups (n=10) to balance the average tumour size and body weight. Animals are dosed orally for days 1-14 twice daily and days 15-28 once daily with vehicle, vemurafenib 50 mg per kg, or PLX7904 50 mg per kg. 12-O-tetradecanoylphorbol-13-acetate (TPA) is put on the skin of all mice twice a week during weeks 3 and 4 at a dose of 2 µg in 200 µL acetone.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (279 KB)
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SDS (396 KB)
- English - EN (396 KB)
- Français - FR (396 KB)
- Deutsch - DE (396 KB)
- Norwegian - NO (396 KB)
- Español - ES (396 KB)
- Swedish - SV (396 KB)
- Italian - IT (396 KB)
- Korean - KR (396 KB)
- Portuguese - PT (396 KB)
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Handling Instructions (2659 KB)
References
[1]. Zhang C, et al. RAF inhibitors that evade paradoxical MAPK pathway activation. Nature. 2015 Oct 22;526(7574):583-586. [Content Brief]
[2]. Basile KJ, et al. Inhibition of mutant BRAF splice variant signaling by next-generation, selective RAF inhibitors. Pigment Cell Melanoma Res. 2014 May;27(3):479-84 [Content Brief]
[3]. Le K, et al. Selective RAF inhibitor impairs ERK1/2 phosphorylation and growth in mutant NRAS, vemurafenib-resistant melanoma cells. Pigment Cell Melanoma Res. 2013 Jul;26(4):509-17 [Content Brief]
Complete Stock Solution Preparation Table
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.9511 mL | 9.7555 mL | 19.5111 mL | 48.7776 mL |
| 5 mM | 0.3902 mL | 1.9511 mL | 3.9022 mL | 9.7555 mL | |
| 10 mM | 0.1951 mL | 0.9756 mL | 1.9511 mL | 4.8778 mL | |
| 15 mM | 0.1301 mL | 0.6504 mL | 1.3007 mL | 3.2518 mL | |
| 20 mM | 0.0976 mL | 0.4878 mL | 0.9756 mL | 2.4389 mL | |
| 25 mM | 0.0780 mL | 0.3902 mL | 0.7804 mL | 1.9511 mL | |
| 30 mM | 0.0650 mL | 0.3252 mL | 0.6504 mL | 1.6259 mL | |
| 40 mM | 0.0488 mL | 0.2439 mL | 0.4878 mL | 1.2194 mL | |
| 50 mM | 0.0390 mL | 0.1951 mL | 0.3902 mL | 0.9756 mL |
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