PLX7904

Catalog No.S7964 Batch:S796401

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Technical Data

Formula

C24H22F2N6O3S
Molecular Weight 512.53 CAS No. 1393465-84-3
Solubility (25°C)* In vitro DMSO 100 mg/mL (195.11 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.)

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Biological Activity

Description PLX7904, also known as PB04, is a potent and selective paradox-breaker RAF inhibitor. It is able to efficiently inhibit activation of ERK1/2 in mutant BRAF melanoma cells but does not hyperactivate ERK1/2 in mutant RAS-expressing cells.
Targets
Raf [1]
In vitro PLX7940 is able to efficiently inhibit activation of ERK1/2 in mutant BRAF melanoma cells but does not hyperactivate ERK1/2 in mutant RAS-expressing cells. Consistent with ERK1/2 re-activation driving the re-acquisition of malignant properties, PLX7904 promotes apoptosis and inhibits entry into S phase and anchorage-independent growth in mutant N-RAS mediated vemurafenib-resistant cells. PLX7904 is also evaluated in the human SCC cell line A431 and the human breast adenocarcinoma cell line SKBR3 as these cells achieve MAPK pathway activation by upstream signals feeding into RAS (through overexpression of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), respectively)[1][2].
In vivo PLX7904 inhibits the COLO205 xenograft growth in eight mice per group[1].

Protocol (from reference)

Cell Assay:

[2]
  • Cell lines

    WM793, WM115, WM9, WM278, WM1346, WM1366, WM1361A, Sbcl2, 1205Lu, A375, SK-MEL 24, SKMEL-2, and SK-MEL 207 cells

  • Concentrations

    0, 0.5, 1, 5 μM

  • Incubation Time

    24 h

  • Method

    Cells are treated with PB04(PLX7904) at different concentrations (0, 0.05, 0.1, 1, 5 μM) for 24 h. Cells are lysed and analyzed by Western blotting with phospho-MEK1/2, total MEK1/2, phospho-ERK1/2 and total ERK1/2 antibodies.

Selleck's PLX7904 has been cited by 12 publications

Oncogenic BRAF induces whole-genome doubling through suppression of cytokinesis [ Nat Commun, 2022, 13(1):4109] PubMed: 35840569
Increased IRF9-STAT2 signaling leads to adaptive resistance toward targeted therapy in melanoma by restraining GSDME-dependent pyroptosis [ J Invest Dermatol, 2022, S0022-202X(22)00096-3] PubMed: 35148998
A Cell-Based MAPK Reporter Assay Reveals Synergistic MAPK Pathway Activity Suppression by MAPK Inhibitor Combination in BRAF-driven Pediatric Low-Grade Glioma Cells [ Mol Cancer Ther, 2020, 25;molcanther.1021.2019] PubMed: 32451331
Analyses of the oncogenic BRAFD594G variant reveal a kinase-independent function of BRAF in activating MAPK signaling. [ J Biol Chem, 2020, 295(8):2407-2420] PubMed: 31929109
Distinct Binding Preferences between Ras and Raf Family Members and the Impact on Oncogenic Ras Signaling. [ Mol Cell, 2019, 76(6):872-884] PubMed: 31606273
Synthetic Lethal Interaction of SHOC2 Depletion with MEK Inhibition in RAS-Driven Cancers [ Cell Rep, 2019, 29(1):118-134] PubMed: 31577942
Identification and characterization of a BRAF fusion oncoprotein with retained autoinhibitory domains. [ Oncogene, 2019, 10.1038/s41388-019-1021-] PubMed: 31558800
Identifying the ErbB/MAPK Signaling Cascade as a Therapeutic Target in Canine Bladder Cancer [ Mol Pharmacol, 2019, 96(1):36-46] PubMed: 31048548
Biochemical Characterization of Full-Length Oncogenic BRAFV600E together with Molecular Dynamics Simulations Provide Insight into the Activation and Inhibition Mechanisms of RAF Kinases. [ Chembiochem, 2019, 10.1002/cbic.201900266] PubMed: 31152574
SOX2‐mediated upregulation of CD24 promotes adaptive resistance toward targeted therapy in melanoma [Hüser L Int J Cancer, 2018, 143(12):3131-3142] PubMed: 29905375

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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