PLX-4720

• CAT Number: I005477
• CAS Number: 918505-84-7
• Molecular Formula: C₁₇H₁₄ClF₂N₃O₃S
• Molecular Weight: 413.83
• Purity: ≥95%
• Target: Raf
• Solubility: DMSO ≥80mg/mL Water <1.2mg/mL Ethanol <1.2mg/mL
• Storage: 3 years -20℃ powder
• IC50: 13/6.7 nM( B-RafV600E/c-Raf-1Y340D/Y341D) [1]
• IUPAC Name: N-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl]propane-1-sulfonamide
• 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)
• InChIKey: YZDJQTHVDDOVHR-UHFFFAOYSA-N
• SMILES: CCCS(=O)(=O)NC1=C(C(=C(C=C1)F)C(=O)C2=CNC3=NC=C(C=C23)Cl)F

PLX-4720 (Cat.No:I005477) is a selective inhibitor of the kinase BRAF V600E, a mutant form found in various cancers, particularly melanoma. It blocks the abnormal activation of the BRAF protein, inhibiting tumor growth. PLX-4720 has shown promising results in preclinical and clinical studies, leading to its investigation as a targeted therapy for BRAF-mutant cancers.

Reference

1:Br J Ophthalmol. 2015 Dec;99(12):1739-45. doi: 10.1136/bjophthalmol-2015-306689. Epub 2015 Sep 7. B-Raf inhibition in conjunctival melanoma cell lines with PLX 4720.Riechardt AI,Maier AK,Nonnenmacher A,Reichhart N,Keilholz U,Kociok N,Strauss O,Joussen AM,Gundlach E, PMID: 26347528 DOI: 10.1136/bjophthalmol-2015-306689 Abstract: 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 µM, 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 µM) 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.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/