Vemurafenib (PLX4032)

製品コードS1267 バッチS126711

印刷

化学情報

Chemical Structure Synonyms RG7204, RO5185426,PLX4032 Storage
(From the date of receipt)		 3 years -20°C(in the dark) powder
1 year -80°C(in the dark) in solvent
化学式

C23H18ClF2N3O3S
分子量 489.92 CAS No. 918504-65-1
Solubility (25°C)* 体外 DMSO 97 mg/mL (197.99 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Vemurafenib (RG7204, RO5185426,PLX4032) is a novel and potent inhibitor of B-RafV600E with IC50 of 31 nM in cell-free assay. 10-fold selective for B-RafV600E over wild-type B-Raf in enzymatic assays and the cellular selectivity can exceed 100-fold. Vemurafenib (PLX4032, RG7204) induces autophagy.
in vitro PLX4032 inhibits B-RAFV600E, C-RAF, as well as wildtype B-RAF, with IC50 of 31 nM, 48 nM and 100 nM, respectively. PLX4032 also inhibits several non-RAF kinases, including ACK1, KHS1, and SRMS, with IC50 of 18 nM to 51 nM. [1] In melanoma cell lines, the inhibitory effect by PLX4032 depends on B-RAF mutational status, because PLX4032 potently inhibits those harboring B-RAF V600 mutants, including V600E, V600D, V600K, and V600R, but not wildtype or other mutants. The IC50 values of PLX4032 on these cells, including MALME-3M, Colo829, Colo38, A375, SK-MEL28, and A2058, ranges from 20 nM to 1 μM. In these cells, PLX4032 (0.1 μM to 30 μM) also inhibits the phosphorylation of both MEK1/2 and ERK1/2. [2] PLX4032 is highly effective in the treatment of melanoma, for its ability of inhibiting B-RAFV600E. However, PLX4032 displays limited effect in colon cancer patients that also carrying B-RAFV600E oncoprotein. The reason for this is that, in colon cancer cells, B-RAFV600E inhibition by PLX4032 results in a rapid feedback EGFR activation, which compensates for the PLX4032-inhibited cell proliferation. [3]
in vivo In B-RAFV600E-mutant mice xenograft models, PLX4032 (6 mg/kg–20 mg/kg) inhibits tumor growth. [1] In mice xenograft models of LOX, Colo829, and A375 cells, PLX4032 (12.5 mg/kg–100 mg/kg) inhibits tumor growth and prolongs mice survival. [2]
特徴 A novel and potent inhibitor of the B-RAFV600E oncoprotein.

プロトコル(参考用のみ)

キナーゼアッセイ RAF kinase activity measurements
The kinase activities of wild-type RAF and mutants are determined by measuring phosphorylation of biotinylated-BAD protein. For each enzyme (0.01 ng), 20 μL reactions are carried out in 20 mM Hepes (pH 7.0), 10 mM MgCl2, 1 mM DTT, 0.01% (v/v) Tween-20, 50 nM biotin-BAD protein, and 1 mM ATP at room temperature. Reactions are stopped at 5 min with 5 μL of a solution containing 20 mM Hepes (pH 7.0), 200 mM NaCl, 80 mM EDTA, 0.3% (w/v) bovine serum albumin (BSA). The stop solution also includes phospho-BAD (Ser112) antibody, streptavidin-coated donor beads, and protein A acceptor beads. The antibody and beads are pre-incubated in stop solution in the dark at room temperature for 30 min. The final dilution of antibody is 1/2000 and the final concentration of each bead is 10 μg/mL. The assay plates are incubated at room temperature for one hour and then are read on a PerkinElmer AlphaQuest reader. Mutant activities are the average of two different batches of purified protein assayed in duplicate in three different experiments.
細胞アッセイ 細胞株 MALME-3M, Colo829, Colo38, A375, SK-MEL28, and A2058 cells
濃度 0–10 μM , dissolved in DMSO
反応時間 5 days
実験の流れ

Cellular proliferation is evaluated by MTT assay. Briefly, cells are plated in 96-well microtiter plates at a density of 1000 to 5000 cells per well in a volume of 180 μL. PLX4032 is prepared at 10 times the final assay concentration in media containing 1% DMSO. Twenty-four hours after cell plating, 20 μL of the appropriate dilution of PLX4032 are added to plates in duplicate. The plates are assayed for proliferation 6 days after the cells are plated. Percent inhibition is calculated and the IC50 is determined from the regression of a plot of the logarithm of the concentration versus percent inhibition.
動物実験 動物モデル Mice (athymic nude) xenograft models of LOX, Colo829, and A375 cells
投薬量 12.5 mg/kg–100 mg/kg
投与方法 Oral gavage twice daily

カスタマーフィードバック

Data from [Data independently produced by Nature, 2015, 520(7547), 368-72]

Data from [Data independently produced by Nature, 2015, 520(7547), 368-72]

Data from [Data independently produced by Oncogene, 2015, 10.1038/onc.2015.97]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

The ribotoxic stress response drives UV-mediated cell death [ Cell, 2024, 187(14):3652-3670.e40] PubMed: 38843833
Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis [ Nat Commun, 2024, 15(1):4108] PubMed: 38750011
Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis [ Nat Commun, 2024, 15(1):4108] PubMed: 38750011
Mi-2β promotes immune evasion in melanoma by activating EZH2 methylation [ Nat Commun, 2024, 15(1):2163] PubMed: 38461299
The CoREST repressor complex mediates phenotype switching and therapy resistance in melanoma [ J Clin Invest, 2024, 134(6)e171063] PubMed: 38300709
Ubiquitin-specific protease 22 controls melanoma metastasis and vulnerability to ferroptosis through targeting SIRT1/PTEN/PI3K signaling [ MedComm (2020), 2024, 5(8):e684] PubMed: 39135915
Genomic deletions explain the generation of alternative BRAF isoforms conferring resistance to MAPK inhibitors in melanoma [ Cell Rep, 2024, S2211-1247(24)00376-0] PubMed: 38614086
ERK1/2 interaction with DHPS regulates eIF5A deoxyhypusination independently of ERK kinase activity [ Cell Rep, 2024, 43(10):114831] PubMed: 39392755
ZEB1 controls a lineage-specific transcriptional program essential for melanoma cell state transitions [ Oncogene, 2024, 43(20):1489-1505] PubMed: 38519642
Antibody dependent cellular cytotoxicity-inducing anti-EGFR antibodies as effective therapeutic option for cutaneous melanoma resistant to BRAF inhibitors [ Front Immunol, 2024, 15:1336566] PubMed: 38510242

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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