Vemurafenib (PLX4032)

製品コードS1267 バッチS126714

印刷

化学情報

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

98 mg/mL (200.03 mM)

Water

Insoluble

Ethanol

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension

CMC-NA

≥5mg/ml

Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

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

プロトコル(参考用のみ)

キナーゼアッセイ	RAF kinase activity measurements
キナーゼアッセイ	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. Vemurafenib (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 this compound 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

参考

https://pubmed.ncbi.nlm.nih.gov/20823850/
https://pubmed.ncbi.nlm.nih.gov/20551065/
https://pubmed.ncbi.nlm.nih.gov/22281684/

https://pubmed.ncbi.nlm.nih.gov/15808862/
https://pubmed.ncbi.nlm.nih.gov/22180495/

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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：

Pan-inhibition of super-enhancer-driven oncogenic transcription by next-generation synthetic ecteinascidins yields potent anti-cancer activity [ Nat Commun, 2025, 16(1):512]	PubMed: 39779693
Blocking interplay between TERT and c-Myc: a new therapeutic strategy for BRAFV600E/pTERT double mutated tumors [ Int J Biol Sci, 2025, 21(11):4961-4978]	PubMed: 40860184
Downregulated ALDH2 Contributes to Tumor Progression and Targeted Therapy Resistance in Human Metastatic Melanoma Cells [ Cells, 2025, 14(12)913]	PubMed: 40558540
Inter-Relationship Between Melanoma Vemurafenib Tolerance Thresholds and Metabolic Pathway Choice [ Cells, 2025, 14(12)923]	PubMed: 40558548
Exploiting Paradoxical Activation of Oncogenic MAPK Signaling by Targeting Mitochondria to Sensitize NRAS Mutant-Melanoma to Vemurafenib [ Int J Mol Sci, 2025, 26(6)2675]	PubMed: 40141318
Acquired resistance to vemurafenib restrains thyroid cancer stem cell self-renewal by suppressing STAT3 activation [ Cell Signal, 2025, 133:111845]	PubMed: 40345509
Dihydrotanshinone I enhanced BRAF mutant melanoma treatment efficacy by inhibiting the STAT3/SOX2 signaling pathway [ Front Oncol, 2025, 15:1429018]	PubMed: 39944829
Selective inhibition of p300 by a novel small molecule EPS496 promotes cell death in vemurafenib-resistant BRAFV600E mutated melanoma cells [ Biochem Biophys Res Commun, 2025, 750:151382]	PubMed: 39884005
Increased Mitochondrial Superoxide Level Is Partially Associated With Vemurafenib-Induced Renal Tubular Toxicity [ Basic Clin Pharmacol Toxicol, 2025, 136(4):e70015]	PubMed: 40018909
Anti-tumor efficacy of RAF/MEK inhibitor VS6766 in KRAS-mutated colorectal cancer cells [ Cancer Chemother Pharmacol, 2025, 95(1):78]	PubMed: 40742567

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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