Vemurafenib (PLX4032)

Catalog No.S1267 Batch:S126715

Technical Data

Formula

C₂₃H₁₈ClF₂N₃O₃S

Molecular Weight

489.92

CAS No.

918504-65-1

Solubility (25°C)*

In vitro

DMSO

98 mg/mL (200.03 mM)

Water

Insoluble

Ethanol

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution

5%DMSO 1 Corn oil

5.0mg/ml

Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

* <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.)

Preparing Stock Solutions

Biological Activity

Description

Vemurafenib (PLX4032, RG7204, RO5185426) 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.

Targets

SRMS ^[1] (Cell-free assay)	ACK1 ^[1] (Cell-free assay)	B-Raf (V600E) ^[1] (Cell-free assay)	C-Raf ^[1] (Cell-free assay)	MAP4K5 (KHS1) ^[1] (Cell-free assay)	View More
18 nM	19 nM	31 nM	48 nM	51 nM	View More

In vitro

PLX4032 inhibits B-RAF^V600E, 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-RAF^V600E. However, PLX4032 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 PLX4032 results in a rapid feedback EGFR activation, which compensates for the PLX4032-inhibited cell proliferation. ^[3]

In vivo

In B-RAF^V600E-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]

Features

A novel and potent inhibitor of the B-RAF^V600E oncoprotein.

Protocol (from reference)

Kinase Assay:^{^[1]}	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.
Cell Assay:^{^[2]}	Cell lines MALME-3M, Colo829, Colo38, A375, SK-MEL28, and A2058 cells Concentrations 0–10 μM , dissolved in DMSO Incubation Time 5 days Method 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.
Animal Study:^{^[2]}	Animal Models Mice (athymic nude) xenograft models of LOX, Colo829, and A375 cells Dosages 12.5 mg/kg–100 mg/kg Administration Oral gavage twice daily

References

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Customer Product Validation

: 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]

: Data from [Data independently produced by Nature, 2014, 508(7494), 118-22]

Selleck's Vemurafenib (PLX4032) has been cited by 718 publications

Mi-2β promotes immune evasion in melanoma by activating EZH2 methylation [ Nat Commun, 2024, 15(1):2163]	PubMed: 38461299
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
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
Melanocortin receptor 4 as a new target in melanoma therapy: Anticancer activity of the inhibitor ML00253764 alone and in association with B-raf inhibitor vemurafenib [ Biochem Pharmacol, 2024, 219:115952]	PubMed: 38036189
Repurposing of the Cardiovascular Drug Statin for the Treatment of Cancers: Efficacy of Statin-Dipyridamole Combination Treatment in Melanoma Cell Lines [ Biomedicines, 2024, 12(3)698]	PubMed: 38540310
Saracatinib prompts hemin-induced K562 erythroid differentiation but suppresses erythropoiesis of hematopoietic stem cells [ Hum Cell, 2024, 10.1007/s13577-024-01034-5]	PubMed: 38388899
Reporter cell lines to screen for inhibitors or regulators of the KRAS-RAF-MEK1/2-ERK1/2 pathway [ Biochem J, 2024, 481(6):405-422]	PubMed: 38381045
A reversible SRC-relayed COX2 inflammatory program drives resistance to BRAF and EGFR inhibition in BRAFV600E colorectal tumors [ Nat Cancer, 2023, 4(2):240-256]	PubMed: 36759733
Disrupting cellular memory to overcome drug resistance [ Nat Commun, 2023, 14(1):7130]	PubMed: 37932277
Epigenetic suppression of PGC1α (PPARGC1A) causes collateral sensitivity to HMGCR-inhibitors within BRAF-treatment resistant melanomas [ Nat Commun, 2023, 14(1):3251]	PubMed: 37277330

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