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Customer Reviews(6) in vivo invitation

Quality Control & MSDS

Related Compound Libraries

Vemurafenib (PLX4032) is available in the following compound libraries:

Cambridge Cancer Compound Library(96-well) Chemical Library (96-well) Inhibitor Library (96-well) Kinase Inhibitor Library (96-well)

Products used with Vemurafenib (PLX4032) in previous publications

Targets	Related Products	References	Purpose
Raf inhibitors	PLX-4720	[1][2][3]	Positive Control. Compared to the Raf inhibition potency of PLX4032, PLX-47720, and SB590885.
Raf inhibitors	SB590885	[2]
MEK inhibitors	AZD6244	[2][4][6]	The combination of Raf inhibitors with MEK inhibitors for targeting the Ras-Raf-MEK-MAPK pathways as effective treatments for cancer.MEK inhibitors inhibit ERK phosphorylation in all normal and tumor cells, whereas PLX4032 inhibits ERK signaling only in tumor cells. This selectivity may lead to a broader therapeutic index and help explain the greater antitumor activity observed with MEK inhibitors than with Raf inhibitors.
	PD0325901	[7][8]
	U0126-EtOH	[2][9]
	GSK1120212	[2]
PI3K inhibitors	LY294002	[5][10][11]	The combination of Raf inhibitors and PI3K inhibitors consistently trigger apoptosis in a highly efficient manner.
	NVP-BEZ235	[5]
	Wortmannin	[5]
mTOR inhibitors	Rapamycin	[11]	Combined Raf, PI3k and mTOR inhibition results in a highly synergistic growth inhibitory response but less efficient cytotoxic response.
mTOR inhibitors	AZD8055	[5]
c-Met inhibitors	PHA-665752	[9][2]	Cotreatment with c-Met inhibitors and PLX4032 produces a synergistic interaction, inhibits growth, invasion, and migration. The c-Met inhibition can cooperate with Raf inhibition.
c-Met inhibitors	SU11274	[9]

Product Information

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Research Area
Research Area
Vemurafenib (PLX4032) Mechanism
Vemurafenib (PLX4032) Mechanism
The RAF protein kinase domain consists of the characteristic small N-terminal lobe and large C-terminal lobe. The small lobe has a predominantly antiparallel beta-sheet structure, anchoring and orienting the ATP. It contains a glycine-rich ATP-phosphate-binding loop (P-loop). The large lobe is mainly alpha-helical. The large lobe binds MEK1/2, the protein substrates. The catalytic site lies in the cleft between the small and large lobes.^[1]
PLX4032 is crystallized with a protein construct that contained the kinase domain of B-RAFV600E. PLX4032 binds in the active site of one of the protomers in the non-crystallographic-symmetry related dimer. The PLX4032-bound protomer adopts the DFG-in conformation to enable the formation of a unique hydrogen bond between the backbone NH of Asp594 and the sulfonamide nitrogen of PLX4032. In addition, PLX4032-binding causes an outward shift in the regulatory αC helix. The apo-protomer displays the DFG-in conformation with the activation loop locked away from the ATP-binding site by a salt-bridge between Glu600 and Lys507. ^[2]
References
[1] Robert Roskoski Jr. Biochem Biophys Res Commun. 2010, 399(3), 313-317.
[2] Bollag G, et al. Nature. 2010, 467(7315), 596-599.

Cat.No.	Product Name	Solubility (25°C)
S1267	Vemurafenib (PLX4032)	<1 mg/mL	98 mg/mL	<1 mg/mL
S1040	Sorafenib (Nexavar)	<1 mg/mL	127 mg/mL	<1 mg/mL
S1178	Regorafenib (BAY 73-4506)	<1 mg/mL	97 mg/mL	<1 mg/mL
S1152	PLX-4720	<1 mg/mL	83 mg/mL	<1 mg/mL
S2807	Dabrafenib (GSK2118436)	<1 mg/mL	30 mg/mL	2 mg/mL
S1104	GDC-0879	<1 mg/mL	67 mg/mL	5 mg/mL
S2161	RAF265 (CHIR-265)	<1 mg/mL	100 mg/mL	33 mg/mL
S2746	AZ628	<1 mg/mL	90 mg/mL	<1 mg/mL
S2720	ZM 336372	<1 mg/mL	78 mg/mL	2 mg/mL
S2220	SB590885	<1 mg/mL	5 mg/mL	<1 mg/mL
S2202	NVP-BHG712	<1 mg/mL	101 mg/mL	3 mg/mL
S2872	GW5074	<1 mg/mL	104 mg/mL	<1 mg/mL
S2200	Raf265 derivative	<1 mg/mL	101 mg/mL	101 mg/mL
S8015	CEP-32496	<1 mg/mL	9 mg/mL	<1 mg/mL

Combination Therapy

Dr. Antonino Maria Sparta demonstrates a breakthrough in leukemia research by utilizing two inhibitors produced by Selleck Chemicals.

Product Description

Biological Activity Protocol Chemical Information Customer Reviews Product Citations Tech Support & FAQs

Biological Activity

Description	PLX4032 (Vemurafenib, RG7204, Zelboraf, RO5185426) is a novel and potent inhibitor of B-Raf^V600E with IC50 of 31 nM.
Targets	B-Raf^V600E	C-Raf	MAP4K5 (KHS1)	SRMS	ACK1	FGR
IC50	31 nM	48 nM	51 nM	18 nM	19 nM	63 nM ^[1]
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]
Clinical Trials	PLX4032 has recently been approved by US Food and Drug Administration (FDA) for the treatment of advanced metastatic melanoma with a B-RAF^V600E mutation.
Features	PLX4032 is a novel and potent inhibitor of B-RAF^V600E oncoprotein.

Protocol(Only for 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.

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
Formulation	Formulated as microprecipitated bulk powder (MBP), suspended at the desired concentration in an aqueous vehicle containing 2% Klucel LF, and adjusted to pH 4 with dilute HCl
Dosages	12.5 mg/kg–100 mg/kg
Administration	Oral gavage twice daily

1

References

Chemical Information

Download Vemurafenib (PLX4032) SDF

Molecular Weight (MW)	489.92
Formula	C₂₃H₁₈ClF₂N₃O₃S
CAS No.	918504-65-1
Synonyms	RG7204

Solubility (25°C) DMSO 98 mg/mL Water <1 mg/mL Ethanol <1 mg/mL
Storage	2 years -20°CPowder
	2 weeks4°Cin DMSO
	6 months-80°Cin DMSO

Chemical Name

Molarity Calculator Dilution Calculator Molecular Weight Calculator

Research Area

Customer Reviews (6)

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Rating

Source

J Invest Dermatol, 2013, ahead of print. Vemurafenib (PLX4032) purchased from Selleck

Method

Western blot

Cell Lines

A375 melanoma cells

Concentrations

0-10 μM

Incubation Time

6 h

Results

The activation of Stat3 and the protein expression of PAX3 were both repressed in vemurafenib-sensitive (parental) A375 and UACC62 melanoma cells, but higher vemurafenib concentration were required in resistant A375 and UACC62 melanoma cells. Specifically, vemurafenib at 1 μM inhibited the expression of phospho-Stat3 in sensitive cells, but not in resistant cells. These results suggest that inhibition of Stat3 signaling represents a potential therapeutic strategy to overcome the acquired resistance to vemurafenib in melanoma cells.

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Rating

Source

Oncoimmunology, 2012, 1(9), 1476-1483. Vemurafenib (PLX4032) purchased from Selleck

Method

flow cytometry

Cell Lines

tumor-infiltrating lymphocytes

Concentrations

100-250 nM

Incubation Time

72 h

Results

Treatment with Vem significantly increased the frequency of TILs recognizing autologous melanoma cells and responding to them by producing Type 1 helper cytokines (Fig. A ) or by mobilizing cytotoxic granules (Fig. B ), confirming the polyfunctionality of newly-induced responses.

Click to enlarge

Rating

Source

J Invest Dermatol, 2011, 131(10), 2087-95.. Vemurafenib (PLX4032) purchased from Selleck

Method

Clonogenic assays

Cell Lines

VM21/VM1 (c) cells

Concentrations

0.1 μM

Incubation Time

14 d

Results

Combination of PD166866 with the V600E BRAF-specific inhibitor RG7204 (PLX4032) potently reduced clonogenic growth of VM21 and VM1 cells.

Click to enlarge

Rating

Source

Dr Zhe-Sheng Chen of St. John's University. Vemurafenib (PLX4032) purchased from Selleck

Method

Cell cytotoxicity assay

Cell Lines

HEK293 cells, HEK293/MRP7 cells

Concentrations

20 μM

Incubation Time

Results

Click to enlarge

Rating

Source

Dr Zhe-Sheng Chen of St. John's University. Vemurafenib (PLX4032) purchased from Selleck

Method

Cell cytotoxicity assay

Cell Lines

H460 cells, H460/MX20 cells

Concentrations

20 μM

Incubation Time

Results

Click to enlarge

Rating

Source

Dr Zhe-Sheng Chen of St. John's University. Vemurafenib (PLX4032) purchased from Selleck

Method

[3H]-Mitoxantrone accumulation analysis

Cell Lines

H460 cells, H460/MX20 cells

Concentrations

20 μM

Incubation Time

96 h

Results

Vemurafenib increased the intra-cellular accumulation of Mitoxantrone in ABCG2 overexpressing H460/MX20 cells compared with parental H460 cells.

Product Citations (16)

Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. [Prahallad A, et al. Nature 2012;483(7387), 100-103]
PubMed: 22281684
MED12 controls the response to multiple cancer drugs through regulation of TGF-β receptor signaling. [Huang S, et al. Cell 2012;151(5):937-50]
PubMed: 23178117
MDM4 is a key therapeutic target in cutaneous melanoma. [Gembarska A, et al. Nat Med 2012;ahead of print]
PubMed: 22820643

Lung cancers with acquired resistance to EGFR inhibitors occasionally harbor BRAF gene mutations but lack mutations in KRAS, NRAS, or MEK1. [Ohashi K, et al. Proc Natl Acad Sci U S A 2012;109(31), E2127-33]
PubMed: 22773810
Colloidal Aggregation Affects the Efficacy of Anticancer Drugs in Cell Culture. [Owen SC, et al. ACS Chem Biol 2012;7(8):1429-35]
PubMed: 22625864
Oncogenic B-RAF(V600E) Signaling Induces the T-Box3 Transcriptional Repressor to Repress E-Cadherin and Enhance Melanoma Cell Invasion. [Boyd SC, et al. J Invest Dermatol 2012;ahead of print]
PubMed: 23190890
Fibroblast growth factor receptors as therapeutic targets in human melanoma: synergism with BRAF inhibition. [Metzner T, et al. J Invest Dermatol 2011;131(10):2087-95]
PubMed: 21753785
Stat3-Targeted Therapies Overcome the Acquired Resistance to Vemurafenib in Melanomas [Liu F, et al. J Invest Dermatol 2013;ahead of print]
PubMed: 23344460
A genome-scale RNA interference screen implicates NF1 loss in resistance to RAF inhibition. [Whittaker SR, et al. Cancer Discov 2013;ahead of print]
PubMed: 23288408
Aurora B is regulated by the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway and is a valuable potential target in melanoma cells. [Bonet C, et al. J Biol Chem 2012;287(35):29887-98]
PubMed: 22767597
Melanoma Chemotherapy Leads to the Selection of ABCB5-Expressing Cells. [Chartrain M, et al. PLoS One 2012;7(5):e36762]
PubMed: 22675422
Functional profiling of live melanoma samples using a novel automated platform. [Schayowitz A, et al. PLoS One 2012;7(12), e52760]
PubMed: 23285177
Anti-Cancer Drugs Elicit Re-Expression of UDP-Glucuronosyltransferases in Melanoma Cells. [Dellinger RW, et al. PLoS One 2012;7(10), e47696]
PubMed: 23110092
Specifically targeting ERK1 or ERK2 kills Melanoma cells. [Qin J, et al. J Transl Med 2012;10, 15]
PubMed: 22277029
Preexisting MEK1 Exon 3 mutations in V600E/KBRAF melanomas do not confer resistance to BRAF inhibitors. [Shi H, et al. Cancer Discov 2012;2(5):414-24]
PubMed: 22588879
BRAF inhibition improves tumor recognition by the immune system: Potential implications for combinatorial therapies against melanoma involving adoptive T-cell transfer. [Donia M, et al. Oncoimmunology 2012;1(9):1476-1483]
PubMed: 23264894

Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Related Raf Inhibitors

GDC-0879

GDC-0879 is a novel potent, selective B-Raf inhibitor for B-Raf^V600E with IC50 of 0.13 nM.
PLX-4720

PLX-4720 is a potent and selective inhibitor of B-Raf^V600E and c-Raf-1^Y340D/Y341D with IC50 of 13 nM and 6.7 nM, respectively.
RAF265 (CHIR-265)
RAF265 (CHIR-265) is a selective and potent inhibitor of B-Raf and VEGFR2 with IC50 of 3-60 nM and EC50 of 30 nM, respectively.
Raf265 derivative
A derivative of Raf265. But the effects of this derivative is not known.
NVP-BHG712
NVP-BHG712 is a specific inhibitor of c-Raf, c-Src and c-Abl with IC50 of 0.395 μM, 1.266 μM and 1.667 μM and also inhibits EphB4 and VEGFR2 with ED50 of 25 nM and 4.2 μM, respectively.
SB590885
SB590885 is a potent B-Raf inhibitor with K_i of 0.16 nM.
ZM 336372
ZM 336372 is a potent and selective c-Raf inhibitor with IC50 of 70 nM.
AZ628
AZ628 is a potent inhibitor for wild-type CRAF and BRAF^V600E with IC50 of 29 nM and 34 nM, respectively.
Dabrafenib (GSK2118436)
Dabrafenib (GSK2118436) is a potent ATP-competitive inhibitor of B-Raf, B-Raf^V600E and c-Raf with IC50 of 3.2 nM, 0.8 nM and 5.0 nM, respectively.
GW5074
GW5074 is a potent and selective c-Raf inhibitor with IC50 of 9 nM.

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Vemurafenib (PLX4032)

Validation & Quality Control

Product Citations(16)

Customer Reviews(6) in vivo invitation

Quality Control & MSDS

Related Compound Libraries

Vemurafenib (PLX4032) is available in the following compound libraries:

Products used with Vemurafenib (PLX4032) in previous publications

Product Information

Compare Raf Inhibitors

Research Area

Vemurafenib (PLX4032) Mechanism

Combination Therapy

Product Description

Biological Activity

Protocol(Only for Reference)

Kinase Assay: ^[1]

Cell Assay: ^[2]

Animal Study: ^[2]

References

Chemical Information

Research Area

Customer Reviews (6)

Product Citations (16)

Tech Support & FAQs

If you have any other enquiries, please leave a message.

Related Raf Inhibitors

MAPK Pathway Products

Recently Viewed Items

Cat.No.	Product Name	Solubility (25°C)
Cat.No.	Product Name	Water	DMSO	Ethanol
S1267	Vemurafenib (PLX4032)	<1 mg/mL	98 mg/mL	<1 mg/mL
S1040	Sorafenib (Nexavar)	<1 mg/mL	127 mg/mL	<1 mg/mL
S1178	Regorafenib (BAY 73-4506)	<1 mg/mL	97 mg/mL	<1 mg/mL
S1152	PLX-4720	<1 mg/mL	83 mg/mL	<1 mg/mL
S2807	Dabrafenib (GSK2118436)	<1 mg/mL	30 mg/mL	2 mg/mL
S1104	GDC-0879	<1 mg/mL	67 mg/mL	5 mg/mL
S2161	RAF265 (CHIR-265)	<1 mg/mL	100 mg/mL	33 mg/mL
S2746	AZ628	<1 mg/mL	90 mg/mL	<1 mg/mL
S2720	ZM 336372	<1 mg/mL	78 mg/mL	2 mg/mL
S2220	SB590885	<1 mg/mL	5 mg/mL	<1 mg/mL
S2202	NVP-BHG712	<1 mg/mL	101 mg/mL	3 mg/mL
S2872	GW5074	<1 mg/mL	104 mg/mL	<1 mg/mL
S2200	Raf265 derivative	<1 mg/mL	101 mg/mL	101 mg/mL
S8015	CEP-32496	<1 mg/mL	9 mg/mL	<1 mg/mL

Choose Your Country or Region

Product Categories

Vemurafenib (PLX4032)

Validation & Quality Control

Product Citations(16)

Customer Reviews(6) in vivo invitation

Quality Control & MSDS

Related Compound Libraries

Vemurafenib (PLX4032) is available in the following compound libraries:

Products used with Vemurafenib (PLX4032) in previous publications

Product Information

Compare Raf Inhibitors

Research Area

Vemurafenib (PLX4032) Mechanism

Combination Therapy

Product Description

Biological Activity

Protocol(Only for Reference)

Kinase Assay: [1]

Cell Assay: [2]

Animal Study: [2]

References

Chemical Information

Research Area

Customer Reviews (6)

Product Citations (16)

Tech Support & FAQs

If you have any other enquiries, please leave a message.

Related Raf Inhibitors

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Kinase Assay: ^[1]

Cell Assay: ^[2]

Animal Study: ^[2]