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Vemurafenib (PLX4032, RG7204)BRAF kinase inhibitor

Vemurafenib (PLX4032, RG7204)

Catalog No. A3004
Size Price Stock Qty
10mM (in 1mL DMSO) $55.00 In stock
10mg $50.00 In stock
50mg $120.00 In stock
200mg $300.00 In stock
500mg $440.00 In stock

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Sample solution is provided at 25 µL, 10mM.

Quality Control

Chemical structure

PLX4032

Related Biological Data

PLX4032
PLX4032 decreases pERK levels and inhibits growth of D4M cells. (A, B) Immunoblots of 2.5 μg of protein lysate for pERK or pAKT from (A) D4M.3A and (B) VMM5 cells, treated with DMSO, 3 μM PLX4032, or 10 μM U0126 over a time course (minutes post-treatment). Total ERK and total AKT were used as loading controls.

Biological Activity

Description Vemurafenib (PLX4032, RG7204) is a novel and potent inhibitor of B-RafV600E with IC50 of 31 nM.
Targets B-RafV600E C-Raf MAP4K5 (KHS1) SRMS ACK1 FGR
IC50 31 nM 48 nM 51 nM 18 nM 19 nM 63 nM

Protocol

Cell experiment:

Cell lines

MALME-3M melanoma cell lines

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Reaction Conditions

24 h; 10 μM

Applications

In melanoma cell lines, RG7204 was a potent inhibitor of proliferation in those expressing BRAFV600E but not BRAFWT. RG7204 also potently inhibited proliferation of melanoma cell lines expressing other codon 600 BRAF mutations (V600D, V600 K, and V600R).

Animal experiment:

Animal models

Athymic nude mice

Dosage form

100 mg/kg bid; oral taken.

Applications

In mice bearing Colo829 tumor xenografts, RG7204 at 100 mg/kg bid for 21 days showed greatly improved antitumor activity compared both with vehicle (P = 0.001) at the end of the study on day 38 after the tumor cell implant. There was complete tumor regression in all 10 mice treated with RG7204 by the end of the study. Survival in the mice treated with RG7204 was significantly better than in those treated with vehicle (P = 0.0008).

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Yang H, Higgins B, Kolinsky K, et al. RG7204 (PLX4032), a selective BRAFV600E inhibitor, displays potent antitumor activity in preclinical melanoma models[J]. Cancer research, 2010, 70(13): 5518-5527.

Vemurafenib (PLX4032, RG7204) Dilution Calculator

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Chemical Properties

Cas No. 918504-65-1 SDF Download SDF
Synonyms Vemurafenib,Zelboraf,PLX-4032,RG7204,RO5185426,
Chemical Name N-[3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluorophenyl]propane-1-sulfonamide
Canonical SMILES CCCS(=O)(=O)NC1=C(C(=C(C=C1)F)C(=O)C2=CNC3=NC=C(C=C23)C4=CC=C(C=C4)Cl)F
Formula C23H18ClF2N3O3S M.Wt 489.93
Solubility >24.5mg/mL in DMSO Storage Store at -20°C
General tips No
Shipping Condition No

View Related Products By Research Topics

Research Update

1. Impact of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) on the brain distribution of a novel BRAF inhibitor: vemurafenib (PLX4032). J Pharmacol Exp Ther. 2012 Jul;342(1):33-40. doi: 10.1124/jpet.112.192195. Epub 2012 Mar 27.
Abstract
Vemurafenib is a BRAF inhibitor that has been approved by FDA for the treatment of metastatic melanoma patients with a BRAF(V600E) mutation. Active efflux by P-gp and BCRP significantly restricted the brain distribution of vemurafenib at the blood-brain barrier, where active efflux by P-gp and BCRP restricted intracellular accumulation of vemurafenib and altered bidirectional net flux of vemurafenib.
2. Vemurafenib (RG67204, PLX4032): a potent, selective BRAF kinase inhibitor. Future Oncol. 2012 May;8(5):509-23. doi: 10.2217/fon.12.31.
Abstract
Vemurafenib is a mutated BRAF kinase inhibitor that showed response rates of >50% in metastatic melanoma patients with BRAF mutation. In a Phase III study, the treatment of vemurafenib in previously untreated patients led to over survival of 84%, response rates of 48% and prolonged progression-free survival with largely reduced risk of death and disease progression.
4. Combination therapy with vemurafenib (PLX4032/RG7204) and metformin in melanoma cell lines with distinct driver mutations. J Transl Med. 2011 May 24;9:76. doi: 10.1186/1479-5876-9-76.
Abstract
The combined MAPK oncogene inhibition and metabolic modulation of AMPK is an effective treatment of melanoma cells due to a molecular linkage between the MAPK and the LKB1-AMPK pathways.
5. Stat3-targeted therapies overcome the acquired resistance to vemurafenib in melanomas. J Invest Dermatol. 2013 Aug;133(8):2041-9. doi: 10.1038/jid.2013.32. Epub 2013 Jan 23.
Abstract
Although the treatment of vemurafenib, a Braf inhibitor, in melanoma patients with Braf(V600E) mutations resulted in dramatic improvement with decreased risk of death and tumor progression, melanoma cells rapidly acquire vemurafenib resistance, which can be overcome by targeting Stat3-PAX3 signaling pathway.

Background

Vemurafenib is an inhibitor of BRAF kinase. It inhibits BRAFV600E and also has inhibitory activity in vitro against several other kinds of kinases, including CRAF, ARAF and wild-type BRAF. Vemurafenib is a competitive small-molecule serine–threonine kinase inhibitor that functions by binding to the ATP-binding domain of mutant BRAF. Vemurafenib can also give rise to activation of downstream MEK by normal RAF homo- and heterodimers in non-BRAF mutated cells, which has been shown to be caused by transactivation of the nondrug-bound partner in BRAF to CRAF heterodimers and CRAF to CRAF homodimers.

Reference

Keith. T Flaherty, Uma Yasothan and Peter Kirkpatrick. Vemurafenib. Nature Reviews Drug Discovery. 2011; 10: 811 – 812.

Jason J. Luke, F. Stephen Hodi. Vemurafenib and BRAF Inhibition: A New Class of Treatment for Metastatic Melanoma. Clinical Cancer Research. 2012; 18: 9 – 14.