PLX-4720

Catalog No.

A3016

BRAF kinase inhibitor

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Grouped product items
Size	Price	Stock
10mM (in 1mL DMSO)	$61.00	In stock
Evaluation Sample	$30.00	In stock
10mg	$55.00	In stock
25mg	$121.00	In stock
100mg	$330.00	In stock

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Background
Product Citation
Chemical Properties
Protocol
Biological Activity
Quality Control

Background

PLX-4720, a 7-azaindole derivative discovered by a structure-guided discovery approach, is a potent inhibitor of B-Raf^V600E, the most frequent oncogenic protein kinase mutation, with the value of 50% inhibition concentration IC₅₀ of 13 nM. PLX-4720 exhibits selective inhibition against B-Raf^V600Erather than wild type B-Raf (IC₅₀ = 160 nM) as well as a wide range of other kinases, such as FRK, CSK, SRC, FAK, FGFR, and Aurora A (IC₅₀ > 1000 nM for all). PLX-4720 potently inhibits ERK phosphorylation in tumor cell lines harboring B-Raf^V600E, induces cell cycle arrest and apoptosis in B-Raf^V600E-positive melanoma cells and causes tumor growth delays in B-Raf^V600E-dependent tumor xenograft models through oral administration.

Reference

Tsai J, Lee JT, Wang W, Zhang J, Cho H, Mamo S, Bremer R, Gillette S, Kong J, Haass NK, Sproesser K, Li L, Smalley KS, Fong D, Zhu YL, Marimuthu A, Nguyen H, Lam B, Liu J, Cheung I, Rice J, Suzuki Y, Luu C, Settachatgul C, Shellooe R, Cantwell J, Kim SH, Schlessinger J, Zhang KY, West BL, Powell B, Habets G, Zhang C, Ibrahim PN, Hirth P, Artis DR, Herlyn M, Bollag G. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3041-3046

Product Citation

1. Sieber J, Wieder N, et al. "GDC-0879, a BRAF(V600E) Inhibitor, Protects Kidney Podocytes from Death." Cell Chem Biol. 2017 Dec 6. PMID:29249695

Chemical Properties

Physical Appearance	A solid
Storage	Store at 4°C
M.Wt	413.83
Cas No.	918505-84-7
Formula	C₁₇H₁₄ClF₂N₃O₃S
Synonyms	PLX4720, PLX-4720, PLX 4720
Solubility	≥20.69 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O
Chemical Name	N-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl]propane-1-sulfonamide
SDF	Download SDF
Canonical SMILES	CCCS(=O)(=O)NC1=C(C(=C(C=C1)F)C(=O)C2=CNC3=NC=C(C=C23)Cl)F
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Cell experiment: [1]
Cell lines	WM793 cells
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	0.5 μM, 96 hours
Applications	Viable cells were identified following 96 h incubation with PLX-4720. Cell viability was further evaluated after re-plating onto non-fibrillar collagen gels, in the continued presence of the drug. Viable cells were identified in ~63% of PLX-4720 treated cultures. These data indicate that melanoma cells harboring a BRAFV600E mutation can survive despite reductions in BRAF activation of the MEK-ERK signaling cascade.
Animal experiment: [2]
Animal models	Athymic nude mice injected with melanoma A375 cells
Dosage form	Intraperitoneal injection, 25–50mg/kg daily
Applications	PLX-4720 decreased tumor growth as single therapy. When combined with the CRM1 inhibitor KPT-276 (75 mg/kg every day), the two inhibitors induced complete tumor regression per RECIST criteria. The difference between both single therapy and the combination therapy was statistically significant. The effect on apoptosis was believed to be the greatest contribution of the combination since it was significantly increased by the drug combination.
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] Klein R M, Higgins P J. A switch in RND3-RHOA signaling is critical for melanoma cell invasion following mutant-BRAF inhibition. Mol Cancer, 2011, 10: 114. [2] Fragomeni R A S, Chung H W, Landesman Y, et al. CRM1 and BRAF inhibition synergize and induce tumor regression in BRAF-mutant melanoma. Molecular cancer therapeutics, 2013, 12(7): 1171-1179.

Biological Activity

Description	PLX4720 is a potent and selective inhibitor of B-RafV600E with IC50 of 13 nM, equally potent to c-Raf-1(Y340D and Y341D mutations), 10-fold selectivity for B-RafV600E than wild-type B-Raf.
Targets	B-Raf^V600E	c-Raf-1^Y340D/Y341D
IC50	13 nM	6.7 nM