PLX4720
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 202272

CAS#: 918505-84-7

Description: PLX4720 is a 7-azaindole derivative that inhibits B-Raf(V600E) with an IC(50) of 13 nM, defines a class of kinase inhibitor with marked selectivity in both biochemical and cellular assays. PLX4720 preferentially inhibits the active B-Raf(V600E) kinase compared with a broad spectrum of other kinases, and potent cytotoxic effects are also exclusive to cells bearing the V600E allele.


Price and Availability

Size
Price

25mg
USD 90
200mg
USD 450
2g
USD 1250
20g
USD 5950
Size
Price

50mg
USD 150
500mg
USD 550
5g
USD 2250
50g
USD 9850
Size
Price

100mg
USD 250
1g
USD 750
10g
USD 3850
100g
Ask price

PLX4720, purity > 98%, is in stock. The same day shipping out after order is received. Delivery time: overnight (USA/Canada); 3-5 days (worldwide). Shipping fee: from $30.00 (USA); from $45.00 (Canada); from $70.00 (international). Note: Shipping out time for orders > 10g is about 2 weeks after PO is received.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 202272
Name: PLX4720
CAS#: 918505-84-7
Chemical Formula: C17H14ClF2N3O3S
Exact Mass: 413.04125
Molecular Weight: 413.82
Elemental Analysis: C, 49.34; H, 3.41; Cl, 8.57; F, 9.18; N, 10.15; O, 11.60; S, 7.75


Synonym: PLX 4720; PLX4720; PLX-4720.

IUPAC/Chemical Name: N-(3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl)propane-1-sulfonamide

InChi Key: YZDJQTHVDDOVHR-UHFFFAOYSA-N

InChi Code: InChI=1S/C17H14ClF2N3O3S/c1-2-5-27(25,26)23-13-4-3-12(19)14(15(13)20)16(24)11-8-22-17-10(11)6-9(18)7-21-17/h3-4,6-8,23H,2,5H2,1H3,(H,21,22)

SMILES Code: CCCS(=O)(NC1=CC=C(F)C(C(C2=CNC3=NC=C(Cl)C=C32)=O)=C1F)=O


Technical Data

Appearance:
white solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Safety Data Sheet (MSDS):

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not in water

Shelf Life:
>5 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


Additional Information

PLX4720, a 7-azaindole derivative that inhibits B-Raf(V600E) with an IC(50) of 13 nM, defines a class of kinase inhibitor with marked selectivity in both biochemical and cellular assays. PLX4720 preferentially inhibits the active B-Raf(V600E) kinase compared with a broad spectrum of other kinases, and potent cytotoxic effects are also exclusive to cells bearing the V600E allele. Consistent with the high degree of selectivity, ERK phosphorylation is potently inhibited by PLX4720 in B-Raf(V600E)-bearing tumor cell lines but not in cells lacking oncogenic B-Raf. In melanoma models, PLX4720 induces cell cycle arrest and apoptosis exclusively in B-Raf(V600E)-positive cells. In B-Raf(V600E)-dependent tumor xenograft models, orally dosed PLX4720 causes significant tumor growth delays, including tumor regressions, without evidence of toxicity. The work described here represents the entire discovery process, from initial identification through structural and biological studies in animal models to a promising therapeutic for testing in cancer patients bearing B-Raf(V600E)-driven tumors. see http://www.ncbi.nlm.nih.gov/pubmed/18287029.
 
 


References

1: Kamata T, Dankort D, Kang J, Giblett S, Pritchard CA, McMahon M, Leavitt AD. Hematopoietic expression of oncogenic BRAF promotes aberrant growth of monocyte-lineage cells resistant to PLX4720. Mol Cancer Res. 2013 Dec;11(12):1530-41. doi: 10.1158/1541-7786.MCR-13-0294. Epub 2013 Oct 23. PubMed PMID: 24152792; PubMed Central PMCID: PMC3869667.

2: Eum KH, Ahn SK, Kang H, Lee M. Differential inhibitory effects of two Raf-targeting drugs, sorafenib and PLX4720, on the growth of multidrug-resistant cells. Mol Cell Biochem. 2013 Jan;372(1-2):65-74. doi: 10.1007/s11010-012-1446-0. Epub 2012 Sep 2. PubMed PMID: 22941213.

3: Shao Y, Aplin AE. BH3-only protein silencing contributes to acquired resistance to PLX4720 in human melanoma. Cell Death Differ. 2012 Dec;19(12):2029-39. doi: 10.1038/cdd.2012.94. Epub 2012 Aug 3. PubMed PMID: 22858545; PubMed Central PMCID: PMC3504716.

4: Oikonomou E, Koc M, Sourkova V, Andera L, Pintzas A. Selective BRAFV600E inhibitor PLX4720, requires TRAIL assistance to overcome oncogenic PIK3CA resistance. PLoS One. 2011;6(6):e21632. doi: 10.1371/journal.pone.0021632. Epub 2011 Jun 27. PubMed PMID: 21738740; PubMed Central PMCID: PMC3124547.

5: Nucera C, Nehs MA, Nagarkatti SS, Sadow PM, Mekel M, Fischer AH, Lin PS, Bollag GE, Lawler J, Hodin RA, Parangi S. Targeting BRAFV600E with PLX4720 displays potent antimigratory and anti-invasive activity in preclinical models of human thyroid cancer. Oncologist. 2011;16(3):296-309. doi: 10.1634/theoncologist.2010-0317. Epub 2011 Feb 25. PubMed PMID: 21355020; PubMed Central PMCID: PMC3073446.

6: Nehs MA, Nagarkatti S, Nucera C, Hodin RA, Parangi S. Thyroidectomy with neoadjuvant PLX4720 extends survival and decreases tumor burden in an orthotopic mouse model of anaplastic thyroid cancer. Surgery. 2010 Dec;148(6):1154-62; discussion 1162. doi: 10.1016/j.surg.2010.09.001. PubMed PMID: 21134546; PubMed Central PMCID: PMC3413092.

7: Jiang CC, Lai F, Thorne RF, Yang F, Liu H, Hersey P, Zhang XD. MEK-independent survival of B-RAFV600E melanoma cells selected for resistance to apoptosis induced by the RAF inhibitor PLX4720. Clin Cancer Res. 2011 Feb 15;17(4):721-30. doi: 10.1158/1078-0432.CCR-10-2225. Epub 2010 Nov 18. PubMed PMID: 21088259.

8: Kaplan FM, Shao Y, Mayberry MM, Aplin AE. Hyperactivation of MEK-ERK1/2 signaling and resistance to apoptosis induced by the oncogenic B-RAF inhibitor, PLX4720, in mutant N-RAS melanoma cells. Oncogene. 2011 Jan 20;30(3):366-71. doi: 10.1038/onc.2010.408. Epub 2010 Sep 6. PubMed PMID: 20818433.