PLX-4720

Catalog No.S1152

PLX4720 is a potent and selective inhibitor of B-RafV600E with IC50 of 13 nM in a cell-free assay, equally potent to c-Raf-1(Y340D and Y341D mutations), 10-fold selectivity for B-RafV600E than wild-type B-Raf.

Price Stock Quantity  
USD 156 In stock
USD 120 In stock
USD 270 In stock
USD 670 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

PLX-4720 Chemical Structure

PLX-4720 Chemical Structure
Molecular Weight: 413.83

Validation & Quality Control

Product Use Citation(44)

Customer Product Validation(9)

Quality Control & MSDS

Related Compound Libraries

PLX-4720 is available in the following compound libraries:

Raf Inhibitors with Unique Features

  • Pan Raf Inhibitor

    AZ 628 Pan-Raf inhibitor, BRAF, IC50=105 nM; BRAFV600E, IC50=34 nM; c-Raf-1, IC50=29 nM.

  • Most Potent Raf Inhibitor

    PF-04880594 C-Raf, IC50=0.39 nM; B-Raf, IC50=0.19 nM.

  • FDA-approved Raf Inhibitor

    Sorafenib Tosylate Approved by FDA for advanced renal cancer。

  • Newest Raf Inhibitor

    TAK-632 Potent pan-Raf inhibitor with IC50 of 8.3 nM and 1.4 nM for B-Raf(wt) and C-Raf, respectively, showing less or no inhibition against other tested kinases.

Product Information

  • Compare Raf Inhibitors
    Compare Raf Products
  • Research Area
  • Inhibition Profile
  • PLX-4720 Mechanism

Product Description

Biological Activity

Description PLX4720 is a potent and selective inhibitor of B-RafV600E with IC50 of 13 nM in a cell-free assay, equally potent to c-Raf-1(Y340D and Y341D mutations), 10-fold selectivity for B-RafV600E than wild-type B-Raf.
Targets C-Raf-1 (Y340D/Y341D) [1]
(Cell-free assay)
B-Raf (V600E) [1]
(Cell-free assay)
BRK [1]
(Cell-free assay)
B-Raf [1]
(Cell-free assay)

 View  More

IC50 6.7 nM 13 nM 130 nM 160 nM
In vitro PLX-4720 displays >10 times selectivity against wild type B-Raf, and >100 times selectivity over other kinases such as Frk, Src, Fak, FGFR, and Aurora A with IC50 of 1.3-3.4 μM. PLX-4720 significantly inhibits the ERK phosphorylation in cell lines bearing B-RafV600E with IC50 of 14-46 nM, but not the cells with wild-type B-Raf. PLX-4720 significantly inhibits the growth of tumor cell lines bearing the B-RafV600E oncogene, such as COLO205, A375, WM2664, and COLO829 with GI50 of 0.31 μM, 0.50 μM, 1.5 μM, and 1.7 μM, respectively. In addition, PLX-4720 treatment at 1 μM induces cell cycle arrest and apoptosis exclusively in the B-RafV600E-positive 1205Lu cells, but not in the B-Raf wild-type C8161 cells. [1] PLX-4720 treatment (10 μM) significantly induces >14-fold expression of BIM in the PTEN+ cells, compared with the PTEN- cell lines (4-fold), giving an explanation of the resistance of PTEN- cells to PLX-4720-induced apoptosis. [2]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
DU-4475NIrab3RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M4rPbGlEPTB;MD6wO|Q2PyEQvF2=NV3I[G9SW0GQR1XS
EoL-1-cellNEHpNmNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MVzJR|UxRTBwMUSxOlYh|ryPNIfvRXRUSU6JRWK=
C32MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MVTJR|UxRTBwMUWxN|Eh|ryPM3:yRnNCVkeHUh?=
M14MnW1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M3j2WmlEPTB;MD6yNVc2PyEQvF2=MYLTRW5ITVJ?
CP50-MEL-BM1P3c2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7M1voXWlEPTB;MD6yPVc5PCEQvF2=NIfoVGhUSU6JRWK=
A101DNXX0XmNYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MlTMTWM2OD1yLkOyOVg6KM7:TR?=NGPhTYhUSU6JRWK=
G-361MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NGDBOpVKSzVyPUCuN|Q3OzdizszNMX3TRW5ITVJ?
HT-144NXTtPY9JT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NVTsTIVIUUN3ME2wMlM3OzJ7IN88US=>NHXXN5NUSU6JRWK=
ACNMXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MXvJR|UxRTBwM{i0O|ch|ryPMULTRW5ITVJ?
COLO-829M3fIdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NFfGRlFKSzVyPUCuN|g6PjhizszNNYDNcnhrW0GQR1XS
MEL-HONYTyeFZsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NHHwNpNKSzVyPUCuOFEyPzlizszNMkLNV2FPT0WU
SH-4M1\zZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7Mki3TWM2OD1yLkSxOFIzKM7:TR?=MmmzV2FPT0WU
SK-MEL-3M1zuO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7NWC5TIdJUUN3ME2wMlUyPTZ6IN88US=>MY\TRW5ITVJ?
A375NE\sPG5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MoPBTWM2OD1yLk[3N|U6KM7:TR?=NFH4NZdUSU6JRWK=
MMAC-SFMWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MnXKTWM2OD1yLk[4OlE1KM7:TR?=M4nHcXNCVkeHUh?=
BHT-101NEnFUnBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=Mo\2TWM2OD1yLkewO|AzKM7:TR?=MVLTRW5ITVJ?
K5MnvBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M4rZbGlEPTB;MD63OlE1QCEQvF2=NXnOSYxGW0GQR1XS
BV-173NWD2W2s3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M1jPcGlEPTB;MD63PVY1PCEQvF2=NVniV2JoW0GQR1XS
RVH-421NUfJWXZRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M3jTXWlEPTB;MD64Olc6PiEQvF2=Mm\mV2FPT0WU
HCC2218MnTuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M4XMWWlEPTB;MD64O|g1PCEQvF2=NInnR41USU6JRWK=
WM-115M2P5[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NVnjcmNvUUN3ME2wMlg5Pjl{IN88US=>MYPTRW5ITVJ?
SK-MEL-28Mn;GS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M1;vR2lEPTB;MT6wOFU3QSEQvF2=Mm\WV2FPT0WU
COLO-679NVTy[WJ6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NXv5U25nUUN3ME2xMlExPDZ2IN88US=>NHLa[pBUSU6JRWK=
MZ7-melMX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M13YeWlEPTB;MT6xOFk3OyEQvF2=MXvTRW5ITVJ?
SK-MEL-30M2P3fGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NEHlS|BKSzVyPUGuN|M{QDZizszNM1vOcXNCVkeHUh?=
NCI-H209NWfPfllUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MV3JR|UxRTFwNkC4OkDPxE1?NGj0NoFUSU6JRWK=
HTC-C3NGjocHRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MnvnTWM2OD1zLk[2Nlk1KM7:TR?=NIf6T5lUSU6JRWK=
KARPAS-45M3T5cmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7M1LjUGlEPTB;Mj6wOFk4QCEQvF2=MmXKV2FPT0WU
NCI-SNU-5MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MlHTTWM2OD1{LkGxPVY6KM7:TR?=NX;BdGp5W0GQR1XS
KP-4NXTlR5hIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NWfBWmFGUUN3ME2yMlMxPzh5IN88US=>MkPIV2FPT0WU
PA-1M3LSOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MYfJR|UxRTJwN{K2O|Mh|ryPM1zwNnNCVkeHUh?=
HuO-3N1NXjUNoZTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M{X5TGlEPTB;Mj64O|k1PiEQvF2=NHmyeYhUSU6JRWK=
NCI-H358M1rxNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MWnJR|UxRTJwOUKyN|Ih|ryPNIPRSmhUSU6JRWK=
CTB-1NVzETlJFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NVTxbo5xUUN3ME2zMlQxOTd4IN88US=>M{LTUHNCVkeHUh?=
697MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NF7oPIdKSzVyPUOuOVUzPjZizszNNW\6dZdRW0GQR1XS
CP66-MELNXXlWJNWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NH;T[I9KSzVyPUSuNVU6OjdizszNNIK1W3hUSU6JRWK=
NB13M4L6SWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NHjFSJFKSzVyPUSuOFkyPzlizszNNFTyWYNUSU6JRWK=
DBTRG-05MGNIjOPVZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MojPTWM2OD12LkWzN|I2KM7:TR?=MVvTRW5ITVJ?
A2058MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M4X4dmlEPTB;ND63NlE3PCEQvF2=MWjTRW5ITVJ?
KG-1M4\pZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7MXzJR|UxRTRwN{O5NFgh|ryPNFLNVnBUSU6JRWK=
8305CMm\GS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NFy2UXRKSzVyPUWuNVg4OyEQvF2=M3m3UHNCVkeHUh?=
RPMI-7951NXzPW|RnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MoK5TWM2OD13LkiwNlg{KM7:TR?=MVHTRW5ITVJ?
CHL-1NGOzcnRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M3\0bmlEPTB;NT65O|YxOyEQvF2=NXHrXng4W0GQR1XS
TI-73NIP3THBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MWPJR|UxRTZwMEC5NFIh|ryPM{\CSXNCVkeHUh?=
HT-1080NV;4dmk1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MXTJR|UxRTZwMUC5OFYh|ryPMVHTRW5ITVJ?
ES5NXqydmFOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NV3xSoJwUUN3ME22MlE1QTJ2IN88US=>MkH2V2FPT0WU
8-MG-BANEjJZ4hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MXHJR|UxRTZwMUixNlkh|ryPNXK5N2d[W0GQR1XS
NB7M4rlOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NHnUWJFKSzVyPU[uNlE{PzNizszNM{nkO3NCVkeHUh?=
H4MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NGLoNYVKSzVyPU[uNlI1QTNizszNMVrTRW5ITVJ?
CAL-72NF\NVolIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NX;hUGRtUUN3ME22MlQ2PDJ|IN88US=>M160VHNCVkeHUh?=
HCC1806MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MY\JR|UxRTZwOEG5N|Eh|ryPNWHmPZgzW0GQR1XS
BCPAPMXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MYnJR|UxRTdwMkG3OlQh|ryPNWTyXJNnW0GQR1XS
LB2241-RCCMWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M1TCUmlEPTB;Nz6zOlkxPyEQvF2=Moj2V2FPT0WU
COLO-741M{faV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7MUTJR|UxRThwMEG2O|kh|ryPNH7ocZJUSU6JRWK=
HSC-3MlnHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NIrXTG9KSzVyPUiuNFcxPjhizszNNHzpeYNUSU6JRWK=
SW982MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MV\JR|UxRThwNEG1NVYh|ryPMVPTRW5ITVJ?
GCTMnLTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NYHLNnhNUUN3ME24Mlc2OzF2IN88US=>MWTTRW5ITVJ?
KY821M{XtXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NGTZcmRKSzVyPUmuNFUyPzhizszNMnTZV2FPT0WU
JVM-3MoLMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NUHS[pVFUUN3ME25MlU3QTl7IN88US=>MYTTRW5ITVJ?
RS4-11NIfWeZVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NHf6W2hKSzVyPUmuOlA1QCEQvF2=NFHzeZJUSU6JRWK=
VA-ES-BJM{HsPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NF3iSodKSzVyPUGwMlAyPDlizszNMXXTRW5ITVJ?
A431MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?Ml;GTWM2OD1zMD60NlEzKM7:TR?=NV;xTmJwW0GQR1XS
LXF-289MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MU\JR|UxRTFyLkS1PEDPxE1?MnO2V2FPT0WU
SK-MEL-24NXT2OYR7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MUHJR|UxRTFyLkiyO|Qh|ryPMnXPV2FPT0WU
NOS-1NVvRSINIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NFLBUmtKSzVyPUGwMlg1PzJizszNNU\CTGp2W0GQR1XS
KNS-62M{TWSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MnyxTWM2OD1zMT6yOFA1KM7:TR?=NHuxNYJUSU6JRWK=
SK-HEP-1MoWyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NYW5fIVuUUN3ME2xNU4{PTJ5IN88US=>MoLkV2FPT0WU
A3-KAWNHLPNW5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NFnGZWhKSzVyPUGxMlcyPzhizszNNVnBW3NXW0GQR1XS
SK-LU-1M1\sW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7MWLJR|UxRTF{LkK2OVUh|ryPNH62Zo5USU6JRWK=
TYK-nuNYnkbXRMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M1fhXGlEPTB;MUKuN|k{OiEQvF2=MnPxV2FPT0WU
NMC-G1M2\ueGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7M3rUemlEPTB;MUKuOlA3OiEQvF2=NX\tUVNwW0GQR1XS
BB65-RCCNUT6cHVKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M2Ts[mlEPTB;MUKuO|E3QSEQvF2=MoK3V2FPT0WU
QIMR-WILNV7lbZFNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MWTJR|UxRTF{Lki4N|Mh|ryPNEHr[YVUSU6JRWK=
D-566MGM33hW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7MVvJR|UxRTF|Lkm1O|Yh|ryPNYjXSlR[W0GQR1XS
KYSE-140MnX4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NEHGblVKSzVyPUG0MlA4PTNizszNNH65N4xUSU6JRWK=
SCC-4M4LrV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7MmPjTWM2OD1zND6zN|U6KM7:TR?=NF;Y[3lUSU6JRWK=
U251MlK1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MYfJR|UxRTF2Lki0PVIh|ryPMUfTRW5ITVJ?
D-542MGNWfKO5NwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NYXkTFlDUUN3ME2xOE46OjJ{IN88US=>MmizV2FPT0WU
LAMA-84NUHXZVFIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NHyxRVhKSzVyPUG0Mlk6OzJizszNNH;HPWJUSU6JRWK=
NCI-H720NWnGdZpJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NXXaRlFHUUN3ME2xOU4zPjh2IN88US=>NIDEfY9USU6JRWK=
DELNVHjcWFbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MWjJR|UxRTF3LkSyPVMh|ryPMkPXV2FPT0WU
SBC-1MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M1[yNGlEPTB;MUWuOFMxPSEQvF2=NIHpSFdUSU6JRWK=
ECC10NIPTVpFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NXPhWm9rUUN3ME2xOU41PDV6IN88US=>NFrrcJJUSU6JRWK=
DaoyMnGwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NGP0dJpKSzVyPUG1Mlc3OTZizszNNYLYTm9CW0GQR1XS
SCHM1nNVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MkG4TWM2OD1zNT63PFM2KM7:TR?=M1TuXnNCVkeHUh?=
MZ2-MELNYHudoNNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NH;BU4dKSzVyPUG2MlA3PDZizszNM4nIVnNCVkeHUh?=
CAL-12TNXPCXW5HT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=Mn:wTWM2OD1zNj60PFYzKM7:TR?=MWPTRW5ITVJ?
KE-37MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M2PydmlEPTB;MU[uPFExPyEQvF2=NFHXZ49USU6JRWK=
LS-411NNXXq[m5VT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MlTQTWM2OD1zNz6xNVgh|ryPMlLZV2FPT0WU
NCI-H2228NYWzUoNWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NEHuUWVKSzVyPUG3MlMxPzFizszNNVvnNWRrW0GQR1XS
SK-MEL-2NH\ESohIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NYezb|k3UUN3ME2xO{41QTZ3IN88US=>M2nGWXNCVkeHUh?=
HNNVjVXlNFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NYLDeXZnUUN3ME2xO{44OjR6IN88US=>MoGzV2FPT0WU
NCI-H1648NXnFeGhFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NGHVPFlKSzVyPUG3MlgyQCEQvF2=MV\TRW5ITVJ?
IA-LMNXr4d2h1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MkDtTWM2OD1zOD6zNVczKM7:TR?=MoXiV2FPT0WU
EW-13NWrBdXdlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MWLJR|UxRTF6LkW3NFgh|ryPMonHV2FPT0WU
YKG-1NEW0bGdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NUDMN2N6UUN3ME2xPU42PzFzIN88US=>MVvTRW5ITVJ?
KNS-81-FDMXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MkHxTWM2OD1zOT61PFU5KM7:TR?=NFTXbnhUSU6JRWK=
23132-87NIi0dHFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NIPGWFBKSzVyPUG5Mlc3PDJizszNMV7TRW5ITVJ?
NUGC-3MnS5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NX\Jc4p{UUN3ME2xPU46QDh5IN88US=>NYfwW4tWW0GQR1XS
5637NUDofGxJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MXnJR|UxRTJyLkC0O|gh|ryPMXPTRW5ITVJ?
NCI-H1755Moj0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?Ml6wTWM2OD1{MD60O|Y1KM7:TR?=MXHTRW5ITVJ?
RH-18NFP2SGJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NI\XT5hKSzVyPUKwMlU4PDhizszNMoi4V2FPT0WU
RXF393NFnsOXlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M{e3SWlEPTB;MkCuOlc2PiEQvF2=Mn\WV2FPT0WU
LU-134-ANH7NWoxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M1zFNGlEPTB;MkCuO|A2PiEQvF2=M13FW3NCVkeHUh?=
TE-12MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NVrq[I0xUUN3ME2yNE44OjBzIN88US=>NXTYS|liW0GQR1XS
MOLT-4MnjyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MUjJR|UxRTJzLkG5NVUh|ryPNFj4WFlUSU6JRWK=
IGR-1MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NITDOWRKSzVyPUKxMlM4QTZizszNM4D2WHNCVkeHUh?=
HOP-92NHTUZXhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NXftT2Z[UUN3ME2yNU41QTh5IN88US=>M1O4NHNCVkeHUh?=
SK-MES-1Mm\0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NXzhO3VpUUN3ME2yNU44OzhzIN88US=>NELWcpRUSU6JRWK=
LU-65MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MVrJR|UxRTJzLki2NlQh|ryPMojvV2FPT0WU
MS-1MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MYjJR|UxRTJ{LkGyNFMh|ryPMU\TRW5ITVJ?
LoVoMYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NFHBXHJKSzVyPUKyMlI1PCEQvF2=NF\INm5USU6JRWK=
A704NGLiU5lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M1:xUmlEPTB;MkKuOVE2PSEQvF2=M{HpXnNCVkeHUh?=
HT-1376M37w[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7NGfTcWRKSzVyPUKyMlYxPTlizszNNWnFTnVJW0GQR1XS
IST-MEL1Mn7IS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MYHJR|UxRTJ{Lk[3OVEh|ryPMmjyV2FPT0WU
Ramos-2G6-4C10NXPQdJVsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M{DJbmlEPTB;MkKuO|M3PiEQvF2=MnPGV2FPT0WU
T47DNVLVR3RIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NELDU21KSzVyPUKyMlc6PzlizszNMXXTRW5ITVJ?
HT-1197NUS4bHR6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M3zzbWlEPTB;MkOuNFgyPyEQvF2=MoD1V2FPT0WU
LB2518-MELMn:1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NUXHemtzUUN3ME2yN{43PDF{IN88US=>Mn;VV2FPT0WU
J-RT3-T3-5NUnQSnBZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NIPzVo9KSzVyPUK0Mlc2QTVizszNM2f0RXNCVkeHUh?=
SK-NEP-1M2XrWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NH7s[WVKSzVyPUK0Mlg4PDRizszNNVW5dXlnW0GQR1XS
NCI-H526NViwTnVqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NHLZ[4xKSzVyPUK1MlAxOjNizszNNIj0OmxUSU6JRWK=
IST-SL1NFzCO4tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NH;qRVVKSzVyPUK1MlI4PTFizszNNEXVRlRUSU6JRWK=
HHNFfaZYZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M2XCTGlEPTB;MkWuN|E6OiEQvF2=MUnTRW5ITVJ?
NCI-H82MlrZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M2HRWmlEPTB;MkWuPVM5KM7:TR?=MnXNV2FPT0WU
SNU-449M1K5TGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7M4fFSmlEPTB;MkeuNlAyQCEQvF2=NEe5[VJUSU6JRWK=
COR-L23M1zY[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MX;JR|UxRTJ5LkK4NVMh|ryPNIT4[WVUSU6JRWK=
LOXIMVINX7JOYF5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NV3vfYhnUUN3ME2yO{4{PjhizszNM1LXN3NCVkeHUh?=
GR-STMUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MYTJR|UxRTJ5Lk[3NFYh|ryPNWjPXYloW0GQR1XS
NCI-SNU-1MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?Mn7CTWM2OD1{Nz65OFQh|ryPNWHScIJzW0GQR1XS
ALL-POMWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MYXJR|UxRTJ6LkG2NFQh|ryPMmXTV2FPT0WU
ML-2MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NH3UdodKSzVyPUK4MlI5OTRizszNNVjEOlI4W0GQR1XS
HOP-62M4r1V2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7MmTnTWM2OD1{OD63NVMh|ryPM{e0WXNCVkeHUh?=
EGI-1MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NILJU4VKSzVyPUK4Mlg5PDVizszNMXTTRW5ITVJ?
TCCSUPMl3ES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MmfSTWM2OD1{OD65NlczKM7:TR?=NFLqc|BUSU6JRWK=
LB996-RCCMmewS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MUjJR|UxRTJ7LkW2PFIh|ryPMofXV2FPT0WU
LCLC-97TM1MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?Mly2TWM2OD1|Mj6xPVY1KM7:TR?=M{fHUHNCVkeHUh?=
NCI-H1304M4Tj[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7M4LTNmlEPTB;M{KuN|MxOSEQvF2=MontV2FPT0WU
KP-N-YSM4Tmdmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NUDOdmY5UUN3ME2zNk42QTd|IN88US=>MWPTRW5ITVJ?
NCI-H1770NVXTVHJmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MUnJR|UxRTN|LkG2OFgh|ryPNEnV[GVUSU6JRWK=
EM-2NV32c5RzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NH:xPZdKSzVyPUOzMlY2ODRizszNM131WHNCVkeHUh?=
ChaGo-K-1NEjBe5VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M{DGWWlEPTB;M{OuO|I{PiEQvF2=NWLnU|FGW0GQR1XS
ACHNNGnSS2RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M13ncWlEPTB;M{OuPFM5PSEQvF2=MYnTRW5ITVJ?
MN-60NWLlTpVLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NWjMSZh7UUN3ME2zN{45PTR2IN88US=>MYDTRW5ITVJ?
EW-18MoX4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?Mo\sTWM2OD1|Mz64PVcyKM7:TR?=MY\TRW5ITVJ?
KGNMY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NIrSVFJKSzVyPUO1MlczQTJizszNMoHqV2FPT0WU
U031M1vOUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MonITWM2OD1|NT64NVMzKM7:TR?=M1v0SXNCVkeHUh?=
HMV-IINGHyVXJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MV7JR|UxRTN4LkC3O|Qh|ryPNXzmfJVQW0GQR1XS
L-363NH;ZSnRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NV7PN|B[UUN3ME2zO{43PDV3IN88US=>MorDV2FPT0WU
NCI-H1155M1HGVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MlntTWM2OD1|OD6wNFE2KM7:TR?=NYXJbm91W0GQR1XS
NCI-H1793NWTvNVh{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MnHITWM2OD1|OD6xNFI3KM7:TR?=NXLyfIE6W0GQR1XS
P30-OHKM{jSSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MoPLTWM2OD1|OD6xN|MzKM7:TR?=MXrTRW5ITVJ?
AN3-CAMX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NFjxVINKSzVyPUO4MlE3OTVizszNMUHTRW5ITVJ?
UACC-257MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MVzJR|UxRTN6Lke5JO69VQ>?M2fx[nNCVkeHUh?=
MCF7MnHJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M3ux[GlEPTB;M{muPFYzQSEQvF2=NXXubXBlW0GQR1XS
KP-N-YNNYfoXGkzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NX\JepJKUUN3ME20NE41Ojh3IN88US=>MVzTRW5ITVJ?
T98GNXn1WnhnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NUSzNXhGUUN3ME20NE41QTV5IN88US=>MkfmV2FPT0WU
HGC-27M3[1Wmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MlXLTWM2OD12Mz6yO|Qh|ryPNFLZPGZUSU6JRWK=
NCI-H1092NEjGb5BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NVL4NlN[UUN3ME20N{4zQDl3IN88US=>MX7TRW5ITVJ?
KARPAS-299MoXSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M2XrUWlEPTB;NEOuN|A4OSEQvF2=Mlz0V2FPT0WU
LB1047-RCCM4e1fGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NILFeZZKSzVyPUS0Mlk6PTlizszNMXHTRW5ITVJ?
786-0M4\EcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NFq3[VFKSzVyPUS1MlY2KM7:TR?=M3r2e3NCVkeHUh?=
HCC2157NF[1cm5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M{P2fGlEPTB;NE[uNFM2QSEQvF2=MYDTRW5ITVJ?
NYM2fDdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NYSzPYxmUUN3ME20Ok4yPzd6IN88US=>M3\GNnNCVkeHUh?=
EFM-19MoHwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NG\WNHBKSzVyPUS2Mlc2OzNizszNMULTRW5ITVJ?
EW-16MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MWTJR|UxRTR4Lke4NFYh|ryPMoDCV2FPT0WU
UM-UC-3M3;KWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NX3sWXAyUUN3ME20Ok45ODV7IN88US=>NYe3WWp3W0GQR1XS
HT-29M1TrT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7M4fXdWlEPTB;NEeuPFc6OiEQvF2=MYfTRW5ITVJ?
LN-405M1fJfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7M1jNdmlEPTB;NEiuNFgzPyEQvF2=MoP2V2FPT0WU
NCI-H727M4DLOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MWPJR|UxRTR6Lke3NlYh|ryPM3L6V3NCVkeHUh?=
D-502MGNFzFXpRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MmnnTWM2OD12OD65Olc3KM7:TR?=MkPKV2FPT0WU
GMS-10MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MV;JR|UxRTR7LkK5O|Qh|ryPMkjxV2FPT0WU
MEL-JUSONVLuTFFxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NYn1WIF6UUN3ME20PU4{PDdizszNMUnTRW5ITVJ?

... Click to View More Cell Line Experimental Data

In vivo Oral administration of PLX-4720 at 20 mg/kg/day induces significant tumor growth delays and regressions in B-RafV600E-dependent COLO205 tumor xenografts, without obvious adverse effects in mice even at dose of 1 g/kg. PLX-4720 at 100 mg/kg twice daily almost completely eliminates the 1205Lu xenografts bearing B-RafV600E, while has no activity against C8161 xenografts bearing wild-type B-Raf. The anti-tumor effects of PLX-4720 correlate with the blockade of MAPK pathway in those cells harboring the V600E mutation. [1] PLX-4720 treatment at 30 mg/kg/day significant inhibits the tumor growth of 8505c xenografts by >90%, and dramatically decreases distant lung metastases. [3]
Features

Protocol(Only for Reference)

Kinase Assay: [1]

In vitro Raf kinase activities The in vitro kinase activities of wild type Raf and mutants are determined by measuring phosphorylation of biotinylated-MEK protein using Perkin-Elmer's AlphaScreen Technology. For each enzyme (0.1 ng), 20-μL reactions are carried out in 20 mM Hepes (pH 7.0), 10 mM MgCl2, 1 mM DTT, 0.01% Tween-20, 100 nM biotin-MEK protein, various ATP concentrations, and increasing concentrations of PLX-4720 at room temperature. Reactions are stopped at 2, 5, 8, 10, 20, and 30 minutes with 5 μL of a solution containing 20 mM Hepes (pH 7.0), 200 mM NaCl, 80 mM EDTA, and 0.3% BSA. The stop solution also includes phospho-MEK Antibody, Streptavidin-coated Donor beads and Protein A Acceptor beads from the AlphaScreen Protein A Detection Kit. The antibody and beads are preincubated in stop solution in the dark at room temperature for 30 minutes. The final dilution of antibody is 1/2,000, and the final concentration of each bead is 10 μg/mL. The assay plates are incubated at room temperature for one hour then are read on a PerkinElmer AlphaQuest reader.

Cell Assay: [1]

Cell lines COLO205, A375, WM2664, COLO829, HT716, SW620, H460, Calu-6, HCT116, SK-MEL2, SK-MEL3, Lovo, H1299, 1205Lu, and C8161 cells
Concentrations Dissolved in DMSO, final concentrations ~1 mM
Incubation Time 24, 48, and 72 hours
Method Cells are treated with various concentrations PLX-4720 for 24, 48, and 72 hours. Cell proliferation is measured by using the CellTiter-Glo Luminescent Cell Viability Assay or MTT assay. For cell cycle analysis, supernatant and cells are collected, pelleted, and fixed with 70% ethanol. Before staining with propidium iodide (10 μg/mL), cells are incubated for 1 hour at 37 °C in 0.5 mg/mL RNase I to rid samples of residual RNA contamination. Samples are then analyzed by using the EPICS XL apparatus. For the assessment of apoptosis, media and cells are harvested and pelleted before staining with annexin-FITC and propidium iodide. Samples are subsequently analyzed by using the EPICS XL apparatus.

Animal Study: [1]

Animal Models Female athymic mice (NCr nu/nu) implanted s.c. with COLO205 cells, and SCID mice with 1205Lu or C8161 cells
Formulation Suspended in vehicle (5% DMSO, 1% methylcellulose)
Dosages 5, 20, or 100 mg/kg
Administration Oral gavage once or twice daily

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Tsai J, et al. Proc Natl Acad Sci U S A, 2008, 105(8), 3041-3046.

[2] Paraiso KH, et al. Cancer Res, 2011, 71(7), 2750-2760.

view more

Chemical Information

Download PLX-4720 SDF
Molecular Weight (MW) 413.83
Formula

C17H14ClF2N3O3S

CAS No. 918505-84-7
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 83 mg/mL (200.56 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 1% CMC+0.5% Tween-80 30 mg/mL
* <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.
Chemical Name N-(3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl)propane-1-sulfonamide

Customer Product Validation (9)


Click to enlarge
Rating
Source Cancer Discov 2013 3, 350-62. PLX-4720 purchased from Selleck
Method Western blot
Cell Lines A375 cells
Concentrations 1 uM
Incubation Time 16 h
Results Associated with the increased RAS-GTP, it's observed a concomitant increase in C-RAF activation, as measured by phosphorylation of Ser338. Under conditions of combined C-RAF/NF1 knockdown, ERK phosphorylation was inhibited more effectively compared to knockdown of NF1 alone. Moreover, whereas cyclin D1 levels were inhibited by PLX4720 in A375 cells, but NF1 silencing partially alleviated this effect.

Click to enlarge
Rating
Source Genes Dev 2012 26, 1055-69. PLX-4720 purchased from Selleck
Method Western blot
Cell Lines Melanoma cell lines
Concentrations 1, 2, 3 uM
Incubation Time 4 h, 3 days
Results Treatment with Pi-103 and PLX4720 (a BRAFV600E inhibitor) inhibited the activity of AKT and ERK, respectively (D). More importantly, Pi-103 treatment profoundly cooperated with PLX4720 of inhibition in dose response curves(E).

Click to enlarge
Rating
Source Proc Natl Acad Sci USA 2011 108, 6067-6072. PLX-4720 purchased from Selleck
Method Western blotting
Cell Lines Cells overexpressing myc-CRAF and BRAF
Concentrations 10/50 µM
Incubation Time 1/2 h
Results GDC0879 but not PLX4720 induced BRAF/CRAF dimer formation (Fig. A). However, both drugs induced complexes between KSR1 and CRAF and enhanced interactions between KSR1 and BRAF (Fig. B and C), which suggested that KSR1/RAF complexes induced by the drug might explain the effects ofthe type I BRAF specific inhibitors. As reported previously, treatment of wild-type cells with either drug strongly induced ERK activation at low to intermediate doses but inhibited ERK activation at higher doses (Fig. D and E). Similar results were obtained with cells expressing constitutively active RAS (Fig. D and E) or after serum treatment. Strikingly, in KSR deficient cells, ERK activation was significantly attenuated after PLX4720 or GDC0879 treatment (Fig. D and E), which demonstrates that the ability of PLX4720 and GDC0879 to activate ERK requires the presence of KSR1. We found that, when KSR1 was overexpressed withCRAF, MEK activation was induced by PLX4720 or GDC0879 treatment (Fig. F). this result suggested that induction of the CRAF/KSR1 complex might be important in the activation of MEK. In vitro kinase activity toward MEK was detected but only after drug treatment (Fig. G), which suggests KSR1/CRAF complex formation kinase activity toward MEK.

Click to enlarge
Rating
Source Cancer Res 2011 71, 2750-2760. PLX-4720 purchased from Selleck
Method Western blotting, MTT assay, flow cytometry
Cell Lines PTEN+/ PTEN- melanoma cell lines
Concentrations 0.001-10 µmol/L
Incubation Time 48 h
Results The PTEN+ cell lines had lower constitutive levels of pAKT (Ser473) compared with the PTEN(Fig. A). Similar levels of pAKT (Thr308) were observed in the PTEN and PTEN þ cell lines. Analysis of the growth inhibitory effects of PLX4720 by the MTT and Alamar Blue assays (Fig. B) did not reveal any statistically significant differences in the GI 50 values between the PTEN+/ PTEN- cell lines. We observed that following PLX4720 treatment (3 and 10 µmol/L, 48 hours), the PTEN-melanoma cell lines showed significantly less apoptosis than the PTEN+ (P < 0.05: Fig. C)

Click to enlarge
Rating
Source Cancer Res 2011 71, 2750-2760. PLX-4720 purchased from Selleck
Method Western blotting
Cell Lines PTEN+/ PTEN- melanoma cell lines
Concentrations 0.03-3 µmol/L
Incubation Time 24 h
Results Treatment of the PTEN+/ PTEN- cell line panels with PLX4720 increased pPDK1andpAKTsignaling only in the melanoma cell lines lacking PTEN expression (Fig. A). Addition of PLX4720 also led to the inhibition of mTOR activity in the PTEN+ cell lines only (Fig. A). The requirement for PTEN in the increased AKT signaling was confirmed by studies showing that PLX4720 stimulated pAKT in WM35 cells (PTEN+) when PTEN was knocked down by siRNA (Fig. B). The effects of PLX4720 upon pAKT signaling were BRAF specific, with BRAF siRNA knockdown found to increase pAKT in PTEN- cells only (Fig. C).

Click to enlarge
Rating
Source Cancer Res 2011 71, 2750-2760. PLX-4720 purchased from Selleck
Method Western blot, Immunofluorescence staining, flow cytometry
Cell Lines 1205Lu cells
Concentrations 3 µmol/L
Incubation Time 48 h
Results Combined PI3K and BRAF inhibition increased the level of BIM expression in both Western blot and immunofluorescence studies (Fig. A). Consistent with a role for increased AKT signaling suppressing BIM expression in PTEN- cells, dual BRAF and PI3K inhibition increased nuclear FOXO3a localization in the PTEN- cell lines (Fig. B) and enhanced the level of BIM mRNA (Fig. B). the combination of PLX4720 with the PI3K inhibitor GDC-0941 significantly enhanced the levels of apoptosis observed in PTEN melanoma cell lines compared to either the BRAF or PI3K inhibitor alone (Fig. C). Similar results were also observed in a 3D spheroid assay, where combined PLX4720 (3 µmol/L) and LY294002 (10 µmol/L) treatment prevented the recovery of cell growth observed when melanoma spheroids were treated with either drug alone (Fig. D).

Click to enlarge
Rating
Source Cancer Res 2011 71, 2750-2760. PLX-4720 purchased from Selleck
Method LC-MRM analysis, Western blotting, immunofluorescence staining
Cell Lines PTEN+/ PTEN- melanoma cell lines
Concentrations 3/10 µmol/L
Incubation Time 0-48 h
Results We next used LC-MRM to quantify the PLX4720-induced changes in the expression of 17 members of the Bcl-2 protein family (Fig. A shows results for 9 proteins). The only proapoptotic protein to demonstrate significant differences between the PTEN+/ PTEN- cell lines was BIM (Fig. A). Western blots and immunofluorescence staining confirmed the LC-MRM data and showed a greater degree of PLX4720-induced BIM expression in the PTEN+ cell lines compared to PTEN- cell lines (Fig. B,C). In parallel, we observed that PLX4720 also increased the inactivation of BAD (as shown by increased phospho-BAD) in the PTEN- cells (Fig. D) and that overexpression of BAD in the PTEN- cells enhanced PLX4720-mediated apoptosis (Fig. D).

Click to enlarge
Rating
Source Dr. Jong-In Park of Medical College of Wisconsin. PLX-4720 purchased from Selleck
Method Western blot
Cell Lines SK-MEL-28 cell line
Concentrations 0-1 µM
Incubation Time 4/22 h
Results B-RafV600E mutated melanoma line, SK-MEL-28, was treated with different doses of PLX-4720 for 4 h or 22 h. Cell lysates were analyzed by Western blotting to determine the levels of phosphorylated MEK1/2 (pMEK1/2) and phosphorylated ERK1/2 (pERK1/2). MEK1/2 is the substrate of B-Raf while ERK1/2 is the substrate of MEK1/2. Data show that phosphorylation of MEK1/2 and ERK1/2 was significantly inhibited by PLX-4720 treatment although total MEK1/2 or ERK1/2 protein levels were not affected. No pMEK1/2 or pERK1/2 signal was detected even after prolonged exposure, indicating that the inhibitor at 1 μM is very effective in blocking the constitutive kinase activity of B-RafV600E. This data is consistent with the previous result demonstrating the effect of PLX-4720 in the B-RafV600E mutated melanoma line, A375-Fig. 2A

Click to enlarge
Rating
Source Dr. Daniel C.Cho of Harvard Medical School. PLX-4720 purchased from Selleck
Method MTT assay, Western blotting
Cell Lines A375 melanoma cells
Concentrations 0-1000 nM
Incubation Time
Results A dose titration of PLX-4720 in A375 melanoma cells which possess a V600E B-Raf mutation.Effects of increasing PLX-4720 dose on Erk phosphorylation and on tumor cell proliferation as determined by MTT assay are shown.

Tech Support

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.

Tel: +1-832-582-8158 Ext:3

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

* Indicates a Required Field

Related Raf Products

  • LY3009120

    LY03009120 is a potent pan-Raf inhibitor with IC50 of 44 nM, 31-47 nM, and 42 nM for A-raf, B-Raf, and C-Raf in A375 cells, respectively. Phase 1.

  • GDC-0994

    GDC-0994 is a potent, orally available ERK1/2 inhibitor with IC50 of 1.1 nM and 0.3 nM, respectively. Phase 1.

  • Ulixertinib (BVD-523, VRT752271)

    Ulixertinib (BVD-523, VRT752271) is a potent and reversible ERK1/ERK2 inhibitor with IC50 of <0.3 nM for ERK2. Phase 1.

  • Vemurafenib (PLX4032, RG7204)

    Vemurafenib (PLX4032, RG7204) is a novel and potent inhibitor of B-RafV600E with IC50 of 31 nM in cell-free assay.

    Features:A novel and potent inhibitor of the B-RAFV600E oncoprotein.

  • Dabrafenib (GSK2118436)

    Dabrafenib (GSK2118436) is a mutant BRAFV600 specific inhibitor with IC50 of 0.8 nM in cell-free assays, with 4- and 6-fold less potency against B-Raf(wt) and c-Raf, respectively.

  • Sorafenib

    Sorafenib is a multikinase inhibitor of Raf-1, B-Raf and VEGFR-2 with IC50 of 6 nM, 22 nM and 90 nM in cell-free assays, respectively.

  • Sorafenib Tosylate

    Sorafenib Tosylate is a multikinase inhibitor of Raf-1, B-Raf and VEGFR-2 with IC50 of 6 nM, 22 nM and 90 nM in cell-free assays, respectively.

  • TAK-632

    TAK-632 is a potent pan-Raf inhibitor with IC50 of 8.3 nM and 1.4 nM for B-Raf(wt) and C-Raf in cell-free assays, respectively, showing less or no inhibition against other tested kinases.

  • GDC-0879

    GDC-0879 is a novel, potent, and selective B-Raf inhibitor with IC50 of 0.13 nM in A375 and Colo205 cells with activity against c-Raf as well; no inhibition known to other protein kinases.

  • GW5074

    GW5074 is a potent and selective c-Raf inhibitor with IC50 of 9 nM, no effect on the activities of JNK1/2/3, MEK1, MKK6/7, CDK1/2, c-Src, p38 MAP, VEGFR2 or c-Fms is noted.

Recently Viewed Items

Tags: buy PLX-4720 | PLX-4720 supplier | purchase PLX-4720 | PLX-4720 cost | PLX-4720 manufacturer | order PLX-4720 | PLX-4720 distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Contact Us