AZ 628

For research use only.

Catalog No.S2746

27 publications

AZ 628 Chemical Structure

Molecular Weight(MW): 451.52

AZ628 is a new pan-Raf inhibitor for BRAF, BRAFV600E, and c-Raf-1 with IC50 of 105 nM, 34 nM and 29 nM in cell-free assays, also inhibits VEGFR2, DDR2, Lyn, Flt1, FMS, etc.

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Selleck's AZ 628 has been cited by 27 publications

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Biological Activity

Description AZ628 is a new pan-Raf inhibitor for BRAF, BRAFV600E, and c-Raf-1 with IC50 of 105 nM, 34 nM and 29 nM in cell-free assays, also inhibits VEGFR2, DDR2, Lyn, Flt1, FMS, etc.
Targets
C-Raf-1 [1]
(Cell-free assay)
B-Raf (V600E) [1]
(Cell-free assay)
B-Raf [1]
(Cell-free assay)
29 nM 34 nM 105 nM
In vitro

AZ628 prevents activation of number of tyrosine protein kinases including VEGFR2, DDR2, Lyn, Flt1, FMS and others. AZ628 suppresses anchorage-dependent and -independent growth, gives rise to cell cycle arrest, and induces apoptosis in colon and melanoma cell lines harboring B-RafV600E mutation. The profile of AZ628 cross-reactivity suggests that similar to sorafenib, AZ628 may be antiangiogenic based on prevention of VEGFR2. [1] AZ628-resistant clones are approximately 100-fold more resistant to AZ628 than the parental cell line, exhibiting IC50 of approximately 10 μM, compared with 0.1 μM for the parental cell line. Effective suppression of p-ERK1/2 levels is observed in the M14 parental cell line following treatment with increasing concentrations of AZ628. AZ628-resistant clones express elevated CRAF. Elevated CRAF expression is a potential mechanism of acquired resistance to continuous AZ628 exposure, resulting in sustained activation of ERK1/2. p-ERK1/2 activity is not significantly inhibited by exposure to AZ628 in one of these three AZ628-insensitive cell lines (Wm1552C). Unlike in the AZ628-resistant M14 cells in which AZ628 fails to suppress the activation of ERK, AZ628 treatment efficiently attenuates ERK activation in the NRAS mutant melanoma cells.[2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
ACN cell MlTES5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MmnKTY5pcWKrdHnvckBw\iCqdX3hckBCS05iY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OD1yLkGwNUBvVQ>? M{fN[nNCVkeHUh?=
SH-4 cell NYDPRpl5T3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MV7Jcohq[mm2aX;uJI9nKGi3bXHuJHNJNTRiY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OD1|LkCxJI5O MXjTRW5ITVJ?
LB2518-MEL cell NFHjZlBIem:5dHigbY5pcWKrdHnvckBie3OjeR?= M2rsUGlvcGmkaYTpc44hd2ZiaIXtZY4hVEJ{NUG4MW1GVCClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR|UxRTRwN{[gcm0> MVnTRW5ITVJ?
A101D cell Mo\mS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NFjsTW5KdmirYnn0bY9vKG:oIHj1cYFvKEFzMEHEJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9OU45OiCwTR?= NFfnPFZUSU6JRWK=
HT-144 cell M3fyfWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MVjJcohq[mm2aX;uJI9nKGi3bXHuJGhVNTF2NDDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPU[uOlEhdk1? NXLKSFg6W0GQR1XS
SIG-M5 cell MXnHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MojJTY5pcWKrdHnvckBw\iCqdX3hckBUUUdvTUWgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME25MlQ2KG6P NVHyWm1TW0GQR1XS
DU-4475 cell M2TO[mdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NYTHW3U4UW6qaXLpeIlwdiCxZjDoeY1idiCGVT20OFc2KGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OTBwMkOgcm0> M4C4cHNCVkeHUh?=
A375 cells MV\GeY5kfGmxbjDhd5NigQ>? MlyxO|UhdWmwcx?= M3rYOmlvcGmkaYTpc44hd2ZiQmLBSkBXPjByRTDteZRidnRvbXXkbYF1\WRiRWLLJJBpd3OyaH;yfYxifGmxbjDpckBpfW2jbjDBN|c2KGOnbHzzJIFnfGW{IEe1JI1qdnNuIFnDOVA:OC5yMUWg{txO MWqyN|M6QDR3Mx?=
OCI-AML2 cell M1vtNWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NV;R[ZpGUW6qaXLpeIlwdiCxZjDoeY1idiCRQ1mtRW1NOiClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR|UxRTBwMEG3{txO NYnqdHB1W0GQR1XS
COLO-829 cell MmP0S5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? M1zHc2lvcGmkaYTpc44hd2ZiaIXtZY4hS0:OTz24Nlkh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0zPS54NTDuUS=> M{fDVHNCVkeHUh?=
PSN1 cell NV7HNplvT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NELNN|NKdmirYnn0bY9vKG:oIHj1cYFvKFCVTkGgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2yO{4{PyCwTR?= NYL1eGcyW0GQR1XS
UACC-257 cell MV7Hdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NXz2dIZUUW6qaXLpeIlwdiCxZjDoeY1idiCXQVPDMVI2PyClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR|UxRTJ5LkS5JI5O NXKxcJhxW0GQR1XS
RKO cell NGewNmtIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NHf3PGJKdmirYnn0bY9vKG:oIHj1cYFvKFKNTzDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUO3MlY4KG6P M2LBNnNCVkeHUh?=
MMAC-SF cell M3fCcWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MWLJcohq[mm2aX;uJI9nKGi3bXHuJG1OSUNvU1[gZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME20NE4xPyCwTR?= MnzpV2FPT0WU
Calu-6 cell NVvLfHk6T3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= M2DlZmlvcGmkaYTpc44hd2ZiaIXtZY4hS2GudT22JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9OVEvPDdibl2= NVPNNZFmW0GQR1XS
LS-513 cell NETjZ5hIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NYTsfJBPUW6qaXLpeIlwdiCxZjDoeY1idiCOUz21NVMh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF04PC5zNTDuUS=> MlP5V2FPT0WU
NOS-1 cell M4PCZmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NIiyU2dKdmirYnn0bY9vKG:oIHj1cYFvKE6RUz2xJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9PVIvPjVibl2= NX3TVotIW0GQR1XS
SW872 cell NWXRTFBMT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MWPJcohq[mm2aX;uJI9nKGi3bXHuJHNYQDd{IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;OU[uOFghdk1? Mn\LV2FPT0WU
KMOE-2 cell NFvvUHVIem:5dHigbY5pcWKrdHnvckBie3OjeR?= M3TmN2lvcGmkaYTpc44hd2ZiaIXtZY4hU02RRT2yJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NVE2Njh6IH7N M13G[3NCVkeHUh?=
MZ7-mel cell NEPYWlBIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MXTJcohq[mm2aX;uJI9nKGi3bXHuJG1bPy2vZXygZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xNVcvOjdibl2= MWrTRW5ITVJ?
CGTH-W-1 cell M2L6cmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MVjJcohq[mm2aX;uJI9nKGi3bXHuJGNIXEhvVz2xJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NVIyNjNibl2= M3XCVnNCVkeHUh?=
CP66-MEL cell Mo\QS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MkjDTY5pcWKrdHnvckBw\iCqdX3hckBEWDZ4LV3FUEBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVE{OS55NjDuUS=> MVLTRW5ITVJ?
K5 cell NVHYfGRpT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= Mk\lTY5pcWKrdHnvckBw\iCqdX3hckBMPSClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR|UxRTF|ND6yJI5O NFHLXFhUSU6JRWK=
HL-60 cell M2Dkd2dzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NF;tTHZKdmirYnn0bY9vKG:oIHj1cYFvKEiOLU[wJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NVU1NjRzIH7N NUW5eVh2W0GQR1XS
ONS-76 cell MlzFS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NWXSS5puUW6qaXLpeIlwdiCxZjDoeY1idiCRTmOtO|Yh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0yPjZwNkKgcm0> Mmm0V2FPT0WU
NB69 cell MmniS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NGewT|JKdmirYnn0bY9vKG:oIHj1cYFvKE6ENkmgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xPVEvOzFibl2= M1XrVHNCVkeHUh?=
LAMA-84 cell MonyS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NIDROZpKdmirYnn0bY9vKG:oIHj1cYFvKEyDTVGtPFQh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0yQTJwNEKgcm0> M1XBOnNCVkeHUh?=
EM-2 cell  M3WwXWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MkHETY5pcWKrdHnvckBw\iCqdX3hckBGVS1{IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MUm1MlkyKG6P NVTMOWFPW0GQR1XS
IST-MEL1 cell MYXHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MU\Jcohq[mm2aX;uJI9nKGi3bXHuJGlUXC2PRVyxJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NlA1NjF|IH7N MXfTRW5ITVJ?
HCC2998 cell NH\HWXlIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NHrtfIdKdmirYnn0bY9vKG:oIHj1cYFvKEiFQ{K5PVgh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0xNjJ{MUi3JO69VQ>? MofEV2FPT0WU
GDM-1 cell MVzHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MmHpTY5pcWKrdHnvckBw\iCqdX3hckBITE1vMTDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUCuNlI6PDdizszN MnrWV2FPT0WU
MZ1-PC cell MYPHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M2\SPGlvcGmkaYTpc44hd2ZiaIXtZY4hVVpzLWDDJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE4zPzl7OTFOwG0> NIXmcZBUSU6JRWK=
BB49-HNC cell M17BcGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NH;vfnNKdmirYnn0bY9vKG:oIHj1cYFvKEKENEmtTG5EKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OC5|NUG4JO69VQ>? NVL2OnNVW0GQR1XS
D-392MG cell MmXrS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MX;Jcohq[mm2aX;uJI9nKGi3bXHuJGQuOzl{TVegZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2wMlM2PjB5IN88US=> MULTRW5ITVJ?
697 cell MmjMS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? M1vDTmlvcGmkaYTpc44hd2ZiaIXtZY4hPjl5IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;M{[zMlg5KM7:TR?= MXHTRW5ITVJ?
ML-2 cell NEj3UIpIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MVrJcohq[mm2aX;uJI9nKGi3bXHuJG1NNTJiY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OD1|NkiuPFYhdk1? M3;2PXNCVkeHUh?=
MEG-01 cell MkPrS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NHfZc|FKdmirYnn0bY9vKG:oIHj1cYFvKE2HRz2wNUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVAvOzd4IN88US=> MVPTRW5ITVJ?
SK-MEL-1 cell NF3j[IdIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NGrXb2xKdmirYnn0bY9vKG:oIHj1cYFvKFONLV3FUE0yKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OC5|OEO2NkDPxE1? NUPhd2Y6W0GQR1XS
KS-1 cell MmnhS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MkDxTY5pcWKrdHnvckBw\iCqdX3hckBMWy1zIHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MD6zPVM{PyEQvF2= MVPTRW5ITVJ?
NB14 cell M1vmNGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MnGxTY5pcWKrdHnvckBw\iCqdX3hckBPSjF2IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MD60PVM{OSEQvF2= NIfsfGRUSU6JRWK=
NCI-H747 cell MVTHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NIrYZXZKdmirYnn0bY9vKG:oIHj1cYFvKE6FST3IO|Q4KGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OC53ME[zO{DPxE1? MmDZV2FPT0WU
K-562 cell NHHNcHBIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MnrMTY5pcWKrdHnvckBw\iCqdX3hckBMNTV4MjDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUCuOlY3QTVizszN NGm1bFNUSU6JRWK=
NCI-H1648 cell NWn6RmpIT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NIns[HNKdmirYnn0bY9vKG:oIHj1cYFvKE6FST3INVY1QCClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR|UxRTBwNkeyOlYh|ryP MlS4V2FPT0WU
LAN-6 cell MmDYS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? Ml:zTY5pcWKrdHnvckBw\iCqdX3hckBNSU5vNjDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUCuOlgzOzZizszN M1P2OnNCVkeHUh?=

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
p-ERK / ERK / p-MEK / MEK / BIM / BRAF / CRAF ; 

PubMed: 21098728     


Western blots of RAF-MEK pathway components and effectors in parental and AR cells treated with the indicated concentrations of AZ628 for 24 hours.

21098728
Growth inhibition assay
Cell viability ; 

PubMed: 21098728     


Parental (solid lines) COLO201 and COLO206F cells and AR (dashed lines) COLO201-AR and COLO206F-AR cells were treated in triplicate with the indicated concentrations of drug for 72 hours. Viable cell titer was determined, and the average values are shown relative to untreated controls for each cell line. Error bars represent the SD for each measurement. For each cell line, the IC50s for each inhibitor are shown in tabular form along with the increase in IC50 in AR cells relative to parental cells.

21098728

Protocol

Cell Research:[1]
- Collapse
  • Cell lines: M14 expressing the V600E BRAF mutation
  • Concentrations: 0.01-10 μM
  • Incubation Time: Overnight
  • Method: Approximately 0.5-2.5 × 105 M14 cells are seeded in 12 or 24 - well plates, respectively, in medium supplemented with 5% FBS. After overnight incubation, the cells are treated with various concentrations of AZ628. Fresh medium and drug is replaced every 2 days until the untreated control wells reached confluence. At this time-point, the media is removed and the cells are fixed in 4% formaldehyde in PBS for 20 minutes at room temperature. Cells are then washed twice with PBS and stained with a 1:5000 solution of the fluorescent nucleic acid stain Syto60. Quantitation of fluorescent signal intensity is carried out at 700 nm, using an Odyssey Infrared Imager. Each experiment is performed in quadruplicate and the results shown represent the average of the four values compared to untreated wells. Error bars represent standard deviation of the 4 values from the mean. High-throughput cell growth/viability assays are performed.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 90 mg/mL (199.32 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
2% DMSO+40% PEG 300+2% Tween 80+ddH2O
For best results, use promptly after mixing.
6mg/mL

* 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 Information

Molecular Weight 451.52
Formula

C27H25N5O2

CAS No. 878739-06-1
Storage powder
in solvent
Synonyms N/A
Smiles CN1C=NC2=C(C=C(NC3=CC(=CC=C3C)NC(=O)C4=CC(=CC=C4)C(C)(C)C#N)C=C2)C1=O

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID