AZ 628

For research use only. Not for use in humans.

Catalog No.S2746

23 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 23 publications

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Choose Selective Raf Inhibitors

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 MlXkS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MmXTTY5pcWKrdHnvckBw\iCqdX3hckBCS05iY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OD1yLkGwNUBvVQ>? M{DHe3NCVkeHUh?=
SH-4 cell NVzFcFNCT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NETacoNKdmirYnn0bY9vKG:oIHj1cYFvKFOKLUSgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2zMlAyKG6P Mm\kV2FPT0WU
LB2518-MEL cell NGjaVYJIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NYC4ZVNqUW6qaXLpeIlwdiCxZjDoeY1idiCOQkK1NVguVUWOIHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;ND63OkBvVQ>? Mo\FV2FPT0WU
A101D cell NUSyPXJOT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NETMRndKdmirYnn0bY9vKG:oIHj1cYFvKEFzMEHEJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9OU45OiCwTR?= NH2yN29USU6JRWK=
HT-144 cell NV2xdnVYT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MoD6TY5pcWKrdHnvckBw\iCqdX3hckBJXC1zNESgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME22MlYyKG6P M2XrcnNCVkeHUh?=
SIG-M5 cell M2HDSmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 M3XS[2lvcGmkaYTpc44hd2ZiaIXtZY4hW0mJLV21JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9PU41PSCwTR?= M1PUV3NCVkeHUh?=
DU-4475 cell NIT0PIxIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MVTJcohq[mm2aX;uJI9nKGi3bXHuJGRWNTR2N{WgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xNE4zOyCwTR?= M1zqWnNCVkeHUh?=
A375 cells MVvGeY5kfGmxbjDhd5NigQ>? M4fPcVc2KG2rboO= M1TSPGlvcGmkaYTpc44hd2ZiQmLBSkBXPjByRTDteZRidnRvbXXkbYF1\WRiRWLLJJBpd3OyaH;yfYxifGmxbjDpckBpfW2jbjDBN|c2KGOnbHzzJIFnfGW{IEe1JI1qdnNuIFnDOVA:OC5yMUWg{txO Mnj3NlM{QTh2NUO=
OCI-AML2 cell NXS4bndIT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= Mn[wTY5pcWKrdHnvckBw\iCqdX3hckBQS0lvQV3MNkBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVAvODF5zszN M4\ON3NCVkeHUh?=
COLO-829 cell MmrQS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NEX5[o1KdmirYnn0bY9vKG:oIHj1cYFvKEORTF:tPFI6KGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OjVwNkWgcm0> NEH6SpFUSU6JRWK=
PSN1 cell M2jaSmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 M{TjTGlvcGmkaYTpc44hd2ZiaIXtZY4hWFOQMTDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUK3MlM4KG6P NWfOWZd7W0GQR1XS
UACC-257 cell Mk\LS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? M2nCRWlvcGmkaYTpc44hd2ZiaIXtZY4hXUGFQz2yOVch[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0zPy52OTDuUS=> MVjTRW5ITVJ?
RKO cell NGXNSnhIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NEK0VXFKdmirYnn0bY9vKG:oIHj1cYFvKFKNTzDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUO3MlY4KG6P MW\TRW5ITVJ?
MMAC-SF cell MYfHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? Mn7rTY5pcWKrdHnvckBw\iCqdX3hckBOVUGFLWPGJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9OFAvODdibl2= M{LSdHNCVkeHUh?=
Calu-6 cell NVPFO4h5T3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MnzJTY5pcWKrdHnvckBw\iCqdX3hckBE[Wy3LU[gZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME21NU41PyCwTR?= NHHhNGpUSU6JRWK=
LS-513 cell MnuyS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? M{fhb2lvcGmkaYTpc44hd2ZiaIXtZY4hVFNvNUGzJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9O|QvOTVibl2= NUnlTHBiW0GQR1XS
NOS-1 cell NGPEcHRIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MVjJcohq[mm2aX;uJI9nKGi3bXHuJG5QWy1zIHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;OUKuOlUhdk1? M3vBWHNCVkeHUh?=
SW872 cell NGX4co9Iem:5dHigbY5pcWKrdHnvckBie3OjeR?= M3vpWGlvcGmkaYTpc44hd2ZiaIXtZY4hW1d6N{KgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME25Ok41QCCwTR?= MlTxV2FPT0WU
KMOE-2 cell MnjBS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NGPkWWhKdmirYnn0bY9vKG:oIHj1cYFvKEuPT1WtNkBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVEyPS56ODDuUS=> Ml;lV2FPT0WU
MZ7-mel cell MmTBS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NW\0UnNbUW6qaXLpeIlwdiCxZjDoeY1idiCPWketcYVtKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OTF5LkK3JI5O M2X0WnNCVkeHUh?=
CGTH-W-1 cell NFHWWG5Iem:5dHigbY5pcWKrdHnvckBie3OjeR?= Mle1TY5pcWKrdHnvckBw\iCqdX3hckBET1SKLWetNUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVEzOS5|IH7N Mk\MV2FPT0WU
CP66-MEL cell NV7zcYRZT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= M1XlXGlvcGmkaYTpc44hd2ZiaIXtZY4hS1B4Nj3NSWwh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0yOzFwN{[gcm0> MmTSV2FPT0WU
K5 cell Mo[5S5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? M{XvV2lvcGmkaYTpc44hd2ZiaIXtZY4hUzViY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OD1zM{SuNkBvVQ>? MVXTRW5ITVJ?
HL-60 cell MkDsS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MljFTY5pcWKrdHnvckBw\iCqdX3hckBJVC14MDDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUG1OE41OSCwTR?= MYrTRW5ITVJ?
ONS-76 cell MVLHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MlrXTY5pcWKrdHnvckBw\iCqdX3hckBQVlNvN{[gZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xOlYvPjJibl2= MYDTRW5ITVJ?
NB69 cell MlXhS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MmnNTY5pcWKrdHnvckBw\iCqdX3hckBPSjZ7IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MUmxMlMyKG6P NWfWbVZKW0GQR1XS
LAMA-84 cell M1vjfmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NITXUlFKdmirYnn0bY9vKG:oIHj1cYFvKEyDTVGtPFQh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0yQTJwNEKgcm0> NV3QcplHW0GQR1XS
EM-2 cell  MoPmS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NFPacIdKdmirYnn0bY9vKG:oIHj1cYFvKEWPLUKgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xPVUvQTFibl2= M1vZRXNCVkeHUh?=
IST-MEL1 cell NWnhUVk5T3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NIm3eVlKdmirYnn0bY9vKG:oIHj1cYFvKEmVVD3NSWwyKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OjB2LkGzJI5O NFnHNpVUSU6JRWK=
HCC2998 cell MYnHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MX\Jcohq[mm2aX;uJI9nKGi3bXHuJGhESzJ7OUigZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2wMlIzOTh5IN88US=> NGn4OYFUSU6JRWK=
GDM-1 cell NW[5PJZ3T3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NHnXdm9KdmirYnn0bY9vKG:oIHj1cYFvKEeGTT2xJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE4zOjl2NzFOwG0> Mmi1V2FPT0WU
MZ1-PC cell NIPabIlIem:5dHigbY5pcWKrdHnvckBie3OjeR?= M3HiWGlvcGmkaYTpc44hd2ZiaIXtZY4hVVpzLWDDJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE4zPzl7OTFOwG0> MVPTRW5ITVJ?
BB49-HNC cell NH;lfohIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MV7Jcohq[mm2aX;uJI9nKGi3bXHuJGJDPDlvSF7DJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE4{PTF6IN88US=> NV32cZdEW0GQR1XS
D-392MG cell NGPUcYpIem:5dHigbY5pcWKrdHnvckBie3OjeR?= M3ywdGlvcGmkaYTpc44hd2ZiaIXtZY4hTC1|OULNS{Bk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVAvOzV4MEeg{txO MofsV2FPT0WU
697 cell NUS3U3FiT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MnnzTY5pcWKrdHnvckBw\iCqdX3hckA3QTdiY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OD1|NkOuPFgh|ryP M4TzU3NCVkeHUh?=
ML-2 cell M2Dobmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MWfJcohq[mm2aX;uJI9nKGi3bXHuJG1NNTJiY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OD1|NkiuPFYhdk1? Ml63V2FPT0WU
MEG-01 cell MlfHS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MYLJcohq[mm2aX;uJI9nKGi3bXHuJG1GTy1yMTDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUCuN|c3KM7:TR?= M1:4SnNCVkeHUh?=
SK-MEL-1 cell NH7v[29Iem:5dHigbY5pcWKrdHnvckBie3OjeR?= NIe4eVVKdmirYnn0bY9vKG:oIHj1cYFvKFONLV3FUE0yKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OC5|OEO2NkDPxE1? M2f3R3NCVkeHUh?=
KS-1 cell NXHlO5p3T3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NEnubldKdmirYnn0bY9vKG:oIHj1cYFvKEuVLUGgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2wMlM6OzN5IN88US=> NVfUcGVzW0GQR1XS
NB14 cell MorPS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MYPJcohq[mm2aX;uJI9nKGi3bXHuJG5DOTRiY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OD1yLkS5N|MyKM7:TR?= Ml;lV2FPT0WU
NCI-H747 cell MUXHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M{\0WmlvcGmkaYTpc44hd2ZiaIXtZY4hVkOLLVi3OFch[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0xNjVyNkO3JO69VQ>? MofIV2FPT0WU
K-562 cell Ml[4S5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MYHJcohq[mm2aX;uJI9nKGi3bXHuJGsuPTZ{IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MD62OlY6PSEQvF2= MlPuV2FPT0WU
NCI-H1648 cell MVnHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M3\POGlvcGmkaYTpc44hd2ZiaIXtZY4hVkOLLVixOlQ5KGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OC54N{K2OkDPxE1? MUnTRW5ITVJ?
LAN-6 cell MV\Hdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M1L3VmlvcGmkaYTpc44hd2ZiaIXtZY4hVEGQLU[gZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2wMlY5OjN4IN88US=> MYfTRW5ITVJ?

... 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