AZ 628

Catalog No.S2746

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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Cited by 14 Publications

2 Customer Reviews

  • A375 cells were infected with the indicated shRNAs/ORFs. In parallel to the above, cells were also treated with 0.2 uM AZ628 for 16 h, cell lysates were analyzed by Western blotting for the indicated proteins.

    Cancer Discov 2013 3(3), 350-62. AZ 628 purchased from Selleck.

  • Enzymatic activity of RIP3 from Abcam, the concentration-effect relationship of RIP3 inhibition by the tested protein kinase inhibitors and the mode of action of RIP3 inhibition by dabrafenib. The RIP3 inhibition rates of AZ628 at different concentrations were measured by the luminescent RIP3 assay. The data (mean ?SD from 3 independent experiments) were presented as the Lineweaver-Burk plots using Graphpad Prism 5.

    Cell Death Dis 2014 5, e1278. AZ 628 purchased from Selleck.

Purity & Quality Control

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 M{fjZ2dzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MljPTY5pcWKrdHnvckBw\iCqdX3hckBCS05iY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OD1yLkGwNUBvVQ>? MkLsV2FPT0WU
SH-4 cell Mnj6S5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MXTJcohq[mm2aX;uJI9nKGi3bXHuJHNJNTRiY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OD1|LkCxJI5O MlrkV2FPT0WU
LB2518-MEL cell M1\WbGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MkLnTY5pcWKrdHnvckBw\iCqdX3hckBNSjJ3MUitUWVNKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:PC55NjDuUS=> MljqV2FPT0WU
A101D cell M1LXXGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MkLtTY5pcWKrdHnvckBw\iCqdX3hckBCOTBzRDDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUWuPFIhdk1? NXfCTWN5W0GQR1XS
HT-144 cell NXvSVowyT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NYfJfXlZUW6qaXLpeIlwdiCxZjDoeY1idiCKVD2xOFQh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF03NjZzIH7N NXX1OXIyW0GQR1XS
SIG-M5 cell NWrabpk6T3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MX\Jcohq[mm2aX;uJI9nKGi3bXHuJHNKTy2PNTDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUmuOFUhdk1? MVLTRW5ITVJ?
DU-4475 cell MoDFS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? M{n3WmlvcGmkaYTpc44hd2ZiaIXtZY4hTFVvNES3OUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVExNjJ|IH7N NVfNTlRyW0GQR1XS
A375 cells NGDaUmFHfW6ldHnvckBie3OjeR?= MVO3OUBucW6| NUDKTYg{UW6qaXLpeIlwdiCxZjDCVmFHKFZ4MEDFJI12fGGwdD3t[YRq[XSnZDDFVmsheGixc4Doc5J6dGG2aX;uJIlvKGi3bXHuJGE{PzViY3XscJMh[W[2ZYKgO|UhdWmwczygTWM2OD1yLkCxOUDPxE1? NXW5[ZhHOjN|OUi0OVM>
OCI-AML2 cell NWDjclNCT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NXnKWJF2UW6qaXLpeIlwdiCxZjDoeY1idiCRQ1mtRW1NOiClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR|UxRTBwMEG3{txO Mn7NV2FPT0WU
COLO-829 cell NFGwU5ZIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NUDLS4I2UW6qaXLpeIlwdiCxZjDoeY1idiCFT1zPMVgzQSClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR|UxRTJ3Lk[1JI5O NWDyNHZ2W0GQR1XS
PSN1 cell Mo\uS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MlLmTY5pcWKrdHnvckBw\iCqdX3hckBRW05zIHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MkeuN|chdk1? NEfWTWtUSU6JRWK=
UACC-257 cell M4PrTGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NWHXcmw5UW6qaXLpeIlwdiCxZjDoeY1idiCXQVPDMVI2PyClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR|UxRTJ5LkS5JI5O MVXTRW5ITVJ?
RKO cell MXvHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M2HBOWlvcGmkaYTpc44hd2ZiaIXtZY4hWkuRIHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;M{euOlchdk1? NEfqbVBUSU6JRWK=
MMAC-SF cell MmDWS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MVXJcohq[mm2aX;uJI9nKGi3bXHuJG1OSUNvU1[gZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME20NE4xPyCwTR?= NVKzO|FDW0GQR1XS
Calu-6 cell NEjy[otIem:5dHigbY5pcWKrdHnvckBie3OjeR?= M3m3NGlvcGmkaYTpc44hd2ZiaIXtZY4hS2GudT22JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9OVEvPDdibl2= NF;2Tm5USU6JRWK=
LS-513 cell NFv1UlZIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NFTnOGNKdmirYnn0bY9vKG:oIHj1cYFvKEyVLUWxN{Bk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVc1NjF3IH7N NYjOSZlYW0GQR1XS
NOS-1 cell NFLZToxIem:5dHigbY5pcWKrdHnvckBie3OjeR?= Mo\2TY5pcWKrdHnvckBw\iCqdX3hckBPV1NvMTDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUmyMlY2KG6P NGfLZ2hUSU6JRWK=
SW872 cell NGPpdnFIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MUTJcohq[mm2aX;uJI9nKGi3bXHuJHNYQDd{IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;OU[uOFghdk1? M2PQU3NCVkeHUh?=
KMOE-2 cell NYqwVIE5T3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NI\XXoVKdmirYnn0bY9vKG:oIHj1cYFvKEuPT1WtNkBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVEyPS56ODDuUS=> M2rvZ3NCVkeHUh?=
MZ7-mel cell M4TBdGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NYXqVItZUW6qaXLpeIlwdiCxZjDoeY1idiCPWketcYVtKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OTF5LkK3JI5O MlnjV2FPT0WU
CGTH-W-1 cell MnPRS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NVzkOXN5UW6qaXLpeIlwdiCxZjDoeY1idiCFR2TIMXcuOSClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR|UxRTF{MT6zJI5O MoH1V2FPT0WU
CP66-MEL cell M4\lUGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MmDKTY5pcWKrdHnvckBw\iCqdX3hckBEWDZ4LV3FUEBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVE{OS55NjDuUS=> NFPwenBUSU6JRWK=
K5 cell NV;sZWtnT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MnjVTY5pcWKrdHnvckBw\iCqdX3hckBMPSClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR|UxRTF|ND6yJI5O NYjjNGllW0GQR1XS
HL-60 cell MkHRS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MXvJcohq[mm2aX;uJI9nKGi3bXHuJGhNNTZyIHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MUW0MlQyKG6P MYrTRW5ITVJ?
ONS-76 cell M3;nO2dzd3e2aDDpcohq[mm2aX;uJIF{e2G7 M{n0dWlvcGmkaYTpc44hd2ZiaIXtZY4hV06VLUe2JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NVY3NjZ{IH7N MU\TRW5ITVJ?
NB69 cell NHLWOlRIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NYr3WZdvUW6qaXLpeIlwdiCxZjDoeY1idiCQQk[5JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NVkyNjNzIH7N Mm\3V2FPT0WU
LAMA-84 cell M2LXVGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MkHaTY5pcWKrdHnvckBw\iCqdX3hckBNSU2DLUi0JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NVkzNjR{IH7N Mnv3V2FPT0WU
EM-2 cell  M1fpeWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NFPMbYtKdmirYnn0bY9vKG:oIHj1cYFvKEWPLUKgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xPVUvQTFibl2= MVnTRW5ITVJ?
IST-MEL1 cell MmPtS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MkDQTY5pcWKrdHnvckBw\iCqdX3hckBKW1RvTVXMNUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVIxPC5zMzDuUS=> NUniOWV4W0GQR1XS
HCC2998 cell NE[5e21Iem:5dHigbY5pcWKrdHnvckBie3OjeR?= NVjNU|NSUW6qaXLpeIlwdiCxZjDoeY1idiCKQ1OyPVk5KGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OC5{MkG4O{DPxE1? MkW5V2FPT0WU
GDM-1 cell MXTHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MonPTY5pcWKrdHnvckBw\iCqdX3hckBITE1vMTDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUCuNlI6PDdizszN NV;XZmFHW0GQR1XS
MZ1-PC cell MmrsS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? M4nvNmlvcGmkaYTpc44hd2ZiaIXtZY4hVVpzLWDDJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE4zPzl7OTFOwG0> MWfTRW5ITVJ?
BB49-HNC cell NWHYOZRHT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MV3Jcohq[mm2aX;uJI9nKGi3bXHuJGJDPDlvSF7DJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE4{PTF6IN88US=> MoXCV2FPT0WU
D-392MG cell Mn:3S5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? M{e2[WlvcGmkaYTpc44hd2ZiaIXtZY4hTC1|OULNS{Bk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVAvOzV4MEeg{txO MWHTRW5ITVJ?
697 cell NEPLUmZIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NV;MOWI1UW6qaXLpeIlwdiCxZjDoeY1idiB4OUegZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2zOlMvQDhizszN MVLTRW5ITVJ?
ML-2 cell M2jRU2dzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NHntXGlKdmirYnn0bY9vKG:oIHj1cYFvKE2OLUKgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2zOlgvQDZibl2= Mn;GV2FPT0WU
MEG-01 cell MVnHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MonNTY5pcWKrdHnvckBw\iCqdX3hckBOTUdvMEGgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2wMlM4PiEQvF2= MWfTRW5ITVJ?
SK-MEL-1 cell M3frS2dzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MWrJcohq[mm2aX;uJI9nKGi3bXHuJHNMNU2HTD2xJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE4{QDN4MjFOwG0> M3LHZ3NCVkeHUh?=
KS-1 cell NGjzXVdIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NYHETm05UW6qaXLpeIlwdiCxZjDoeY1idiCNUz2xJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE4{QTN|NzFOwG0> NEHGXGNUSU6JRWK=
NB14 cell M4j3fWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NYPUclVZUW6qaXLpeIlwdiCxZjDoeY1idiCQQkG0JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE41QTN|MTFOwG0> MnLOV2FPT0WU
NCI-H747 cell MkW0S5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NXLzXVdbUW6qaXLpeIlwdiCxZjDoeY1idiCQQ1mtTFc1PyClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR|UxRTBwNUC2N|ch|ryP MYrTRW5ITVJ?
K-562 cell MW\Hdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M3rvXWlvcGmkaYTpc44hd2ZiaIXtZY4hUy13NkKgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2wMlY3Pjl3IN88US=> NFTpNlFUSU6JRWK=
NCI-H1648 cell NH\6dIlIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NGr6T2dKdmirYnn0bY9vKG:oIHj1cYFvKE6FST3INVY1QCClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR|UxRTBwNkeyOlYh|ryP NH\YeWpUSU6JRWK=
LAN-6 cell MXTHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M2[ySmlvcGmkaYTpc44hd2ZiaIXtZY4hVEGQLU[gZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2wMlY5OjN4IN88US=> MUTTRW5ITVJ?

... 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

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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.

Handling Instructions

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID