AZ 628

For research use only.

Catalog No.S2746

29 publications

AZ 628 Chemical Structure

CAS No. 878739-06-1

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. AZ628 induces apoptosis.

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10mM (1mL in DMSO) RMB 2191.76 In stock
RMB 1225.39 In stock
RMB 3841.45 In stock
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Selleck's AZ 628 has been cited by 29 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. AZ628 induces apoptosis.
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 NYjOWo1vT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= M{nWcWlvcGmkaYTpc44hd2ZiaIXtZY4hSUOQIHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MD6xNFEhdk1? NYjmOJV4W0GQR1XS
SH-4 cell NVnpW49bT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NWDTOYxIUW6qaXLpeIlwdiCxZjDoeY1idiCVSD20JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9N{4xOSCwTR?= Mn;QV2FPT0WU
LB2518-MEL cell MoPDS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MlzJTY5pcWKrdHnvckBw\iCqdX3hckBNSjJ3MUitUWVNKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:PC55NjDuUS=> NVzjOWNDW0GQR1XS
A101D cell MVLHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M4PTdWlvcGmkaYTpc44hd2ZiaIXtZY4hSTFyMVSgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME21MlgzKG6P MVrTRW5ITVJ?
HT-144 cell M{DjcWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NEnsS2pKdmirYnn0bY9vKG:oIHj1cYFvKEiWLUG0OEBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVYvPjFibl2= MU\TRW5ITVJ?
SIG-M5 cell MWLHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M2\RVGlvcGmkaYTpc44hd2ZiaIXtZY4hW0mJLV21JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9PU41PSCwTR?= M3T0NnNCVkeHUh?=
DU-4475 cell MV\Hdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NVi1[ZhQUW6qaXLpeIlwdiCxZjDoeY1idiCGVT20OFc2KGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OTBwMkOgcm0> MWXTRW5ITVJ?
A375 cells NEjqXXVHfW6ldHnvckBie3OjeR?= M4PUOVc2KG2rboO= NHHKR5VKdmirYnn0bY9vKG:oIFLSRWYhXjZyMFWgcZV1[W62LX3l[IlifGWmIFXST{BxcG:|cHjvdplt[XSrb36gbY4hcHWvYX6gRVM4PSClZXzsd{Bi\nSncjC3OUBucW6|LDDJR|UxRTBwMEG1JO69VQ>? NU[4ZXh5OjN|OUi0OVM>
OCI-AML2 cell MXvHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NXrh[ZM{UW6qaXLpeIlwdiCxZjDoeY1idiCRQ1mtRW1NOiClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR|UxRTBwMEG3{txO M17WXXNCVkeHUh?=
COLO-829 cell MVnHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NELuZZZKdmirYnn0bY9vKG:oIHj1cYFvKEORTF:tPFI6KGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OjVwNkWgcm0> NYfEeWJVW0GQR1XS
PSN1 cell NX;XOFM1T3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NYD0OJJLUW6qaXLpeIlwdiCxZjDoeY1idiCSU16xJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NlcvOzdibl2= NXT5bFRYW0GQR1XS
UACC-257 cell NY[5c45mT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NIPMSoNKdmirYnn0bY9vKG:oIHj1cYFvKFWDQ1OtNlU4KGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OjdwNEmgcm0> NV7UfJNZW0GQR1XS
RKO cell Moj1S5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? M3n2e2lvcGmkaYTpc44hd2ZiaIXtZY4hWkuRIHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;M{euOlchdk1? M2TQRXNCVkeHUh?=
MMAC-SF cell M1rPd2dzd3e2aDDpcohq[mm2aX;uJIF{e2G7 Mk\1TY5pcWKrdHnvckBw\iCqdX3hckBOVUGFLWPGJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9OFAvODdibl2= M{D0VHNCVkeHUh?=
Calu-6 cell NH[1WmlIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MVTJcohq[mm2aX;uJI9nKGi3bXHuJGNidHVvNjDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUWxMlQ4KG6P NIOzb2lUSU6JRWK=
LS-513 cell NG[4UYlIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NYrjUnBjUW6qaXLpeIlwdiCxZjDoeY1idiCOUz21NVMh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF04PC5zNTDuUS=> MmrmV2FPT0WU
NOS-1 cell NVzXbYNiT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= M37BW2lvcGmkaYTpc44hd2ZiaIXtZY4hVk:VLUGgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME25Nk43PSCwTR?= NWe3Zo5IW0GQR1XS
SW872 cell NYToenRST3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MXHJcohq[mm2aX;uJI9nKGi3bXHuJHNYQDd{IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;OU[uOFghdk1? MXPTRW5ITVJ?
KMOE-2 cell M1XheGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NHnycoNKdmirYnn0bY9vKG:oIHj1cYFvKEuPT1WtNkBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVEyPS56ODDuUS=> NVXKUmNUW0GQR1XS
MZ7-mel cell MXzHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M{faeGlvcGmkaYTpc44hd2ZiaIXtZY4hVVp5LX3lcEBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVEyPy5{NzDuUS=> NFrkSI5USU6JRWK=
CGTH-W-1 cell NYjvcIRET3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MWLJcohq[mm2aX;uJI9nKGi3bXHuJGNIXEhvVz2xJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NVIyNjNibl2= NYLSZ|RPW0GQR1XS
CP66-MEL cell MoXiS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NH:zNVVKdmirYnn0bY9vKG:oIHj1cYFvKEOSNk[tUWVNKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OTNzLke2JI5O NUi3T25EW0GQR1XS
K5 cell M3nCTGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MVTJcohq[mm2aX;uJI9nKGi3bXHuJGs2KGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OTN2LkKgcm0> NF[xWIFUSU6JRWK=
HL-60 cell MkKxS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MmXBTY5pcWKrdHnvckBw\iCqdX3hckBJVC14MDDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUG1OE41OSCwTR?= MkfEV2FPT0WU
ONS-76 cell M1\uTGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 M3XvSmlvcGmkaYTpc44hd2ZiaIXtZY4hV06VLUe2JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NVY3NjZ{IH7N M1W1dnNCVkeHUh?=
NB69 cell MUTHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NVrDU5AyUW6qaXLpeIlwdiCxZjDoeY1idiCQQk[5JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NVkyNjNzIH7N MWXTRW5ITVJ?
LAMA-84 cell MlfLS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NITsbIdKdmirYnn0bY9vKG:oIHj1cYFvKEyDTVGtPFQh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0yQTJwNEKgcm0> Mn;VV2FPT0WU
EM-2 cell  MWnHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MnjlTY5pcWKrdHnvckBw\iCqdX3hckBGVS1{IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MUm1MlkyKG6P MnrlV2FPT0WU
IST-MEL1 cell M4nXXmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NVnFPWw6UW6qaXLpeIlwdiCxZjDoeY1idiCLU2StUWVNOSClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR|UxRTJyND6xN{BvVQ>? M3PwWnNCVkeHUh?=
HCC2998 cell Mmn5S5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MljHTY5pcWKrdHnvckBw\iCqdX3hckBJS0N{OUm4JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE4zOjF6NzFOwG0> MV3TRW5ITVJ?
GDM-1 cell MYfHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MnfYTY5pcWKrdHnvckBw\iCqdX3hckBITE1vMTDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUCuNlI6PDdizszN NGrRbldUSU6JRWK=
MZ1-PC cell MlHZS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MkK0TY5pcWKrdHnvckBw\iCqdX3hckBOYjFvUFOgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2wMlI4QTl7IN88US=> Mk\4V2FPT0WU
BB49-HNC cell M4\DNWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MVPJcohq[mm2aX;uJI9nKGi3bXHuJGJDPDlvSF7DJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE4{PTF6IN88US=> NUnxbJJKW0GQR1XS
D-392MG cell NI\aeYlIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NXn0WZpbUW6qaXLpeIlwdiCxZjDoeY1idiCGLUO5Nm1IKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OC5|NU[wO{DPxE1? MnLPV2FPT0WU
697 cell MmLHS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NFL1TYRKdmirYnn0bY9vKG:oIHj1cYFvKDZ7NzDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUO2N{45QCEQvF2= MUHTRW5ITVJ?
ML-2 cell NVLCSYJUT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NXO0PIRIUW6qaXLpeIlwdiCxZjDoeY1idiCPTD2yJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9N|Y5Njh4IH7N MlmwV2FPT0WU
MEG-01 cell MmLqS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? M3;XS2lvcGmkaYTpc44hd2ZiaIXtZY4hVUWJLUCxJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE4{PzZizszN NEHVNWNUSU6JRWK=
SK-MEL-1 cell MXPHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MnXQTY5pcWKrdHnvckBw\iCqdX3hckBUUy2PRVytNUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVAvOzh|NkKg{txO M3nCd3NCVkeHUh?=
KS-1 cell NHXUSlZIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NYK1SVN1UW6qaXLpeIlwdiCxZjDoeY1idiCNUz2xJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE4{QTN|NzFOwG0> NXT4UJVJW0GQR1XS
NB14 cell M1jSTGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 M3q4NmlvcGmkaYTpc44hd2ZiaIXtZY4hVkJzNDDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUCuOFk{OzFizszN MnPvV2FPT0WU
NCI-H747 cell NYHvVIRPT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MVzJcohq[mm2aX;uJI9nKGi3bXHuJG5EUS2KN{S3JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE42ODZ|NzFOwG0> MWXTRW5ITVJ?
K-562 cell M4TFWmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MWnJcohq[mm2aX;uJI9nKGi3bXHuJGsuPTZ{IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MD62OlY6PSEQvF2= MoPvV2FPT0WU
NCI-H1648 cell Mn\LS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NHm0ZpNKdmirYnn0bY9vKG:oIHj1cYFvKE6FST3INVY1QCClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR|UxRTBwNkeyOlYh|ryP M3rUfHNCVkeHUh?=
LAN-6 cell MV\Hdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NUHwenJoUW6qaXLpeIlwdiCxZjDoeY1idiCOQV6tOkBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVAvPjh{M{[g{txO M{j5OnNCVkeHUh?=

... 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 CC1=C(C=C(C=C1)NC(=O)C2=CC(=CC=C2)C(C)(C)C#N)NC3=CC4=C(C=C3)N=CN(C4=O)C

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID