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AZ 628

For research use only.

Catalog No.S2746

32 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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Selleck's AZ 628 has been cited by 32 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. 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 MnzuS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MlPpTY5pcWKrdHnvckBw\iCqdX3hckBCS05iY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OD1yLkGwNUBvVQ>? NX3teYhkW0GQR1XS
SH-4 cell NWL3eZgxT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MlLhTY5pcWKrdHnvckBw\iCqdX3hckBUUC12IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;Mz6wNUBvVQ>? MmqyV2FPT0WU
LB2518-MEL cell MoTzS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MXzJcohq[mm2aX;uJI9nKGi3bXHuJGxDOjVzOD3NSWwh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF01Njd4IH7N MXzTRW5ITVJ?
A101D cell MYDHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MkTJTY5pcWKrdHnvckBw\iCqdX3hckBCOTBzRDDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUWuPFIhdk1? MkPtV2FPT0WU
HT-144 cell M1HwV2dzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MVzJcohq[mm2aX;uJI9nKGi3bXHuJGhVNTF2NDDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPU[uOlEhdk1? M1fNd3NCVkeHUh?=
SIG-M5 cell Mn;LS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NV7xboJ7UW6qaXLpeIlwdiCxZjDoeY1idiCVSVetUVUh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF06NjR3IH7N NUfnXYprW0GQR1XS
DU-4475 cell M2\yZ2dzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MnjTTY5pcWKrdHnvckBw\iCqdX3hckBFXS12NEe1JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NVAvOjNibl2= MkP3V2FPT0WU
A375 cells NX2yXY1rTnWwY4Tpc44h[XO|YYm= NGnLXHA4PSCvaX7z M{XjT2lvcGmkaYTpc44hd2ZiQmLBSkBXPjByRTDteZRidnRvbXXkbYF1\WRiRWLLJJBpd3OyaH;yfYxifGmxbjDpckBpfW2jbjDBN|c2KGOnbHzzJIFnfGW{IEe1JI1qdnNuIFnDOVA:OC5yMUWg{txO NXfpN441OjN|OUi0OVM>
OCI-AML2 cell NEHuPJNIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MX3Jcohq[mm2aX;uJI9nKGi3bXHuJG9EUS2DTVyyJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE4xOTgQvF2= NWLoN4loW0GQR1XS
COLO-829 cell MoDPS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? Mnn5TY5pcWKrdHnvckBw\iCqdX3hckBEV0yRLUiyPUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVI2NjZ3IH7N NH65cmhUSU6JRWK=
PSN1 cell NFTBW4NIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MUXJcohq[mm2aX;uJI9nKGi3bXHuJHBUVjFiY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OD1{Nz6zO{BvVQ>? NWCzTFVHW0GQR1XS
UACC-257 cell NYnUcVhQT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NYPlfYhRUW6qaXLpeIlwdiCxZjDoeY1idiCXQVPDMVI2PyClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR|UxRTJ5LkS5JI5O MWHTRW5ITVJ?
RKO cell MUjHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NHqwcFNKdmirYnn0bY9vKG:oIHj1cYFvKFKNTzDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUO3MlY4KG6P NV3aTGJmW0GQR1XS
MMAC-SF cell M37Ddmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MlfXTY5pcWKrdHnvckBw\iCqdX3hckBOVUGFLWPGJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9OFAvODdibl2= NHnDXG1USU6JRWK=
Calu-6 cell NWrkdYJRT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MYfJcohq[mm2aX;uJI9nKGi3bXHuJGNidHVvNjDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUWxMlQ4KG6P MmLXV2FPT0WU
LS-513 cell M1LDXmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MYLJcohq[mm2aX;uJI9nKGi3bXHuJGxUNTVzMzDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUe0MlE2KG6P M4PxZXNCVkeHUh?=
NOS-1 cell M2DVOWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NUn4blZuUW6qaXLpeIlwdiCxZjDoeY1idiCQT2OtNUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVkzNjZ3IH7N NIW4doNUSU6JRWK=
SW872 cell NWj2Z2hLT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MkW1TY5pcWKrdHnvckBw\iCqdX3hckBUXzh5MjDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUm2MlQ5KG6P NELrcZVUSU6JRWK=
KMOE-2 cell NFr3VYNIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MVzJcohq[mm2aX;uJI9nKGi3bXHuJGtOV0VvMjDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUGxOU45QCCwTR?= MmXiV2FPT0WU
MZ7-mel cell MUjHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M2jrT2lvcGmkaYTpc44hd2ZiaIXtZY4hVVp5LX3lcEBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVEyPy5{NzDuUS=> MnPYV2FPT0WU
CGTH-W-1 cell NV;kXHUyT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= M1zYOmlvcGmkaYTpc44hd2ZiaIXtZY4hS0eWSD3XMVEh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0yOjFwMzDuUS=> NUfNSYVUW0GQR1XS
CP66-MEL cell MoDSS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NFPNfIFKdmirYnn0bY9vKG:oIHj1cYFvKEOSNk[tUWVNKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OTNzLke2JI5O MkX1V2FPT0WU
K5 cell MkXvS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NE[wenlKdmirYnn0bY9vKG:oIHj1cYFvKEt3IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MUO0MlIhdk1? MV7TRW5ITVJ?
HL-60 cell NUL3Vo1CT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NXj2NmR{UW6qaXLpeIlwdiCxZjDoeY1idiCKTD22NEBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVE2PC52MTDuUS=> MYDTRW5ITVJ?
ONS-76 cell M4Syemdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NF7kXG5KdmirYnn0bY9vKG:oIHj1cYFvKE:QUz23OkBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVE3Pi54MjDuUS=> M3HQWnNCVkeHUh?=
NB69 cell NGTxSZNIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NYDFU|llUW6qaXLpeIlwdiCxZjDoeY1idiCQQk[5JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NVkyNjNzIH7N MkXoV2FPT0WU
LAMA-84 cell Mmn2S5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MlW4TY5pcWKrdHnvckBw\iCqdX3hckBNSU2DLUi0JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NVkzNjR{IH7N NYnkcWZMW0GQR1XS
EM-2 cell  MVfHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M3THTGlvcGmkaYTpc44hd2ZiaIXtZY4hTU1vMjDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUG5OU46OSCwTR?= NHnT[3hUSU6JRWK=
IST-MEL1 cell NYf4ZXVrT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= M{LOS2lvcGmkaYTpc44hd2ZiaIXtZY4hUVOWLV3FUFEh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0zODRwMUOgcm0> NE\mV|lUSU6JRWK=
HCC2998 cell MoTmS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MlS2TY5pcWKrdHnvckBw\iCqdX3hckBJS0N{OUm4JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE4zOjF6NzFOwG0> NXXYe3JYW0GQR1XS
GDM-1 cell MnT3S5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MoXtTY5pcWKrdHnvckBw\iCqdX3hckBITE1vMTDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUCuNlI6PDdizszN MVjTRW5ITVJ?
MZ1-PC cell M2jJS2dzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NFTBN4NKdmirYnn0bY9vKG:oIHj1cYFvKE2cMT3QR{Bk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVAvOjd7OUmg{txO NIXSTIdUSU6JRWK=
BB49-HNC cell M1\kOWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 Mlu2TY5pcWKrdHnvckBw\iCqdX3hckBDSjR7LVjOR{Bk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVAvOzVzODFOwG0> NGPIO3VUSU6JRWK=
D-392MG cell MnfaS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NV3vZVZHUW6qaXLpeIlwdiCxZjDoeY1idiCGLUO5Nm1IKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OC5|NU[wO{DPxE1? NIqzfpNUSU6JRWK=
697 cell M3vJUWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MkiwTY5pcWKrdHnvckBw\iCqdX3hckA3QTdiY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OD1|NkOuPFgh|ryP M17DNnNCVkeHUh?=
ML-2 cell M1e4Smdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NFnZUGRKdmirYnn0bY9vKG:oIHj1cYFvKE2OLUKgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2zOlgvQDZibl2= M{WyWHNCVkeHUh?=
MEG-01 cell M1nyUmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MkL2TY5pcWKrdHnvckBw\iCqdX3hckBOTUdvMEGgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2wMlM4PiEQvF2= M17qR3NCVkeHUh?=
SK-MEL-1 cell M{\Me2dzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MUjJcohq[mm2aX;uJI9nKGi3bXHuJHNMNU2HTD2xJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE4{QDN4MjFOwG0> NWHycGNFW0GQR1XS
KS-1 cell NUf2R2o6T3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MknaTY5pcWKrdHnvckBw\iCqdX3hckBMWy1zIHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MD6zPVM{PyEQvF2= NVvBemZQW0GQR1XS
NB14 cell MoD2S5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MlrYTY5pcWKrdHnvckBw\iCqdX3hckBPSjF2IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MD60PVM{OSEQvF2= NGPUZ2ZUSU6JRWK=
NCI-H747 cell MoCyS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NIXjboNKdmirYnn0bY9vKG:oIHj1cYFvKE6FST3IO|Q4KGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OC53ME[zO{DPxE1? MWfTRW5ITVJ?
K-562 cell Ml7QS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NG\n[oxKdmirYnn0bY9vKG:oIHj1cYFvKEtvNU[yJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE43PjZ7NTFOwG0> MlXkV2FPT0WU
NCI-H1648 cell Mnn4S5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MWfJcohq[mm2aX;uJI9nKGi3bXHuJG5EUS2KMU[0PEBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVAvPjd{Nk[g{txO MVXTRW5ITVJ?
LAN-6 cell NWjBU2pmT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= M3fxcWlvcGmkaYTpc44hd2ZiaIXtZY4hVEGQLU[gZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2wMlY5OjN4IN88US=> NXjrW2drW0GQR1XS

... 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