AZ 628

For research use only.

Catalog No.S2746

30 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 30 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 MVnHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NXy4SZhyUW6qaXLpeIlwdiCxZjDoeY1idiCDQ16gZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2wMlExOSCwTR?= M4rafXNCVkeHUh?=
SH-4 cell NITYeItIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NWfNW|Q6UW6qaXLpeIlwdiCxZjDoeY1idiCVSD20JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9N{4xOSCwTR?= M4\a[3NCVkeHUh?=
LB2518-MEL cell MlzsS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NGHLbpBKdmirYnn0bY9vKG:oIHj1cYFvKEyEMkWxPE1OTUxiY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OD12Lke2JI5O MYDTRW5ITVJ?
A101D cell M3S2fGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NYj5XpZ{UW6qaXLpeIlwdiCxZjDoeY1idiCDMUCxSEBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVUvQDJibl2= MlPGV2FPT0WU
HT-144 cell MkjJS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? M1HZc2lvcGmkaYTpc44hd2ZiaIXtZY4hUFRvMUS0JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9Ok43OSCwTR?= M4DwVHNCVkeHUh?=
SIG-M5 cell NEXiTZNIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MUnJcohq[mm2aX;uJI9nKGi3bXHuJHNKTy2PNTDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUmuOFUhdk1? MWfTRW5ITVJ?
DU-4475 cell NWfkc2JpT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MWPJcohq[mm2aX;uJI9nKGi3bXHuJGRWNTR2N{WgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xNE4zOyCwTR?= NGnIXFlUSU6JRWK=
A375 cells NWfIb41wTnWwY4Tpc44h[XO|YYm= M1jOelc2KG2rboO= MYHJcohq[mm2aX;uJI9nKEKUQV[gWlYxOEVibYX0ZY51NW2nZHnheIVlKEWUSzDwbI9{eGixconsZZRqd25iaX6gbJVu[W5iQUO3OUBk\WyuczDh[pRmeiB5NTDtbY5{NCCLQ{WwQVAvODF3IN88US=> MUeyN|M6QDR3Mx?=
OCI-AML2 cell MWXHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MVrJcohq[mm2aX;uJI9nKGi3bXHuJG9EUS2DTVyyJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE4xOTgQvF2= MlTvV2FPT0WU
COLO-829 cell NX;IXoR5T3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MYHJcohq[mm2aX;uJI9nKGi3bXHuJGNQVE9vOEK5JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NlUvPjVibl2= MonrV2FPT0WU
PSN1 cell MXXHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M{\1cGlvcGmkaYTpc44hd2ZiaIXtZY4hWFOQMTDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUK3MlM4KG6P MVPTRW5ITVJ?
UACC-257 cell M4D6NGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 M3S2TWlvcGmkaYTpc44hd2ZiaIXtZY4hXUGFQz2yOVch[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0zPy52OTDuUS=> NVj6eFcxW0GQR1XS
RKO cell M1fLZWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NIHBWJFKdmirYnn0bY9vKG:oIHj1cYFvKFKNTzDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUO3MlY4KG6P MkDEV2FPT0WU
MMAC-SF cell M3;xV2dzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MlrETY5pcWKrdHnvckBw\iCqdX3hckBOVUGFLWPGJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9OFAvODdibl2= MVLTRW5ITVJ?
Calu-6 cell MlOyS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? M3[zRWlvcGmkaYTpc44hd2ZiaIXtZY4hS2GudT22JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9OVEvPDdibl2= MnvLV2FPT0WU
LS-513 cell NH;6OVNIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NF[yfVZKdmirYnn0bY9vKG:oIHj1cYFvKEyVLUWxN{Bk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVc1NjF3IH7N MlfBV2FPT0WU
NOS-1 cell NHPCbVhIem:5dHigbY5pcWKrdHnvckBie3OjeR?= M3[2UGlvcGmkaYTpc44hd2ZiaIXtZY4hVk:VLUGgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME25Nk43PSCwTR?= NImzdYZUSU6JRWK=
SW872 cell MlfQS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NHLTPWVKdmirYnn0bY9vKG:oIHj1cYFvKFOZOEeyJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9PVYvPDhibl2= MkXGV2FPT0WU
KMOE-2 cell M4j2Umdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MYrJcohq[mm2aX;uJI9nKGi3bXHuJGtOV0VvMjDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUGxOU45QCCwTR?= NHf0RolUSU6JRWK=
MZ7-mel cell NFzzZm9Iem:5dHigbY5pcWKrdHnvckBie3OjeR?= NGD4RWRKdmirYnn0bY9vKG:oIHj1cYFvKE2cNz3t[Ywh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0yOTdwMkegcm0> NIfLOGZUSU6JRWK=
CGTH-W-1 cell M{\GdWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NVLu[2p{UW6qaXLpeIlwdiCxZjDoeY1idiCFR2TIMXcuOSClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR|UxRTF{MT6zJI5O NF33[JBUSU6JRWK=
CP66-MEL cell NVqwcIhjT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= M2ewSWlvcGmkaYTpc44hd2ZiaIXtZY4hS1B4Nj3NSWwh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0yOzFwN{[gcm0> M3TvbHNCVkeHUh?=
K5 cell MmjYS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? M{LZPWlvcGmkaYTpc44hd2ZiaIXtZY4hUzViY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OD1zM{SuNkBvVQ>? MkHLV2FPT0WU
HL-60 cell NHvFfYNIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NX\zemQ4UW6qaXLpeIlwdiCxZjDoeY1idiCKTD22NEBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVE2PC52MTDuUS=> MX3TRW5ITVJ?
ONS-76 cell NVywSZVGT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NH;ZVphKdmirYnn0bY9vKG:oIHj1cYFvKE:QUz23OkBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVE3Pi54MjDuUS=> M4POcXNCVkeHUh?=
NB69 cell M33RNWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 M{XsTWlvcGmkaYTpc44hd2ZiaIXtZY4hVkJ4OTDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUG5NU4{OSCwTR?= M4LYZ3NCVkeHUh?=
LAMA-84 cell MV\Hdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NVPD[3dkUW6qaXLpeIlwdiCxZjDoeY1idiCOQV3BMVg1KGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OTl{LkSyJI5O MVfTRW5ITVJ?
EM-2 cell  M1Tafmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 Ml;sTY5pcWKrdHnvckBw\iCqdX3hckBGVS1{IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MUm1MlkyKG6P MYDTRW5ITVJ?
IST-MEL1 cell NHTIXZhIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MVTJcohq[mm2aX;uJI9nKGi3bXHuJGlUXC2PRVyxJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NlA1NjF|IH7N M2TFbHNCVkeHUh?=
HCC2998 cell MmK3S5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MVfJcohq[mm2aX;uJI9nKGi3bXHuJGhESzJ7OUigZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2wMlIzOTh5IN88US=> MlHJV2FPT0WU
GDM-1 cell NEXnbmxIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NY\U[XlGUW6qaXLpeIlwdiCxZjDoeY1idiCJRF2tNUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVAvOjJ7NEeg{txO MWfTRW5ITVJ?
MZ1-PC cell NFnDcVRIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NGK0T5FKdmirYnn0bY9vKG:oIHj1cYFvKE2cMT3QR{Bk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVAvOjd7OUmg{txO MkjyV2FPT0WU
BB49-HNC cell MnXBS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NFPmNYJKdmirYnn0bY9vKG:oIHj1cYFvKEKENEmtTG5EKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OC5|NUG4JO69VQ>? Ml3nV2FPT0WU
D-392MG cell MV7Hdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? Mn3nTY5pcWKrdHnvckBw\iCqdX3hckBFNTN7Ml3HJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE4{PTZyNzFOwG0> MWXTRW5ITVJ?
697 cell NWL1bINQT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= M1;qd2lvcGmkaYTpc44hd2ZiaIXtZY4hPjl5IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;M{[zMlg5KM7:TR?= NEDVUFNUSU6JRWK=
ML-2 cell MWXHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MnjaTY5pcWKrdHnvckBw\iCqdX3hckBOVC1{IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;M{[4Mlg3KG6P M{nlVnNCVkeHUh?=
MEG-01 cell NV72[JJFT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NVrIZ45jUW6qaXLpeIlwdiCxZjDoeY1idiCPRVetNFEh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0xNjN5NjFOwG0> M3vjVHNCVkeHUh?=
SK-MEL-1 cell MXjHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MX;Jcohq[mm2aX;uJI9nKGi3bXHuJHNMNU2HTD2xJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE4{QDN4MjFOwG0> MVrTRW5ITVJ?
KS-1 cell MVjHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MYPJcohq[mm2aX;uJI9nKGi3bXHuJGtUNTFiY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OD1yLkO5N|M4KM7:TR?= M4Pqb3NCVkeHUh?=
NB14 cell NYexNoRKT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MWTJcohq[mm2aX;uJI9nKGi3bXHuJG5DOTRiY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OD1yLkS5N|MyKM7:TR?= NHnCUo9USU6JRWK=
NCI-H747 cell NVfDeZBrT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NUTQcXVLUW6qaXLpeIlwdiCxZjDoeY1idiCQQ1mtTFc1PyClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR|UxRTBwNUC2N|ch|ryP MkD5V2FPT0WU
K-562 cell MoLQS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MY\Jcohq[mm2aX;uJI9nKGi3bXHuJGsuPTZ{IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MD62OlY6PSEQvF2= M3zTSXNCVkeHUh?=
NCI-H1648 cell NFv4U|dIem:5dHigbY5pcWKrdHnvckBie3OjeR?= Ml7yTY5pcWKrdHnvckBw\iCqdX3hckBPS0lvSEG2OFgh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0xNjZ5Mk[2JO69VQ>? NW\5[HM{W0GQR1XS
LAN-6 cell NF\nZoNIem:5dHigbY5pcWKrdHnvckBie3OjeR?= M4XUS2lvcGmkaYTpc44hd2ZiaIXtZY4hVEGQLU[gZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2wMlY5OjN4IN88US=> NGLyeZdUSU6JRWK=

... 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