AZD7762

Catalog No.S1532

For research use only.

AZD7762 is a potent and selective inhibitor of Chk1 with IC50 of 5 nM in a cell-free assay. It is equally potent against Chk2 and less potent against CAM, Yes, Fyn, Lyn, Hck and Lck. Phase 1.

AZD7762 Chemical Structure

CAS No. 860352-01-8

Selleck's AZD7762 has been cited by 105 publications

Purity & Quality Control

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Biological Activity

Description AZD7762 is a potent and selective inhibitor of Chk1 with IC50 of 5 nM in a cell-free assay. It is equally potent against Chk2 and less potent against CAM, Yes, Fyn, Lyn, Hck and Lck. Phase 1.
Targets
Chk1 [1]
(Cell-free assay)
Chk2 [1]
(Cell-free assay)
5 nM <10 nM
In vitro

AZD7762, a more selective Chk1 inhibitor, inhibits Chk1 phosphorylation of a cdc25C peptide by reversibly binding to the ATP-binding site of Chk1, with IC50 of 5 nM and Ki of 3.6 nM. AZD7762 induces cell arrest with EC50 of 0.620 μM, and significantly abrogates the camptothecin induced G2 arrest with an EC50 of 10 nM, by blocking the chk1 dependent degradation of Cdc25A and activation of Cyclin A. AZD7762 (300 nM) enhances the antitumor efficacy of gemcitabine against SW620 and topotecan against MDA-MB-231 by reducing the GI50 values from 24.1 nM and 2.25 μM to 1.08 nM and 0.15 μM, respectively. [1] AZD7762 shows cytotoxicity against a variety of neuroblastoma cell lines bearing p53 wild type, p53 mutation, Mdm2 amplification or p14 deletion with IC50 values ranging from 82.6-505.9 nM. [2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
KASUMI-1 M1:wS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlXYTWM2OD1yLkCwNFI{PCEQvF2= M4m2SlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFIxPDF7M{OvK|5USU6JRWK8M4E,
NKM-1 NEDHN5JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlvnTWM2OD1yLkCwNFQyPSEQvF2= MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyNFQyQTN|Lze+V2FPT0WUPD;hQi=>
MV-4-11 NX\NflNkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M372dGlEPTB;MD6wNFA1OjVizszN NYHo[49bRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjB2MUmzN{8oRlODTlfFVlww[T5?
NCI-H1703 M4nRUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIHUTnpKSzVyPUCuNFA3PDNizszN MonLQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlA1OTl|Mz:nQnNCVkeHUkyvZV4>
A204 NXrNbXoxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkPrTWM2OD1yLkCwPFU3KM7:TR?= MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyNFQyQTN|Lze+V2FPT0WUPD;hQi=>
CGTH-W-1 MmG1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYjJR|UxRTBwMEG0NkDPxE1? M2XNd|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFIxPDF7M{OvK|5USU6JRWK8M4E,
MLMA NF\NO|BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWTJR|UxRTBwMEK4OFkh|ryP NWL3PZB2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjB2MUmzN{8oRlODTlfFVlww[T5?
GOTO MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXSwXmFEUUN3ME2wMlA{OTJizszN M1f6fFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFIxPDF7M{OvK|5USU6JRWK8M4E,
KE-37 NWH4fXhMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mkj0TWM2OD1yLkCzNVQzKM7:TR?= NGTVOWM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzODRzOUOzM{c,W0GQR1XSQE9iRg>?
ES4 M4C2[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWDJR|UxRTBwMEOyOVEh|ryP NX;MeHZkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjB2MUmzN{8oRlODTlfFVlww[T5?
ATN-1 Mkj6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnTZTWM2OD1yLkCzOFE4KM7:TR?= NF\NSlc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzODRzOUOzM{c,W0GQR1XSQE9iRg>?
MHH-PREB-1 NX3X[2FUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGK3b4RKSzVyPUCuNFM1PDJizszN NYjOWXlNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjB2MUmzN{8oRlODTlfFVlww[T5?
SW756 M2W5eGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF;a[WlKSzVyPUCuNFM2PzlizszN MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyNFQyQTN|Lze+V2FPT0WUPD;hQi=>
CTV-1 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M13tRWlEPTB;MD6wN|g6PiEQvF2= M3rVZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFIxPDF7M{OvK|5USU6JRWK8M4E,
HCC1806 MkW2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYjufY16UUN3ME2wMlA1ODJ{IN88US=> M4n0RlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFIxPDF7M{OvK|5USU6JRWK8M4E,
NEC8 M37ZcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWrJR|UxRTBwMESyNFMh|ryP M1jMW|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFIxPDF7M{OvK|5USU6JRWK8M4E,
P12-ICHIKAWA M2XtOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXLJR|UxRTBwMESzNVYh|ryP MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyNFQyQTN|Lze+V2FPT0WUPD;hQi=>
DEL MlfSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFHMcXRKSzVyPUCuNFQ2QTJizszN M{XVe|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFIxPDF7M{OvK|5USU6JRWK8M4E,
KM12 M3:zWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWDXSJRZUUN3ME2wMlA2OTV6IN88US=> NFO3OWc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzODRzOUOzM{c,W0GQR1XSQE9iRg>?
LB1047-RCC MkXpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXLJR|UxRTBwME[wNlUh|ryP M4\uVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFIxPDF7M{OvK|5USU6JRWK8M4E,
LB2241-RCC M{XUUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYjJR|UxRTBwME[xNFIh|ryP NVuzWmRqRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjB2MUmzN{8oRlODTlfFVlww[T5?
NOMO-1 NYGwe3QzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NE\JVoZKSzVyPUCuNFYyOTVizszN NGn5WJo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzODRzOUOzM{c,W0GQR1XSQE9iRg>?
NB14 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M365RmlEPTB;MD6wOlE{PiEQvF2= NUXTUYc1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjB2MUmzN{8oRlODTlfFVlww[T5?
ONS-76 M1jiSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUTJR|UxRTBwME[xPVYh|ryP NYG2[4o1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjB2MUmzN{8oRlODTlfFVlww[T5?
HD-MY-Z NIj6cXdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVS0PWhwUUN3ME2wMlA3OjV3IN88US=> MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyNFQyQTN|Lze+V2FPT0WUPD;hQi=>
G-402 NVnncHJmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVGwN29uUUN3ME2wMlA3PDZizszN M1nhT|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFIxPDF7M{OvK|5USU6JRWK8M4E,
ES1 NFfvT2tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVfJR|UxRTBwMEexOFYh|ryP NGTPTGQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzODRzOUOzM{c,W0GQR1XSQE9iRg>?
L-363 MnjaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUT5cIprUUN3ME2wMlA4OzlizszN NXT3XnlRRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjB2MUmzN{8oRlODTlfFVlww[T5?
A4-Fuk MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1Lj[GlEPTB;MD6wO|Q5PiEQvF2= MXK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyNFQyQTN|Lze+V2FPT0WUPD;hQi=>
OC-314 NHjBZWlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoTvTWM2OD1yLkC3PFA4KM7:TR?= M{nTWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFIxPDF7M{OvK|5USU6JRWK8M4E,
SK-LU-1 M2nVUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGizfVJKSzVyPUCuNFg1OjFizszN M1rpblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFIxPDF7M{OvK|5USU6JRWK8M4E,
MDA-MB-157 MmOyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3XRU2lEPTB;MD6wPFY2QSEQvF2= NF;IS4I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzODRzOUOzM{c,W0GQR1XSQE9iRg>?
HuP-T3 MlLjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWL0RXFMUUN3ME2wMlA5PzFizszN M2rYOVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFIxPDF7M{OvK|5USU6JRWK8M4E,
A3-KAW Mnq2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHnaNWNKSzVyPUCuNFg5ODZizszN MXK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyNFQyQTN|Lze+V2FPT0WUPD;hQi=>
MOLT-16 M376[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2LiTWlEPTB;MD6wPFgxPyEQvF2= NWLrZ3JIRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjB2MUmzN{8oRlODTlfFVlww[T5?
COLO-679 M4P0ZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVLJR|UxRTBwMEmwPVEh|ryP MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyNFQyQTN|Lze+V2FPT0WUPD;hQi=>
EM-2 MnPKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYO5NVAzUUN3ME2wMlA6QTB|IN88US=> MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyNFQyQTN|Lze+V2FPT0WUPD;hQi=>
ES8 MlXxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{exOWlEPTB;MD6wPVkyQCEQvF2= NXzFUFBrRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjB2MUmzN{8oRlODTlfFVlww[T5?
SK-MEL-2 M4C3emdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXnJR|UxRTBwMUCwN|Mh|ryP NELheXE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzODRzOUOzM{c,W0GQR1XSQE9iRg>?
ES3 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3L1W2lEPTB;MD6xNFIh|ryP MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyNFQyQTN|Lze+V2FPT0WUPD;hQi=>
HSC-4 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUDJR|UxRTBwMUC1OVQh|ryP NGC0RlU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzODRzOUOzM{c,W0GQR1XSQE9iRg>?
697 Mn\KS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGnuW|FKSzVyPUCuNVExPjNizszN NXnzenVXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjB2MUmzN{8oRlODTlfFVlww[T5?
TGBC11TKB NH:ySoFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnjDTWM2OD1yLkGxNFk{KM7:TR?= Mlm2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlA1OTl|Mz:nQnNCVkeHUkyvZV4>
SK-PN-DW MnH4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIrRSZVKSzVyPUCuNVE5PiEQvF2= MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyNFQyQTN|Lze+V2FPT0WUPD;hQi=>
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Assay
Methods Test Index PMID
Western blot pChk1 / Chk1 / Wee1 / p21 / p53 29963769
Growth inhibition assay Cell viability 23715154
In vivo AZD7762 alone at 25 mg/kg shows little antitumor activity in the H460-DNp53 xenograft mice and SW620 xenograft mice, but when administrated in combination with gemcitabine (60 mg/kg), AZD7762 shows significant antitumor efficacy in the two xenografts mice with a log cell kill of 0.9 or percent treated/control (%T/C) of 26 even at low dose of 12.5 mg. Dosing of AZD7762 in combination with gemcitabine (10 mg/kg) in the H460-DNp53 xenograft rat inhibits the tumor volume in a dose-dependent manner with the %T/C values of 48 and 32 for 10 and 20 mg/kg AZD7762, respectively. AZD7762 (25 mg/kg) in combination with irinotecan (25 or 50 mg/kg) causes complete tumor regression in the SW620 xenograft mice with the %T/C increasing significantly to -66% and -67%, respectively. [1]

Protocol (from reference)

Kinase Assay:[1]
  • Chk1 Kinase Assay:

    Recombinant human Chk1 is expressed as a glutathione S-transferase fusion in insect cells using a baculovirus vector and purified by glutathione affinity chromatography. A synthetic peptide substrate (N-biotinylaminohexanoyl-KKVSRSGLYRSPMPENLNRPR) for Chk1 is synthesized. Final assay concentrations of peptide and ATP (cold + 40 nCi [33P]ATP) are 0.8 and 1 μM, respectively. Different concentrations of AZD7762, buffer containing peptide and chk1 kinase and ATP, are added sequentially to a 384-well assay plate. The plate is incubated for 2 hours, reaction is stopped by the addition of buffer containing EDTA and scintillation proximity assay beads, and plates are read using a TopCount reader. Data analysis is carried out to determinate a dose response (IC50).

Cell Research:[1]
  • Cell lines: HT29, SW620 and MDA-MB-231 cells
  • Concentrations: Dissolved in DMSO, final concentration ~12.5 μM
  • Incubation Time: 20 or 48 hours
  • Method: For the checkpoint abrogation assay, HT29 cells are treated for 2 hours with camptothecin (topoisomerase I inhibitor; 0.07 μg/mL) to induce the G2 checkpoint. Cells are then treated for 20 hours with a 12-point titration of AZD7762 (12.5 μM to 6 nM) plus nocodazole. Cells are fixed with 3.7% formaldehyde for 1 hour, permeabilized with PBS containing 0.05% Triton X, and incubated with anti-phH3 antibody for 1 hour followed by Alexa Fluor 488 anti-rabbit and Hoechst stain for 1 hour. Mitotic index is determined on the ArrayScan and expressed as the percentage of cells undergoing mitosis. For the potentiation assays, SW620 or MDA-MB-231 cells are dosed for 24 hours with a 9-point titration of gemcitabine ranging from 0.01 to 100 nM with a constant dose of AZD7762 (300 nM). After 24 hours, medium is removed and AZD7762 alone is added back to the wells for an additional 24 hours. Cells are then incubated in AZD7762-free medium for an additional 72 hours. The effect on cell proliferation is determined by MTT.
Animal Research:[1]
  • Animal Models: Male NCr mice implanted s.c. with H460-DNp53 cells or SW620, and male rnu rats implanted s.c. with H460-DNp53 cells
  • Dosages: ~25 mg/kg
  • Administration: Injection i.v.

Solubility (25°C)

In vitro

DMSO 50 mg/mL
(137.96 mM)
Water Insoluble
Ethanol Insoluble

Chemical Information

Molecular Weight 362.42
Formula

C17H19FN4O2S

CAS No. 860352-01-8
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C1CC(CNC1)NC(=O)C2=C(C=C(S2)C3=CC(=CC=C3)F)NC(=O)N

In vivo Formulation Calculator (Clear solution)

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT00937664 Terminated Drug: AZD7762|Drug: gemcitabine Cancer|Solid Tumors|Advanced Solid Malignancies AstraZeneca July 2009 Phase 1
NCT00473616 Terminated Drug: AZD7762|Drug: Irinotecan Advanced Solid Tumors|Cancer|Advanced Solid Malignancies AstraZeneca May 2007 Phase 1
NCT00413686 Completed Drug: AZD7762|Drug: Gemcitabine Solid Tumors AstraZeneca December 2006 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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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Frequently Asked Questions

Question 1:
If I want to use the inhibitor for i.p. injection, can I use DMSO to dissolve it?

Answer:
Since DMSO has low toxicity with i.p. injection, hydroxyproplyl-β-cyclodextrin is consider a safer co-solvent in compound formulation. In a previous literature report, 11.3% hydroxyproplyl-β-cyclodextrin was used to formulate this compound for i.v. injection.

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