AZD8055

For research use only.

Catalog No.S1555

207 publications

AZD8055 Chemical Structure

CAS No. 1009298-09-2

AZD8055 is a novel ATP-competitive mTOR inhibitor with IC50 of 0.8 nM in MDA-MB-468 cells with excellent selectivity (∼1,000-fold) against PI3K isoforms and ATM/DNA-PK. AZD8055 induces caspase-dependent apoptosis and also induces autophagy. Phase 1.

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Selleck's AZD8055 has been cited by 207 publications

Purity & Quality Control

Choose Selective mTOR Inhibitors

Biological Activity

Description AZD8055 is a novel ATP-competitive mTOR inhibitor with IC50 of 0.8 nM in MDA-MB-468 cells with excellent selectivity (∼1,000-fold) against PI3K isoforms and ATM/DNA-PK. AZD8055 induces caspase-dependent apoptosis and also induces autophagy. Phase 1.
Features First drug to inhibit both types of mTOR protein.
Targets
mTOR (truncated) [1]
(MDA-MB-468 cells)
mTOR (full length) [1]
(MDA-MB-468 cells)
0.13 nM 0.8 nM
In vitro

AZD8055 shows low activity (∼1,000-fold) against all PI3K isoforms (α, β, γ, δ) and other members of the PI3K-like kinase family (ATM and DNA-PK). AZD8055 inhibits the phosphorylation of mTORC1 (p70S6K and 4E-BP1) as well as phosphorylation of the mTORC2 (Akt) and downstream proteins. The rapamycin-resistant T37/46 phosphorylation sites on 4E-BP1 can be fully inhibited by AZD8055, resulting in significant inhibition of cap-dependent translation. AZD8055 potently inhibits proliferation in U87MG, A549 and H838 cells with IC50 of 53, 50 and 20 nM, respectively. AZD8055 also induces autophagy and increased LC3-II levels in H838 and A549 cells. [1] AZD8055 decreases AML blast cell proliferation and cell cycle progression, reduces the clonogenic growth of leukemic progenitors and induces caspase-dependent apoptosis in leukemic cells but not in normal immature CD34+ cells. [2] AZD8055 indicates inhibitory against the pediatric preclinical testing program (PPTP) cell lines with IC50 of 24.7 nM and induces significant differences in EFS distribution. [3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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HT Ml[5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFfz[pNKSzVyPUCuNlk{QCEQvF2= NIDDboM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDBzMkC0M{c,W0GQR1XSQE9iRg>?
A3-KAW MlPuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVTLUJFsUUN3ME2wMlI6PzRizszN NEPC[XM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDBzMkC0M{c,W0GQR1XSQE9iRg>?
LB2241-RCC NGfxN4xIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoLDTWM2OD1yLkOwNVk5KM7:TR?= NInpUnY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDBzMkC0M{c,W0GQR1XSQE9iRg>?
BB65-RCC M4TyO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MY\JR|UxRTBwM{C4NFUh|ryP MkjtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVgxOTJyND:nQnNCVkeHUkyvZV4>
G-401 MlLCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGe4fGxKSzVyPUCuN|A6QDZizszN NVzMNYdlRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOThyMUKwOE8oRlODTlfFVlww[T5?
TYK-nu M3q2U2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX7vbJk3UUN3ME2wMlMyQDZ2IN88US=> NGf5fWk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDBzMkC0M{c,W0GQR1XSQE9iRg>?
NCI-SNU-1 NVLEU4R2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlSxTWM2OD1yLkOyN|MyKM7:TR?= M1vuOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5ODF{MESvK|5USU6JRWK8M4E,
CHL-1 MnTJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUfJR|UxRTBwM{K3NFMh|ryP MkXwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVgxOTJyND:nQnNCVkeHUkyvZV4>
P30-OHK MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1vqNmlEPTB;MD6zNlcxPSEQvF2= M1vaXFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5ODF{MESvK|5USU6JRWK8M4E,
PA-1 MmG2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{TBfGlEPTB;MD6zN|YyQSEQvF2= MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFAyOjB2Lze+V2FPT0WUPD;hQi=>
LB1047-RCC NHXpZmVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGHyS2JKSzVyPUCuN|QxPDdizszN Mm\sQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVgxOTJyND:nQnNCVkeHUkyvZV4>
EM-2 MmnOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4fRN2lEPTB;MD6zOFE5QCEQvF2= NF;pUIs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDBzMkC0M{c,W0GQR1XSQE9iRg>?
VA-ES-BJ NX36NGlCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUjJR|UxRTBwM{SyOlgh|ryP NVTzXIpxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOThyMUKwOE8oRlODTlfFVlww[T5?
NCI-H520 M37pTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWDxbHNQUUN3ME2wMlM1QDN2IN88US=> M{XGWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5ODF{MESvK|5USU6JRWK8M4E,
ECC10 NIXlbZlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFHHWWNKSzVyPUCuN|UxOzVizszN MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFAyOjB2Lze+V2FPT0WUPD;hQi=>
LNCaP-Clone-FGC NUP2SZRzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn\pTWM2OD1yLkO1N|E1KM7:TR?= NIfUVmg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDBzMkC0M{c,W0GQR1XSQE9iRg>?
ES8 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml\4TWM2OD1yLkO2OVU{KM7:TR?= MmHsQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVgxOTJyND:nQnNCVkeHUkyvZV4>
HuO-3N1 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXiwdXMzUUN3ME2wMlM5Ozd7IN88US=> NWLBZY1TRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOThyMUKwOE8oRlODTlfFVlww[T5?
L-363 NV23U4F3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUDJR|UxRTBwM{mwNlYh|ryP NFLTfoc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDBzMkC0M{c,W0GQR1XSQE9iRg>?
SK-LU-1 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVvJR|UxRTBwM{myNFgh|ryP M2LMXVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5ODF{MESvK|5USU6JRWK8M4E,
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HuO9 MnTxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVvyOIt2UUN3ME2wMlQxPjZ5IN88US=> NV7wR|JXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOThyMUKwOE8oRlODTlfFVlww[T5?
BHT-101 NYjXd3d{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3X1fmlEPTB;MD60NFc5PyEQvF2= NGrQPIo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDBzMkC0M{c,W0GQR1XSQE9iRg>?
MZ2-MEL MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX7BVGEyUUN3ME2wMlQxQDh{IN88US=> MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFAyOjB2Lze+V2FPT0WUPD;hQi=>
NOS-1 M1H6S2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkfTTWM2OD1yLkSxNFc1KM7:TR?= MojQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVgxOTJyND:nQnNCVkeHUkyvZV4>
NEC8 NFH1[WtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4H3OmlEPTB;MD60NVY6PSEQvF2= NF[5T5Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDBzMkC0M{c,W0GQR1XSQE9iRg>?
COR-L88 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlHZTWM2OD1yLkSyNlY4KM7:TR?= NWLiXmdJRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOThyMUKwOE8oRlODTlfFVlww[T5?
MFM-223 NFj1cZRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3[z[GlEPTB;MD60NlYyPyEQvF2= NYXLWXJsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOThyMUKwOE8oRlODTlfFVlww[T5?
HSC-3 NILBfI9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV\JR|UxRTBwNEK5NFgh|ryP NIfrfnQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDBzMkC0M{c,W0GQR1XSQE9iRg>?
OVCAR-5 M2n4[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1fwSmlEPTB;MD60Nlk{OyEQvF2= MmnJQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVgxOTJyND:nQnNCVkeHUkyvZV4>
MFE-280 NVnoc3BmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3PGfmlEPTB;MD60N|A{OiEQvF2= M3fq[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5ODF{MESvK|5USU6JRWK8M4E,
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EPLC-272H MljsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUG4[|VvUUN3ME2wMlQ{ODd5IN88US=> M1roclxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5ODF{MESvK|5USU6JRWK8M4E,
KE-37 MlT4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmPjTWM2OD1yLkSzNlQ4KM7:TR?= MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFAyOjB2Lze+V2FPT0WUPD;hQi=>
HuH-7 NEXMV4ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFvXUHRKSzVyPUCuOFM{PzJizszN MnjmQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVgxOTJyND:nQnNCVkeHUkyvZV4>
CHP-212 NYLvepVFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{nrdGlEPTB;MD60N|Y6PyEQvF2= MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFAyOjB2Lze+V2FPT0WUPD;hQi=>
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QIMR-WIL NF3X[otIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2naOWlEPTB;MD60OVE2KM7:TR?= NGr6b4M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDBzMkC0M{c,W0GQR1XSQE9iRg>?
ES4 NHX2WIVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1\VT2lEPTB;MD60OVM{PiEQvF2= M4TnOVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5ODF{MESvK|5USU6JRWK8M4E,
TI-73 M3nM[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlrCTWM2OD1yLkS1Olg3KM7:TR?= NVPvdZpYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOThyMUKwOE8oRlODTlfFVlww[T5?
COLO-684 NHHmSGtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHPrboxKSzVyPUCuOFU4OjZizszN NYSzbnFpRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOThyMUKwOE8oRlODTlfFVlww[T5?
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MPP-89 NYCyW45WT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NELuPYpKSzVyPUCuOFY6PDdizszN Mki5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVgxOTJyND:nQnNCVkeHUkyvZV4>
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TE-9 MlfOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MU\JR|UxRTF5LkWxOlYh|ryP NVPBc3l4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOThyMUKwOE8oRlODTlfFVlww[T5?
TE-10 M{C3VGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF;rPFBKSzVyPUG5MlA3ODdizszN NIHrW5I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDBzMkC0M{c,W0GQR1XSQE9iRg>?
COLO-824 MnvtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWP6UHNTUUN3ME2yNE46Ojd4IN88US=> NYPI[WtJRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOThyMUKwOE8oRlODTlfFVlww[T5?
HuP-T3 M2TzNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVvJR|UxRTJzLkC3OFgh|ryP MoHHQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVgxOTJyND:nQnNCVkeHUkyvZV4>
KALS-1 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYLJR|UxRTJzLkG3OUDPxE1? M{m0NVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5ODF{MESvK|5USU6JRWK8M4E,
L-428 NV[4cpk3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnXnTWM2OD1{MT60NFE3KM7:TR?= Ml\4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVgxOTJyND:nQnNCVkeHUkyvZV4>
JAR NIjBNXFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3Tob2lEPTB;MkGuOVAzKM7:TR?= M{PQflxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5ODF{MESvK|5USU6JRWK8M4E,
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ABC-1 NI\sXHJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYfJR|UxRTJ4Lke5OVch|ryP NGLRSHM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDBzMkC0M{c,W0GQR1XSQE9iRg>?
MHH-NB-11 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV7JR|UxRTN|LkO0OlQh|ryP NIr6Zmo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDBzMkC0M{c,W0GQR1XSQE9iRg>?
SW1463 Ml22S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVPJR|UxRTN|Lkm4N{DPxE1? MlrrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVgxOTJyND:nQnNCVkeHUkyvZV4>
SW1417 NFn2OmdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1zLSWlEPTB;M{euNFk2OiEQvF2= MYC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFAyOjB2Lze+V2FPT0WUPD;hQi=>
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H1048 M2\MN2Fxd3C2b4Ppd{BCe3OjeR?= MXi1NFAhdk1? NXHLboFRPzJiaB?= NEeySWZvcGGwY3XzJGFDXC1{NkRihLNqdmS3Y3XkJIFxd3C2b4Ppdy=> NGi3WoU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUezO|U1Oid-MkW3N|c2PDJ:L3G+
H86 M3LYXmFxd3C2b4Ppd{BCe3OjeR?= NVvUNnFoPTByIH7N NX;w[XJvPzJiaB?= MXrubIFv[2W|IFHCWE0zPjQkgKPpcoR2[2WmIHHwc5B1d3Orcx?= MWG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd|N{W0Nkc,OjV5M{e1OFI9N2F-
H196 MUjBdI9xfG:|aYOgRZN{[Xl? MorROVAxKG6P NHS0OHk4OiCq NFHleWFvcGGwY3XzJGFDXC1{NkRihLNqdmS3Y3XkJIFxd3C2b4Ppdy=> MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd|N{W0Nkc,OjV5M{e1OFI9N2F-
H446 NF3EZWtCeG:ydH;zbZMhSXO|YYm= MVi1NFAhdk1? NX:2dWpNPzJiaB?= MYTubIFv[2W|IFHCWE0zPjQkgKPpcoR2[2WmIHHwc5B1d3Orcx?= MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd|N{W0Nkc,OjV5M{e1OFI9N2F-
TFK-1 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkLKO|IhcA>? NW\EcpdQTE2VTx?= Mo\JTWM2OD12NzDuUS=> NEfkRXc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUG1NlI1PCd-MkWxOVIzPDR:L3G+
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U937 NVL4RWFwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFrWfoUxNjJizszN NFnSd3I1QCCq NXrpSmVs\W6qYX7j[ZMh[2WubDDndo94fGhiaX7obYJqfGmxbjDpcoR2[2WmIHL5JJNmdHWvZYTpcolj NVjZeoFFRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS3N|k{QTNpPkK0O|M6Ozl|PD;hQi=>
MOLM13 NHexd2dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{XqTVAvOiEQvF2= MnfDOFghcA>? NIC0bnNmdmijbnPld{Bk\WyuIHfyc5d1cCCrbnjpZol1cW:wIHnu[JVk\WRiYomgd4VtfW2ndHnubYI> MmGyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR5M{mzPVMoRjJ2N{O5N|k{RC:jPh?=
MCF7 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4DCXFIxKG6P Mor6O|IhcA>? NX3NXJduTkKV M4m2WZJm\HWlZYOgeIhmKFCHTGCxMY1m\GmjdHXkJIlv[3KnYYPlJIlvKGOnbHygeoli[mmuaYT5 M2rWVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2Nki4NFQ3Lz5{NE[4PFA1PjxxYU6=
TamR NI[xeVBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUD0c|FmUUN3ME2xPQKBkW6P MXK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDR3N{C2PUc,OjR2NUewOlk9N2F-
MCF7-X  MnX4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYTJR|UxRTJ2IH7N M{TkXVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NEW3NFY6Lz5{NES1O|A3QTxxYU6=
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Huh7  NVzFdFg{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHXWN|M2NTFyMDDuUS=> MnjaNE0zPCCq NW\sPZl5TE2VTx?= M4PCfYlv[3KnYYPld{Bk\WyuIHTlZZRpKGmwIHGgZ49v[2WwdILheIlwdi1iYX7kJJRqdWVvZHXw[Y5l\W62IH3hco5meg>? NUixfo9{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSyPVc{ODBpPkK0Nlk4OzByPD;hQi=>
Hep3B  NYfOWXc1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M165NlUuOTByIH7N Mke3NE0zPCCq M2DyZWROW09? NXf5No5lcW6lcnXhd4V{KGOnbHyg[IVifGhiaX6gZUBkd26lZX70doF1cW:wLTDhcoQhfGmvZT3k[ZBmdmSnboSgcYFvdmW{ NY\OdnQxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSyPVc{ODBpPkK0Nlk4OzByPD;hQi=>
Huh7  Ml76SpVv[3Srb36gRZN{[Xl? NGjBOZoyODBibl2= M2TaRVEzKGh? MUPEUXNQ M{LKd4lv\HWlZYOgZZV1d3CqYXf5xsA> NGj6UY49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEK5O|MxOCd-MkSyPVc{ODB:L3G+
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 L3.6pl NUmzSYtvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoqwNUDPxE1? MoPnO|IhcA>? NHrMTZpqdmirYnn0d{B1cGViY3XscEBoem:5dHigZ49u[mmwZXSge4l1cCCETWOtO|c4PjB5 M1XyZ|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MkOzN|k6Lz5{NEKzN|M6QTxxYU6=
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RD MWfBdI9xfG:|aYOgRZN{[Xl? MlrKNUDPxE1? NVThR2FsPDhiaB?= NYjpWnhncW6lcnXhd4V{KGOnbHygZZBweHSxc3nzJIlv\HWlZXSgZpkhSUKWLUezOy=> NYq1dHdoRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSxN|MzOThpPkK0NVM{OjF6PD;hQi=>
RMS13 NGXycY9CeG:ydH;zbZMhSXO|YYm= NV25NG5[OSEQvF2= MWK0PEBp M{TuSolv[3KnYYPld{Bk\WyuIHHwc5B1d3OrczDpcoR2[2WmIHL5JGFDXC15M{e= MnLUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRzM{OyNVgoRjJ2MUOzNlE5RC:jPh?=
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Hep-2 NGe5cpBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGKzWlcxNjBzLUGg{txO NYm0UmM4OTJvOU[gbC=> NHXEXlVqdmO{ZXHz[ZMh[2WubDDk[YF1cCCrbjDhJINwdmOnboTyZZRqd25vIHHu[EB1cW2nLXTldIVv\GWwdDDtZY5v\XJ? NWDhdoxRRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSxNFM4PDlpPkK0NVA{PzR7PD;hQi=>
SCC-9 NWLYZZdFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3XBb|AvODFvMTFOwG0> NHW2TI0yOi17NjDo MWjpcoNz\WG|ZYOgZ4VtdCCmZXH0bEBqdiCjIHPvcoNmdnS{YYTpc44uKGGwZDD0bY1mNWSncHXu[IVvfCCvYX7u[ZI> Mk\YQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRzMEO3OFkoRjJ2MUCzO|Q6RC:jPh?=
Hep-2 M1vtVmZ2dmO2aX;uJGF{e2G7 MVKwMlEwOC53IN88US=> MnzTNlQhcA>? MojmZoxw[2u|IH3UU3JEOSCjbnSgcXRQWkN{IHHjeIl3[XSrb36= NGmxbm09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEGwN|c1QSd-MkSxNFM4PDl:L3G+
SCC-9 NXq5Z25jTnWwY4Tpc44hSXO|YYm= MWiwMlEwOC53IN88US=> MkjvNlQhcA>? MonWZoxw[2u|IH3UU3JEOSCjbnSgcXRQWkN{IHHjeIl3[XSrb36= MoDlQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRzMEO3OFkoRjJ2MUCzO|Q6RC:jPh?=
PANC-1 M2Lad2Fxd3C2b4Ppd{BCe3OjeR?= M3HQb|UxOCCwTR?= NHmzOZo1QCCq Mnm0d4Vve2m2aYrld{Bx[W6lcnXheIlkKGOjbnPldkBk\WyuczD0c{Bz[WSrb4To[ZJieHl? MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzh6NkK5OEc,OjN6OE[yPVQ9N2F-
RMG2 M{XOXGFxd3C2b4Ppd{BCe3OjeR?= MV[xMVExODBibl2= MkX6O|IhcA>? MljkSmJU NEj3dVhqdmirYnn0d{B1cGViY3XscEB3cWGkaXzpeJkh[2:wY3XueJJifGmxbjDk[ZBmdmSnboTsfS=> NEfaUIk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{[xOVY{OSd-MkO2NVU3OzF:L3G+
HAC2 MYfBdI9xfG:|aYOgRZN{[Xl? M1fHZ|EuOTByMDDuUS=> MV23NkBp M3zxb2ZDWw>? NUf6fWVUcW6qaXLpeJMhfGinIHPlcIwhfmmjYnnsbZR6KGOxbnPlcpRz[XSrb36g[IVx\W6mZX70cJk> M1nY[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NkG1OlMyLz5{M{[xOVY{OTxxYU6=
HT-29 M4\YcGFxd3C2b4Ppd{BCe3OjeR?= NFfhTGgyKM7:TR?= M{CwZlczKGh? MX3heJRmdnWjdHXzJFUuTlVvaX7keYNm\CClZXzsJIRm[XSq MorQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7NEmxNlEoRjJzOUS5NVIyRC:jPh?=
DLD1 MWPBdI9xfG:|aYOgRZN{[Xl? MkD1NUDPxE1? MVq3NkBp MnTmZZR1\W63YYTld{A2NU[XLXnu[JVk\WRiY3XscEBl\WG2aB?= MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTl2OUGyNUc,OjF7NEmxNlE9N2F-
HT-29 NX7wUW95TnWwY4Tpc44hSXO|YYm= NX;TTohsOSEQvF2= MkTpO|IhcA>? M3\iTYlv\HWlZYOgZZV1d3CqYXf5JJRwKGOxbn\ldkBkgXSxcILveIVkfGmxbh?= MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTl2OUGyNUc,OjF7NEmxNlE9N2F-
DLD1 MYrGeY5kfGmxbjDBd5NigQ>? MnuwNUDPxE1? Mlm4O|IhcA>? NGPVV3JqdmS3Y3XzJIF2fG:yaHHnfUB1dyClb37m[ZIh[3m2b4Dyc5Rm[3Srb36= MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTl2OUGyNUc,OjF7NEmxNlE9N2F-
Rh41 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUPBdGs2UUN3ME2zNE44KG6P M3P5ZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzM{O3Olc6Lz5{MUOzO|Y4QTxxYU6=
Rh18 Mo\zS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{HjemlEPTB;NEGuOEBvVQ>? MmXZQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF|M{e2O|koRjJzM{O3Olc6RC:jPh?=
Rh30 NXHr[VJRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlrETWM2OD1zNDDuUS=> NUHHVpgzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGzN|c3PzlpPkKxN|M4Pjd7PD;hQi=>
BT-12 NFvTbJBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnL2TWM2OD1{ND63JI5O M4XFflxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzM{O3Olc6Lz5{MUOzO|Y4QTxxYU6=
CHLA-266 NH;lOZpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYLWOGxGUUN3ME2xMlEhdk1? Ml;PQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF|M{e2O|koRjJzM{O3Olc6RC:jPh?=
TC-71 M4\pXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVnJR|UxRTR4LkWgcm0> NULRWWJrRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGzN|c3PzlpPkKxN|M4Pjd7PD;hQi=>
CHLA-9 MnvVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NInEdFlKSzVyPUG1MlMhdk1? NIrBSoM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUOzO|Y4QSd-MkGzN|c3Pzl:L3G+
CHLA-10 NFridVdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV3JR|UxRTNwOTDuUS=> M2[0fVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzM{O3Olc6Lz5{MUOzO|Y4QTxxYU6=
CHLA-258 NIPIXm9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYrJR|UxRTFyLkSgcm0> NXnpdJVTRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGzN|c3PzlpPkKxN|M4Pjd7PD;hQi=>
GBM2 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYDJR|UxRTRyLkegcm0> NXfON2hpRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGzN|c3PzlpPkKxN|M4Pjd7PD;hQi=>
NB-1643 M{fRXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{j0W2lEPTB;M{OuPEBvVQ>? NULuPGNzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGzN|c3PzlpPkKxN|M4Pjd7PD;hQi=>
NB-EBc1 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX\JR|UxRTJ5LkGgcm0> MlG2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF|M{e2O|koRjJzM{O3Olc6RC:jPh?=
CHLA-90 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkDYTWM2OD1|ND61JI5O NYHnN5FDRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGzN|c3PzlpPkKxN|M4Pjd7PD;hQi=>
CHLA-136 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVPJR|UxRTF4Mj62JI5O NHLhVnY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUOzO|Y4QSd-MkGzN|c3Pzl:L3G+
NALM-6 NFy2UVBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVPJR|UxRTN{Lkmgcm0> NG\iOnY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUOzO|Y4QSd-MkGzN|c3Pzl:L3G+
COG-LL-317 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXvkbZoyUUN3ME2xMlMhdk1? MkXSQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF|M{e2O|koRjJzM{O3Olc6RC:jPh?=
RS4;11 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnTyTWM2OD1|NTDuUS=> NHz1XpY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUOzO|Y4QSd-MkGzN|c3Pzl:L3G+
MOLT-4 NUfxRXp3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVrJR|UxRThwNjDuUS=> MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTN|N{[3PUc,OjF|M{e2O|k9N2F-
CCRF-CEM NF36[o9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NI\wOYZKSzVyPUSuNUBvVQ>? NGfPOXo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUOzO|Y4QSd-MkGzN|c3Pzl:L3G+
Kasumi-1 NVvmS|QxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NInHPVBKSzVyPUGuOEBvVQ>? M1jqdVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzM{O3Olc6Lz5{MUOzO|Y4QTxxYU6=
Karpas-299 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH3meFJKSzVyPUKxMlchdk1? M2rZNFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzM{O3Olc6Lz5{MUOzO|Y4QTxxYU6=
Ramos-RA1 NIn1UnRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGC4Z5RKSzVyPUiuNkBvVQ>? Mn3EQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF|M{e2O|koRjJzM{O3Olc6RC:jPh?=
H838 MnvPSpVv[3Srb36gRZN{[Xl? M2D6Z|Eh|ryP MojROFghcA>? NHn0UWVqdmS3Y3XzJINmdGxiYYX0c5Bp[We7 NGP5[Y09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MEO2OFEyOyd-MkCzOlQyOTN:L3G+
H838 NUWzbGI5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHzxe4MxNTNizszN NIXGcJI4OiCq NGDjXJRqdmS3Y3XzJIdzd3e2aDDpcohq[mm2aX;uJIFv\CCjdYTvdIhi\3l? Ml62QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjByMki4OVQoRjJyMEK4PFU1RC:jPh?=
A549  M3zBemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYKwMVMh|ryP NVXhVnB5PzJiaB?= NFTVSYpqdmS3Y3XzJIdzd3e2aDDpcohq[mm2aX;uJIFv\CCjdYTvdIhi\3l? NFfTUJY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MECyPFg2PCd-MkCwNlg5PTR:L3G+

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
p-mTOR / p-AKT / p-4EBP1 / p-P70S6K / p-PRAS40; 

PubMed: 24457069     


Western blots of 70% confluent TamR (A) and MCF7-X (B) cells treated for 15 minutes to 24 hours with AZD8055 (0 to 100 nM). Blots were probed with phospho- and total antibodies for mTORC1 and two signalling pathways. In both cell lines mTORC1 and mTORC2 s䲧疝Ỵ疞㧀疜膉痘 瘿삨ՂᾰƌՂĀ 㺣痖帉痖Ѐ瑖堘𢡄빢᎒ՂĀ鑸᎒彿堙奋堙巫堙᎒ﻺ᎒彿堙ﻮ᎒塚堙ﻺ᎒ꍈ堞빢᎒學堙漸堞圔堙빢᎒圞堙

p-EGFR / EGFR; 

PubMed: 25654224     


PANC-1 cells were treated with AZD8055 for the indicated hours and EGFR (T/P), AKT (T/P) and ribosomal protein S6 (S6) (T/P) proteins were examined by western-blot;

p-FOXO1 / FOXO1 / p-FOXO3a / FOXO3a ; 

PubMed: 25654224     


PANC-1 cells were transfected with FoxO1/FoxO3a siRNAs and treated with AZD8055 for 1 h, then AKT (T/P), FoxO1 (T/P), FoxO3a (T/P) and EGFR (T/P) proteins were examined by western-blot.

24457069 25654224
Immunofluorescence
p-4EBP1 / EIF4E / mTOR; 

PubMed: 24600487     


(C) Hoechst 33258 staining of Hep-2 cells after treatment with AZD8055 for 24 hours were shown. The cells were fixed and immunereacted with anti-mTOR antibody followed by incubation with Alexa 488-labeled secondary antibody (C-F). Images were taken by a c䲧疝Ỵ疞㧀疜膉痘 瘿삨ՂᾰƌՂĀ 㺣痖帉痖Ѐ瑖堘𢡄빢᎒ՂĀ鑸᎒彿堙奋堙巫堙᎒ﻺ᎒彿堙ﻮ᎒塚堙ﻺ᎒ꍈ堞빢᎒學堙漸堞圔堙빢᎒圞堙圭堙𢡄玚Wᾰƌ ᾰƌ戤瘯Ɖ�෋䐺痖暼瘿�෋ᾰƌ �෋à㺣痖�෋€𢡄�෋€䀷痗�෋౴�෋㵶痗�෋뺖᎒泌Itemセ᎒Count﫨呂�෋猴፲�෋፲씢痗猸፲髸莤䥷堙᎒セ᎒�堞ﻮ᎒፲露𢡄堚،齃礤v�堞ﻮ᎒猢Wセ᎒䨼Ą鹿齃殺獸W戀醙玛W戀ⶰ໯齃礤v 玚W玢Wⶰ໯﫰礌vtЉᔈැ鲬౴᥊疜犈፲Eo狜፲艘ᎂ艘ᎂ⩈̎䥠̌씢痗狠፲붖᎒i變ﱘ﫰﬐먙堘붖᎒狠፲i變ﱘ﫰먰堘ﱘ붖᎒�堞봆᎒릎堘붖᎒i꣩쯟巰痗ꣵ쯟巰痗Љ镴౴￿￿嶴痗Љ镨౴ᔈැ竗ᔈැ屷痗W竗尊痗

LC3B / p62 ; 

PubMed: 30337536     


Immunofluorescence staining of U87 and U251 GICs, which treated by DMSO, AZD8055 (0.3 μM) and rapamycin (3 μM). The nuclei were stained with DAPI and the antibody against LC3B and p62. Images were captured by laser confocal microscope ( × 400), scale bar 䲧疝Ỵ疞

24600487 30337536
Growth inhibition assay
Cell viability ; 

PubMed: 29263324     


Growth for the indicated cell lines was assessed after 72 h of treatment with AZD8055 (0–250 nM). Results are expressed as a percentage of cell number relative to the DMSO-treated control cells a.

29263324
In vivo AZD8055 inhibits the pS6 and pAkt in U87MG and A549 xenografts at 2.5/10 mg/kg, which leads to tumor growth inhibition. AZD8055 shows significant antitumor activity in many xenografts, including U87MG, BT474c, A549, Calu-3, LoVo, SW620, PC3 and MES-SA at a dose of 10/20 mg/kg. [1] AZD8055 induces ~40% reduction in tumour volume, accompanied by ablation of phosphorylation of Akt, S6K and SGK protein kinases. Administration of AZD8055 (5mg/kg, Bid) and SAHA (100 mg/kg/d) results in complete tumor growth inhibition in PTEN+/−LKB1+/hypo xenografts without side effects on mice by inhibition of mTORC1 and mTORC2 signaling. [4]

Protocol

Kinase Assay:[1]
- Collapse

Cell-based determinations of mTOR inhibition:

A high-throughput screening cell-based assay is developed using MDA-MB-468 cells to detect mTORC1 and mTORC2 activity. Cells are exposed for 2 hours to increasing concentrations of AZD8055. At the end of the incubation period, cells are fixed, washed, and probed with antibodies against S473 pAkt or against S235/236 phosphorylated S6 (pS6). Levels of phosphorylation are assessed using an Acumen laser scanning cytometer.
Cell Research:[1]
- Collapse
  • Cell lines: U87MG, A549 and H838 cells
  • Concentrations: 1 nM - 1 μM
  • Incubation Time: 72 to 96 hours
  • Method: Cells are exposed to AZD8055 for 72 to 96 hours and stained for cell nuclei (0.03 mg/mL Hoechst 33342) and acidic vesicles (1 μg/mL acridine orange). Images are captured at 450 and 536 nm on an ArrayScan II platform, and the percentage of acidic vesicles and the number of cells are quantified. For LC3 assessment, cells are exposed to e64d/pepstatin (10 μg/mL) for 30 to 90 min before incubation with AZD8055. Cells are lysed on ice and analyzed by immunoblotting.
    (Only for Reference)
Animal Research:[1]
- Collapse
  • Animal Models: U87MG, BT474c, A549, Calu-3, LoVo, SW620, PC3 and MES-SA U87-MG and A549 are established in pathogen-free, female nude mice (nu/nu:Alpk).
  • Dosages: 2.5-20 mg/kg
  • Administration: Oral gavage once or twice daily
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 50 mg/mL warmed (107.4 mM)
Ethanol 3 mg/mL (6.44 mM)
Water Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
4% DMSO+30% PEG 300+ddH2O
For best results, use promptly after mixing.
5mg/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 465.54
Formula

C25H31N5O4

CAS No. 1009298-09-2
Storage powder
in solvent
Synonyms N/A
Smiles CC1COCCN1C2=NC(=NC3=C2C=CC(=N3)C4=CC(=C(C=C4)OC)CO)N5CCOCC5C

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT01316809 Completed Drug: AZD8055 Glioblastoma Multiforme|Anaplastic Astrocytoma|Anaplastic Oligodendroglioma|Malignant Glioma|Brainstem Glioma National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) March 4 2011 Phase 1
NCT00999882 Completed Drug: AZD8055 Cancer|Advanced Hepatocellular Carcinoma AstraZeneca October 2009 Phase 1
NCT00973076 Completed Drug: AZD8055 Cancer|Solid Tumors|Advanced Solid Malignancies AstraZeneca August 2009 Phase 1
NCT00731263 Completed Drug: AZD8055 Solid Tumors AstraZeneca July 2008 Phase 1
NCT01194193 Withdrawn Drug: AZD8055 Cancer|Advanced Solid Tumours|Lymphomas AstraZeneca Phase 1

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