BI 2536

For research use only.

Catalog No.S1109

239 publications

BI 2536 Chemical Structure

CAS No. 755038-02-9

BI-2536 is a potent Plk1 inhibitor with IC50 of 0.83 nM in a cell-free assay. BI-2536 inhibits Bromodomain 4 (BRD4) with Kd of 37 nM and potently suppresses c-Myc expression. BI-2536 induces apoptosis and attenuates autophagy. Phase 2.

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Selleck's BI 2536 has been cited by 239 publications

Purity & Quality Control

Choose Selective PLK Inhibitors

Biological Activity

Description BI-2536 is a potent Plk1 inhibitor with IC50 of 0.83 nM in a cell-free assay. BI-2536 inhibits Bromodomain 4 (BRD4) with Kd of 37 nM and potently suppresses c-Myc expression. BI-2536 induces apoptosis and attenuates autophagy. Phase 2.
Features The first potent and selective Plk1 inhibitor that induces all hallmarks of Plk1 inhibition.
Targets
c-Myc [3]
()
PLK1 [1]
(Cell-free assay)
PLK2 [1]
(Cell-free assay)
PLK3 [1]
(Cell-free assay)
BRD4 [3]
(Cell-free assay)
0.83 nM 3.5 nM 9.0 nM 37 nM(Kd)
In vitro

BI 2536 blocks the activities of Plk2 and Plk3 to a slightly lesser extent with IC50 of 3.5 nM and 9.0 nM, respectively. In HeLa cells, BI 2536 treatment ranging from 10-100 nM leads to the blocking of the recruitment of γ-tubulin and phosphorylation of Apc6 at mitotic centrosomes, inhibition of cohesin release from chromosome arms, induction of monopolar spindles, as well as a range of other mitotic processes that are known to depend on Plk1. BI 2536 treatment leads to the HeLa cells arrested in G2/M, subsequently a sub-G1 DNA peak indicative of DNA breakdown and apoptosis, and accumulated cleaved PARP p85 fragments in a concentration-dependent manner. BI 2536 inhibits the growth of a panel of 32 human cancer cell lines with EC50 of 2-25 nM, while blocking the proliferation of exponentially growing hTERT-RPE1, human umbilical vein endothelial cells (HUVECs), and normal rat kidney (NRK) cells with EC50 of 12-31 nM. [1] Plk1 inhibition by BI 2536 reduces the growth and viability of anaplastic thyroid carcinoma (ATC) cells such as CAL62, OCUT-1, SW1736, 8505C, and ACT-1 with EC50 values of 1.4-5.6 nM. [2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
PSN1 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2jHNmlEPTB;MD6wNFc4PiEQvF2= MmHVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
ACN NGPiXIZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1rndGlEPTB;MD6wNFg1OyEQvF2= NFHT[2M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
TE-8 NXrEOFdlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX;6d4dJUUN3ME2wMlAxQTRzIN88US=> NIX6fHU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
LC-2-ad NIjQTJBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml\xTWM2OD1yLkCxNFk{KM7:TR?= NGLzVHA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
ALL-PO MkWwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnzsTWM2OD1yLkCxN{DPxE1? NFPUdZY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
EW-16 MkPrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{XE[mlEPTB;MD6wNVM{PiEQvF2= NYTlZY1TRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
KM12 M2rGS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV\WVZEzUUN3ME2wMlAyOzR6IN88US=> NV;K[3NzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
GI-1 MkXwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXnJR|UxRTBwMEGzPFMh|ryP NEG3UlQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
LS-411N MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3[0OWlEPTB;MD6wNVQxPyEQvF2= MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
ES8 NYK0Z25HT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYPJR|UxRTBwMEG0PVQh|ryP M{e0PFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
SNU-C2B NELYd5BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlW5TWM2OD1yLkCxOVI3KM7:TR?= MlyzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
CESS MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoLOTWM2OD1yLkCxOlAzKM7:TR?= NUjCeoh6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
697 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVHxNnlGUUN3ME2wMlAyPjZ6IN88US=> MYC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
NCI-H1963 NUXaWoJzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{exPGlEPTB;MD6wNVY4OyEQvF2= MWG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
IA-LM MoTZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MY\JR|UxRTBwMEG2PFgh|ryP M4PPWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
SW954 NV7MbXBFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mlq3TWM2OD1yLkCxO|A2KM7:TR?= Mn\FQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
RL95-2 M1H1NWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUPwe|BQUUN3ME2wMlAyPzN6IN88US=> NIjENm49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
LXF-289 NGi4[VdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFfQV4pKSzVyPUCuNFE4PyEQvF2= Mn:5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
OCUB-M NF[we29Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1nl[GlEPTB;MD6wNVgzPiEQvF2= NEn0coc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
RKO NGXVbXNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXj0V|dOUUN3ME2wMlAyQTh5IN88US=> NWrP[Wg2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
LOUCY NWroV49FT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlfMTWM2OD1yLkCyNFUh|ryP NHT1Z3M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
NOS-1 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoHzTWM2OD1yLkCyNFk{KM7:TR?= M4X1WlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
A4-Fuk NV3vSpRIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1\kd2lEPTB;MD6wNlIyQCEQvF2= MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
A388 M2\1bmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH7wd3VKSzVyPUCuNFIzOjdizszN MkezQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
TE-9 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmG0TWM2OD1yLkCyNlYyKM7:TR?= NEXCPIw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
KURAMOCHI M2nre2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX3JR|UxRTBwMEKyPFUh|ryP M1HEUlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
KALS-1 NVzvXGZ4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmPKTWM2OD1yLkCyN|M5KM7:TR?= MoTmQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
HOP-62 M33iWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX;JR|UxRTBwMEK0NkDPxE1? MlPyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
RPMI-8402 NYTsT3RQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{\WVWlEPTB;MD6wNlUxQCEQvF2= NEfERWE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
TE-1 M4fNc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M33uXWlEPTB;MD6wNlUyOiEQvF2= NHTaU4M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
CCRF-CEM Moe2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4HYfWlEPTB;MD6wNlU1OyEQvF2= NVvLO2J5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
HUTU-80 M{XCS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1HCbGlEPTB;MD6wNlYzPCEQvF2= NXHUWHZORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
NCI-H1648 M32zXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{XocWlEPTB;MD6wNlY1PyEQvF2= NWfpeoRLRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
HCE-4 M{GyZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEnEfpJKSzVyPUCuNFI3QDJizszN MnO1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
ETK-1 M13Hcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYW2SWpmUUN3ME2wMlAzPzN4IN88US=> NUDDb3B4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
TE-15 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mo\3TWM2OD1yLkCyO|M5KM7:TR?= M3Xm[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
BE-13 NYDy[nliT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIjacXNKSzVyPUCuNFI4PCEQvF2= MmS4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
KE-37 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEjCVWZKSzVyPUCuNFI4PDFizszN NVTXNmlYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
NCI-H1355 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUXkO5d7UUN3ME2wMlAzPzh|IN88US=> NVXDOGZrRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
TE-11 M4W1TGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXTJR|UxRTBwMEK4NFkh|ryP NULRS|d4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
BL-70 MnrJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWHKb|NGUUN3ME2wMlAzQDV5IN88US=> NYnyVWpkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
ES6 MoLZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1ixUWlEPTB;MD6wNlg5OSEQvF2= M1r5VlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
GT3TKB NXPVOnBMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH[4UWlKSzVyPUCuNFI6PTNizszN MX68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
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KLE M13CbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEKyXppKSzVyPUCuOVIyPzFizszN MoGzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
LB2241-RCC M2jlfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYTJR|UxRTBwNUK1NlUh|ryP NEK4RZI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
NCI-H1417 Ml\vS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4XlXmlEPTB;MD61N|Q{PSEQvF2= Mmm0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
NCI-H2081 NEHXbXRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGPwR2ZKSzVyPUCuOVg3OTFizszN NXr1e3NtRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
NCI-H1522 NYXFTWk2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mmn0TWM2OD1yLkW5N|g{KM7:TR?= MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
NCI-H889 M4DrWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVzuZlF7UUN3ME2wMlU6QDR2IN88US=> NIHkclE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
CGTH-W-1 NEH2SWZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4r1UGlEPTB;MD62NFc2PSEQvF2= NEXJcYw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
EB-3 MmfqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MU\JR|UxRTBwNkGxOVMh|ryP M3\GVVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
D-336MG MoO0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlnlTWM2OD1yLk[xO|kyKM7:TR?= M1vIb|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
LC-1F NFPqUVJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXnJR|UxRTBwNkK1PVIh|ryP MmjzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
MHH-NB-11 MlzPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF\nNlRKSzVyPUCuOlM5ODFizszN MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
SK-N-FI NY\5WWwzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlHaTWM2OD1yLk[zPVEh|ryP MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
NCI-H69 Mm\sS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlzQTWM2OD1yLk[0PFc6KM7:TR?= NHfr[2I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
SCH NWLL[mszT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{\m[mlEPTB;MD62OlAzOyEQvF2= NInHc449[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
LS-513 NF7NVHVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnfjTWM2OD1yLk[3NlU6KM7:TR?= NVPWTG42RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
CP67-MEL MlLJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NY[wXW9jUUN3ME2wMlY4PTl4IN88US=> NXP0bld2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
GCIY NGXsZVhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXrJR|UxRTBwN{CzOlMh|ryP M2nyblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
SHP-77 NGjJWlJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWOwVVQ5UUN3ME2wMlcxPzN2IN88US=> NHn1W5o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
EHEB NFrzPVVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1LyXmlEPTB;MD63NVg2PCEQvF2= Mn;ZQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
D-247MG NV\DW485T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlvtTWM2OD1yLkezNlMzKM7:TR?= MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
Raji NH3jZ5lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUnS[3pHUUN3ME2wMlc1QTh7IN88US=> NVnYN3RpRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
MPP-89 M1vFXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoPDTWM2OD1yLke1PVc5KM7:TR?= MnvrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
EKVX M1jp[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MorXTWM2OD1yLke5NFc{KM7:TR?= NWSxTWk{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
HCC2218 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXTJR|UxRTBwN{mxN|Eh|ryP NVXnWVBXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
KNS-81-FD NWW2XIh2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYXkPFd{UUN3ME2wMlgyODFzIN88US=> MYi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
HCC2157 Mlz0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnLDTWM2OD1yLki0PVUyKM7:TR?= MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
BT-474 M1LJVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXizXW5rUUN3ME2wMlg5QDV2IN88US=> NY[wdIJURGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
NCI-H748 MkjES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXzJR|UxRTBwOUGyJO69VQ>? MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
EW-24 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHOwd25KSzVyPUCuPVIxODJizszN NV3sOY84RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
D-263MG NIjQRoNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWXnVo1IUUN3ME2wMlk1PTF{IN88US=> NIjkNIQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
OMC-1 NEi0TZZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUXJ[3A6UUN3ME2wMlk3Ozd|IN88US=> MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
NCI-H2196 NWTDfmdjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYnQSoxmUUN3ME2wMlk4Pzd5IN88US=> MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
HAL-01 NXToc3hNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUXJR|UxRTBwOUm4O|Ih|ryP NEDhSG89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
NCI-H2107 NH;aeZNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3fUNmlEPTB;MT6wNVg2PCEQvF2= MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
LB996-RCC M374fmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEexNI5KSzVyPUGuNFgxPTFizszN NVvzfZBCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
NCI-H1395 NWLrT5JVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGL6WIpKSzVyPUGuNVA3PyEQvF2= M334U|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
CHP-126 Ml:5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{\nV2lEPTB;MT6xOlE6QSEQvF2= MnH1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
NB69 NW\qVmh{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWjJR|UxRTFwMk[xOFgh|ryP NGPDO5o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
CAS-1 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUPJR|UxRTFwM{SyN|Eh|ryP NI\2NYI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
JVM-3 NHrTbXNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnzRTWM2OD1zLkS3PFU2KM7:TR?= NGPlW3I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
DMS-153 NITHR|JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXnWUYtSUUN3ME2xMlU4Pjd2IN88US=> MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
SK-MEL-2 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWXJR|UxRTFwN{G3PFkh|ryP MmLrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
NCI-H1155 Mmq5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1zzSGlEPTB;MT63N|Y4PiEQvF2= MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
NCI-H1092 MojaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUXJR|UxRTFwN{[xPFIh|ryP MlfiQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
LU-165 NHnkepRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXrJR|UxRTFwOE[0O|Yh|ryP MWC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
HL-60 NEjyZYxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX\vN5FKUUN3ME2xMlk6QTB6IN88US=> M3;qeVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
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NB-EBc1 M4fmU5FJXFNiYYPzZZk> MVLxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVkJvRVLjNUBk\Wyucx?= NYfUNHEzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
LAN-5 MUDxTHRUKGG|c3H5 MkHjdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKEyDTj21JINmdGy| MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
Rh18 NGDKNIpyUFSVIHHzd4F6 MULxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWmhzODDj[Yxtew>? MlzIQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
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SK-N-MC NFXjN5VyUFSVIHHzd4F6 NGL0SGJyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBUUy2QLV3DJINmdGy| MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
SJ-GBM2 NV\ufoNVeUiWUzDhd5NigQ>? MorwdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgV2ouT0KPMjDj[Yxtew>? M{C0R|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
TC32 NUTBO2xCeUiWUzDhd5NigQ>? MXrxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDUR|MzKGOnbHzz MnHlQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
Rh18 MlnmdWhVWyCjc4PhfS=> MWPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDSbFE5KGOnbHzz NY\PVFlURGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
Saos-2 MoPqdWhVWyCjc4PhfS=> MnjjdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgV4Fwey1{IHPlcIx{ M{HSXVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
DU145 NW[5O3JtSXCxcITvd4l{KGG|c3H5 MkfvNVAxKG6P M{LONFI1KGi{cx?= NEHXRWtKdmS3Y4Tpc44hd2ZiYYDvdJRwe2m|IHnuJIh2dWGwIFTVNVQ2KGOnbHzzJIF{e2W|c3XkJIF{KGmwY4LlZZNmKGmwIGDBVnAh[2ynYY\h[4Uh[XRiMUCwJI5OKGGodHXyJFI1KGi{czDifUBqdW23bn;icI91fGmwZzDt[ZRpd2R? MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ6NUm0NUc,OjV4OEW5OFE9N2F-
HeLa NIDlSVBHfW6ldHnvckBie3OjeR?= NIjKPWcyODBibl2= NHz1PJNKdmirYnn0bY9vKG:oIGDMT|EhXGi{MkGwJJBpd3OyaH;yfYxifGmxbjDpckBpfW2jbjDI[WxiKGOnbHzzJIF1KDFyMDDuUUBjgSCrbX31co9jdG:2dHnu[{Bu\XSqb3S= M17mb|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3Nki1PVQyLz5{NU[4OVk1OTxxYU6=
DU145 NYqw[4NKTnWwY4Tpc44h[XO|YYm= NUjCOZZjOTByIH7N NVH2So5KUW6qaXLpeIlwdiCxZjDQUGsyKHC{b4TlbY4h[WOldX31cIF1cW:wIHnuJIh2dWGwIFTVNVQ2KGOnbHzzJIF1KDFyMDDuUUBjgSCrbX31co9jdG:2dHnu[{Bu\XSqb3S= MonvQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV4OEW5OFEoRjJ3Nki1PVQyRC:jPh?=
HeLa MVnGeY5kfGmxbjDhd5NigQ>? NVTxPFBGOTByIH7N MYDJcohq[mm2aX;uJI9nKFCOS{GgdJJwfGWrbjDhZ4N2dXWuYYTpc44hcW5iaIXtZY4hUGWOYTDj[YxteyCjdDCxNFAhdk1iYomgbY1ufW6xYnzveJRqdmdibXX0bI9l NXzOVnJbRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW2PFU6PDFpPkK1Olg2QTRzPD;hQi=>
HeLa NX\DNWlHTnWwY4Tpc44h[XO|YYm= MWqxNFAhdk1? NXfNOWQzOThiaILz NUSyZZpRUW6mdXP0bY9vKG:oIH3vco9xd2yjcjDtbZRwfGmlIIPwbY5ldGW|IHnuJIh2dWGwIFjlUIEh[2WubIOgZZQhOTByIH7NJIlv[3WkYYTl[EBnd3JiMUigbJJ{KGK7IHnu[Ilz\WO2IHntcZVvd2[udX;y[ZNk\W6lZTDtbYNzd3Olb4D5 MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ6NUm0NUc,OjV4OEW5OFE9N2F-
HeLa MX;BdI9xfG:|aYOgZZN{[Xl? NVzyUZpEOTByIH7N MoLqNlQhcHK| M{fJc2lv\HWldHnvckBw\iCjcH;weI9{cXNiaX6gbJVu[W5iSHXMZUBk\WyuczDhd5Nme3OnZDDhd{BqdmO{ZXHz[UBqdiCSQWLQJINt\WG4YXflJIF1KDFyMDDuUUBi\nSncjCyOEBpenNiYomgbY1ufW6xYnzveJRqdmdibXX0bI9l Ml\hQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV4OEW5OFEoRjJ3Nki1PVQyRC:jPh?=
PC3 MVzGeY5kfGmxbjDhd5NigQ>? NXv6V2lsOTByIH7N MmnKNVghcHK| NIXPfFVKdmS3Y4Tpc44hd2ZibX;uc5BwdGG{IH3peI91cWNic4DpcoRt\XNiaX6gbJVu[W5iUFOzJINmdGy|IHH0JFExOCCwTTDpcoN2[mG2ZXSg[o9zKDF6IHjyd{BjgSCrbnTpdoVkfCCrbX31co9ndHWxcnXzZ4Vv[2VibXnjdo9{[2:yeR?= NXnqb2RCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW2PFU6PDFpPkK1Olg2QTRzPD;hQi=>
DU145 MnXOSpVv[3Srb36gZZN{[Xl? MluwNVAxKG6P M1\BWGlvcGmkaYTpc44hd2ZiUFzLNUBVcHJ{MUCgdIhwe3Cqb4L5cIF1cW:wIHnuJIh2dWGwIFTVNVQ2KGOnbHzzJIF1KDFyMDDuUUBjgSCrbX31co9jdG:2dHnu[{Bu\XSqb3S= MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ6NUm0NUc,OjV4OEW5OFE9N2F-

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
pro-caspase-8 / cleaved caspase-8 / cleaved caspase-3 / cleaved caspase-9; 

PubMed: 27699933     


PLKi‐induced caspase activation. HeLa cells were treated with BI 2536 (10 nmol/L), BI 6727 (68 nmol/L), or GSK461364 (11 nmol/L), and HCT 116 cells were treated with BI 2536 (20 nmol/L), BI 6727 (70 nmol/L), or GSK461364 (12 nmol/L) for 48 h. The levels of cleaved caspase (CASP)‐3, ‐8, and ‐9 were examined by Western blot analysis.

p-HH3 / PARP / Myc / p-Myc; 

PubMed: 24771642     


Western blotting showing more mitotic arrested (shown by phospho-histone H3) and apoptotic (shown by PARP) cells as well as lower MYC levels in LNCaP-Pim1 cells after BI 2536 treatment compared with LNCaP-Neo cells. The difference is obvious at lower dose of BI 2536 (10 nM). Both total MYC expression and phosphor-MYC levels were lower in Pim1 cells than Neo cells after BI 2536 treatment.

pMEK / MEK / pERK / ERK / pRSK1 / RSK1; 

PubMed: 28430578     


(A) and (B) Western blot analysis of the expression and activation of components of the MEK-ERK-RSK1 pathway in MKN45 and MKN74 cancer cells treated with BI 2536 and BI 6727 for 24 and 48 hours, respectively.

pPlk1 / Plk1 / pMyt1; 

PubMed: 28430578     


(A) and (B) Western blot analysis of the expression and phosphorylation of Plk1, and phosphorylation of Myt1 in the CSC-like and cancer cells after treatment with BI 2536 and BI 6727 for 24 and 48 hours, respectively.

Aurora B / pAurora B / pAurora C / pH3 / Cyclin B1 / Securin / pBcl-XL / MPM2; 

PubMed: 25169932     


Western blot analysis of cells treated for 24 h with the indicated inhibitor concentrations. Cell lysates were immunoblotted for Plk1, Phospho-Aurora B (T232)/Aurora C (T198), Aurora B, histone H3 phosphorylated at S10 (pH3), Cdk1, Cyclin B1, Securin, Phospho-Bcl-XL, Induced myeloid leukemia cell differentiation protein Mcl-1, MPM-2 and β-Actin. Left (Hela cells); Right (HUVEC)

27699933 24771642 28430578 25169932
Immunofluorescence
p-H2AX / propidium iodide; 

PubMed: 22309939     


Apoptotic images of the cells after BI 2536 treatment, as revealed by HCS (high-content screening) instrument (×10) with phospho-H2AX antibody or PI (propidium iodide) intake. 

Pericentrin / α-tubulin; 

PubMed: 21772266     


MEFs were labelled using Plk1, pericentrin and α-tubulin antibodies and 4,6-diamidino-2-phenylindole for the analysis by immunofluorescence microscopy. Representative examples of BI 2536-treated and control MEFs are depicted. Scale bar, 5 μm.

22309939 21772266
Growth inhibition assay
Cell viability; 

PubMed: 21772266     


Proliferative activity of MEFs at different BI 2536 concentrations (25–250 nM; means±s.d., n=3, for each concentration). *P<0.05, **P<0.01, ***P<0.001, Student's t-test, unpaired and two-tailed.

21772266
In vivo

BI 2536 given i.v. once or twice per week is highly efficacious in diverse xenograft models with acceptable tolerability by inhibiting cell proliferation through a mitotic arrest, and subsequently induction of tumor-cell death. Administration of BI 2536 at 50 mg/kg once or twice per week significantly inhibits growth of HCT 116 xenografts with T/C of 15% and 0.3%, respectively. BI 2536 treatment twice-weekly also leads to excellent tumor-growth in BxPC-3 and A549 models with T/C of 5% and 14%, respectively. [1]

Protocol

Kinase Assay:

[1]

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Plk1 in vitro kinase assay:

Recombinant human Plk1 (residues 1-603) is expressed as N-terminal, GST-tagged fusion protein with a baculoviral expression system and purified by affinity chromatography with Glutathione-agarose. Enzyme activity assays for Plk1 are performed in the presence of serially diluted BI 2536 with 20 ng of recombinant kinase and 10 μg casein from bovine milk as the substrate. Kinase reactions are performed in a final volume of 60 μL for 45 minutes at 30 °C (15 mM MgCl2, 25 mM MOPS [pH 7.0], 1 mM DTT, 1% DMSO, 7.5 mM ATP, 0.3 μCi γ-33P-ATP). Reactions are terminated by the addition of 125 μL of ice-cold 5% TCA. After transfer of the precipitates to Multi-Screen mixed ester cellulose filter plates, plates are washed with 1% TCA and quantified radiometrically. Dose-response curve is used for calculating IC50 value.
Cell Research:

[1]

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  • Cell lines: HeLa, A43, SKOV-3, HT-29, K562, A549, Saos-2, MCF7, HCT116, COLO 205, Hep G2, Raji and PC-3 cells, etc.
  • Concentrations: Dissolved in DMSO, final concentrations ~1 μM
  • Incubation Time: 24 and 72 hours
  • Method:

    Cells are exposed to various concentrations of BI 2536 for 24, and 72 hours. Cell growth is assessed by the measurement of Alamar Blue dye conversion in a fluorescence spectrophotometer. For determining the DNA content of the cultures, cell suspensions are fixed in 80% ethanol, treated for 5 minutes with 0.25% Triton X-100 in PBS, and incubated with 0.1% RNase and 10 μg/mL propidium iodide (PI) in PBS for 20 minutes at RT. Cell-cycle profiles are determined by flow cytometric analysis.


    (Only for Reference)
Animal Research:

[1]

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  • Animal Models: Female BomTac:NMRI-Foxn1nu mice injected subcutaneously with HCT 116, NCI-H460, or A549 cells
  • Dosages: ~50 mg/kg
  • Administration: Injection i.v. once or twice per week
    (Only for Reference)

Solubility (25°C)

In vitro Ethanol 100 mg/mL (191.69 mM)
DMSO 21 mg/mL (40.25 mM)
Water Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
5%DMSO+40%PEG300+5%Tween80+50%ddH2O
For best results, use promptly after mixing.
12.5mg/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 521.66
Formula

C28H39N7O3

CAS No. 755038-02-9
Storage powder
in solvent
Synonyms N/A
Smiles CCC1C(=O)N(C2=CN=C(N=C2N1C3CCCC3)NC4=C(C=C(C=C4)C(=O)NC5CCN(CC5)C)OC)C

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02215044 Terminated Drug: BI 2536 intravenous|Drug: Gemcitabine intravenous Pancreatic Neoplasms Boehringer Ingelheim June 2007 Phase 1
NCT02211833 Completed Drug: BI 2536|Drug: Pemetrexed Carcinoma Non-Small-Cell Lung Boehringer Ingelheim October 2006 Phase 1
NCT00701766 Completed Drug: BI 2536 Leukemia Myeloid Acute Boehringer Ingelheim October 2006 Phase 2
NCT00706498 Completed Drug: BI 2536 Prostatic Neoplasms Boehringer Ingelheim September 2006 Phase 2
NCT00376623 Completed Drug: BI 2536 Carcinoma Non-Small-Cell Lung Boehringer Ingelheim July 2006 Phase 2
NCT02211872 Completed Drug: BI 2536 BS intravenous Neoplasms Boehringer Ingelheim August 2004 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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Frequently Asked Questions

  • Question 1:

    We need to use BI 2536 in preclinical studies using mice, how to formulate the inhibitor for this in vivo study?

  • Answer:

    For in vivo study, DMSO should not be more than 5% because the toxicity. You can formulated BI2536 in hydrochloric acid (0.1 N), and diluted with 0.9% NaCl for animal study according to the reference :( Supplemental Data) http://linkinghub.elsevier.com/retrieve/pii/S0960-9822(06)02671-6

PLK Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID