BI 2536

For research use only.

Catalog No.S1109

209 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 209 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>? MUXJR|UxRTBwMEC3O|Yh|ryP NHLkW5A9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
ACN MofhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWPnU|lxUUN3ME2wMlAxQDR|IN88US=> NYDsOIdSRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
TE-8 NXSydFJHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXrJR|UxRTBwMEC5OFEh|ryP MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
LC-2-ad MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHztenNKSzVyPUCuNFExQTNizszN MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
ALL-PO MlrQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M163bmlEPTB;MD6wNVMh|ryP NUSxR4xHRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
EW-16 NFvQPZJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHfnNWdKSzVyPUCuNFE{OzZizszN MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
KM12 MlrDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1q2NGlEPTB;MD6wNVM1QCEQvF2= Mmm2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
GI-1 NGXGd5FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWfJR|UxRTBwMEGzPFMh|ryP NH3rRnU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
LS-411N Mk\rS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3fUT2lEPTB;MD6wNVQxPyEQvF2= MlX5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
ES8 NVTYS|hFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXjJR|UxRTBwMEG0PVQh|ryP M33iZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
SNU-C2B MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYC1VolxUUN3ME2wMlAyPTJ4IN88US=> NHXBS3M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
CESS NEPMUVZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIW1TGhKSzVyPUCuNFE3ODJizszN MkfpQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
697 NXnu[VNKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkSzTWM2OD1yLkCxOlY5KM7:TR?= M2LWW|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
NCI-H1963 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX;UfGFkUUN3ME2wMlAyPjd|IN88US=> NYPpTHc6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
IA-LM MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXLJR|UxRTBwMEG2PFgh|ryP M4\0WVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
SW954 NEDCTVlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnLLTWM2OD1yLkCxO|A2KM7:TR?= MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
RL95-2 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXHJR|UxRTBwMEG3N|gh|ryP NE\4VnI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
LXF-289 NFrEW3JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEfDXXNKSzVyPUCuNFE4PyEQvF2= NFPsTlA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
OCUB-M Mo\0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVjrc5B4UUN3ME2wMlAyQDJ4IN88US=> M1LTNFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
RKO NV;wUVVHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGS2TJpKSzVyPUCuNFE6QDdizszN NX;l[5E4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
LOUCY Ml;PS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmXZTWM2OD1yLkCyNFUh|ryP NGXXXY49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
NOS-1 M33Xcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWXKWXFNUUN3ME2wMlAzODl|IN88US=> M3vnfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
A4-Fuk MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1\KSmlEPTB;MD6wNlIyQCEQvF2= M{\TclxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
A388 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGXzTnNKSzVyPUCuNFIzOjdizszN M2X1S|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
TE-9 Mkm2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{nHdGlEPTB;MD6wNlI3OSEQvF2= Ml7tQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
KURAMOCHI NVX3fXBXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGSwNmJKSzVyPUCuNFIzQDVizszN NWi2dXlsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
KALS-1 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFOxUHlKSzVyPUCuNFI{OzhizszN MoDaQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
HOP-62 Mn\qS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYLiVFJkUUN3ME2wMlAzPDJizszN MnH4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
RPMI-8402 NX;3UJdIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX;JR|UxRTBwMEK1NFgh|ryP NUPQcJN3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
TE-1 NIHuNHJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3LIRWlEPTB;MD6wNlUyOiEQvF2= NF3k[WE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
CCRF-CEM NXTRXndLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXrEbmVSUUN3ME2wMlAzPTR|IN88US=> MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
HUTU-80 NF\xToNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnroTWM2OD1yLkCyOlI1KM7:TR?= NYC3dpVuRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
NCI-H1648 NIrpPVZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnzQTWM2OD1yLkCyOlQ4KM7:TR?= MoLnQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
HCE-4 MlW1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUOwXJl[UUN3ME2wMlAzPjh{IN88US=> MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
ETK-1 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{Gx[2lEPTB;MD6wNlc{PiEQvF2= NXjUZolpRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
TE-15 M4[5Zmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYLJR|UxRTBwMEK3N|gh|ryP MW[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
BE-13 NUDXOHN[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mo\sTWM2OD1yLkCyO|Qh|ryP NEW1[pU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
KE-37 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFTabIxKSzVyPUCuNFI4PDFizszN NV\ON2JKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
NCI-H1355 Mk\sS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFy3XohKSzVyPUCuNFI4QDNizszN M3vWSFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
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BL-70 MlzOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFP0[2xKSzVyPUCuNFI5PTdizszN NWXrbFllRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
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GT3TKB NETJcodIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUjJR|UxRTBwMEK5OVMh|ryP MojDQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
LB647-SCLC NWf4[ZVzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIO1UJdKSzVyPUCuNFMyQTVizszN Mo\aQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
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KLE NEHVbotIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1fKRmlEPTB;MD61NlE4OSEQvF2= NHnifFY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
LB2241-RCC M33ZdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVjJR|UxRTBwNUK1NlUh|ryP NV3ZfIE2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
NCI-H1417 M2jySWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXLrVY16UUN3ME2wMlU{PDN3IN88US=> NWC0Z21zRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
NCI-H2081 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGrMVlRKSzVyPUCuOVg3OTFizszN Mn7LQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
NCI-H1522 NHewVXVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVv3S3B4UUN3ME2wMlU6Ozh|IN88US=> NXnZSVJxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
NCI-H889 NY\4b4dLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFnKU2RKSzVyPUCuOVk5PDRizszN MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
CGTH-W-1 M1S3Umdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3;PNWlEPTB;MD62NFc2PSEQvF2= NYTrZplORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
EB-3 MlO0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYjxbGgzUUN3ME2wMlYyOTV|IN88US=> MmfJQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
D-336MG M1[3OWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1zFbGlEPTB;MD62NVc6OSEQvF2= M37ZSVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
LC-1F NIXrRphIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH\3To9KSzVyPUCuOlI2QTJizszN NX\WPHNVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
MHH-NB-11 MnfOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MULJR|UxRTBwNkO4NFEh|ryP NVXCOpo3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
SK-N-FI NVfrNlBpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXTJR|UxRTBwNkO5NUDPxE1? NYjOUJE3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
NCI-H69 M2r3[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVPJR|UxRTBwNkS4O|kh|ryP M2j2OVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
SCH NX[2dJJlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEjMTmtKSzVyPUCuOlYxOjNizszN MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
LS-513 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mm\ZTWM2OD1yLk[3NlU6KM7:TR?= Mlz4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
CP67-MEL M2HkSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVfJR|UxRTBwNke1PVYh|ryP MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
GCIY Ml:xS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWjJR|UxRTBwN{CzOlMh|ryP MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
SHP-77 NEiyeFVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYrYNGk6UUN3ME2wMlcxPzN2IN88US=> MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
EHEB MkPtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVrPfpR3UUN3ME2wMlcyQDV2IN88US=> NEfCb4Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
D-247MG NFr5VmRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFHO[|hKSzVyPUCuO|MzOzJizszN M4KxdFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
Raji MoOyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXjRZ2FKUUN3ME2wMlc1QTh7IN88US=> NFrJTIo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
MPP-89 MmLZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFnFdIJKSzVyPUCuO|U6PzhizszN M{XXZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
EKVX NYrPfHhoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV33d2JPUUN3ME2wMlc6ODd|IN88US=> MUG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
HCC2218 NI\5OnVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlLOTWM2OD1yLke5NVMyKM7:TR?= NVnkO3Z7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
KNS-81-FD M4rKRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVrJR|UxRTBwOEGwNVEh|ryP NGD3WI49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
HCC2157 NXu5WphtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmXBTWM2OD1yLki0PVUyKM7:TR?= MlHLQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
BT-474 NIjGc4FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFSxeGhKSzVyPUCuPFg5PTRizszN NFu3dGs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
NCI-H748 Mn\aS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYDqfppzUUN3ME2wMlkyOiEQvF2= NUXk[2Z{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
EW-24 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIrrN2VKSzVyPUCuPVIxODJizszN NX\JXXNyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
D-263MG M1fnRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MY\JR|UxRTBwOUS1NVIh|ryP NI\qeIQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
OMC-1 MnnYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWXrUGU1UUN3ME2wMlk3Ozd|IN88US=> MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
NCI-H2196 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXjJR|UxRTBwOUe3O|ch|ryP MmC1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
HAL-01 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVrsXnNiUUN3ME2wMlk6QDd{IN88US=> NHTLeXM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OTN7MEmvK|5USU6JRWK8M4E,
NCI-H2107 M3LVdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYPJR|UxRTFwMEG4OVQh|ryP MnjuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
LB996-RCC MkjDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH3rdlZKSzVyPUGuNFgxPTFizszN Moq4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
NCI-H1395 NWTWRoRsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlrnTWM2OD1zLkGwOlch|ryP NW\LUnpZRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
CHP-126 NELpcGVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYTJR|UxRTFwMU[xPVkh|ryP NWDsOpF[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
NB69 NIXW[YZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MorGTWM2OD1zLkK2NVQ5KM7:TR?= MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
CAS-1 M2XHR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2PXWmlEPTB;MT6zOFI{OSEQvF2= MlO4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVE{QTB7Lze+V2FPT0WUPD;hQi=>
JVM-3 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{TwSWlEPTB;MT60O|g2PSEQvF2= M3;zPFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
DMS-153 NVvRRplKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mmj4TWM2OD1zLkW3Olc1KM7:TR?= M{HTNFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUyOzlyOT:nQnNCVkeHUkyvZV4>
SK-MEL-2 NHjBOlRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYHJR|UxRTFwN{G3PFkh|ryP MUG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
NCI-H1155 NXe0[JJST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWfJR|UxRTFwN{O2O|Yh|ryP MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
NCI-H1092 NVHSeZplT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn\hTWM2OD1zLke2NVgzKM7:TR?= NWnGc3Q3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
LU-165 M3fv[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mmr4TWM2OD1zLki2OFc3KM7:TR?= NYnjfINYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTF|OUC5M{c,W0GQR1XSQE9iRg>?
HL-60 NITsUWtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVPJR|UxRTFwOUm5NFgh|ryP MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NVM6ODlxJ{7TRW5ITVJ:L3G+
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JURKAT NE\HZlNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoOxNlQhcA>? M1fIUWlEPTB;NEG2MlY3KG6P MorrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR3MUm5PVUoRjJ2NUG5PVk2RC:jPh?=
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SIL-ALL Mn6yS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIX0[4szPCCq NFfje4FKSzVyPUG5PU44PyCwTR?= MWq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDVzOUm5OUc,OjR3MUm5PVU9N2F-
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NALM-16 MoK4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH\pPHozPCCq M2[0ZmlEPTB;OU[uNlghdk1? M4T6SVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NUG5PVk2Lz5{NEWxPVk6PTxxYU6=
JURKAT NV2y[HhDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX[0PEBp NYPVd4ljUUN3ME2xOE45PCCwTR?= NXPmOWNqRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS1NVk6QTVpPkK0OVE6QTl3PD;hQi=>
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RS 4;11 NGT3[o5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkXoOFghcA>? M2TsOWlEPTB;MU[0MlI5KG6P MnfoQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR3MUm5PVUoRjJ2NUG5PVk2RC:jPh?=
697 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYC0PEBp M4S4cWlEPTB;M{C1MlMhdk1? NVHGepo1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS1NVk6QTVpPkK0OVE6QTl3PD;hQi=>
SIL-ALL NFTpVVVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXe0PEBp MX;JR|UxRTd2Lk[yJI5O M3PB[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NUG5PVk2Lz5{NEWxPVk6PTxxYU6=
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NALM-16 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NELUbnc1QCCq MVXJR|UxRTZ|LkK0JI5O NVLHTpBLRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS1NVk6QTVpPkK0OVE6QTl3PD;hQi=>
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SIL-ALL NEL1[W1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2Cze|czKGh? NY\5TFFiUUN3ME23MlIhdk1? MkP0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR3MUm5PVUoRjJ2NUG5PVk2RC:jPh?=
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NALM-16 NESyNZJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NW\OVmdbPzJiaB?= MVzJR|UxRTd5LkezJI5O M2\yUlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NUG5PVk2Lz5{NEWxPVk6PTxxYU6=
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OHS-50 MmjsdWhVWyCjc4PhfS=> NE\YWYVyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBQUFNvNUCgZ4VtdHN? NYrGfFJZRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
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SK-N-MC MV\xTHRUKGG|c3H5 MU\xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0tvTj3NR{Bk\Wyucx?= NIr4bmY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
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LAN-5 NYT6cJJ2eUiWUzDhd5NigQ>? NUP4VGc5eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IFzBUk02KGOnbHzz NHHad|U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
Rh18 M1nJN5FJXFNiYYPzZZk> M2LnW5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCUaEG4JINmdGy| NEnIN3o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
NB1643 NIq1b2RyUFSVIHHzd4F6 Mne2dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgUmIyPjR|IHPlcIx{ NFf3bZI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
SK-N-MC MY\xTHRUKGG|c3H5 M4izTpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHNMNU5vTVOgZ4VtdHN? MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
SJ-GBM2 Ml7CdWhVWyCjc4PhfS=> NUG2OY5FeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhW0pvR1LNNkBk\Wyucx?= MnLKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
TC32 M{Kze5FJXFNiYYPzZZk> M2CzVpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHREOzJiY3XscJM> MkC0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
Rh18 M{THbJFJXFNiYYPzZZk> NHjVPXRyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBTcDF6IHPlcIx{ M3jHNFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Saos-2 MknYdWhVWyCjc4PhfS=> NUjMO|M5eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhW2Gxcz2yJINmdGy| NHXjZXM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
DU145 M2L1fGFxd3C2b4Ppd{Bie3OjeR?= NYrU[JBjOTByIH7N NVjE[W5oOjRiaILz MX\JcoR2[3Srb36gc4Yh[XCxcITvd4l{KGmwIHj1cYFvKESXMUS1JINmdGy|IHHzd4V{e2WmIHHzJIlv[3KnYYPlJIlvKFCDUmCgZ4xm[X[jZ3WgZZQhOTByIH7NJIFnfGW{IEK0JIhzeyCkeTDpcY12dm:kbH;0eIlv\yCvZYToc4Q> MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ6NUm0NUc,OjV4OEW5OFE9N2F-
HeLa MXnGeY5kfGmxbjDhd5NigQ>? MmfRNVAxKG6P NXfacoNZUW6qaXLpeIlwdiCxZjDQUGsyKFSqckKxNEBxcG:|cHjvdplt[XSrb36gbY4hcHWvYX6gTIVN[SClZXzsd{BifCBzMECgcm0h[nliaX3teY5w[myxdITpcochdWW2aH;k M1fuTVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3Nki1PVQyLz5{NU[4OVk1OTxxYU6=
DU145 NEfkZVNHfW6ldHnvckBie3OjeR?= M1HFTVExOCCwTR?= M{\0dmlvcGmkaYTpc44hd2ZiUFzLNUBxem:2ZXnuJIFk[3WvdXzheIlwdiCrbjDoeY1idiCGVUG0OUBk\WyuczDheEAyODBibl2gZpkhcW2vdX7vZoxwfHSrbnegcYV1cG:m NEW3VpU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[4OVk1OSd-MkW2PFU6PDF:L3G+
HeLa M{Tz[mZ2dmO2aX;uJIF{e2G7 Mor0NVAxKG6P NHHkNHJKdmirYnn0bY9vKG:oIGDMT|EheHKxdHXpckBi[2O3bYXsZZRqd25iaX6gbJVu[W5iSHXMZUBk\WyuczDheEAyODBibl2gZpkhcW2vdX7vZoxwfHSrbnegcYV1cG:m M3jMV|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3Nki1PVQyLz5{NU[4OVk1OTxxYU6=
HeLa M3TFSGZ2dmO2aX;uJIF{e2G7 NWTJbVRmOTByIH7N MVGxPEBpenN? NHzIdJlKdmS3Y4Tpc44hd2ZibX;uc5BwdGG{IH3peI91cWNic4DpcoRt\XNiaX6gbJVu[W5iSHXMZUBk\WyuczDheEAyODBibl2gbY5kfWKjdHXkJIZweiBzODDodpMh[nliaX7kbZJm[3RiaX3teY5w\my3b4Lld4NmdmOnIH3pZ5Jwe2OxcIm= NEPibYw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[4OVk1OSd-MkW2PFU6PDF:L3G+
HeLa MmTwRZBweHSxc3nzJIF{e2G7 NE\MTW4yODBibl2= Mnv3NlQhcHK| M4HsZmlv\HWldHnvckBw\iCjcH;weI9{cXNiaX6gbJVu[W5iSHXMZUBk\WyuczDhd5Nme3OnZDDhd{BqdmO{ZXHz[UBqdiCSQWLQJINt\WG4YXflJIF1KDFyMDDuUUBi\nSncjCyOEBpenNiYomgbY1ufW6xYnzveJRqdmdibXX0bI9l M1TYfVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3Nki1PVQyLz5{NU[4OVk1OTxxYU6=
PC3 NF7PN2pHfW6ldHnvckBie3OjeR?= MXixNFAhdk1? NIPOUFIyQCCqcoO= M{jrNGlv\HWldHnvckBw\iCvb37vdI9t[XJibXn0c5Rq[yC|cHnu[IxmeyCrbjDoeY1idiCSQ{OgZ4VtdHNiYYSgNVAxKG6PIHnuZ5Vj[XSnZDDmc5IhOThiaILzJIJ6KGmwZHny[YN1KGmvbYXuc4ZtfW:{ZYPj[Y5k\SCvaXPyc5Nkd3C7 Moi0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV4OEW5OFEoRjJ3Nki1PVQyRC:jPh?=
DU145 NH7TOFRHfW6ldHnvckBie3OjeR?= NUSzcVN3OTByIH7N NVLQVnNXUW6qaXLpeIlwdiCxZjDQUGsyKFSqckKxNEBxcG:|cHjvdplt[XSrb36gbY4hcHWvYX6gSHUyPDViY3XscJMh[XRiMUCwJI5OKGK7IHntcZVvd2Kub4T0bY5oKG2ndHjv[C=> M3rUfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3Nki1PVQyLz5{NU[4OVk1OTxxYU6=

... 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):
30% PEG 400+0.5% Tween 80+5% Propylene glycol
For best results, use promptly after mixing.
15mg/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

In vivo Formulation Calculator (Clear solution)

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Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

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

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

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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

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID