Bortezomib (PS-341) 化学構造
分子量: 384.24

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Quality Control & MSDS

製品説明

  • Compare Proteasome Inhibitors
    Proteasome製品生物活性の比較
  • 研究分野
  • Combination Therapy
    併用療法

製品の説明

生物活性

製品説明 Bortezomib (PS-341)は、強力なプロテアソーム阻害剤で、Kiが0.6nMです。
ターゲット

20S proteasome

IC50

0.6 nM (Ki) [1]

In vitro試験 Bortezomib, a boronic acid dipeptide, is a highly selective, reversible inhibitor of the 26S proteasome which primarily functions in the degradation of mis-folded proteins and is essential for the regulation of the cell cycle. Exposure to Bortezomib has been shown to stabilize p21, p27, and p53, as well as the proapoptotic Bid and Bax proteins, caveolin-1, and inhibitor κB-α, which prevents activation of nuclear factor κB-induced cell survival pathways. Bortezomib also promotes the activation of the proapoptotic c-Jun-NH2 terminal kinase, as well as the endoplasmic reticulum stress response. Alteration of the levels of these cellular proteins leads to inhibition of proliferation, migration, and promotion of apoptosis of cancer cells. [2] Bortezomib is shown to penetrate into cells and inhibit proteasome-mediated intracellular proteolysis of long-lived proteins with a concentration that inhibits 50% of the proteolysis of ∼0.1 μM. The average growth inhibition of 50% value for Bortezomib across the entire panel of 60 cancer cell lines derived from multiple human tumors from the US National Cancer Institute (NCI) is 7 nM. Treatment of PC-3 cells with Bortezomib (100 nM) for 8 h results in the accumulation of cells in G2-M, with a corresponding decrease in the number of cells in G1. Bortezomib kills PC-3 cells at 24 and 48 hr with IC50 of 100 and 20 nM, respectively. Bortezomib induces nuclear condensation at 16–24 hr after treatment. Bortezomib treatment leads to PARP cleavage in a time-dependent manner with concentrations as low as 100 nM being effective at 24 hr. [1]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
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RPMI8226 NHL2V|ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{nZ[lExOCCwTR?= NU\MUlB7PDhiaB?= M{H6TmROW09? MX;JR|UxRTNyIH7N NH7aWIIyOTNyNkS4PS=>
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SK-N-AS MnnRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHzoZYoyKM7:TR?= NYHHc|F7PzJiaB?= M1\PTmlvcGmkaYTzJINmdGxicILvcIln\XKjdHnvckB1dyBzMDW= NXzDdW5nOTd4OEm2PFQ>
NB-1691 MmXRSpVv[3Srb36gRZN{[Xl? MYKxNEBvVQ>? M374XlI1KGh? Mn3EV4lodmmoaXPhcpRtgSC{ZXT1Z4V{KGOnbHzzJIlvKHSqZTDHNE9IOSCyaHHz[S=> Mn\oNVc3QDl4OES=
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H9 NEjWdGhHfW6ldHnvckBCe3OjeR?= MXOxNFAhdk1? MYCyOEBp M{nk[2ROW09? NETudoNFd3ewcnXneYxifGW|IGTHSk3PujFiYX7kJGlNNTFzIHX4dJJme3Orb36= M3mzVVI2PjhzM{O1
HH MULGeY5kfGmxbjDBd5NigQ>? MormNVAxKG6P MUKyOEBp NHTpfZlFVVOR NVzod5Ft\G:5boLl[5Vt[XSnczDUS2Yu|rJzIHHu[EBKVC1zMjDlfJBz\XO|aX;u MV[yOVY5OTN|NR?=
Hut-78 NGP3U3BOcWe{YYTpc44hSXO|YYm= MmXaNVAxKG6P Mmr4NlQhcA>? MXvEUXNQ NF6wUINT\WS3Y3XzJINmdGxibXnndoF1cW:wIHL5JFgx6oDVOUCl M4nmSFI2PjhzM{O1
HH NWf3ZnJmVWmpcnH0bY9vKEG|c3H5 MkfuNVAxKG6P MViyOEBp NWDHTHBCTE2VTx?= MUHS[YR2[2W|IHPlcIwhdWmpcnH0bY9vKGK7IEiw5qCUQTFn NHHkNYMzPTZ6MUOzOS=>
U937 MYfGeY5kfGmxbjDBd5NigQ>? M3jlW|ExOCCwTR?= MXG2JIg> NYPtZYdEUW6mdXPld{BKVC16IHX4dJJme3Orb36gbY4hVFCVLYP0bY12dGG2ZXSgWVk{PyCvYXPyc5Bp[Wencx?= MUmyOVc6OTR5Nx?=
human PBMC MnSwSpVv[3Srb36gRZN{[Xl? NF3UZpoyODBibl2= NISxSnozPCCq NULt[VliUW6mdXPld{BKVC16IILlcIVie2V? MWeyOVc6OTR5Nx?=
ES6 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWjIN|VRUUN3ME2wMlAxOjFibl2= MVnTRW5ITVJ?
SK-UT-1 MlPKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmHjTWM2OD1yLkG2N{BvVQ>? M1nRZnNCVkeHUh?=
SH-4 M4nremdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnLrTWM2OD1yLkG3N{BvVQ>? MojXV2FPT0WU
TE-9 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M332TWlEPTB;MD6xPFIhdk1? NH7YTZhUSU6JRWK=
A253 NX\BTldWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3uzN2lEPTB;MD6yNFghdk1? NUHlSY1VW0GQR1XS
no-10 M{TCZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV;qT3Z2UUN3ME2wMlIyKG6P NHf3PJpUSU6JRWK=
MMAC-SF NUn5eIROT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWLJR|UxRTBwMkG2JI5O Mn;vV2FPT0WU
A101D MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYK5[HdPUUN3ME2wMlIzPSCwTR?= MkXtV2FPT0WU
NTERA-S-cl-D1 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3zmOmlEPTB;MD6yOFMhdk1? MYPTRW5ITVJ?
8-MG-BA M17ObGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1L4cmlEPTB;MD6yOUBvVQ>? NI[1Z5dUSU6JRWK=
KNS-42 Mn;3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHjwXGNKSzVyPUCuNlU5KG6P MkC1V2FPT0WU
LXF-289 MnziS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGfoWXVKSzVyPUCuNlY6KG6P NFvJfXJUSU6JRWK=
OVCAR-4 MlG4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYfJR|UxRTBwMki5JI5O NITiWXRUSU6JRWK=
LOUCY M3nKeGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4PXNmlEPTB;MD6yPVMhdk1? NX\4Z5ZYW0GQR1XS
BB65-RCC NUPvfJlqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWLJR|UxRTBwM{C0JI5O MkDxV2FPT0WU
D-542MG NGDZXJlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUXJR|UxRTBwM{K5JI5O MmfuV2FPT0WU
ONS-76 M{SwbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHy1UplKSzVyPUCuN|Mhdk1? NFvrVmtUSU6JRWK=
BB30-HNC MnLPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIniUnNKSzVyPUCuN|M2KG6P M{T1SnNCVkeHUh?=
KS-1 M3rwSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXXJR|UxRTBwM{Sgcm0> MXjTRW5ITVJ?
A388 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnPPTWM2OD1yLkO1OkBvVQ>? MVvTRW5ITVJ?
ES8 NXPFRYtmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3fVVWlEPTB;MD60JI5O NIrJOItUSU6JRWK=
MZ2-MEL NYT0RoFpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV;JR|UxRTBwNEC3JI5O NEfkeI9USU6JRWK=
HCC2998 NWS2PWJ4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXvJR|UxRTBwNEGyJI5O NF64PXdUSU6JRWK=
D-247MG MnHjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUTlfo51UUN3ME2wMlQyOyCwTR?= MV7TRW5ITVJ?
ACN MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2\6eGlEPTB;MD60NVchdk1? M{DqbHNCVkeHUh?=
LB2518-MEL M{\Hbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHq4dlRKSzVyPUCuOFI2KG6P MX;TRW5ITVJ?
ES1 NGflTYhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{TDWGlEPTB;MD60N{BvVQ>? NH;Re4JUSU6JRWK=
HCE-T MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWjJR|UxRTBwNEO5JI5O NEjXZ5JUSU6JRWK=
OS-RC-2 NIXJZVFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX;hc|B2UUN3ME2wMlQ1KG6P MlPWV2FPT0WU
MFH-ino NWLNVGVYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWT1OYo4UUN3ME2wMlQ1OyCwTR?= NYriT3lTW0GQR1XS
OCUB-M NGDDb5RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWXFXY9mUUN3ME2wMlQ1PyCwTR?= NUPsSmdUW0GQR1XS
CP66-MEL MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlnDTWM2OD1yLkS3N{BvVQ>? NIPtWoNUSU6JRWK=
LB771-HNC NVfZXHBvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHjWZVRKSzVyPUCuOFc1KG6P M3PWZXNCVkeHUh?=
DSH1 NVfWWpRuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVrJR|UxRTBwNEigcm0> NYLseXVNW0GQR1XS
HUTU-80 NE\ORXNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M37YWGlEPTB;MD61N|Mhdk1? MUHTRW5ITVJ?
CESS NIKyV3pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MofXTWM2OD1yLkWzPEBvVQ>? MXzTRW5ITVJ?
NCI-H747 MkPQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoPBTWM2OD1yLkWzPUBvVQ>? NXHXT|JbW0GQR1XS
HT-144 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX;JR|UxRTBwNUe2JI5O NEXy[WRUSU6JRWK=
COLO-829 NULKcVNMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4PacGlEPTB;MD62NVQhdk1? Mn3UV2FPT0WU
A4-Fuk MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHm4W2RKSzVyPUCuOlI{KG6P M3fibnNCVkeHUh?=
GI-ME-N MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MULJR|UxRTBwNkO0JI5O MWHTRW5ITVJ?
LB831-BLC MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3y1ZmlEPTB;MD62OFEhdk1? NG\xTpVUSU6JRWK=
HOP-62 M360Umdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUDIVGRjUUN3ME2wMlY1PyCwTR?= MofYV2FPT0WU
BB49-HNC MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIrpRYhKSzVyPUCuOlUzKG6P NVXU[ZMyW0GQR1XS
D-336MG MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH:0WWRKSzVyPUCuOlU4KG6P NHLpPJJUSU6JRWK=
TK10 Ml;5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYTJR|UxRTBwNke5JI5O Mn:yV2FPT0WU
Ramos-2G6-4C10 NUCzeW9zT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWXJR|UxRTBwNkmzJI5O M{PRPHNCVkeHUh?=
LB373-MEL-D MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWHveZgzUUN3ME2wMlchdk1? MoLkV2FPT0WU
SF126 MlL0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mln3TWM2OD1yLkewNUBvVQ>? NYjLPJlCW0GQR1XS
UACC-257 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHjRVIlKSzVyPUCuO|Ehdk1? MWXTRW5ITVJ?
KINGS-1 NHfTZm1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn:wTWM2OD1yLkeyNkBvVQ>? NF\afVVUSU6JRWK=
LS-513 MkP2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NITacJVKSzVyPUCuO|M6KG6P MmPNV2FPT0WU
GI-1 MlP0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYPJR|UxRTBwN{[0JI5O NUjRWo5xW0GQR1XS
ES7 NUXUUox2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mli3TWM2OD1yLke2OkBvVQ>? NXm2No57W0GQR1XS
LB2241-RCC M{fBcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWrJR|UxRTBwOEC0JI5O NVv1fWZ4W0GQR1XS
D-263MG M{[0SGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NITNdmFKSzVyPUCuPFA4KG6P MV;TRW5ITVJ?
SW684 NHzESpNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH7PcGtKSzVyPUCuPFIyKG6P NI\ocFRUSU6JRWK=
ML-2 NHvSSZFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGXZbIlKSzVyPUCuPFIyKG6P NUnzT4FIW0GQR1XS
SK-LMS-1 NFTxWINIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYiyRoxJUUN3ME2wMlg2PCCwTR?= NWLKd3I6W0GQR1XS
TE-5 MoTSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYKxTm5bUUN3ME2wMlg3PSCwTR?= MoC2V2FPT0WU
QIMR-WIL NFnYc5BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXXJR|UxRTBwOEi5JI5O MVrTRW5ITVJ?
NCI-H1355 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoDMTWM2OD1yLki5OUBvVQ>? MmjUV2FPT0WU
SNB75 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGHyPIFKSzVyPUCuPVEzKG6P M4fNbXNCVkeHUh?=
RXF393 NEPQNHNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkHWTWM2OD1yLkmxOEBvVQ>? NEi4bXFUSU6JRWK=
IST-MEL1 NUPxNXp2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVrJR|UxRTBwOUG3JI5O M3XzOnNCVkeHUh?=
SF268 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4fKb2lEPTB;MD65NlMhdk1? MlmxV2FPT0WU
KALS-1 NX3pO4hYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NULT[ZpHUUN3ME2wMlkzPSCwTR?= M{fSdXNCVkeHUh?=
HC-1 NFOxSHZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1vLPWlEPTB;MD65O|Uhdk1? MVLTRW5ITVJ?
SW872 NXT0cYlqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYHSVXJCUUN3ME2wMlk6PiCwTR?= NF3zZo5USU6JRWK=
PSN1 M4LLOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnzRTWM2OD1zLkCxJI5O MlzRV2FPT0WU
TE-1 NEPYUWxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEXXXnpKSzVyPUGuNFMhdk1? M4r4V3NCVkeHUh?=
TE-10 M37nN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGfoWFFKSzVyPUGuNFMhdk1? MXXTRW5ITVJ?
RKO MnjZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWfVeIR2UUN3ME2xMlA3KG6P MojQV2FPT0WU
LC-2-ad MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1jY[mlEPTB;MT6wPEBvVQ>? M37zVnNCVkeHUh?=
SK-MM-2 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MorPTWM2OD1zLkC5JI5O MXnTRW5ITVJ?
VA-ES-BJ MnrQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUDJR|UxRTFwMEmgcm0> MWTTRW5ITVJ?
MZ7-mel NHmxeWZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnfFTWM2OD1zLkC5JI5O MorsV2FPT0WU
D-392MG NHXBSVRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVnJR|UxRTFwMTDuUS=> NFvDc4VUSU6JRWK=
CCRF-CEM NFzIPIRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUHoZ3VtUUN3ME2xMlE{KG6P NEfwfnhUSU6JRWK=
EM-2 M1\aPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEfwbpNKSzVyPUGuNVYhdk1? M3HwRnNCVkeHUh?=
HAL-01 M2fOOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVq5NVM5UUN3ME2xMlE5KG6P MkTYV2FPT0WU
TE-8 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1\4V2lEPTB;MT6xPUBvVQ>? MkfFV2FPT0WU
NCI-H1882 M3j3VWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVzJR|UxRTFwMjDuUS=> MWXTRW5ITVJ?
Daudi NXH3bHNFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUftWFZ5UUN3ME2xMlIzKG6P MXjTRW5ITVJ?
BL-41 M1vUdmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV3RSpZuUUN3ME2xMlI2KG6P MWDTRW5ITVJ?
SR NVnRbW9NT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGnwflRKSzVyPUGuNlUhdk1? M2PsenNCVkeHUh?=
KM12 NFrVdJBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUT5WG52UUN3ME2xMlI4KG6P MWnTRW5ITVJ?
K5 NFWyXoRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NI\vb3FKSzVyPUGuNlghdk1? NYjPe|ZkW0GQR1XS
A3-KAW M2fRS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYrJR|UxRTFwMkigcm0> NIPvT|VUSU6JRWK=
CMK NX7odWpGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXTJR|UxRTFwMkmgcm0> NVHMV|c6W0GQR1XS
Calu-6 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmnJTWM2OD1zLkK5JI5O MVLTRW5ITVJ?
IST-SL2 M{LENWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2jQOmlEPTB;MT6zNUBvVQ>? NUDq[o9TW0GQR1XS
OPM-2 NGjB[4NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWPJR|UxRTFwM{Ogcm0> NI\3TJBUSU6JRWK=
DU-4475 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mnj0TWM2OD1zLkO2JI5O NGDJ[XdUSU6JRWK=
ECC12 NH20TY1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWrJR|UxRTFwM{egcm0> NIHhfHJUSU6JRWK=
L-540 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWnJR|UxRTFwM{egcm0> MnjxV2FPT0WU
CAS-1 NWLONGhvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWXafolmUUN3ME2xMlM4KG6P NXnzbox1W0GQR1XS
PF-382 NWnNZlNlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NELaZXFKSzVyPUGuOFchdk1? NWXwcGRsW0GQR1XS
LS-411N M2nLZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NI\pdFBKSzVyPUGuOVMhdk1? M3jMcHNCVkeHUh?=
NCI-H69 M2LT[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX[ycWdGUUN3ME2xMlU1KG6P MW\TRW5ITVJ?
NB12 MkTKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUTJR|UxRTFwNU[gcm0> MorKV2FPT0WU
HEL NVPwRpQ2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3TMSWlEPTB;MT62NUBvVQ>? M3vFcHNCVkeHUh?=
GCIY NIGwbWpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVfJR|UxRTFwNkKgcm0> M3;YRnNCVkeHUh?=
EHEB NV;LOGtIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn3PTWM2OD1zLk[3JI5O MnPPV2FPT0WU
TGBC1TKB NWfRVYZkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1f3UGlEPTB;MT63NUBvVQ>? MVnTRW5ITVJ?
KURAMOCHI NIS1N41Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWnHXo5zUUN3ME2xMlczKG6P MlTjV2FPT0WU
U-266 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVHJR|UxRTFwN{[gcm0> M{nBOnNCVkeHUh?=
LC4-1 MoThS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUfJR|UxRTFwN{mgcm0> NEjITFFUSU6JRWK=
NCI-H2126 M{TmPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYLJR|UxRTFwODDuUS=> M2jWUHNCVkeHUh?=
NCI-H1092 NVXBdndpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M37QS2lEPTB;MT64JI5O M1zKZ3NCVkeHUh?=
GB-1 MlqwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUHKeoEyUUN3ME2xMlgyKG6P NXnqZXBSW0GQR1XS
MV-4-11 Mn7NS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH\uO2lKSzVyPUGuPFIhdk1? M4P3Z3NCVkeHUh?=
Becker NUfvWpltT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3LWdGlEPTB;MT64N{BvVQ>? MnW2V2FPT0WU
MPP-89 M4LGXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVHJR|UxRTFwOEmgcm0> MknWV2FPT0WU
BE-13 NYTGOWI{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NITXTFVKSzVyPUGuPVMhdk1? NF7pVI9USU6JRWK=
697 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHryR49KSzVyPUGuPVkhdk1? M2fOZXNCVkeHUh?=
NKM-1 NVqyVpRST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF;EcpdKSzVyPUKgcm0> MnfwV2FPT0WU
NB13 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mo\yTWM2OD1{IH7N MXjTRW5ITVJ?
LS-123 NX;Wb5hvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYnPcHVLUUN3ME2yMlAzKG6P M1\lTXNCVkeHUh?=
NB17 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2jaTmlEPTB;Mj6wOEBvVQ>? NWjFZ5FsW0GQR1XS
LAN-6 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUnJR|UxRTJwMEWgcm0> M4nMTnNCVkeHUh?=
EW-24 M2fXd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWDkO4cxUUN3ME2yMlA5KG6P MlTKV2FPT0WU
NOS-1 NHzEOXFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NG\NN|FKSzVyPUKuNVEhdk1? MlOxV2FPT0WU
BL-70 NV7G[lB1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYPnUWYyUUN3ME2yMlEzKG6P M4i1b3NCVkeHUh?=
GT3TKB MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWrmW4dXUUN3ME2yMlEzKG6P M3XDXHNCVkeHUh?=
HH MlrhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2\SNmlEPTB;Mj6xN{BvVQ>? NGLGbZBUSU6JRWK=
KE-37 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIPG[|NKSzVyPUKuNVMhdk1? M2mwZ3NCVkeHUh?=
MOLT-4 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHnxdlZKSzVyPUKuNVMhdk1? M{S4WXNCVkeHUh?=
EKVX M3uxO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1jtWmlEPTB;Mj6xOEBvVQ>? MoDpV2FPT0WU
KGN M{DBcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4LEVWlEPTB;Mj6xOUBvVQ>? MUnTRW5ITVJ?
ES4 M1z3NWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUHJR|UxRTJwMU[gcm0> Mo\WV2FPT0WU
SJSA-1 NEjzSoNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVu2VnJ{UUN3ME2yMlIyKG6P M3nMO3NCVkeHUh?=
KMOE-2 NUjCfJVVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1ToNmlEPTB;Mj6yN{BvVQ>? MX\TRW5ITVJ?
NB5 MorHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEDBcHhKSzVyPUKuNlchdk1? M3rQZnNCVkeHUh?=
BC-1 NX;OVXZbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlzOTWM2OD1{LkOxJI5O M3nlXXNCVkeHUh?=
NB10 M3zqS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkT1TWM2OD1{LkOyJI5O NIXkclNUSU6JRWK=
RPMI-8226 NYjke3JmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHzRO2xKSzVyPUKuN|Uhdk1? NWfVSJlXW0GQR1XS
SCC-3 NGXVd4JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV7JR|UxRTJwM{egcm0> MVnTRW5ITVJ?
ARH-77 M2H1ZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVXmO2NVUUN3ME2yMlM5KG6P M4HNRXNCVkeHUh?=
NCI-H748 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV;JR|UxRTJwM{mgcm0> NVO0ToUyW0GQR1XS
KU812 M2HpTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmfVTWM2OD1{LkSyJI5O MnqxV2FPT0WU
NCI-H64 M3vDb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXTJR|UxRTJwNESgcm0> NGi3ZndUSU6JRWK=
NB69 Ml3PS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYnJR|UxRTJwNE[gcm0> M{S0cnNCVkeHUh?=
KNS-81-FD NYm2cFVuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIr5[|NKSzVyPUKuOFghdk1? M17NUHNCVkeHUh?=
LB1047-RCC MoHHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH22WGRKSzVyPUKuOVchdk1? M{PEUnNCVkeHUh?=
EB-3 M1jLU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3TudGlEPTB;Mj62OkBvVQ>? NUjVVI13W0GQR1XS
Mo-T NIOy[3RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX;JR|UxRTJwN{Sgcm0> NGT5eodUSU6JRWK=
EW-16 MmHES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHe5RZFKSzVyPUKuO|Uhdk1? MkTaV2FPT0WU
CTV-1 MoDKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1\LUGlEPTB;Mj64JI5O NHflNJFUSU6JRWK=
ETK-1 NVSyUYV2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFm0TZZKSzVyPUKuPFQhdk1? NUjDSG9KW0GQR1XS
C2BBe1 NF;hWm5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYPJR|UxRTJwOEmgcm0> MYjTRW5ITVJ?
MOLT-16 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnrQTWM2OD1{Lki5JI5O NH6xc4hUSU6JRWK=
SW954 NGLuV|NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M370PGlEPTB;Mj65JI5O NUG0UFlQW0GQR1XS
HT NGrrW|hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFS5S2pKSzVyPUOuNFIhdk1? Ml7VV2FPT0WU
KARPAS-299 NEP6doZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnLnTWM2OD1|LkC2JI5O NWTyN|NnW0GQR1XS
MONO-MAC-6 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3;6NmlEPTB;Mz6xJI5O NUTYWVNJW0GQR1XS
CGTH-W-1 M3jZ[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoPKTWM2OD1|LkGgcm0> NVPTd4ZzW0GQR1XS
SK-PN-DW MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYj5[2dIUUN3ME2zMlE1KG6P M2HnT3NCVkeHUh?=
CW-2 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWjJR|UxRTNwMkGgcm0> NY\lV2Q5W0GQR1XS
SK-N-DZ MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M13FRmlEPTB;Mz6yOkBvVQ>? NVPZ[2ZrW0GQR1XS
NEC8 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mk\ITWM2OD1|LkO1JI5O MnPYV2FPT0WU
LB996-RCC M4PFR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUfJR|UxRTNwNDDuUS=> M4Du[XNCVkeHUh?=
DB NIT2T4dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUPMNIdzUUN3ME2zMlQyKG6P NFvpUoJUSU6JRWK=
TE-15 NYTVbmh4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{DtSWlEPTB;Mz60N{BvVQ>? MnvXV2FPT0WU
COR-L88 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF;CVXhKSzVyPUOuOFchdk1? NWS5fJZMW0GQR1XS
LAMA-84 MoruS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUHJR|UxRTNwNEmgcm0> NGHBZ4pUSU6JRWK=
MEG-01 NXX5ZYtuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mkj6TWM2OD1|LkS5JI5O NV6yR3VbW0GQR1XS
LOXIMVI NGPtTppIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVPJR|UxRTNwNTDuUS=> M1TPRXNCVkeHUh?=
RPMI-8402 MlLTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWnnNW16UUN3ME2zMlUhdk1? NGDmRmlUSU6JRWK=
KARPAS-45 M3XxeGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnLmTWM2OD1|LkW0JI5O Ml3FV2FPT0WU
HCC1187 MoHqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3G0NGlEPTB;Mz61OEBvVQ>? MmHyV2FPT0WU
MZ1-PC NF7HXplIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFHyc|hKSzVyPUOuOVQhdk1? NVfYe41ZW0GQR1XS
no-11 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGfpZpBKSzVyPUOuOVUhdk1? MkPUV2FPT0WU
EVSA-T MlTlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUTJR|UxRTNwNjDuUS=> NV2zOXNoW0GQR1XS
DJM-1 MkHtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{DJTWlEPTB;Mz62N{BvVQ>? NVzxWWVvW0GQR1XS
COLO-684 NV7vUpNMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUS1UZVNUUN3ME2zMlY3KG6P NW\DXIdUW0GQR1XS
NMC-G1 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXjJR|UxRTNwNkigcm0> MljEV2FPT0WU
LC-1F M1[z[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2PyTmlEPTB;Mz63OEBvVQ>? NEW4U4lUSU6JRWK=
RL95-2 NYHLbo9kT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkL1TWM2OD1|Lke5JI5O Mk\DV2FPT0WU
COLO-320-HSR MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnW0TWM2OD1|LkmyJI5O M1nESXNCVkeHUh?=
RCC10RGB NYe5RldMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1fSW2lEPTB;Mz65N{BvVQ>? M13PUHNCVkeHUh?=
HD-MY-Z NH;uO3VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVLJR|UxRTNwOUOgcm0> NV;NeYF4W0GQR1XS
NCI-H2141 NFTERoxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlvOTWM2OD12LkC1JI5O M1\YWnNCVkeHUh?=
K-562 NIL1OYlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4LpU2lEPTB;ND6xNkBvVQ>? M1frRXNCVkeHUh?=
NCI-H1648 M33xSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1XXU2lEPTB;ND6xN{BvVQ>? NIj1b|NUSU6JRWK=
OMC-1 NGTVTpNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVjSUVB[UUN3ME20MlE5KG6P Ml\VV2FPT0WU
LB647-SCLC Mn[1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MorFTWM2OD12LkKyJI5O MlPyV2FPT0WU
TE-12 MkfDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFTqSFhKSzVyPUSuNlUhdk1? MmjsV2FPT0WU
NOMO-1 MoXzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWjJR|UxRTRwM{Ogcm0> MoS5V2FPT0WU
Raji M13yO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXzlZmFDUUN3ME20MlQ3KG6P MmD3V2FPT0WU
NALM-6 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWnJR|UxRTRwNEmgcm0> NWnVPXFmW0GQR1XS
HL-60 NVrYd4d[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHH0eVJKSzVyPUSuOlchdk1? NG\Q[mNUSU6JRWK=
IST-SL1 M33LbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWLhNIlDUUN3ME20MlY5KG6P NES3eolUSU6JRWK=
MHH-PREB-1 MmqyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4HkPGlEPTB;ND64OkBvVQ>? NVvzV4NVW0GQR1XS
MHH-NB-11 MorFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHXZc3VKSzVyPUSuPVEhdk1? M{jEPXNCVkeHUh?=
JiyoyeP-2003 MoHlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXfJR|UxRTVibl2= Ml64V2FPT0WU
SBC-1 M{S1VGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnS2TWM2OD13LkCxJI5O MoHTV2FPT0WU
CHP-126 MlvnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVuxUo54UUN3ME21MlA3KG6P MWfTRW5ITVJ?
LU-139 NFroW4ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3zEWGlEPTB;NT6xN{BvVQ>? MmLtV2FPT0WU
NCI-SNU-5 MmrFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYrJR|UxRTVwMUegcm0> M2DaV3NCVkeHUh?=
SW962 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFGwbGxKSzVyPUWuNlEhdk1? MonqV2FPT0WU
EW-1 NFzrOFBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NI\OW4tKSzVyPUWuN|Ehdk1? MY\TRW5ITVJ?
NCI-H1417 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV30eZZlUUN3ME21MlUyKG6P MmHXV2FPT0WU
LU-65 NFXzVYpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXvjUW5vUUN3ME21Mlg1KG6P Mn;qV2FPT0WU
D-502MG NWDacGtmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4PCbWlEPTB;Nj6zO{BvVQ>? M33rWnNCVkeHUh?=
BC-3 MkH4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUHMV|ljUUN3ME22MlYyKG6P NFH3WGhUSU6JRWK=
GDM-1 NVu3OmJQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmnJTWM2OD14Lke3JI5O Mnq3V2FPT0WU
NCI-H2196 Ml2xS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEL2SnpKSzVyPU[uPEBvVQ>? NULYfVMxW0GQR1XS
NB1 MmOzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUTJR|UxRTZwOEigcm0> Mo\LV2FPT0WU
NCI-H345 MkS1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3zTOWlEPTB;Nz6yJI5O M4\ZOHNCVkeHUh?=
SU-DHL-1 MoXYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYfJR|UxRTdwMkSgcm0> MmfzV2FPT0WU
JVM-2 MmDHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{LrWWlEPTB;Nz6yPEBvVQ>? Ml74V2FPT0WU
LU-134-A NGHTSGlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWLINGppUUN3ME23MlM6KG6P MUDTRW5ITVJ?
NCI-H1694 MkP3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2LicmlEPTB;Nz61PEBvVQ>? NUPScZpwW0GQR1XS
NCI-SNU-16 NEjX[4VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3nm[GlEPTB;Nz62OUBvVQ>? NWfLemlOW0GQR1XS
L-363 NHzxelNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYHJR|UxRTdwNzDuUS=> MUnTRW5ITVJ?
KG-1 NWj4V4VJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX3JR|UxRTdwOUSgcm0> MmXaV2FPT0WU
MN-60 MmrFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHPudohKSzVyPUiuNVQhdk1? M3O5ZnNCVkeHUh?=
NB6 NE\TUm9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkTMTWM2OD16LkS4JI5O MnLaV2FPT0WU
MLMA MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1nyRmlEPTB;OD64OUBvVQ>? Mk\mV2FPT0WU
ATN-1 M1yxVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkLRTWM2OD16Lki5JI5O MoTCV2FPT0WU
SK-NEP-1 NE\GXGpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnO0TWM2OD17LkCxJI5O NUHVVIpYW0GQR1XS
DMS-114 NEDXOpdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWrFSm1pUUN3ME25MlYzKG6P MnXIV2FPT0WU
CTB-1 NHfrblBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2D3NWlEPTB;OT62O{BvVQ>? NIXRNGFUSU6JRWK=
NCI-H2081 M3z4TWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mnv3TWM2OD1zMD6wPUBvVQ>? M4LBcHNCVkeHUh?=
ES5 MnqyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{TUWGlEPTB;MUCuN|ghdk1? NEX6Z|FUSU6JRWK=
HCC1599 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1HrNGlEPTB;MUGuPVEhdk1? NFXsPIhUSU6JRWK=
NCI-H23 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYHmT|NjUUN3ME2xNk4yOiCwTR?= NXXvZ|VLW0GQR1XS
NCI-H1581 NXrQRmVqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmPHTWM2OD1zMj6yPEBvVQ>? NGO4SYlUSU6JRWK=
JVM-3 NFLUeo9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYfTW|h2UUN3ME2xNk46QSCwTR?= NX\p[XhVW0GQR1XS
NCI-SNU-1 NFfsPXpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF3XPJJKSzVyPUGzMlE6KG6P MkL3V2FPT0WU
NB7 MlvrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoruTWM2OD1zNT65NkBvVQ>? NFi3blVUSU6JRWK=
JAR MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWrvNHBzUUN3ME2xOk4yOyCwTR?= NXvGWIdmW0GQR1XS
TGW NX7OXo9[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGDnT3lKSzVyPUG2MlQ5KG6P MmXhV2FPT0WU
U-87-MG NYHQTGFiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NETjZYlKSzVyPUG2Mlc3KG6P MUHTRW5ITVJ?
NCI-H1436 M3;BZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NETR[JlKSzVyPUG3MlAyKG6P NXu2S4F2W0GQR1XS
GOTO NED3OVZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWLJR|UxRTF5LkC2JI5O M2XIUnNCVkeHUh?=
COLO-800 NYPFem9NT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mof2TWM2OD1zNz62OEBvVQ>? MlG1V2FPT0WU
MFM-223 NIrrd5hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4PxU2lEPTB;MUeuPVEhdk1? Moj1V2FPT0WU
EW-18 NHf0SmlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIjTRlVKSzVyPUG3Mlk3KG6P NIHnTGFUSU6JRWK=
NB14 M3qyZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlXQTWM2OD1zNz65PEBvVQ>? MX7TRW5ITVJ?
EB2 M3e4Z2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NILuSnNKSzVyPUG4MlA5KG6P M1nOS3NCVkeHUh?=
EoL-1- M{\GO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoO4TWM2OD1zOD6zNUBvVQ>? MXPTRW5ITVJ?
NCCIT MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUi5SJprUUN3ME2xPE4{PiCwTR?= MYTTRW5ITVJ?
DG-75 NIrEV2hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIDMbVFKSzVyPUG4MlYyKG6P NGD3NlNUSU6JRWK=
HCC2218 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MojLTWM2OD1zOT61JI5O NH23VphUSU6JRWK=
TE-6 NWTwfINOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mm\ETWM2OD1{MD6wPEBvVQ>? MVfTRW5ITVJ?
SF539 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4K4bmlEPTB;MkCuOlchdk1? M4jjSXNCVkeHUh?=
NCI-H446 NFy5e4JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NETYbJRKSzVyPUKxMlE5KG6P NIPhcINUSU6JRWK=
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... Click to View More Cell Line Experimental Data

In vivo試験 The anticancer effects of bortezomib as a single agent have been demonstrated in xenograft models of multiple myeloma, adult T-cell leukemia, lung, breast, prostate, pancreatic, head and neck, and colon cancer, and in melanoma. [2] Oral bortezomib 1.0 mg/ kg daily for 18 days causes tumor growth delays, as well as a decrease in the number of metastases in the Lewis lung cancer model. Bortezomib at a single dose of up to 5 mg/kg significantly decreased the surviving fraction of breast tumor cells. Bortezomib 1.0 mg/kg administrated weekly for 4 weeks reduces tumor growth by 60% in murine xenograft models of prostate cancer. 1.0 mg/kg Bortezomib administration for 4 weeks results in a 72% or 84% reduction in pancreatic cancer murine xenografts growth, as well as an increase in tumor cell apoptosis. 1.0 mg/kg Bortezomib treatment results in significant inhibition of human plasmacytoma xenograft growth, increase in tumor cells apoptosis and overall survival, and a decrease in tumor angiogenesis. [3]
臨床試験 A phase I study of weekly subcutaneous Bortezomib in patients with steroid-refractory or -dependent chronic graft versus host disease is currently in recruiting.
特集

プロトコル (参考用のみ)

キナーゼアッセイ:

[4]

Kinetic Methods In a typical kinetic run, 2.00 mL of assay buffer (20 mM HEPES, 0.5 mM EDTA, 0.035% SDS, pH 7.8) and Suc-Leu-Leu-Val-Tyr-AMC in DMSO are added to a 3 mL fluorescence cuvette, and the cuvette is placed in the jacketed cell holder of a fluorescence spectrophotometer. Reaction temperature is maintained at 37℃ by a circulating water bath. After the reaction solution has reached thermal equilibrium (5 minutes), 1 μL−10 μL of the stock enzyme solution is added to the cuvette. Reaction progress is monitored by the increase in fluorescence emission at 440 nm (λex= 380 nm) that accompanies cleavage of AMC from peptide-AMC substrates.

細胞アッセイ:

[5]

細胞株 Human multiple myeloma cells line U266
濃度 ~10 μM
反応時間 2 days
実験の流れ

The inhibitory effect of Bortezomib on cell growth is assessed by measuring MTT dye absorbance of the cells. Cells from 48-hour cultures are pulsed with 10 μL of 5 mg/mL MTT to each well for the last 4 hour of 48-hour cultures, followed by 100 μL of isopropanol containing 0.04 N HCl. Absorbance is measured at 570 nm using a spectrophotometer.

動物実験:

[3]

動物モデル Human plasmacytoma xenografts RPMI 8226
製剤 Saline
投薬量 1 mg/kg
投与方法 i.v. twice weekly for 4 weeks, then once weekly

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download Bortezomib (PS-341) SDF
分子量 384.24
化学式

C19H25BN4O4

CAS No. 179324-69-7
保管 2年-20℃
6月-80℃in solvent
別名 LDP-341, MLM341
溶解度 (25°C) * In vitro DMSO 76 mg/mL (197.79 mM)
<1 mg/mL (<1 mM)
エタノール <1 mg/mL (<1 mM)
In vivo 2% DMSO+30% PEG 300+ddH2O 5mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* 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.
化学名 B-​[(1R)​-​3-​methyl-​1-​[[(2S)​-​1-​oxo-​3-​phenyl-​2-​[(2-​pyrazinylcarbonyl)​amino]​propyl]​amino]​butyl]​-boronic acid

カスタマーフィードバック (20)


Click to enlarge
Rating
Source Sci Transl Med, 2015, 6(250), 250ra112. Bortezomib (PS-341) purchased from Selleck
Method Western blots
Cell Lines Primary myoblasts
Concentrations 10, 50 uM
Incubation Time 24 h
Results To demonstrate the biological functionality of the salvaged missense mutated dysferlin protein, we performed membrane resealing experiments on primary myoblasts derived from percutaneous muscle biopsies taken from patient 2. Bortezomib treatment of primary myoblasts increased dysferlin expression in a dose-dependent manner, and bortezomib-treated myoblasts regained their capability to reseal laser-induced plasma membrane injuries.

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Source J Clin Invest, 2014, 124(9), 3757-66. Bortezomib (PS-341) purchased from Selleck
Method Fluorescence
Cell Lines Primary myoblasts
Concentrations 2 mg/kg
Incubation Time 2 weeks
Results To examine this further, it determined whether inhibition of the proteasome with bortezomib blocked proplatelet formation in murine megakaryocytes. Similar responses were observed in human megakaryocytes, and removal of bortezomib from the incubation media restored proplatelet formation.

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Source J Cell Biol, 2014, 205(6), 771-80. Bortezomib (PS-341) purchased from Selleck
Method Immunofluorescence
Cell Lines Mouse primary osteoblasts
Concentrations 25 nM
Incubation Time 2 h
Results In support of this idea, the PTH-induced decrease of HDAC4 accumulation in osteoblasts was prevented by the addition of an inhibitor of proteasomal degradation, bortezomib.

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Source Cancer Res, 2015, 75(8), 1714-24. Bortezomib (PS-341) purchased from Selleck
Method H&E staining, Western blots, TUNEL assays
Cell Lines Foxp3flox/yxPBCre4+ mice
Concentrations 1 mg/kg
Incubation Time 60 weeks
Results Reduced cell proliferation was also observed in prostate epithelial cells of bortezomib-treated mice by Ki67 staining analysis (A). Furthermore, lack of nuclear p65 was observed in the bortezomib-treated prostate at 12 hours after LPS injection (B). To verify the impact of bortezomib treatment on NF-kB activation, we observed the expression of NF-kB targets in the mouse prostate. In contrast to the prostate-specific expression in untreated Foxp3cKO mice, the expression levels of Bcl2l1 and Traf1/2 were significantly downregulated in the prostates of treated mice (C). Importantly, the percentage of apoptotic prostate epithelial cells increased after bortezomib treatment (D).

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Source Cell Death Differ, 2014, 21(12), 1838-51. Bortezomib (PS-341) purchased from Selleck
Method Immunofluorescence microscopy
Cell Lines HeLa cells
Concentrations 100 nM
Incubation Time 45 min
Results Bortezomib and NH4Cl also increased the adjacency of DRIPs to SGs.

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Source Development, 2011, 138, 2903-2908. Bortezomib (PS-341) purchased from Selleck
Method Immunofluorescence
Cell Lines wild-type oocytes, Fmn2-/-oocytes
Concentrations 0.1 μM
Incubation Time 90 min
Results Endogenous Fmn2, localized in the cortex of prophase I oocytes, disappeared at NEBD, reappeared later and was enriched in the cortex opposite the spindle. Fmn2 -/-oocytes lacked cortical Fmn2 staining, suggesting that the staining is specific. Cortical localization was maintained at NEBD in wild-type oocytes treated with the proteasome inhibitor, Bortezomib, indicating that Fmn2 is degraded at NEBD.

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Source Oncotarget, 2015, 51: S659-S660. Bortezomib (PS-341) purchased from Selleck
Method Immunofluorescence Analysis
Cell Lines RS4;11cells
Concentrations 2.5 nM
Incubation Time 22 h
Results In RS4;11 samples combined treatment induces Ser536 p-NF-κB nuclear translocation (see white arrows).

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Source Carcinogenesis , 2010, 31, 1948–1955. Bortezomib (PS-341) purchased from Selleck
Method Luciferase assay
Cell Lines LNCaP-AI cells, LNCaP cells
Concentrations 20 μM
Incubation Time 24 h
Results EGF significantly stimulates the promoter activity of sPLA2-IIa gene in both LNCaP and LNCaP-AI cells (shown in LNCaP-AI cells), whereas Bortezomib and other inhibitors tested downregulated the promoter activity both at the basal level (shown in LNCaP cells) and in response to EGF stimulation (shown in LNCaP-AI cells).

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Source Carcinogenesis, 2010, 31, 1948–1955. Bortezomib (PS-341) purchased from Selleck
Method ELISA
Cell Lines LNCaP-AI cells
Concentrations 20 μM
Incubation Time 24 h
Results Bortezomib, Lapatinib, and LY294002 significantly inhibited sPLA2-IIa secretion, whereas Erlotinib, Gefitinib and CI-1033 had a moderate effect in LNCaP-AI cells.

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Source J Biol Chem, 2010, 285, 41074-41086. Bortezomib (PS-341) purchased from Selleck
Method Real Time PCR
Cell Lines HepAD38 cells
Concentrations 2-50 nM
Incubation Time 18 h
Results An inhibitory effect of proteasome inhibition by bortezomib on HBV replication can be observed in cell culture.Therefore, proteasome activation seems to be a valuable strategy of the infected cells to reduce the stress resulting from misfolded proteins.

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Source J Virol, 2010, 84, 9439–9451. Bortezomib (PS-341) purchased from Selleck
Method Proteasome activity assay, Standard plaque assay
Cell Lines A549 cells
Concentrations 10-100 nM
Incubation Time 1 h
Results As expected bortezomib treatment resulted in a block of viral replication of the avian influenzavirus strain A/FPV/Bratislava/79 (H7N7; FPV) in a concentration-dependent manner. While concentrations of 10 nM had no antiviral effect, 50 nM led to a significant titer reduction of up to 3 orders of magnitude (Fig.A). The highest concentration used (100 nM) led to a titer reduction of up to 4 orders of magnitude.These results were also confirmed in a virus growth kinetics study in infected cells that received a single dose of 50nM bortezomib. Virus titers were reduced at every time point analyzed (Fig.C).Since bortezomib is a proteasome inhibitor, we investigated whether the antiviral concentrations of bortezomib may have an inhibitory effect on the 26S proteasome in A549 cells. A concentration-dependent inhibition of the proteasome was observed in FPV-infected A549 cells at 24 h p.i. (Fig. B).

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Source J Virol, 2010, 84, 9439–9451. Bortezomib (PS-341) purchased from Selleck
Method Standard plaque assay, Western blot
Cell Lines A549 cells
Concentrations 50 nM
Incubation Time 1-10 h
Results A strong antiviral activity of bortezomib was observed upon addition of the compound up to 2 h p.i. At time points of 4 h p.i. and later, a dramatic decrease in the antiviral efficacy was observed. This indicates that the event in the viral life cycle that is affected by bortezomib occurs within the first 4 h. Since this correlates with the strong onset of viral gene and protein expression, we analyzed whether viral protein accumu-lation is affected by bortezomib. Indeed, we observed a strong reduction in viral matrix protein (M1) and PB1 polymerase synthesis in FPV- and PR8-infected cells at 5 h and 8 h p.i.

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Source J Virol, 2010, 84, 9439–9451. Bortezomib (PS-341) purchased from Selleck
Method Western blot
Cell Lines A549 cells
Concentrations 50 nM
Incubation Time 1/6/24 h
Results After a 6-h treatment with 50 nM bortezomib, activation of JNK was detected as evidenced by phosphorylation of the kinase at Thr183 and Tyr185 (lane 4). This was even enhanced upon a 24-h treatment (lane 6). Downstream substrates of JNK are the AP-1 transcription factors c-Jun and ATF-2, which are activated by JNK-mediated phosphorylation at Ser63 and Thr71, respectively. Consistent with JNK activation, we also found c-Jun and ATF-2 were phosphorylated and activated( lane 6), leading to the conclusion that, besides NF-κB, the JNK/c-Jun/ATF-2 pathway is also activated in A549 upon bortezomib treatment.

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Source J Virol, 2011, 85, 2781–2792. Bortezomib (PS-341) purchased from Selleck
Method Western blot
Cell Lines MA104 cells
Concentrations 0.1-10 μM
Incubation Time 1/7 h
Results Proteasome inhibitors which have different inhibition mechanisms, such as bortezomib and lactacystin, had a strong effect on virus replication in parallel with an increase in p53 accumulation.

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Source J Virol, 2011, 85, 2781–2792. Bortezomib (PS-341) purchased from Selleck
Method Western blot
Cell Lines MA104 cells
Concentrations 10 μM
Incubation Time 5-10 h
Results Further kinetic experiments were performed to better define the time window within the viral replication cycle in which proteasome activity was required. For this, cells were infected for 1 h and treated with MG132 or bortezomib for 4h at different times postinfection (Fig. A). As shown in Fig. B, a more clear arrest on viral protein accumulation was observed when bortezomib or MG132 was added at relatively earlier time points. Indeed, when inhibitors were added at 5 h p.i. or later, the effect was much reduced, suggesting that once the infection was well established with a robust accumulation of viroplasms, the requirement for proteasome activity was less significant.

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Source J Virol, 2011, 85, 2781–2792. Bortezomib (PS-341) purchased from Selleck
Method Immunofluorescence
Cell Lines NSP5-EGFP cells
Concentrations 10 μM
Incubation Time 2-8 h
Results Both MG132 and bortezomib induced a significant arrest on the formation of viroplasms, which appeared in reduced number and with smaller size with respect to those in control cells, particularly when added at time points between 1 h and 5 h p.i.

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Source J Virol, 2011, 85, 2781–2792. Bortezomib (PS-341) purchased from Selleck
Method Quantification of viroplasms
Cell Lines NSP5-EGFP cells, MA104 cells
Concentrations 10 μM
Incubation Time 4 h
Results The number of viroplasms per cell in cells treated for 4 h with MG132 or bortezomib was almost the same as that found in cells fixed at the beginning of each treatment, strongly suggesting that inhibition of proteasome activity affected the assembly of new viroplasms and their growth.

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Source PLoS One, 2011, 6, e23712. Bortezomib (PS-341) purchased from Selleck
Method Western blotting
Cell Lines HEK293 cells
Concentrations 50 μM
Incubation Time 4 h
Results Upon proteasome inhibition by Bortezomib an increased amount of around 5-6 fold of biotinylated molecules was detected, both in the absence and presence of US2 and US11.

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Source 2011, Mireia Vila Gasull University of Porto. Bortezomib (PS-341) purchased from Selleck
Method Western Blotting
Cell Lines KKU-M213 cells
Concentrations 0/20/40 nM
Incubation Time 0-12 h
Results We checked the effects of BTZ on the NF-κB pathway in KKU-M213 (Fig. a, b). BTZ induced IκB phosphorylation in dose- and time-dependent manners (Fig. a). Interestingly, reduced IκB was observed over time until it was barely detectable 12 h after treatment; as a result, nuclear NF-κB (p65) was markedly increased (Fig. b).

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Source Mireia Vila Gasull University of Porto. 2011;Mireia Vila Gasull . Bortezomib (PS-341) purchased from Selleck
Method PB assay
Cell Lines S2-013
Concentrations
Incubation Time 24 h
Results It is noticed more deleterious effects by free bortezomib than by BTZ CS/GA nanoparticles.

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