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
MCF-7 M2jkWWN6fG:2b4jpZ{BCe3OjeR?= MVu1NEDPxE1? MWe0PEBp NFnXdI9FVVOR Moe1T4ltdHNiY3XscJMh[nlibX;y[UB1cGGwIEm5KS=> M3LZc|ExPDl7NkSz
OVCA 429 M1PhSGZ2dmO2aX;uJGF{e2G7 NWPITGxyOzByIH7N MWK0PEBp NUD6TG1qTE2VTx?= MWjEbZNzfXC2czDpcpRi[3RibYXseIlk\WyudXzhdkB1fW2xcjDzdIhmem:rZIO= NYrQ[JM1OTB7OUm3OlY>
RPMI8226 MonrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYHTN3RrOTByIH7N NFLaSmM1QCCq MmDRSG1UVw>? NUfaOXRWUUN3ME2zNEBvVQ>? NX7VVY5nOTF|ME[0PFk>
Dox40 M1jBc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M372ZVExOCCwTR?= M{fiPVQ5KGh? MWrEUXNQ NXHi[plWUUN3ME20NEBvVQ>? MWGxNVMxPjR6OR?=
MR20 NFvvZ21Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUCxNFAhdk1? MlTmOFghcA>? MWnEUXNQ NXXDXFNmUUN3ME2yNEBvVQ>? NGjuVZEyOTNyNkS4PS=>
LR5 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUTFPGhoOTByIH7N NV25cnY2PDhiaB?= M4r4dWROW09? MUDJR|UxRTJyIH7N M4PCdVEyOzB4NEi5
U266 NHTx[GtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVPsPI1wOTByIH7N MXi0PEBp NVXEWlkxTE2VTx?= MX3JR|UxRTNibl2= NV3CRoc2OTF|ME[0PFk>
IM-9 NHjEOo1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVvTOmF5OTByIH7N MkjvOFghcA>? MlPDSG1UVw>? MUDJR|UxRTZibl2= MX:xNVMxPjR6OR?=
Hs Sultan M3TJV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUWxNFAhdk1? NVnXdoJZPDhiaB?= NE\VVHNFVVOR NHq5NlJKSzVyPUKwJI5O MVOxNVMxPjR6OR?=
PAM-LY2 NETiZYJHfW6ldHnvckBCe3OjeR?= M1XXXlExOCCwTR?= MY[xNkBp NXrR[JVOTE2VTx?= NHTiR41KdmirYnn0d{BPTi4QulKgZYN1cX[jdHnvci=> NGK3S5QyOTN3MEmxNy=>
PAM 212 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIPTd4MyODBibl2= MVe3NkBp Mn\BSG1UVw>? NFXKZmJKdmirYnn0d{Bk\WyuII\pZYJqdGm2eR?= NF63NJMyOTN3MEmxNy=>
PAM-LY2 NGfr[4FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV2xNFAhdk1? NIL4cWk4OiCq MXrEUXNQ M2fGfmlvcGmkaYTzJINmdGxidnnhZoltcXS7 MYSxNVM2ODlzMx?=
B4B8 NI\hUWlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF3zWJgyODBibl2= M17L[VczKGh? M1ztTmROW09? NWjVWnltUW6qaXLpeJMh[2WubDD2bYFjcWyrdIm= NUWxdo5tOTF|NUC5NVM>
B7E3 M3\GTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWmxNFAhdk1? MkP1O|IhcA>? NXXZe4tXTE2VTx?= MVTJcohq[mm2czDj[YxtKH[rYXLpcIl1gQ>? M{HKVFEyOzVyOUGz
UM-SCC-9 NWW3V5ptT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXGxNFAhdk1? MYS3NkBp NH3mcVZFVVOR NV;zS4xKUW6qaXLpeJMh[2WubDD2bYFjcWyrdIm= NFrsNWcyOTN3MEmxNy=>
UM-SCC-11B NWfjemZoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlTINVAxKG6P M{fZ[|czKGh? MoTmSG1UVw>? M1LaeWlvcGmkaYTzJINmdGxidnnhZoltcXS7 M1PF[|EyOzVyOUGz
H460 NIPXXXRHfW6ldHnvckBCe3OjeR?= NILNOFEyOCEQvF2= NV[4dZY1OjRiaB?= NUDsNJc5TE2VTx?= M{K1VGlv\HWlZYOgRoNtNTJicHjvd5Bpd3K7bHH0bY9vKGGwZDDjcIVifmGpZTDjc5Jz\WyjdHXkJJdqfGhiR{KtUUBxcGG|ZTDhdpJme3R? NXfCUG9JOTJ2OUKxNVc>
U266 NEfYS3hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnKzOVAxKG6pL33s NX73fWQ5PDhiaB?= M3iwNmROW09? MmnhTY5pcWKrdIOgZ4VtdCCpcn;3eIg> MVixNlY{OTZzOR?=
ARH77 NHzxUJZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYizPY44PTByIH7nM41t NEjGO2w1QCCq NFTvS2NFVVOR NHvxXpRKdmirYnn0d{Bk\WyuIHfyc5d1cA>? NIXVRmMyOjZ|MU[xPS=>
WAD-1 NWmzeXNQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFO1dmU2ODBibnevcYw> MkjKOFghcA>? MVrEUXNQ M17lNGlvcGmkaYTzJINmdGxiZ4Lve5Rp M2LtS|EzPjNzNkG5
U266/LR7 NIHQOGZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWG1NFAhdmdxbXy= Mn;XOFghcA>? Mke5SG1UVw>? NWXue3RtUW6qaXLpeJMh[2WubDDndo94fGh? MVKxNlY{OTZzOR?=
U266/dox4 NGLPfWJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYq1NFAhdmdxbXy= MVy0PEBp MnTLSG1UVw>? MmXjTY5pcWKrdIOgZ4VtdCCpcn;3eIg> NYrjUmFyOTJ4M{G2NVk>
RPMI8226/LR5 NEfIRm1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3j3VFUxOCCwZz;tcC=> MXy0PEBp MVLEUXNQ MUfJcohq[mm2czDj[YxtKGe{b4f0bC=> MoHTNVI3OzF4MUm=
H460 NITjXIlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NW\yfYFJOTBizszN NXvhRZZIPzJiaB?= MYDEUXNQ NHXmW4dKSzVyPUGwNEBvVQ>? NIPVb4wyOjZ|MU[yNC=>
H358 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4XOWVExKM7:TR?= MlLyO|IhcA>? NYq5XHBZTE2VTx?= MXrJR|UxRTdyIH7N NInGXFkyOjZ|MU[yNC=>
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H460 NI\NOYRHfW6ldHnvckBCe3OjeR?= NEH6U3gyODBibl2= NYK3fJExOjRiaB?= Ml\nSG1UVw>? MYfJcoR2[2W|IFeyMW0ueGijc3WgZZJz\XO2IHHu[EB1fWK3bHnuJIF{e2WvYnz5MYRqe2G|c3XtZox6 M{W2b|EzPjNzNkKw
LNCap-Pro5 M4LWW2Z2dmO2aX;uJGF{e2G7 MmT5NUDPxE1? MVe0JIg> NYjkdo9jTE2VTx?= M17pRXN1[WKrbHn6[ZMheDV| MkfZNVQ3OTJ3M{K=
T29 NEHD[FBCeG:ydH;zbZMhSXO|YYm= M4LLb|UxKG6P MXO0PEBpKA>? MknISG1UVw>? Mn;GTY5lfWOnczDj[YxtKGGyb4D0c5Nqew>? M2HnUlE3Pzd6MUe5
T29Kt1 MUXBdI9xfG:|aYOgRZN{[Xl? NHfvXIM2OCCwTR?= NWHsc|lbPDhiaDC= MW\EUXNQ Mn:1TY5lfWOnczDj[YxtKGGyb4D0c5Nqew>? MUmxOlc4QDF5OR?=
HCT116 M364ZmFxd3C2b4Ppd{BCe3OjeR?= NX\wV|JjPTBibl2= NWPoXnZ7PDhiaDC= NWDXWVY5TE2VTx?= M3rO[Glv\HWlZYOgZ4VtdCCjcH;weI9{cXN? NXfnUppwOTZ5N{ixO|k>
HKe-3 NEnvfpFCeG:ydH;zbZMhSXO|YYm= MXe1NEBvVQ>? NIHvOFE1QCCqIB?= NVjtXmhUTE2VTx?= M3jtb2lv\HWlZYOgZ4VtdCCjcH;weI9{cXN? MXWxOlc4QDF5OR?=
NB-1691 NUjKSllyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3XFbFEh|ryP NEHOPHE4OiCq M13ueWlvcGmkaYTzJINmdGxicILvcIln\XKjdHnvckB1dyB3JR?= M2fpWlE4Pjh7Nki0
CHLA-255 M4e0e2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmTZNUDPxE1? M4X3WFczKGh? NFi1fpZKdmirYnn0d{Bk\WyuIIDyc4xq\mW{YYTpc44hfG9iMjW= NXzH[Wc5OTd4OEm2PFQ>
SK-N-AS NVz3fFg6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGrySokyKM7:TR?= MmDwO|IhcA>? MYHJcohq[mm2czDj[YxtKHC{b3zp[oVz[XSrb36geI8hOTBn MWexO|Y5QTZ6NB?=
NB-1691 NYKyUlBzTnWwY4Tpc44hSXO|YYm= M1TJWVExKG6P MXKyOEBp MmS3V4lodmmoaXPhcpRtgSC{ZXT1Z4V{KGOnbHzzJIlvKHSqZTDHNE9IOSCyaHHz[S=> M1\X[VE4Pjh7Nki0
CHLA-255 M3vuPWZ2dmO2aX;uJGF{e2G7 NHO5OJYyOCCwTR?= NEPlc4kzPCCq NEHGU2VOd2Snc4TsfUBz\WS3Y3XzJINmdGy|IHnuJJRp\SCJMD;HNUBxcGG|ZR?= M1H4WVE4Pjh7Nki0
RPMI 8226 NHXle3lHfW6ldHnvckBCe3OjeR?= MkKwNlAhdk1? MXu4JIg> M3TNenNq\26rZnnjZY51dHliZX7oZY5k\XNiTl[t{tpDKGGldHn2bZR6 MXSxPVQ{PjB3MB?=
MM.1S M3nOVmZ2dmO2aX;uJGF{e2G7 M4PaR|IxKG6P NFGzdGQ5KGh? MV7TbYdvcW[rY3HueIx6KGWwaHHuZ4V{KE6ILd86RkBi[3Srdnn0fS=> MUixPVQ{PjB3MB?=
U266 NU\YcVN4TnWwY4Tpc44hSXO|YYm= NYK2TYc5OjBibl2= M1fhVFghcA>? M{O2d3Nq\26rZnnjZY51dHliZX7oZY5k\XNiTl[t{tpDKGGldHn2bZR6 M1TkXVE6PDN4MEWw
OPM1 M1rwT2Z2dmO2aX;uJGF{e2G7 NYD5OHUxOjBibl2= M{jyOFghcA>? MoroV4lodmmoaXPhcpRtgSCnbnjhcoNmeyCQRj5OvmIh[WO2aY\peJk> MYOxPVQ{PjB3MB?=
INA6 MmTKSpVv[3Srb36gRZN{[Xl? M4HZZVIxKG6P M2Sz[|ghcA>? MonDV4lodmmoaXPhcpRtgSCnbnjhcoNmeyCQRj5OvmIh[WO2aY\peJk> NYPkVWRHOTl2M{[wOVA>
OPM2 MlLCSpVv[3Srb36gRZN{[Xl? M{XYbVIxKG6P NGDUbWo5KGh? NFLITI5UcWewaX\pZ4FvfGy7IHXubIFv[2W|IF7GMe67SiCjY4Tpeol1gQ>? NUe0PY1lOTl2M{[wOVA>
RPMI 8226 M1LvUGZ2dmO2aX;uJGF{e2G7 M4fiVFIxKG6P NIf3S4Q5KGh? M4XTVGlv\HWlZYOgSG5CKHO7boTo[ZNqew>? M1jvNlE6PDN4MEWw
BaF/3 MlPkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn\zNVAxKG6P MVi0PEBp MkjXTWM2OD14LkKgcm0> NEPLXIgzODNyNU[5Ni=>
BaF/3-p210 NYTnPVJJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGXwcGkyODBibl2= NHP6RmQ1QCCq NF\2elBKSzVyPUSuO{BvVQ>? NFzF[pAzODNyNU[5Ni=>
TCC-S Mn;qS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUjjTWhsOTByIH7N NGPZOnI1QCCq NH3ycWtKSzVyPUKuPEBvVQ>? MX6yNFMxPTZ7Mh?=
BaF/3 MYXGeY5kfGmxbjDBd5NigQ>? MkXQOkBvVQ>? MWC0PEBp NHywd5ZKdmS3Y3XzJIEh\3KnYYSgS|Eh[2WubD3jfYNt\SCjcoLld5Q> NEnvXIozODNyNU[5Ni=>
BaF/3-p210 MYDGeY5kfGmxbjDBd5NigQ>? NIPq[YQ3KG6P NX2xWpZoPDhiaB?= MorhTY5lfWOnczDhJJNtcWeqdDDHNUBk\WyuLXP5Z4xmKGG{cnXzeC=> MWmyNFMxPTZ7Mh?=
BaF/3-p210 NYm3WZhZTnWwY4Tpc44hSXO|YYm= NV;MUHZGPiCwTR?= MX:yOEBp MUfS[YR2[2W|IITo[UBxcG:|cHjvdplt[XSrb36gZY5lKHSqZTDhZ5Rqfmm2eTDv[kBT[g>? NEOwUWkzODNyNU[5Ni=>
Raji M3rUWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH:xTnkyKM7:TR?= M1rHR|I1KGh? NFXZVG9T\WS3Y3XzJINmdGxidnnhZoltcXS7wrC= NWXkbFRQOjFzN{C5PFg>
LCL-1 MnTxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXGxJO69VQ>? NGDrcJQzPCCq NUL2bZFNWmWmdXPld{Bk\WyuII\pZYJqdGm2edMg MmrSNlEyPzB7OEi=
LCL-2 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1niVVEh|ryP NVnXWJpiOjRiaB?= MoXDVoVlfWOnczDj[YxtKH[rYXLpcIl1gcLi NVrKcHRQOjFzN{C5PFg>
BJAB Mo\DS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGi5eWwyKM7:TR?= MUCyOEBp M2HxNnJm\HWlZYOgZ4VtdCC4aXHibYxqfHoEoB?= MVyyNVE4ODl6OB?=
SNT-13 NYTCU21ET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHXmfYUyKM7:TR?= Ml;nNlQhcA>? MYLS[YR2[2W|IHPlcIwhfmmjYnnsbZR6yqB? NFTmcGkzOTF5MEm4PC=>
SNT-16 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHzUWmYyKM7:TR?= NG\WUlkzPCCq MUfS[YR2[2W|IHPlcIwhfmmjYnnsbZR6yqB? NVXyTpZDOjFzN{C5PFg>
Jurkat MlW0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2fWWVEh|ryP MlrzNlQhcA>? NXTrb2RPWmWmdXPld{Bk\WyuII\pZYJqdGm2edMg NHnMPGEzOTF5MEm4PC=>
KAI-3 NUDMZZJPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXHY[phROSEQvF2= NUXqb3diOjRiaB?= M{f4dnJm\HWlZYOgZ4VtdCC4aXHibYxqfHoEoB?= NYXGXpF3OjFzN{C5PFg>
SNK-6 NHP0OIxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3\sUlEh|ryP NXLwcHN[OjRiaB?= NF3nc41T\WS3Y3XzJINmdGxidnnhZoltcXS7wrC= NUnpUJV7OjFzN{C5PFg>
KHYG-1 NHvY[pFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3vYb|Eh|ryP NVvJSG5EOjRiaB?= M33oeHJm\HWlZYOgZ4VtdCC4aXHibYxqfHoEoB?= MY[yNVE4ODl6OB?=
SNT-16 NVOwR4g2SXCxcITvd4l{KEG|c3H5 MWCxJO69VQ>? MXy2JIg> MUfJcoR2[2W|IHPlcIwh[XCxcITvd4l{ NULxbHZQOjFzN{C5PFg>
Jurkat Mn:3RZBweHSxc3nzJGF{e2G7 NWHDN2pIOSEQvF2= NIHRW2Y3KGh? M3nIWWlv\HWlZYOgZ4VtdCCjcH;weI9{cXN? MWKyNVE4ODl6OB?=
KAI-3 MnK2RZBweHSxc3nzJGF{e2G7 NIflboYyKM7:TR?= MoHwOkBp NH3Yb|dKdmS3Y3XzJINmdGxiYYDvdJRwe2m| MVWyNVE4ODl6OB?=
KHYG-1 Mn7HRZBweHSxc3nzJGF{e2G7 MW[xJO69VQ>? MluzOkBp NYrMU5dxUW6mdXPld{Bk\WyuIHHwc5B1d3Orcx?= NYP6UZRvOjFzN{C5PFg>
SNT-13 MXjBcpRqfmm{YXygRZN{[Xl? MlHsNUDPxE1? M{TjcVI1KGh? NWOxTmNEUW6mdXPld{BtgXSrYzDpcoZm[3Srb36gc4YhTUKY MkPXNlEyPzB7OEi=
SNT-16 MVPBcpRqfmm{YXygRZN{[Xl? NVvEW3A5OSEQvF2= MW[yOEBp NFTWT49KdmS3Y3XzJIx6fGmlIHnu[oVkfGmxbjDv[kBGSlZ? MlK4NlEyPzB7OEi=
KAI-3 MmnZRY51cX[rcnHsJGF{e2G7 M2L6[|Eh|ryP NUO5dnMzOjRiaB?= M1LxVGlv\HWlZYOgcJl1cWNiaX7m[YN1cW:wIH;mJGVDXg>? M{nPPVIyOTdyOUi4
SNK-6 NGnLRo5CdnSrdnnyZYwhSXO|YYm= NGDaPVgyKM7:TR?= NF:wVoEzPCCq MXvJcoR2[2W|IHz5eIlkKGmwZnXjeIlwdiCxZjDFRnY> NYWwWow5OjFzN{C5PFg>
RAW 264.7 Mmn5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUexNFAhdk1? NFvpZXM1QCCq NGq1bVVT\WS3Y3XzJINmdGxidnnhZoltcXS7wrC= MX[yNlQzPzF3NB?=
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BLM M1\jcmFxd3C2b4Ppd{BCe3OjeR?= NYXaeY96OTBibl2= NHjRc2EzPCCq NESzVHhKdmS3Y3XzJINmdGxiYYDvdJRwe2m| NUTJR3pWOjNyN{mwPFM>
A375 MVXBeZRweGijZ4mgRZN{[Xl? MnvjNVAhdk1? M4PyRVEzKGh? M2G4O2lv\HWlZYOg[o9zdWG2aX;uJI9nKGG3dH;wbIFod3OxbXXz NXy0RopVOjNyN{mwPFM>
BLM M4m4VGF2fG:yaHHnfUBCe3OjeR?= MVixNEBvVQ>? NUXpUG93OTJiaB?= M3jPdGlv\HWlZYOg[o9zdWG2aX;uJI9nKGG3dH;wbIFod3OxbXXz NYLPW4toOjNyN{mwPFM>
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Hut-78 M3HrcGZ2dmO2aX;uJGF{e2G7 M1LuUlExOCCwTR?= NV;lTIR[OjRiaB?= NX71T2RnTE2VTx?= NW\tZ5dFTG:5boLl[5Vt[XSnczDUS2Yu|rJzIHHu[EBKVC1zMDDlfJBz\XO|aX;u NWqyZngyOjV4OEGzN|U>
H9 MmnCSpVv[3Srb36gRZN{[Xl? MkflNVAxKG6P MYCyOEBp NHKzTWRFVVOR Ml\ZSI94dnKnZ4XsZZRmeyCWR1[t{tIyKGGwZDDJUE0yOSCneIDy[ZN{cW:w MVyyOVY5OTN|NR?=
HH MV;GeY5kfGmxbjDBd5NigQ>? NX7DbJlNOTByIH7N MWeyOEBp NFjyWW5FVVOR M1X0W4Rwf26{ZXf1cIF1\XNiVFfGMe6zOSCjbnSgTWwuOTJiZYjwdoV{e2mxbh?= MoXINlU3QDF|M{W=
Hut-78 NYPlXZRkVWmpcnH0bY9vKEG|c3H5 NHvYbokyODBibl2= M4fXPFI1KGh? NIrZelhFVVOR MmPjVoVlfWOnczDj[YxtKG2rZ4LheIlwdiCkeTC4NQKBmzlyJR?= NIPDNFczPTZ6MUOzOS=>
HH MljyUYloemG2aX;uJGF{e2G7 NFPCV5EyODBibl2= MmXXNlQhcA>? NVu2cmNYTE2VTx?= NVzVO3BMWmWmdXPld{Bk\WyuIH3p[5JifGmxbjDifUA5OOLCk{mxKS=> NXTwVHlROjV4OEGzN|U>
U937 NHS3ZZlHfW6ldHnvckBCe3OjeR?= NFLtPXMyODBibl2= NIfjeJY3KGh? NHXBemFKdmS3Y3XzJGlNNThiZYjwdoV{e2mxbjDpckBNWFNvc4TpcZVt[XSnZDDVPVM4KG2jY4LvdIhi\2W| M3nKbVI2PzlzNEe3
human PBMC MknCSpVv[3Srb36gRZN{[Xl? M4TXe|ExOCCwTR?= M3;jclI1KGh? M4HzSmlv\HWlZYOgTWwuQCC{ZXzlZZNm MlXaNlU4QTF2N{e=
ES6 Mke4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEn4d4lKSzVyPUCuNFAzOSCwTR?= MonMV2FPT0WU
SK-UT-1 M4TqeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3fzc2lEPTB;MD6xOlMhdk1? NVGwcWdlW0GQR1XS
SH-4 M4X3U2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkXZTWM2OD1yLkG3N{BvVQ>? MXLTRW5ITVJ?
TE-9 NV3ufXBPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3;hTmlEPTB;MD6xPFIhdk1? NVraVlVQW0GQR1XS
A253 NGHROYtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkDsTWM2OD1yLkKwPEBvVQ>? NEi0emVUSU6JRWK=
no-10 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF;FZ|VKSzVyPUCuNlEhdk1? MlPaV2FPT0WU
MMAC-SF MorES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEPqOGhKSzVyPUCuNlE3KG6P MmPBV2FPT0WU
A101D NF3kV3RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUHJR|UxRTBwMkK1JI5O M1e5fHNCVkeHUh?=
NTERA-S-cl-D1 NGXLcpBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NES5NnFKSzVyPUCuNlQ{KG6P NIO1R5lUSU6JRWK=
8-MG-BA NXjSW45rT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGrEdZRKSzVyPUCuNlUhdk1? NH;qPHJUSU6JRWK=
KNS-42 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFTUc25KSzVyPUCuNlU5KG6P MYPTRW5ITVJ?
LXF-289 NHXZb|BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnPkTWM2OD1yLkK2PUBvVQ>? MVLTRW5ITVJ?
OVCAR-4 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4LJU2lEPTB;MD6yPFkhdk1? M4XwT3NCVkeHUh?=
LOUCY MorqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1P3TWlEPTB;MD6yPVMhdk1? NXG1doI2W0GQR1XS
BB65-RCC MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVTJR|UxRTBwM{C0JI5O MV7TRW5ITVJ?
D-542MG MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnPkTWM2OD1yLkOyPUBvVQ>? MlTWV2FPT0WU
ONS-76 MmfYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF;tSZRKSzVyPUCuN|Mhdk1? NXnTfHNbW0GQR1XS
BB30-HNC MojSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGfFPW1KSzVyPUCuN|M2KG6P NF3QZVJUSU6JRWK=
KS-1 MoX0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1XodWlEPTB;MD6zOEBvVQ>? MVvTRW5ITVJ?
A388 NIL2VoNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYLJR|UxRTBwM{W2JI5O NXvTWW5tW0GQR1XS
ES8 M3z6PWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2L0c2lEPTB;MD60JI5O M13QbnNCVkeHUh?=
MZ2-MEL NVHMcVN{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYX0NGJNUUN3ME2wMlQxPyCwTR?= NGnxZopUSU6JRWK=
HCC2998 NEPpPIJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoPKTWM2OD1yLkSxNkBvVQ>? NIDBb41USU6JRWK=
D-247MG NGe4WGNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml7QTWM2OD1yLkSxN{BvVQ>? NHnrXVBUSU6JRWK=
ACN M3T3TWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVTJR|UxRTBwNEG3JI5O Ml3uV2FPT0WU
LB2518-MEL MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NW\sW2VWUUN3ME2wMlQzPSCwTR?= MVTTRW5ITVJ?
ES1 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M36yfGlEPTB;MD60N{BvVQ>? M4jCRXNCVkeHUh?=
HCE-T MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF3pTXJKSzVyPUCuOFM6KG6P MVLTRW5ITVJ?
OS-RC-2 M1rpWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4nPW2lEPTB;MD60OEBvVQ>? NWTTbYxLW0GQR1XS
MFH-ino NFjHTVRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVfJR|UxRTBwNESzJI5O NUL4RnJWW0GQR1XS
OCUB-M NITQcZhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3rmV2lEPTB;MD60OFchdk1? NFLqNWRUSU6JRWK=
CP66-MEL NYG1U25UT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlrlTWM2OD1yLkS3N{BvVQ>? MmnmV2FPT0WU
LB771-HNC NXHadmdtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3P3SmlEPTB;MD60O|Qhdk1? NXrYdGZ{W0GQR1XS
DSH1 Mn73S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWnn[JN[UUN3ME2wMlQ5KG6P NVjycJVCW0GQR1XS
HUTU-80 NWfQeHdDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVn6bodoUUN3ME2wMlU{OyCwTR?= MUjTRW5ITVJ?
CESS Mni2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml;vTWM2OD1yLkWzPEBvVQ>? M37rU3NCVkeHUh?=
NCI-H747 NXm4OmxOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHTIV4lKSzVyPUCuOVM6KG6P NVjKZ2lEW0GQR1XS
HT-144 Ml;aS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MULJR|UxRTBwNUe2JI5O NHHGWpZUSU6JRWK=
COLO-829 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYnJR|UxRTBwNkG0JI5O Mlj3V2FPT0WU
A4-Fuk M1;acWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2TXUmlEPTB;MD62NlMhdk1? NXG1XYZ{W0GQR1XS
GI-ME-N MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGjiUoFKSzVyPUCuOlM1KG6P NGfkbpFUSU6JRWK=
LB831-BLC MnjUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHrsXoZKSzVyPUCuOlQyKG6P MUXTRW5ITVJ?
HOP-62 NFTNXYJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3TTcWlEPTB;MD62OFchdk1? M1HOVHNCVkeHUh?=
BB49-HNC MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3zhSGlEPTB;MD62OVIhdk1? NYTQcIVqW0GQR1XS
D-336MG MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1zsemlEPTB;MD62OVchdk1? NWLMdFd3W0GQR1XS
TK10 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXvJR|UxRTBwNke5JI5O M33YdXNCVkeHUh?=
Ramos-2G6-4C10 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYnOT5BLUUN3ME2wMlY6OyCwTR?= NHXKR3ZUSU6JRWK=
LB373-MEL-D Mk\6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmXkTWM2OD1yLkegcm0> NWD1dId7W0GQR1XS
SF126 NULjS5RxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnPBTWM2OD1yLkewNUBvVQ>? MXHTRW5ITVJ?
UACC-257 NFrrNZpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWHJR|UxRTBwN{Ggcm0> Mn;zV2FPT0WU
KINGS-1 MkjwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NITI[ohKSzVyPUCuO|IzKG6P NILDfFFUSU6JRWK=
LS-513 M17ocWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnTvTWM2OD1yLkezPUBvVQ>? M3i5cXNCVkeHUh?=
GI-1 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIL6c4JKSzVyPUCuO|Y1KG6P NUjYU3plW0GQR1XS
ES7 NXvRSFkxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mnj3TWM2OD1yLke2OkBvVQ>? NYf2VHRlW0GQR1XS
LB2241-RCC M4XORmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2SwfWlEPTB;MD64NFQhdk1? Mo[4V2FPT0WU
D-263MG MofLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHnlOnNKSzVyPUCuPFA4KG6P MXfTRW5ITVJ?
SW684 M4n5Rmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXmzbGNWUUN3ME2wMlgzOSCwTR?= NGnpOY5USU6JRWK=
ML-2 M1[0cmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFzaWJJKSzVyPUCuPFIyKG6P NIS1OVNUSU6JRWK=
SK-LMS-1 NETG[Y9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4\m[GlEPTB;MD64OVQhdk1? MlfUV2FPT0WU
TE-5 MkfoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4HQUWlEPTB;MD64OlUhdk1? MkXxV2FPT0WU
QIMR-WIL MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXLJR|UxRTBwOEi5JI5O MYDTRW5ITVJ?
NCI-H1355 NUO5WXpnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3z6N2lEPTB;MD64PVUhdk1? MYfTRW5ITVJ?
SNB75 M{CxTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mnf6TWM2OD1yLkmxNkBvVQ>? M2X3dnNCVkeHUh?=
RXF393 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFLZR2tKSzVyPUCuPVE1KG6P MYrTRW5ITVJ?
IST-MEL1 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NE\2RlBKSzVyPUCuPVE4KG6P MWnTRW5ITVJ?
SF268 NHrrdIFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2Hh[2lEPTB;MD65NlMhdk1? NULaeHV1W0GQR1XS
KALS-1 M2TNbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIDibnlKSzVyPUCuPVI2KG6P MliwV2FPT0WU
HC-1 NX72ZY1ET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYjISnJYUUN3ME2wMlk4PSCwTR?= M4TzbXNCVkeHUh?=
SW872 NIf1fI9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEntZWRKSzVyPUCuPVk3KG6P MofFV2FPT0WU
PSN1 M4fEfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHnqUW1KSzVyPUGuNFEhdk1? MUPTRW5ITVJ?
TE-1 NFnOclRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4PafGlEPTB;MT6wN{BvVQ>? NXHFXZp7W0GQR1XS
TE-10 NF3YVZlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWrJR|UxRTFwMEOgcm0> NX3Rb4tCW0GQR1XS
RKO MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{LmXWlEPTB;MT6wOkBvVQ>? NHzCdIxUSU6JRWK=
LC-2-ad NGL4OHpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MonqTWM2OD1zLkC4JI5O MVvTRW5ITVJ?
SK-MM-2 M4XzV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXjJR|UxRTFwMEmgcm0> M2Xi[XNCVkeHUh?=
VA-ES-BJ MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVHJR|UxRTFwMEmgcm0> Mm\rV2FPT0WU
MZ7-mel M{LXWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIfDbnRKSzVyPUGuNFkhdk1? NIH2VIxUSU6JRWK=
D-392MG M3nab2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGjxWZdKSzVyPUGuNUBvVQ>? NF;wSndUSU6JRWK=
CCRF-CEM MmP0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUjJR|UxRTFwMUOgcm0> NUCwPVdXW0GQR1XS
EM-2 NEjIVFZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mm\kTWM2OD1zLkG2JI5O MWPTRW5ITVJ?
HAL-01 NVK1dJAzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoDSTWM2OD1zLkG4JI5O MkPlV2FPT0WU
TE-8 MnThS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYXaTZp[UUN3ME2xMlE6KG6P MnrBV2FPT0WU
NCI-H1882 M2HjVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV3iTXU2UUN3ME2xMlIhdk1? M3Oy[HNCVkeHUh?=
Daudi NGDrPHJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVHJR|UxRTFwMkKgcm0> NEC3[pJUSU6JRWK=
BL-41 MnLyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1fQOWlEPTB;MT6yOUBvVQ>? NFXNVpBUSU6JRWK=
SR M4fnTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mk\3TWM2OD1zLkK1JI5O NXjwUnUyW0GQR1XS
KM12 Mkm0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYnJR|UxRTFwMkegcm0> MXLTRW5ITVJ?
K5 NIXFT|FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWrJR|UxRTFwMkigcm0> NWfzeGJLW0GQR1XS
A3-KAW MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYPBSFZ6UUN3ME2xMlI5KG6P M2fzTXNCVkeHUh?=
CMK MknZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3noTmlEPTB;MT6yPUBvVQ>? NV\WdpQ2W0GQR1XS
Calu-6 NX\ETGtyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVz0bGpHUUN3ME2xMlI6KG6P NF6wNJNUSU6JRWK=
IST-SL2 MnX2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYP1VJVCUUN3ME2xMlMyKG6P MX7TRW5ITVJ?
OPM-2 M3jJXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2XWNWlEPTB;MT6zN{BvVQ>? M1K5N3NCVkeHUh?=
DU-4475 M3j3ZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWflO|JuUUN3ME2xMlM3KG6P NXLSbVVTW0GQR1XS
ECC12 M1q1dmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVvJR|UxRTFwM{egcm0> NFWyUG9USU6JRWK=
L-540 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGnaOYlKSzVyPUGuN|chdk1? NVjhUpBmW0GQR1XS
CAS-1 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWDoU4dIUUN3ME2xMlM4KG6P MkD0V2FPT0WU
PF-382 MlLnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUjpNWNwUUN3ME2xMlQ4KG6P MXPTRW5ITVJ?
LS-411N NUfqZYM{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml\QTWM2OD1zLkWzJI5O NUDWfIFSW0GQR1XS
NCI-H69 M3;jcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHXuVnlKSzVyPUGuOVQhdk1? NXr2OGNGW0GQR1XS
NB12 M4rNOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX;ye2t{UUN3ME2xMlU3KG6P MWHTRW5ITVJ?
HEL NVLGR4x1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYDpbG5bUUN3ME2xMlYyKG6P M3HoTXNCVkeHUh?=
GCIY NVHjRWhnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn61TWM2OD1zLk[yJI5O NYTIdnBUW0GQR1XS
EHEB M{TjdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX:2[okxUUN3ME2xMlY4KG6P NGTBZ2tUSU6JRWK=
TGBC1TKB MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2\o[2lEPTB;MT63NUBvVQ>? MkjtV2FPT0WU
KURAMOCHI NFvG[5dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3rjW2lEPTB;MT63NkBvVQ>? MnjaV2FPT0WU
U-266 NFXzO5RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVy2RotkUUN3ME2xMlc3KG6P MmH2V2FPT0WU
LC4-1 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHG3NJZKSzVyPUGuO|khdk1? M3H4OHNCVkeHUh?=
NCI-H2126 NF;rclJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmPLTWM2OD1zLkigcm0> MYPTRW5ITVJ?
NCI-H1092 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVrJR|UxRTFwODDuUS=> Mk\kV2FPT0WU
GB-1 NEXWeolIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHHtZ5ZKSzVyPUGuPFEhdk1? NXjQcHh3W0GQR1XS
MV-4-11 Mlf3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3jac2lEPTB;MT64NkBvVQ>? NU\5c4g{W0GQR1XS
Becker NH7NV3ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIjKbY9KSzVyPUGuPFMhdk1? MY\TRW5ITVJ?
MPP-89 NFnkVW1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NE\EVmlKSzVyPUGuPFkhdk1? MUXTRW5ITVJ?
BE-13 MkDrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2nIfmlEPTB;MT65N{BvVQ>? NX30O|IzW0GQR1XS
697 NGfNPIdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGTPOW5KSzVyPUGuPVkhdk1? NF64O2FUSU6JRWK=
NKM-1 NH\NeoVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVLJR|UxRTJibl2= MVjTRW5ITVJ?
NB13 Mn70S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFTyVpRKSzVyPUKgcm0> M{nIbnNCVkeHUh?=
LS-123 MkG4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYXJR|UxRTJwMEKgcm0> NYfpVYdIW0GQR1XS
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DB Mm\zS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4OzRWlEPTB;Mz60NUBvVQ>? NHzSNJVUSU6JRWK=
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JiyoyeP-2003 M3HlPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1HpSmlEPTB;NTDuUS=> MmeyV2FPT0WU
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NCI-H1417 MnXhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHjVUVBKSzVyPUWuOVEhdk1? Mmj2V2FPT0WU
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NCI-H2196 MlWxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXHmNHNRUUN3ME22Mlghdk1? M4nMfnNCVkeHUh?=
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SU-DHL-1 NE\4RYRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUDJR|UxRTdwMkSgcm0> M4X2SXNCVkeHUh?=
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LU-134-A MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXLJR|UxRTdwM{mgcm0> MnvNV2FPT0WU
NCI-H1694 NHzDUmtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1PifmlEPTB;Nz61PEBvVQ>? M2nsfXNCVkeHUh?=
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DMS-114 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mmj2TWM2OD17Lk[yJI5O M1jNTXNCVkeHUh?=
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NCI-H23 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mo\hTWM2OD1zMj6xNkBvVQ>? MUnTRW5ITVJ?
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NCI-H1436 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUfJR|UxRTF5LkCxJI5O MVXTRW5ITVJ?
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HCC2218 Ml\wS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGfaRYNKSzVyPUG5MlUhdk1? MXPTRW5ITVJ?
TE-6 NFHIVVBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUTOUW17UUN3ME2yNE4xQCCwTR?= NXjifGV7W0GQR1XS
SF539 M{ftXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NG[zeFlKSzVyPUKwMlY4KG6P MnjqV2FPT0WU
NCI-H446 M1;GZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlPCTWM2OD1{MT6xPEBvVQ>? MkTTV2FPT0WU
IST-MES1 NYTHbmVLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUDJR|UxRTJ{Lke3JI5O MV3TRW5ITVJ?
NCI-H82 NYTVfHhHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVryXXozUUN3ME2yN{4xOiCwTR?= MmH3V2FPT0WU
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EW-12 MknqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1zKcGlEPTB;MkOuNVchdk1? MlL6V2FPT0WU
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EC-GI-10 NH3ZSmpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2GwNmlEPTB;MkSuNlMhdk1? NELoUXhUSU6JRWK=
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NH-12 NV7Xd4dvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXrJR|UxRTJ5Lk[3JI5O Ml;CV2FPT0WU
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ECC4 NHizVmlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2fnOmlEPTB;MkiuO|khdk1? MVLTRW5ITVJ?
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ES3 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4CzNmlEPTB;M{WuNVkhdk1? MWTTRW5ITVJ?
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D-283MED MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnS5TWM2OD1|Nz63PUBvVQ>? MVzTRW5ITVJ?
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NCI-H2227 NIf1ZlhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn7OTWM2OD12MD60PUBvVQ>? MmDiV2FPT0WU
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SCLC-21H NFLLOldIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWTZ[4RTUUN3ME2xOVkvPDFibl2= MYTTRW5ITVJ?
NCI-H1304 MmDBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUDYTVdoUUN3ME2xOlkvOjFibl2= NXHVXIU6W0GQR1XS
NCI-H510A MlzRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MULJR|UxRTF6NT6zO{BvVQ>? M3ToT3NCVkeHUh?=
NCI-H209 NXTIS2VCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFuzPFlKSzVyPUG5Ok42OiCwTR?= NV61NZY2W0GQR1XS
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NCI-H1395 NHmzTHNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX;JR|UxRTJzMD6xN{BvVQ>? NUHsflJ2W0GQR1XS
NCI-H1155 M1XocWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWTJZ3ZHUUN3ME2yN|AvOzJibl2= Mn3aV2FPT0WU
COR-L279 NYfMTHhQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV[0c4NRUUN3ME2yOVIvOTdibl2= MVXTRW5ITVJ?
NCI-H1299 NFXKfJpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYTJR|UxRTJ4MT63NUBvVQ>? MXzTRW5ITVJ?
EW-22 Ml\iS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{i0VWlEPTB;Mk[zMlc2KG6P MmjTV2FPT0WU
SK-MEL-2 MnHwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF;oSW5KSzVyPUK4NU46KG6P Ml:zV2FPT0WU
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NCI-H187 NH\4SYFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFnhUmZKSzVyPUK4O{4xQCCwTR?= NV\icmpsW0GQR1XS
NCI-H2171 NHrDNFFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml[0TWM2OD1{OEiuPVIhdk1? NETwOmtUSU6JRWK=
LNCaP-Clone-FGC NGT0W2hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4q2T2lEPTB;Mkm1MlI3KG6P M2T1fXNCVkeHUh?=
NCI-H1522 NVnwTYl6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF74fo5KSzVyPUOwO{4xPSCwTR?= NGPPVoNUSU6JRWK=
SCH NXvGb4hFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnHSTWM2OD1|MkKuNlIhdk1? NX3ldIl6W0GQR1XS
THP-1 NGK1c2VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUfndVRQUUN3ME2zNlIvPiCwTR?= NEPEVHpUSU6JRWK=
SNU-C1 NVTWPHN6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4DDPWlEPTB;M{[yMlA6KG6P MUPTRW5ITVJ?
CA46 M{XpRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXfJR|UxRTN5Mz62N{BvVQ>? NXTJfnMxW0GQR1XS
NCI-H1963 NYjkOYdrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4TsZmlEPTB;M{i2MlE6KG6P MWTTRW5ITVJ?
DEL MlO5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1;DRmlEPTB;M{mxMlI4KG6P NYH4[ZduW0GQR1XS
TUR MlrNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkDNTWM2OD1|OU[uOlEhdk1? NVfMRnlQW0GQR1XS
NCI-H226 NFz2SJZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWLJR|UxRTRyMz6yN{BvVQ>? NGiyOGxUSU6JRWK=
COLO-668 MoPIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml20TWM2OD12MEOuOVchdk1? MkLqV2FPT0WU
CPC-N NYPsb2tHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1TwWGlEPTB;NECzMlc4KG6P MkS2V2FPT0WU
NCI-H889 M1ztfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX\0ToUxUUN3ME20OlEvQTJibl2= NUW0[Xd7W0GQR1XS
J-RT3-T3-5 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXzmeZpGUUN3ME21N|IvPTdibl2= MWnTRW5ITVJ?
MSTO-211H MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4PESGlEPTB;NUe0MlI3KG6P M4\jbHNCVkeHUh?=
SCC-15 NELBSoNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmTJTWM2OD14NkeuOFchdk1? NYnDPYRJW0GQR1XS
SUP-T1 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFn2TI1KSzVyPU[4Ok4xPCCwTR?= MUDTRW5ITVJ?
DMS-153 NUm4[lRRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NELkSFBKSzVyPUe0Ok45OyCwTR?= M4G1O3NCVkeHUh?=
MS-1 NXrwSGhQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2rVdGlEPTB;N{W5MlQzKG6P NVqxVGE{W0GQR1XS
TC-YIK MmP3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1rZfGlEPTB;N{ixMlAyKG6P M1GxeXNCVkeHUh?=
RPMI-8866 NXfWfWpTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGPWUmhKSzVyPUGwNFYvOjhizszN MnX1V2FPT0WU
KY821 NVjlT3JUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4jUUmlEPTB;MUCzOk4xPCEQvF2= NHLxOGZUSU6JRWK=
P31-FUJ M4e3U2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWXJR|UxRTFzMUKuO|Uh|ryP MlexV2FPT0WU
COLO-824 NUfFeZpRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnOxTWM2OD1zMk[xMlc5KM7:TR?= MW\TRW5ITVJ?
U-698-M NVjVWmlzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXzXd3RSUUN3ME2yNlYzNjF3IN88US=> NF\aW|lUSU6JRWK=
TE-441-T M1vvemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml\DTWM2OD1{NUKxMlch|ryP MUPTRW5ITVJ?
IMR-5 M3m5Umdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml;5TWM2OD1|NEC5MlYzKM7:TR?= MoPHV2FPT0WU
NCI-H1838 MkLrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEPCWJhKSzVyPUSxPFYvOzJizszN NX3mUXI4W0GQR1XS

... 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)


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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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