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 MoXDR5l1d3SxeHnjJGF{e2G7 NGLQOIs2OCEQvF2= Mn\BOFghcA>? MlHCSG1UVw>? NVLJOYxvU2mubIOgZ4VtdHNiYomgcY9z\SC2aHHuJFk6LQ>? NHnj[VYyODR7OU[0Ny=>
OVCA 429 NX\kTGdpTnWwY4Tpc44hSXO|YYm= MkPrN|AxKG6P NFL0SmU1QCCq NITu[HhFVVOR M1PLU2Rqe3K3cITzJIlvfGGldDDteYx1cWOnbHz1cIFzKHS3bX;yJJNxcGW{b3nkdy=> M3;Vb|ExQTl7N{[2
RPMI8226 NXi3[G85T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEexU4MyODBibl2= NYXJR2RQPDhiaB?= M2SzXWROW09? M1rvcmlEPTB;M{Cgcm0> M2m1dFEyOzB4NEi5
Dox40 NVvmbpBLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{L5clExOCCwTR?= M3v3blQ5KGh? M2OyWWROW09? NF\TNnFKSzVyPUSwJI5O NFn6XFUyOTNyNkS4PS=>
MR20 NWOwNIM6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUTacoptOTByIH7N MUi0PEBp NETIToJFVVOR M33BZmlEPTB;MkCgcm0> Mn;2NVE{ODZ2OEm=
LR5 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MU[xNFAhdk1? M1j0ZVQ5KGh? MmPYSG1UVw>? NVHOeW1MUUN3ME2yNEBvVQ>? MX[xNVMxPjR6OR?=
U266 M4DDW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3zIOVExOCCwTR?= NGfJe401QCCq M2nOUmROW09? NFrFeGZKSzVyPUOgcm0> M{XrWlEyOzB4NEi5
IM-9 NEXuTpBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NY\C[2I5OTByIH7N M1LkcVQ5KGh? NULYXWNRTE2VTx?= M{DaW2lEPTB;NjDuUS=> MXixNVMxPjR6OR?=
Hs Sultan NIrWbnRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIrZO4YyODBibl2= NWXKdmp7PDhiaB?= NH[zUZJFVVOR M1HLPGlEPTB;MkCgcm0> NYfLR4tjOTF|ME[0PFk>
PAM-LY2 NV7OZVVXTnWwY4Tpc44hSXO|YYm= M2q1clExOCCwTR?= NYLHeWs5OTJiaB?= NVrV[ZoxTE2VTx?= MX\Jcohq[mm2czDOSk3PwkJiYXP0bZZifGmxbh?= NX:zfIt2OTF|NUC5NVM>
PAM 212 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWjiNnhYOTByIH7N MlfaO|IhcA>? MV\EUXNQ NWryPZNYUW6qaXLpeJMh[2WubDD2bYFjcWyrdIm= NF\kcGsyOTN3MEmxNy=>
PAM-LY2 M2PScWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWWxNFAhdk1? NWTnSXdwPzJiaB?= NUnSSnhiTE2VTx?= NXz2WpJkUW6qaXLpeJMh[2WubDD2bYFjcWyrdIm= M4TZTlEyOzVyOUGz
B4B8 MlP2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXqzVpdZOTByIH7N M17RXVczKGh? NGjxfJBFVVOR M2\0RWlvcGmkaYTzJINmdGxidnnhZoltcXS7 MlLRNVE{PTB7MUO=
B7E3 NITK[IZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlrFNVAxKG6P MVK3NkBp MoTFSG1UVw>? MnrxTY5pcWKrdIOgZ4VtdCC4aXHibYxqfHl? NHz1eoYyOTN3MEmxNy=>
UM-SCC-9 NHnyW2NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnHuNVAxKG6P NFO2[IQ4OiCq M3zrUGROW09? M{LHe2lvcGmkaYTzJINmdGxidnnhZoltcXS7 MXmxNVM2ODlzMx?=
UM-SCC-11B MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX2xV5UyOTByIH7N M2KyTFczKGh? MVLEUXNQ NH2welFKdmirYnn0d{Bk\WyuII\pZYJqdGm2eR?= NE\XO5IyOTN3MEmxNy=>
H460 NGTKRWhHfW6ldHnvckBCe3OjeR?= NHj4XWgyOCEQvF2= M1zlfVI1KGh? M3rueGROW09? M13rOWlv\HWlZYOgRoNtNTJicHjvd5Bpd3K7bHH0bY9vKGGwZDDjcIVifmGpZTDjc5Jz\WyjdHXkJJdqfGhiR{KtUUBxcGG|ZTDhdpJme3R? MkTrNVI1QTJzMUe=
U266 M3fNUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUDnOY1PPTByIH7nM41t MY[0PEBp NGDteZZFVVOR MlHXTY5pcWKrdIOgZ4VtdCCpcn;3eIg> NXLlWWdIOTJ4M{G2NVk>
ARH77 NHexfYlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1O2ZVUxOCCwZz;tcC=> MVy0PEBp M1HGNGROW09? MVjJcohq[mm2czDj[YxtKGe{b4f0bC=> NEm1NogyOjZ|MU[xPS=>
WAD-1 NVm5PGJzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2SzZlUxOCCwZz;tcC=> NYfJdnNDPDhiaB?= MVvEUXNQ M4fvdmlvcGmkaYTzJINmdGxiZ4Lve5Rp MnPrNVI3OzF4MUm=
U266/LR7 MojWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUC1NFAhdmdxbXy= MnfxOFghcA>? M3\TfWROW09? MWXJcohq[mm2czDj[YxtKGe{b4f0bC=> MXWxNlY{OTZzOR?=
U266/dox4 NHnWe4NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml7FOVAxKG6pL33s M1y5VVQ5KGh? NV;B[WpLTE2VTx?= M2XmVGlvcGmkaYTzJINmdGxiZ4Lve5Rp NUHU[4ZbOTJ4M{G2NVk>
RPMI8226/LR5 NVflNZl5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHjYXGU2ODBibnevcYw> NYPZPYhHPDhiaB?= NEHkSodFVVOR MlzaTY5pcWKrdIOgZ4VtdCCpcn;3eIg> M1m2UVEzPjNzNkG5
H460 NX;DeW9HT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnqwNVAh|ryP MYm3NkBp M{X3OGROW09? NYnHVmVuUUN3ME2xNFAhdk1? MmS4NVI3OzF4MkC=
H358 MonCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYWxNEDPxE1? MoLxO|IhcA>? NIjl[|hFVVOR M2fPcGlEPTB;N{Cgcm0> NHfnXmIyOjZ|MU[yNC=>
H322 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmDYNVAh|ryP M3;XOlczKGh? NFnWRYJFVVOR M2fmTWlEPTB;NkKwJI5O NWHZd3V3OTJ4M{G2NlA>
H460 MoPySpVv[3Srb36gRZN{[Xl? MXixNFAhdk1? MnvDNlQhcA>? Mlz0SG1UVw>? MWjJcoR2[2W|IFeyMW0ueGijc3WgZZJz\XO2IHHu[EB1fWK3bHnuJIF{e2WvYnz5MYRqe2G|c3XtZox6 M1jhV|EzPjNzNkKw
LNCap-Pro5 NVLXU5RXTnWwY4Tpc44hSXO|YYm= NYTxWnRsOSEQvF2= MX[0JIg> MUPEUXNQ M3HFNXN1[WKrbHn6[ZMheDV| MWixOFYyOjV|Mh?=
T29 NH\OUZNCeG:ydH;zbZMhSXO|YYm= NGn3NFg2OCCwTR?= MX:0PEBpKA>? MmiwSG1UVw>? M1HwNGlv\HWlZYOgZ4VtdCCjcH;weI9{cXN? NXm0cVd1OTZ5N{ixO|k>
T29Kt1 NEnYdIJCeG:ydH;zbZMhSXO|YYm= NETDeVI2OCCwTR?= MYK0PEBpKA>? M4nnU2ROW09? NX\nZVVIUW6mdXPld{Bk\WyuIHHwc5B1d3Orcx?= M2DWSFE3Pzd6MUe5
HCT116 M4DsXGFxd3C2b4Ppd{BCe3OjeR?= M3vYbVUxKG6P M1fqNFQ5KGhi MULEUXNQ NHrYbGRKdmS3Y3XzJINmdGxiYYDvdJRwe2m| MX:xOlc4QDF5OR?=
HKe-3 NGK1fpJCeG:ydH;zbZMhSXO|YYm= M3\HTlUxKG6P MoH3OFghcCB? NFPtUpZFVVOR NUnUe3JZUW6mdXPld{Bk\WyuIHHwc5B1d3Orcx?= MnXzNVY4PzhzN{m=
NB-1691 NYXxPYdVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEnqe44yKM7:TR?= NF\1fos4OiCq M1vJdmlvcGmkaYTzJINmdGxicILvcIln\XKjdHnvckB1dyB3JR?= NETEc40yPzZ6OU[4OC=>
CHLA-255 MmPGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV72WphMOSEQvF2= NI\OWoY4OiCq M4HEeWlvcGmkaYTzJINmdGxicILvcIln\XKjdHnvckB1dyB{JR?= MV2xO|Y5QTZ6NB?=
SK-N-AS M1fmeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF;xPHUyKM7:TR?= NVzaXJFXPzJiaB?= MYLJcohq[mm2czDj[YxtKHC{b3zp[oVz[XSrb36geI8hOTBn M1XmS|E4Pjh7Nki0
NB-1691 NF7KOHhHfW6ldHnvckBCe3OjeR?= NV\mN2lZOTBibl2= NFXCUo8zPCCq MmjRV4lodmmoaXPhcpRtgSC{ZXT1Z4V{KGOnbHzzJIlvKHSqZTDHNE9IOSCyaHHz[S=> MXOxO|Y5QTZ6NB?=
CHLA-255 M2L3TmZ2dmO2aX;uJGF{e2G7 NFzvTGsyOCCwTR?= NU\t[|N6OjRiaB?= NGXZV2VOd2Snc4TsfUBz\WS3Y3XzJINmdGy|IHnuJJRp\SCJMD;HNUBxcGG|ZR?= NWqyUphrOTd4OEm2PFQ>
RPMI 8226 MlnNSpVv[3Srb36gRZN{[Xl? MnrJNlAhdk1? MXi4JIg> MXrTbYdvcW[rY3HueIx6KGWwaHHuZ4V{KE6ILd86RkBi[3Srdnn0fS=> MkTzNVk1OzZyNUC=
MM.1S NUHSfIJjTnWwY4Tpc44hSXO|YYm= MX[yNEBvVQ>? NYD2bGVtQCCq NXjjeoNSW2mpbnnmbYNidnSueTDlcohidmOnczDOSk3PwkJiYXP0bZZqfHl? M4fMPFE6PDN4MEWw
U266 MUPGeY5kfGmxbjDBd5NigQ>? MVGyNEBvVQ>? MkjZPEBp MXHTbYdvcW[rY3HueIx6KGWwaHHuZ4V{KE6ILd86RkBi[3Srdnn0fS=> NWrPUXRbOTl2M{[wOVA>
OPM1 NFvHXlNHfW6ldHnvckBCe3OjeR?= NV30dXBDOjBibl2= NHvhdJI5KGh? MXHTbYdvcW[rY3HueIx6KGWwaHHuZ4V{KE6ILd86RkBi[3Srdnn0fS=> M{[xPFE6PDN4MEWw
INA6 NWHNXmdTTnWwY4Tpc44hSXO|YYm= MUmyNEBvVQ>? MoXyPEBp Ml;MV4lodmmoaXPhcpRtgSCnbnjhcoNmeyCQRj5OvmIh[WO2aY\peJk> MVWxPVQ{PjB3MB?=
OPM2 Ml;TSpVv[3Srb36gRZN{[Xl? MmfoNlAhdk1? NYTteFVsQCCq NI[0bJlUcWewaX\pZ4FvfGy7IHXubIFv[2W|IF7GMe67SiCjY4Tpeol1gQ>? MnjwNVk1OzZyNUC=
RPMI 8226 NGXHN5FHfW6ldHnvckBCe3OjeR?= NUPTZo5qOjBibl2= MWq4JIg> MXPJcoR2[2W|IFTORUB{gW62aHXzbZM> M2jGVFE6PDN4MEWw
BaF/3 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYCxNFAhdk1? MXW0PEBp NGXGVllKSzVyPU[uNkBvVQ>? MlvpNlA{ODV4OUK=
BaF/3-p210 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF;zb2gyODBibl2= NEHlfpg1QCCq NH63eXpKSzVyPUSuO{BvVQ>? M{PkZVIxOzB3Nkmy
TCC-S Ml65S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEL0WZMyODBibl2= MoHuOFghcA>? MkDKTWM2OD1{Lkigcm0> M1faRlIxOzB3Nkmy
BaF/3 NGTCUHhHfW6ldHnvckBCe3OjeR?= NEPjWII3KG6P NYjmcVl7PDhiaB?= NX;qSoNEUW6mdXPld{BiKGe{ZXH0JGcyKGOnbHytZ5lkdGViYYLy[ZN1 MnLpNlA{ODV4OUK=
BaF/3-p210 M1u3TWZ2dmO2aX;uJGF{e2G7 NV:4UplOPiCwTR?= NYnI[HVtPDhiaB?= NEPVcJdKdmS3Y3XzJIEhe2yrZ3j0JGcyKGOnbHytZ5lkdGViYYLy[ZN1 NXW0RnZ[OjB|MEW2PVI>
BaF/3-p210 Mmm5SpVv[3Srb36gRZN{[Xl? M33ueFYhdk1? MWqyOEBp Mn30VoVlfWOnczD0bIUheGixc4Doc5J6dGG2aX;uJIFv\CC2aHWgZYN1cX[rdImgc4YhWmJ? M3zWdVIxOzB3Nkmy
Raji MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUOxJO69VQ>? Mmn0NlQhcA>? MY\S[YR2[2W|IHPlcIwhfmmjYnnsbZR6yqB? NXq5VWhoOjFzN{C5PFg>
LCL-1 MkDHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4fuWFEh|ryP MnS0NlQhcA>? NGPNXYlT\WS3Y3XzJINmdGxidnnhZoltcXS7wrC= M4TuVFIyOTdyOUi4
LCL-2 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3Xt[VEh|ryP M13XdlI1KGh? NFfGRppT\WS3Y3XzJINmdGxidnnhZoltcXS7wrC= NVPXTGw4OjFzN{C5PFg>
BJAB MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEHWXFEyKM7:TR?= NYHBZoFMOjRiaB?= NIHL[FNT\WS3Y3XzJINmdGxidnnhZoltcXS7wrC= NFvON|EzOTF5MEm4PC=>
SNT-13 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHzOUmIyKM7:TR?= MYiyOEBp NX7WT2l3WmWmdXPld{Bk\WyuII\pZYJqdGm2edMg NG\kUm8zOTF5MEm4PC=>
SNT-16 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGnSdJQyKM7:TR?= NHPmfHYzPCCq MmTQVoVlfWOnczDj[YxtKH[rYXLpcIl1gcLi NWjaOGpGOjFzN{C5PFg>
Jurkat NYLuO2tUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYCxJO69VQ>? NF7HV3ozPCCq NFzvdFRT\WS3Y3XzJINmdGxidnnhZoltcXS7wrC= NY\z[4JlOjFzN{C5PFg>
KAI-3 NGPBTFdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MomyNUDPxE1? MmK1NlQhcA>? M2H6eHJm\HWlZYOgZ4VtdCC4aXHibYxqfHoEoB?= NYnh[4drOjFzN{C5PFg>
SNK-6 NXvaTpdFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlGxNUDPxE1? NWrSRplvOjRiaB?= NHv3TYFT\WS3Y3XzJINmdGxidnnhZoltcXS7wrC= MX6yNVE4ODl6OB?=
KHYG-1 MlThS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4jNPVEh|ryP MXyyOEBp NXTFbVNPWmWmdXPld{Bk\WyuII\pZYJqdGm2edMg M37qPVIyOTdyOUi4
SNT-16 MlPBRZBweHSxc3nzJGF{e2G7 MlywNUDPxE1? M1\PTFYhcA>? M1\yNGlv\HWlZYOgZ4VtdCCjcH;weI9{cXN? MVmyNVE4ODl6OB?=
Jurkat Ml;XRZBweHSxc3nzJGF{e2G7 NXnFbmIyOSEQvF2= MlfPOkBp M4\JOmlv\HWlZYOgZ4VtdCCjcH;weI9{cXN? NFrZXHQzOTF5MEm4PC=>
KAI-3 M3jROWFxd3C2b4Ppd{BCe3OjeR?= NGDkc4QyKM7:TR?= NFzPZmI3KGh? MlrmTY5lfWOnczDj[YxtKGGyb4D0c5Nqew>? NIXEXoYzOTF5MEm4PC=>
KHYG-1 MonURZBweHSxc3nzJGF{e2G7 NYHWc4o2OSEQvF2= NVnGfHVnPiCq NYTjNZNnUW6mdXPld{Bk\WyuIHHwc5B1d3Orcx?= MXyyNVE4ODl6OB?=
SNT-13 MkjpRY51cX[rcnHsJGF{e2G7 NXroNJR1OSEQvF2= NFmzflEzPCCq NXfBZ5JSUW6mdXPld{BtgXSrYzDpcoZm[3Srb36gc4YhTUKY NWHUW3NqOjFzN{C5PFg>
SNT-16 MX\BcpRqfmm{YXygRZN{[Xl? NI\ZVFMyKM7:TR?= M{\hWlI1KGh? NX\WUlFqUW6mdXPld{BtgXSrYzDpcoZm[3Srb36gc4YhTUKY NFnFS5czOTF5MEm4PC=>
KAI-3 MYrBcpRqfmm{YXygRZN{[Xl? MnG0NUDPxE1? MWSyOEBp MYDJcoR2[2W|IHz5eIlkKGmwZnXjeIlwdiCxZjDFRnY> M{W4WFIyOTdyOUi4
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A375 M{[5VGF2fG:yaHHnfUBCe3OjeR?= M3zwOlExKG6P NEO0PVEyOiCq Mne5TY5lfWOnczDmc5Ju[XSrb36gc4Yh[XW2b4DoZYdwe2:vZYO= NFnlSW0zOzB5OUC4Ny=>
BLM M2X4cWF2fG:yaHHnfUBCe3OjeR?= MnPkNVAhdk1? NXrHeZBrOTJiaB?= MXjJcoR2[2W|IH\vdo1ifGmxbjDv[kBifXSxcHjh[49{d22ncx?= NWfGSJJEOjNyN{mwPFM>
H1299 MWDBdI9xfG:|aYOgRZN{[Xl? NWSzOopFQDBibl2= MoKxNlQhcA>? NYfwV2U3TE2VTx?= MUXT[Y5{cXSrenXzJG5US0yFIHPlcIx{KHSxIF3TR{1l\XKrdnXkJIlEQS2rbnT1Z4VlKGGyb4D0c5Nqew>? MlXsNlU{OjN4OUO=
Hut-78 M1TkcGZ2dmO2aX;uJGF{e2G7 NXf0XldWOTByIH7N MXuyOEBp NF7sZWlFVVOR M3ntZmRwf26{ZXf1cIF1\XNiVFfGMe6zOSCjbnSgTWwuOTBiZYjwdoV{e2mxbh?= M4nldlI2PjhzM{O1
H9 MY\GeY5kfGmxbjDBd5NigQ>? NWPVdHhIOTByIH7N MmDLNlQhcA>? NXTve5hnTE2VTx?= M3nMVWRwf26{ZXf1cIF1\XNiVFfGMe6zOSCjbnSgTWwuOTFiZYjwdoV{e2mxbh?= Ml24NlU3QDF|M{W=
HH M4n3RWZ2dmO2aX;uJGF{e2G7 M2DtXlExOCCwTR?= M4jR[VI1KGh? NW[0VIs{TE2VTx?= NX7hVooy\G:5boLl[5Vt[XSnczDUS2Yu|rJzIHHu[EBKVC1zMjDlfJBz\XO|aX;u NVGyb4xbOjV4OEGzN|U>
Hut-78 M4fTRm1q\3KjdHnvckBCe3OjeR?= NH3UOo4yODBibl2= NHHBTWczPCCq M2L0eWROW09? M{XySHJm\HWlZYOgZ4VtdCCvaXfyZZRqd25iYomgPFDjiJN7MDW= Ml3RNlU3QDF|M{W=
HH MYnNbYdz[XSrb36gRZN{[Xl? NUHXZnNJOTByIH7N MkTtNlQhcA>? NIroUIlFVVOR MmXRVoVlfWOnczDj[YxtKG2rZ4LheIlwdiCkeTC4NQKBmzlzJR?= Mni3NlU3QDF|M{W=
U937 Mkf1SpVv[3Srb36gRZN{[Xl? MojCNVAxKG6P MnL0OkBp NXf2UXFRUW6mdXPld{BKVC16IHX4dJJme3Orb36gbY4hVFCVLYP0bY12dGG2ZXSgWVk{PyCvYXPyc5Bp[Wencx?= MWGyOVc6OTR5Nx?=
human PBMC MoXvSpVv[3Srb36gRZN{[Xl? M3vNSVExOCCwTR?= MlWyNlQhcA>? NFjWUVRKdmS3Y3XzJGlNNThicnXs[YF{\Q>? NGSxZWQzPTd7MUS3Oy=>
ES6 NYPpWmc4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGG4U2tKSzVyPUCuNFAzOSCwTR?= MmLzV2FPT0WU
SK-UT-1 MmnRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWfJR|UxRTBwMU[zJI5O NIfJUVFUSU6JRWK=
SH-4 NITiOZVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV;JR|UxRTBwMUezJI5O M2fwbHNCVkeHUh?=
TE-9 NG\LUXBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHfVUHdKSzVyPUCuNVgzKG6P M2PycXNCVkeHUh?=
A253 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4\3Z2lEPTB;MD6yNFghdk1? MlHiV2FPT0WU
no-10 NVPOZYFNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYLm[49OUUN3ME2wMlIyKG6P M4\Ze3NCVkeHUh?=
MMAC-SF NIPLU4NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEHTTlBKSzVyPUCuNlE3KG6P MY\TRW5ITVJ?
A101D MkHXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnXHTWM2OD1yLkKyOUBvVQ>? NIDHd4JUSU6JRWK=
NTERA-S-cl-D1 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4W4TmlEPTB;MD6yOFMhdk1? MVjTRW5ITVJ?
8-MG-BA NXu1SGVnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFvOUI5KSzVyPUCuNlUhdk1? NVTVNIVYW0GQR1XS
KNS-42 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlnhTWM2OD1yLkK1PEBvVQ>? NVXjPIdvW0GQR1XS
LXF-289 Mni4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{Dmc2lEPTB;MD6yOlkhdk1? MVvTRW5ITVJ?
OVCAR-4 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4XKT2lEPTB;MD6yPFkhdk1? NW\wO2tvW0GQR1XS
LOUCY M1flWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVz0WoM2UUN3ME2wMlI6OyCwTR?= NWXqUXhMW0GQR1XS
BB65-RCC NIjyUZJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWTJR|UxRTBwM{C0JI5O NWHoNWJkW0GQR1XS
D-542MG M1\kV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHvabpVKSzVyPUCuN|I6KG6P NUHGT4xrW0GQR1XS
ONS-76 NXi3b3U4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVzrfId3UUN3ME2wMlM{KG6P MmrwV2FPT0WU
BB30-HNC NX;JXnc5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUjJR|UxRTBwM{O1JI5O NGjhTnlUSU6JRWK=
KS-1 MnrrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnKyTWM2OD1yLkO0JI5O M2noZnNCVkeHUh?=
A388 NXvlUHh{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYXJR|UxRTBwM{W2JI5O MXnTRW5ITVJ?
ES8 M1zCRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWfJR|UxRTBwNDDuUS=> MkToV2FPT0WU
MZ2-MEL NF3BWXRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIXNO4pKSzVyPUCuOFA4KG6P M323UnNCVkeHUh?=
HCC2998 NUDESWxwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGDx[pRKSzVyPUCuOFEzKG6P NUXPOoxIW0GQR1XS
D-247MG NGLPXFFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnjXTWM2OD1yLkSxN{BvVQ>? MojpV2FPT0WU
ACN MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXTWT3p{UUN3ME2wMlQyPyCwTR?= M3HVeXNCVkeHUh?=
LB2518-MEL NHvVcpVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVPPRnB6UUN3ME2wMlQzPSCwTR?= MkntV2FPT0WU
ES1 MoHIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFHFN3hKSzVyPUCuOFMhdk1? NV;MTIN6W0GQR1XS
HCE-T NIDoZ|ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1W5ZmlEPTB;MD60N|khdk1? MlfmV2FPT0WU
OS-RC-2 NYfIb4pXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYD6eGhzUUN3ME2wMlQ1KG6P M3zrSnNCVkeHUh?=
MFH-ino NYPhe|VrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkO4TWM2OD1yLkS0N{BvVQ>? NUW0WGVKW0GQR1XS
OCUB-M NXS2UXBlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1jxPWlEPTB;MD60OFchdk1? Mn71V2FPT0WU
CP66-MEL NV21NXlwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEi0fJFKSzVyPUCuOFc{KG6P MXTTRW5ITVJ?
LB771-HNC NUHOb3BpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlnSTWM2OD1yLkS3OEBvVQ>? M3TQbXNCVkeHUh?=
DSH1 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NY\tOFVGUUN3ME2wMlQ5KG6P Mmn5V2FPT0WU
HUTU-80 NGf3epNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX;YUppvUUN3ME2wMlU{OyCwTR?= NGnVcpVUSU6JRWK=
CESS NFjkfpdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVTJR|UxRTBwNUO4JI5O NWO5PZZLW0GQR1XS
NCI-H747 MornS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVHJR|UxRTBwNUO5JI5O MlLWV2FPT0WU
HT-144 M3HrNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXn0W2drUUN3ME2wMlU4PiCwTR?= MVrTRW5ITVJ?
COLO-829 Mk\SS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV;JR|UxRTBwNkG0JI5O NELZdI5USU6JRWK=
A4-Fuk NGL2c45Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH35dHNKSzVyPUCuOlI{KG6P MVjTRW5ITVJ?
GI-ME-N M2L1b2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF7aOFFKSzVyPUCuOlM1KG6P NXSyNGxuW0GQR1XS
LB831-BLC MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4TIfWlEPTB;MD62OFEhdk1? NGSw[5lUSU6JRWK=
HOP-62 MkPHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MojsTWM2OD1yLk[0O{BvVQ>? MVrTRW5ITVJ?
BB49-HNC M{W2eGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEPzWW9KSzVyPUCuOlUzKG6P NYHvXFZZW0GQR1XS
D-336MG MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYfJR|UxRTBwNkW3JI5O MWfTRW5ITVJ?
TK10 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXzrcm1GUUN3ME2wMlY4QSCwTR?= NV;5OJN3W0GQR1XS
Ramos-2G6-4C10 MoHNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXTJR|UxRTBwNkmzJI5O M2PiR3NCVkeHUh?=
LB373-MEL-D NXnLNmZJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mmn2TWM2OD1yLkegcm0> NYPQXIdSW0GQR1XS
SF126 NF\EcolIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHfIOVZKSzVyPUCuO|AyKG6P M1XC[3NCVkeHUh?=
UACC-257 M3rIPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH\F[2FKSzVyPUCuO|Ehdk1? M2XDSXNCVkeHUh?=
KINGS-1 MlXyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIewWHRKSzVyPUCuO|IzKG6P NHvlb|RUSU6JRWK=
LS-513 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGfZZ2RKSzVyPUCuO|M6KG6P NFK5c49USU6JRWK=
GI-1 MlK3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{\idGlEPTB;MD63OlQhdk1? NUfMcHhCW0GQR1XS
ES7 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWHJR|UxRTBwN{[2JI5O M121SnNCVkeHUh?=
LB2241-RCC NYPLfodMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVPJR|UxRTBwOEC0JI5O MlTvV2FPT0WU
D-263MG NGO0c|BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M37rWWlEPTB;MD64NFchdk1? NFj1ZWtUSU6JRWK=
SW684 NH;KNo9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUD6bploUUN3ME2wMlgzOSCwTR?= NG[0[4dUSU6JRWK=
ML-2 Mn\GS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVTVTW1KUUN3ME2wMlgzOSCwTR?= MWHTRW5ITVJ?
SK-LMS-1 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVPF[ZAxUUN3ME2wMlg2PCCwTR?= MmjUV2FPT0WU
TE-5 M2e4bGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVLJR|UxRTBwOE[1JI5O NIXpUW1USU6JRWK=
QIMR-WIL MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX7OZZJqUUN3ME2wMlg5QSCwTR?= MkXlV2FPT0WU
NCI-H1355 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2DQNmlEPTB;MD64PVUhdk1? MmrCV2FPT0WU
SNB75 Mn\hS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmG1TWM2OD1yLkmxNkBvVQ>? NUXQO41sW0GQR1XS
RXF393 MkXHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3nrbGlEPTB;MD65NVQhdk1? MlTBV2FPT0WU
IST-MEL1 NEXhdYpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEHqb|ZKSzVyPUCuPVE4KG6P MnGxV2FPT0WU
SF268 NFq0XpFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFr0dnRKSzVyPUCuPVI{KG6P M2e4dHNCVkeHUh?=
KALS-1 NX30XlNpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUPoW|U1UUN3ME2wMlkzPSCwTR?= NH\ZcVZUSU6JRWK=
HC-1 M2jZZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFmxO5RKSzVyPUCuPVc2KG6P Mly0V2FPT0WU
SW872 MkLzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1XaPGlEPTB;MD65PVYhdk1? M3TOdHNCVkeHUh?=
PSN1 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYHJR|UxRTFwMEGgcm0> MnPGV2FPT0WU
TE-1 MnW1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXzH[nVsUUN3ME2xMlA{KG6P MmHYV2FPT0WU
TE-10 NHvZVHJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIPsZ5NKSzVyPUGuNFMhdk1? NYDyO5k1W0GQR1XS
RKO MoDkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXr5e4FWUUN3ME2xMlA3KG6P MkK5V2FPT0WU
LC-2-ad MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUfJR|UxRTFwMEigcm0> MUPTRW5ITVJ?
SK-MM-2 NWHRTGVrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX23[|E4UUN3ME2xMlA6KG6P NF7LfHhUSU6JRWK=
VA-ES-BJ NXW3RpBHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGLl[ZdKSzVyPUGuNFkhdk1? NULHbIw5W0GQR1XS
MZ7-mel NHvI[|hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUDJR|UxRTFwMEmgcm0> NWPt[GhnW0GQR1XS
D-392MG M3PqdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIXQW2hKSzVyPUGuNUBvVQ>? MUnTRW5ITVJ?
CCRF-CEM NYjHSJg5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV:3dIZPUUN3ME2xMlE{KG6P NWrjWWM6W0GQR1XS
EM-2 NVLYW292T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1q5V2lEPTB;MT6xOkBvVQ>? MkH2V2FPT0WU
HAL-01 M{PlNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX34VXpmUUN3ME2xMlE5KG6P NYrrVmhmW0GQR1XS
TE-8 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVvJR|UxRTFwMUmgcm0> MmTBV2FPT0WU
NCI-H1882 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGLFfGhKSzVyPUGuNkBvVQ>? NYrzeHViW0GQR1XS
Daudi M1LlWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFO5VWdKSzVyPUGuNlIhdk1? MVzTRW5ITVJ?
BL-41 NWHUVVVXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIHFSXpKSzVyPUGuNlUhdk1? NY\rbJE1W0GQR1XS
SR M37rfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlLpTWM2OD1zLkK1JI5O NVfqOHNJW0GQR1XS
KM12 M1r4cWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3;3b2lEPTB;MT6yO{BvVQ>? MXLTRW5ITVJ?
K5 MmX6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Moj6TWM2OD1zLkK4JI5O NHPvbpRUSU6JRWK=
A3-KAW MmT0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUG1e3dqUUN3ME2xMlI5KG6P MYrTRW5ITVJ?
CMK Mny0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXL0XWxyUUN3ME2xMlI6KG6P NHjaSXRUSU6JRWK=
Calu-6 MoHoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFTqXFdKSzVyPUGuNlkhdk1? MnXZV2FPT0WU
IST-SL2 NEnnZohIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MY\JR|UxRTFwM{Ggcm0> M3;sU3NCVkeHUh?=
OPM-2 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVTJR|UxRTFwM{Ogcm0> MX;TRW5ITVJ?
DU-4475 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2PwUWlEPTB;MT6zOkBvVQ>? NEXxR3FUSU6JRWK=
ECC12 M1\rZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWHpb5BUUUN3ME2xMlM4KG6P MWnTRW5ITVJ?
L-540 M2XzWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXPJR|UxRTFwM{egcm0> MnWyV2FPT0WU
CAS-1 MlHYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXXsZXBNUUN3ME2xMlM4KG6P MVHTRW5ITVJ?
PF-382 NELOPGhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXPJR|UxRTFwNEegcm0> MWnTRW5ITVJ?
LS-411N NECwXHVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MY\JR|UxRTFwNUOgcm0> NXrnd|VLW0GQR1XS
NCI-H69 M1LIe2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlziTWM2OD1zLkW0JI5O Mn;3V2FPT0WU
NB12 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX3JR|UxRTFwNU[gcm0> MmDsV2FPT0WU
HEL M1X3[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXPJR|UxRTFwNkGgcm0> M13Rd3NCVkeHUh?=
GCIY M{j4WGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWTvUJBMUUN3ME2xMlYzKG6P M4PMfXNCVkeHUh?=
EHEB Mo[3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXTJR|UxRTFwNkegcm0> NFTVeJRUSU6JRWK=
TGBC1TKB MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFLNNZFKSzVyPUGuO|Ehdk1? M2e0U3NCVkeHUh?=
KURAMOCHI MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVfJR|UxRTFwN{Kgcm0> NFfkWWNUSU6JRWK=
U-266 NHT2PJRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmXYTWM2OD1zLke2JI5O NYDqSGY1W0GQR1XS
LC4-1 NULLSFBiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV3JdplFUUN3ME2xMlc6KG6P NWXrR|FUW0GQR1XS
NCI-H2126 NEjaU49Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGPXeplKSzVyPUGuPEBvVQ>? NEDocW1USU6JRWK=
NCI-H1092 NIX0UI9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MojjTWM2OD1zLkigcm0> M2OwTnNCVkeHUh?=
GB-1 NHT0ZndIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWnJR|UxRTFwOEGgcm0> MV;TRW5ITVJ?
MV-4-11 NWrOWYJOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWrtZmlLUUN3ME2xMlgzKG6P MmDpV2FPT0WU
Becker M1fkc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWjJR|UxRTFwOEOgcm0> M1j4fHNCVkeHUh?=
MPP-89 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlzWTWM2OD1zLki5JI5O NFjEXXVUSU6JRWK=
BE-13 NFzOcmxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVfJR|UxRTFwOUOgcm0> MkLsV2FPT0WU
697 M{L4NGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYHJR|UxRTFwOUmgcm0> NVXMXnNRW0GQR1XS
NKM-1 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWjJR|UxRTJibl2= M{PncXNCVkeHUh?=
NB13 NIXBd|RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoLETWM2OD1{IH7N MULTRW5ITVJ?
LS-123 M{DXSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkThTWM2OD1{LkCyJI5O NUjLbJJWW0GQR1XS
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NCI-H1963 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1HqUGlEPTB;M{i2MlE6KG6P MVfTRW5ITVJ?
DEL NED1dVZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MljYTWM2OD1|OUGuNlchdk1? NF\BS3RUSU6JRWK=
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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)


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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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