Bortezomib (PS-341)

Catalog No.S1013 Synonyms: Velcade, LDP-341, MLM341, NSC 681239,PS-341

For research use only.

Bortezomib (PS-341, Velcade, LDP-341, MLM341, NSC 681239) is a potent 20S proteasome inhibitor with Ki of 0.6 nM. It exhibits favorable selectivity towards tumor cells over normal cells. Bortezomib (PS-341) inhibits NF-κB and induces ERK phosphorylation to suppress cathepsin B and inhibit the catalytic process of autophagy in ovarian cancer and other solid tumors.

Bortezomib (PS-341) Chemical Structure

CAS No. 179324-69-7

Selleck's Bortezomib (PS-341) has been cited by 857 publications

Purity & Quality Control

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Biological Activity

Description Bortezomib (PS-341, Velcade, LDP-341, MLM341, NSC 681239) is a potent 20S proteasome inhibitor with Ki of 0.6 nM. It exhibits favorable selectivity towards tumor cells over normal cells. Bortezomib (PS-341) inhibits NF-κB and induces ERK phosphorylation to suppress cathepsin B and inhibit the catalytic process of autophagy in ovarian cancer and other solid tumors.
Targets
NF-κB [6] 20S proteasome [1]
(Cell-free assay)
0.6 nM(Ki)
In vitro

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 Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
NCI-H1838 M3HUNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVrJR|UxRTRzOE[uN|Ih|ryP MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyzNlUxPDFxJ{7TRW5ITVJ:L3G+
IMR-5 NXn6e5M4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIT2UYVKSzVyPUO0NFkvPjJizszN NWXWeWt6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOzJ3MESxM{c,W0GQR1XSQE9iRg>?
TE-441-T NHT5dHFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWO5boY5UUN3ME2yOVIyNjdizszN MnznQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMN|I2ODRzLze+V2FPT0WUPD;hQi=>
U-698-M NFzDW5FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVHJR|UxRTJ{NkKuNVUh|ryP MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyzNlUxPDFxJ{7TRW5ITVJ:L3G+
COLO-824 NX:wXZV5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnLPTWM2OD1zMk[xMlc5KM7:TR?= MnvuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMN|I2ODRzLze+V2FPT0WUPD;hQi=>
P31-FUJ MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkTXTWM2OD1zMUGyMlc2KM7:TR?= NIHlfpY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw{OjVyNEGvK|5USU6JRWK8M4E,
KY821 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkS3TWM2OD1zMEO2MlA1KM7:TR?= M2O5OlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
RPMI-8866 NUXUPGp{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVnZcVVlUUN3ME2xNFA3NjJ6IN88US=> M17zS|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
TC-YIK MkLmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYLJR|UxRTd6MT6wNUBvVQ>? M3n3SFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
MS-1 M371bmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVmwRZB4UUN3ME23OVkvPDJibl2= NXn6WFZyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOzJ3MESxM{c,W0GQR1XSQE9iRg>?
DMS-153 M2XwN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIXLTnFKSzVyPUe0Ok45OyCwTR?= MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyzNlUxPDFxJ{7TRW5ITVJ:L3G+
SUP-T1 NVK2fGhNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEfB[nFKSzVyPU[4Ok4xPCCwTR?= M{DjdlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
SCC-15 MorQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXeyNoFlUUN3ME22OlcvPDdibl2= MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyzNlUxPDFxJ{7TRW5ITVJ:L3G+
MSTO-211H NH3OV45Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH7TT|hKSzVyPUW3OE4zPiCwTR?= MXG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyzNlUxPDFxJ{7TRW5ITVJ:L3G+
J-RT3-T3-5 NXXNb|ZXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2rGOmlEPTB;NUOyMlU4KG6P MkP6QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMN|I2ODRzLze+V2FPT0WUPD;hQi=>
NCI-H889 NXGxXodMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEfsZmpKSzVyPUS2NU46OiCwTR?= Mlf3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMN|I2ODRzLze+V2FPT0WUPD;hQi=>
CPC-N M{\ne2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NI[0V|dKSzVyPUSwN{44PyCwTR?= NFj0bYg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw{OjVyNEGvK|5USU6JRWK8M4E,
COLO-668 NV3YVYVUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkH3TWM2OD12MEOuOVchdk1? M{m0VFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
NCI-H226 NUXPb|lOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYjJR|UxRTRyMz6yN{BvVQ>? NXfIV|g4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOzJ3MESxM{c,W0GQR1XSQE9iRg>?
TUR M{j1XWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF;EXZBKSzVyPUO5Ok43OSCwTR?= MlLyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMN|I2ODRzLze+V2FPT0WUPD;hQi=>
DEL M3fzNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlfaTWM2OD1|OUGuNlchdk1? MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyzNlUxPDFxJ{7TRW5ITVJ:L3G+
NCI-H1963 NEHUSFJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYLJR|UxRTN6Nj6xPUBvVQ>? M2Xnb|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
CA46 MoLES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4fzO2lEPTB;M{ezMlY{KG6P MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyzNlUxPDFxJ{7TRW5ITVJ:L3G+
SNU-C1 NHriWWVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoTrTWM2OD1|NkKuNFkhdk1? NXnPVVA2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOzJ3MESxM{c,W0GQR1XSQE9iRg>?
THP-1 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWPGTJJwUUN3ME2zNlIvPiCwTR?= NI\HWpY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw{OjVyNEGvK|5USU6JRWK8M4E,
SCH MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4S0RWlEPTB;M{KyMlIzKG6P NIiyNmI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw{OjVyNEGvK|5USU6JRWK8M4E,
NCI-H1522 NHvCTWZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3TldWlEPTB;M{C3MlA2KG6P NVrSOVhrRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOzJ3MESxM{c,W0GQR1XSQE9iRg>?
LNCaP-Clone-FGC MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEDtbpNKSzVyPUK5OU4zPiCwTR?= Mmj5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMN|I2ODRzLze+V2FPT0WUPD;hQi=>
NCI-H2171 Mo\IS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn3iTWM2OD1{OEiuPVIhdk1? M4\tOVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
NCI-H187 NIX5OXhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4LhOmlEPTB;Mki3MlA5KG6P NUWycmhDRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOzJ3MESxM{c,W0GQR1XSQE9iRg>?
KASUMI-1 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXjIc|YxUUN3ME2yPFMvODVibl2= NEjaRWI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw{OjVyNEGvK|5USU6JRWK8M4E,
SK-MEL-2 NGLRUYRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYHJR|UxRTJ6MT65JI5O MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyzNlUxPDFxJ{7TRW5ITVJ:L3G+
EW-22 NFHVcppIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1nueWlEPTB;Mk[zMlc2KG6P MWm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyzNlUxPDFxJ{7TRW5ITVJ:L3G+
NCI-H1299 MnLZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVfoPHFUUUN3ME2yOlEvPzFibl2= NH3DOYM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw{OjVyNEGvK|5USU6JRWK8M4E,
COR-L279 NWTQTZdHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHrhZlRKSzVyPUK1Nk4yPyCwTR?= NIXRZ4Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw{OjVyNEGvK|5USU6JRWK8M4E,
NCI-H1155 M2LmbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXXJR|UxRTJ|MD6zNkBvVQ>? M1zleVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
NCI-H1395 M{PD[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVHIVFlrUUN3ME2yNVAvOTNibl2= NGPWflA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw{OjVyNEGvK|5USU6JRWK8M4E,
KM-H2 M{fWSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUX1ZoZCUUN3ME2xPVcvODVibl2= MkflQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMN|I2ODRzLze+V2FPT0WUPD;hQi=>
NCI-H209 M4q1d2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3PnfGlEPTB;MUm2MlUzKG6P M{O2S|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
NCI-H510A Mn3US5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUnJR|UxRTF6NT6zO{BvVQ>? MkXQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMN|I2ODRzLze+V2FPT0WUPD;hQi=>
NCI-H1304 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoPjTWM2OD1zNkmuNlEhdk1? Ml\NQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMN|I2ODRzLze+V2FPT0WUPD;hQi=>
SCLC-21H MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYTQc|IxUUN3ME2xOVkvPDFibl2= NVSwTnBHRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOzJ3MESxM{c,W0GQR1XSQE9iRg>?
NCI-H524 MnjQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NULjenRwUUN3ME2xOVkvOSCwTR?= M1rWXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
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697 NEXVWlRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3X3UWlEPTB;MT65PUBvVQ>? M3zS[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
BE-13 NF\obWNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHnlSVdKSzVyPUGuPVMhdk1? MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyzNlUxPDFxJ{7TRW5ITVJ:L3G+
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Becker NX[4TYRyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVjrdpl[UUN3ME2xMlg{KG6P MlLrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMN|I2ODRzLze+V2FPT0WUPD;hQi=>
MV-4-11 NUL2[XlFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWK0WVltUUN3ME2xMlgzKG6P MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyzNlUxPDFxJ{7TRW5ITVJ:L3G+
GB-1 M4frXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUPJR|UxRTFwOEGgcm0> M4S1V|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
NCI-H1092 NYTX[nFUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXSyNm9wUUN3ME2xMlghdk1? M3;zdVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
NCI-H2126 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEHQdJNKSzVyPUGuPEBvVQ>? M3Oy[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
LC4-1 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3nGUWlEPTB;MT63PUBvVQ>? MnPrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMN|I2ODRzLze+V2FPT0WUPD;hQi=>
U-266 MmPlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUe3PGFKUUN3ME2xMlc3KG6P NFTkOpY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw{OjVyNEGvK|5USU6JRWK8M4E,
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TGBC1TKB MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1zqPWlEPTB;MT63NUBvVQ>? NH3OOWY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw{OjVyNEGvK|5USU6JRWK8M4E,
EHEB MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUTJR|UxRTFwNkegcm0> MWm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyzNlUxPDFxJ{7TRW5ITVJ:L3G+
GCIY MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1zqR2lEPTB;MT62NkBvVQ>? M2ryZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
HEL Mn3FS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGCz[2lKSzVyPUGuOlEhdk1? NH;YOHI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw{OjVyNEGvK|5USU6JRWK8M4E,
NB12 NFnjOWxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWH1d3JvUUN3ME2xMlU3KG6P M{XzVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
NCI-H69 NVn4RmlLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYewUYtDUUN3ME2xMlU1KG6P NXm4cmdWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOzJ3MESxM{c,W0GQR1XSQE9iRg>?
LS-411N M{H3Vmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEfpTHhKSzVyPUGuOVMhdk1? NETSW289[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw{OjVyNEGvK|5USU6JRWK8M4E,
PF-382 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGDLS4FKSzVyPUGuOFchdk1? M4C1TlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
CAS-1 M2HGO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmjxTWM2OD1zLkO3JI5O M2HtS|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
L-540 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHr3UFFKSzVyPUGuN|chdk1? MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyzNlUxPDFxJ{7TRW5ITVJ:L3G+
ECC12 M{H1TGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUPJR|UxRTFwM{egcm0> NX;MWYtQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOzJ3MESxM{c,W0GQR1XSQE9iRg>?
DU-4475 M3TBOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlHCTWM2OD1zLkO2JI5O NH\o[lI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw{OjVyNEGvK|5USU6JRWK8M4E,
OPM-2 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmjtTWM2OD1zLkOzJI5O M1fIblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
IST-SL2 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnfHTWM2OD1zLkOxJI5O M4POSFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
Calu-6 M4q2dWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmPCTWM2OD1zLkK5JI5O NXvwWW9XRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOzJ3MESxM{c,W0GQR1XSQE9iRg>?
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A3-KAW M1zIXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH\3TIpKSzVyPUGuNlghdk1? NGnaXoo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw{OjVyNEGvK|5USU6JRWK8M4E,
K5 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlTITWM2OD1zLkK4JI5O NIH3ZmY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw{OjVyNEGvK|5USU6JRWK8M4E,
KM12 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{jBNmlEPTB;MT6yO{BvVQ>? NUXwRZI4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOzJ3MESxM{c,W0GQR1XSQE9iRg>?
SR MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWfJR|UxRTFwMkWgcm0> MUG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyzNlUxPDFxJ{7TRW5ITVJ:L3G+
BL-41 MlK5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVzucmpyUUN3ME2xMlI2KG6P NIPzdGk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw{OjVyNEGvK|5USU6JRWK8M4E,
Daudi NVzoWFVqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmjCTWM2OD1zLkKyJI5O M1rsSVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
NCI-H1882 M2SwOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoXHTWM2OD1zLkKgcm0> MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyzNlUxPDFxJ{7TRW5ITVJ:L3G+
TE-8 NHv6cnNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NU\Me2dxUUN3ME2xMlE6KG6P NYjqUW16RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOzJ3MESxM{c,W0GQR1XSQE9iRg>?
HAL-01 NIPRcWpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoTCTWM2OD1zLkG4JI5O NHLmdZU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw{OjVyNEGvK|5USU6JRWK8M4E,
EM-2 M3vMT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF7TV|RKSzVyPUGuNVYhdk1? MkTHQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMN|I2ODRzLze+V2FPT0WUPD;hQi=>
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D-392MG MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH:xd5lKSzVyPUGuNUBvVQ>? MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyzNlUxPDFxJ{7TRW5ITVJ:L3G+
MZ7-mel M1rL[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4C2U2lEPTB;MT6wPUBvVQ>? NFXPSYw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw{OjVyNEGvK|5USU6JRWK8M4E,
VA-ES-BJ NGroWJRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH;F[ndKSzVyPUGuNFkhdk1? NELtN449[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw{OjVyNEGvK|5USU6JRWK8M4E,
SK-MM-2 M{PEOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIfiSGFKSzVyPUGuNFkhdk1? NYPYR4Q5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOzJ3MESxM{c,W0GQR1XSQE9iRg>?
LC-2-ad M3eySWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEi4cXVKSzVyPUGuNFghdk1? Mne5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMN|I2ODRzLze+V2FPT0WUPD;hQi=>
RKO MmDjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX3JR|UxRTFwME[gcm0> M1m4eFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
TE-10 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVLJR|UxRTFwMEOgcm0> M4PZeFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
TE-1 MoK0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4DWWWlEPTB;MT6wN{BvVQ>? MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyzNlUxPDFxJ{7TRW5ITVJ:L3G+
PSN1 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIDhZnVKSzVyPUGuNFEhdk1? M1\SSVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
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KS-1 NG\QepdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1noOmlEPTB;MD6zOEBvVQ>? M{ntUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
BB30-HNC M1ixUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFLVSHFKSzVyPUCuN|M2KG6P NVfRUnpNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOzJ3MESxM{c,W0GQR1XSQE9iRg>?
ONS-76 NHWwWllIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFL3NpdKSzVyPUCuN|Mhdk1? NFXaboQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw{OjVyNEGvK|5USU6JRWK8M4E,
D-542MG NWTPWWgzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHzQNItKSzVyPUCuN|I6KG6P M3LTZ|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
BB65-RCC M17p[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEfJSlFKSzVyPUCuN|A1KG6P M3;aNFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
LOUCY NICydnRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWXJR|UxRTBwMkmzJI5O NUPKSXBwRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOzJ3MESxM{c,W0GQR1XSQE9iRg>?
OVCAR-4 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnHITWM2OD1yLkK4PUBvVQ>? NF7GOnU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw{OjVyNEGvK|5USU6JRWK8M4E,
LXF-289 NIXTbJdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoPsTWM2OD1yLkK2PUBvVQ>? MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyzNlUxPDFxJ{7TRW5ITVJ:L3G+
KNS-42 MkPmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXvJR|UxRTBwMkW4JI5O MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyzNlUxPDFxJ{7TRW5ITVJ:L3G+
8-MG-BA MkGyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVXJR|UxRTBwMkWgcm0> Ml\HQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMN|I2ODRzLze+V2FPT0WUPD;hQi=>
NTERA-S-cl-D1 NXSxSnFlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWfJR|UxRTBwMkSzJI5O MWO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyzNlUxPDFxJ{7TRW5ITVJ:L3G+
A101D NXrSWoFkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFvsbYZKSzVyPUCuNlI2KG6P M163UVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
MMAC-SF NUfr[I1ET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX32cYVOUUN3ME2wMlIyPiCwTR?= NV3H[WpKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOzJ3MESxM{c,W0GQR1XSQE9iRg>?
no-10 MlXUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoDyTWM2OD1yLkKxJI5O NX;MOlZKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOzJ3MESxM{c,W0GQR1XSQE9iRg>?
A253 NWPIS4JxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUmxV|A6UUN3ME2wMlIxQCCwTR?= NEG3OYw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw{OjVyNEGvK|5USU6JRWK8M4E,
TE-9 MnPLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXfJR|UxRTBwMUiyJI5O NWrnNXV2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOzJ3MESxM{c,W0GQR1XSQE9iRg>?
SH-4 NEnkR5pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn:yTWM2OD1yLkG3N{BvVQ>? M1r0VVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFMzPTB2MT:nQnNCVkeHUkyvZV4>
SK-UT-1 NID1dJBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3vtdGlEPTB;MD6xOlMhdk1? MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyzNlUxPDFxJ{7TRW5ITVJ:L3G+
ES6 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1LocmlEPTB;MD6wNFIyKG6P NF3ZSZU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw{OjVyNEGvK|5USU6JRWK8M4E,
human PBMC Mlj3SpVv[3Srb36gRZN{[Xl? NUK5WoI5OTByIH7N NECxOYgzPCCq MWfJcoR2[2W|IFnMMVghemWuZXHz[S=> MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd7MUS3O{c,OjV5OUG0O|c9N2F-
U937 M1;BUWZ2dmO2aX;uJGF{e2G7 MWSxNFAhdk1? NFLXZlI3KGh? MkHXTY5lfWOnczDJUE05KGW6cILld5Nqd25iaX6gUHBUNXO2aX31cIF1\WRiVUmzO{Bu[WO{b4DoZYdmew>? NGTPPFc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUe5NVQ4Pyd-MkW3PVE1Pzd:L3G+
HH MWrNbYdz[XSrb36gRZN{[Xl? MnzPNVAxKG6P M4jycFI1KGh? MWHEUXNQ NHX6OmZT\WS3Y3XzJINmdGxibXnndoF1cW:wIHL5JFgx6oDVOUGl MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ6MUOzOUc,OjV4OEGzN|U9N2F-
Hut-78 MmLHUYloemG2aX;uJGF{e2G7 MXuxNFAhdk1? MXyyOEBp M4XycGROW09? NFPDRpBT\WS3Y3XzJINmdGxibXnndoF1cW:wIHL5JFgx6oDVOUCl NUTa[mFpRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW2PFE{OzVpPkK1OlgyOzN3PD;hQi=>
HH NIX6N4xHfW6ldHnvckBCe3OjeR?= NEPhNGMyODBibl2= NXnQdm1ZOjRiaB?= M4K1TWROW09? NX;ncZdZ\G:5boLl[5Vt[XSnczDUS2Yu|rJzIHHu[EBKVC1zMjDlfJBz\XO|aX;u NX:wV|FSRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW2PFE{OzVpPkK1OlgyOzN3PD;hQi=>
H9 MlTuSpVv[3Srb36gRZN{[Xl? NF;yUWMyODBibl2= NUfXcmFwOjRiaB?= M2jRS2ROW09? M2W4c2Rwf26{ZXf1cIF1\XNiVFfGMe6zOSCjbnSgTWwuOTFiZYjwdoV{e2mxbh?= NFnKO4s9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[4NVM{PSd-MkW2PFE{OzV:L3G+
Hut-78 MUPGeY5kfGmxbjDBd5NigQ>? NWrxVFlIOTByIH7N MnjxNlQhcA>? M4\S[GROW09? MVXEc5dvemWpdXzheIV{KFSJRj5OtlEh[W6mIFnMMVExKGW6cILld5Nqd25? MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ6MUOzOUc,OjV4OEGzN|U9N2F-
H1299 NUnrZWdvSXCxcITvd4l{KEG|c3H5 NV7vbYtlQDBibl2= NIfnem0zPCCq MX7EUXNQ Mm\GV4Vve2m2aYrld{BPW0OOQzDj[YxteyC2bzDNV2Mu\GW{aY\l[EBqSzlvaX7keYNm\CCjcH;weI9{cXN? NFHRUYE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUOyN|Y6Oyd-MkWzNlM3QTN:L3G+
BLM MW\BeZRweGijZ4mgRZN{[Xl? NH65O|YyOCCwTR?= M1zTcFEzKGh? NITvb3pKdmS3Y3XzJIZwem2jdHnvckBw\iCjdYTvdIhi\2:|b33ldy=> NX;hUHFORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOwO|kxQDNpPkKzNFc6ODh|PD;hQi=>
A375 Mn\ERZV1d3CqYXf5JGF{e2G7 MUOxNEBvVQ>? NGDE[FQyOiCq M1zNO2lv\HWlZYOg[o9zdWG2aX;uJI9nKGG3dH;wbIFod3OxbXXz NHGzPXo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{C3PVA5Oyd-MkOwO|kxQDN:L3G+
BLM NF:2b5FCeG:ydH;zbZMhSXO|YYm= NGG4eYYyOCCwTR?= MVqyOEBp MY\JcoR2[2W|IHPlcIwh[XCxcITvd4l{ MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzB5OUC4N{c,OjNyN{mwPFM9N2F-
A375 MX3BdI9xfG:|aYOgRZN{[Xl? NEX1eIQyOCCwTR?= MViyOEBp MV\JcoR2[2W|IHPlcIwh[XCxcITvd4l{ NVH0VFByRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOwO|kxQDNpPkKzNFc6ODh|PD;hQi=>
RAW 264.7 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3L4SVExOCCwTR?= M3fHeFQ5KGh? NELxS5RT\WS3Y3XzJINmdGxidnnhZoltcXS7wrC= NFewb|g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkSyO|E2PCd-MkK0NlcyPTR:L3G+
SNK-6 NE\5NmxCdnSrdnnyZYwhSXO|YYm= MVyxJO69VQ>? MUiyOEBp M3\TRmlv\HWlZYOgcJl1cWNiaX7m[YN1cW:wIH;mJGVDXg>? M3[2WFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUewPVg5Lz5{MUG3NFk5QDxxYU6=
KAI-3 Mnq2RY51cX[rcnHsJGF{e2G7 NFrwS5AyKM7:TR?= MYqyOEBp NHP4OVlKdmS3Y3XzJIx6fGmlIHnu[oVkfGmxbjDv[kBGSlZ? NH[0[4c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUG3NFk5QCd-MkGxO|A6QDh:L3G+
SNT-16 Ml;BRY51cX[rcnHsJGF{e2G7 NYDpfpZjOSEQvF2= MUmyOEBp MmHiTY5lfWOnczDsfZRq[yCrbn\lZ5Rqd25ib3[gSWJX MkTQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzN{C5PFgoRjJzMUewPVg5RC:jPh?=
SNT-13 NYq1WIVGSW62aY\pdoFtKEG|c3H5 M1j1SFEh|ryP NYDme3c3OjRiaB?= NUHVU5JRUW6mdXPld{BtgXSrYzDpcoZm[3Srb36gc4YhTUKY M2DYWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUewPVg5Lz5{MUG3NFk5QDxxYU6=
KHYG-1 NF:1WnhCeG:ydH;zbZMhSXO|YYm= NYHaTWVNOSEQvF2= M175fFYhcA>? MWnJcoR2[2W|IHPlcIwh[XCxcITvd4l{ NFPXcY09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUG3NFk5QCd-MkGxO|A6QDh:L3G+
KAI-3 M2nMNmFxd3C2b4Ppd{BCe3OjeR?= MUCxJO69VQ>? NVLDXZF{PiCq NU\0UVczUW6mdXPld{Bk\WyuIHHwc5B1d3Orcx?= M4PnOVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUewPVg5Lz5{MUG3NFk5QDxxYU6=
Jurkat MXTBdI9xfG:|aYOgRZN{[Xl? Moi5NUDPxE1? NXTiV|lGPiCq NGC5VoFKdmS3Y3XzJINmdGxiYYDvdJRwe2m| MljFQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzN{C5PFgoRjJzMUewPVg5RC:jPh?=
SNT-16 MVvBdI9xfG:|aYOgRZN{[Xl? M4XuTVEh|ryP M1fjTlYhcA>? MoWyTY5lfWOnczDj[YxtKGGyb4D0c5Nqew>? MkPQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzN{C5PFgoRjJzMUewPVg5RC:jPh?=
KHYG-1 M3jW[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUDIUog5OSEQvF2= M{H1[|I1KGh? MmHiVoVlfWOnczDj[YxtKH[rYXLpcIl1gcLi MnfoQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzN{C5PFgoRjJzMUewPVg5RC:jPh?=
SNK-6 NHTCVVJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX\ucJMzOSEQvF2= NFrzTmszPCCq MmTDVoVlfWOnczDj[YxtKH[rYXLpcIl1gcLi MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF5MEm4PEc,OjFzN{C5PFg9N2F-
KAI-3 MnXvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV;YfJlnOSEQvF2= NGjweIUzPCCq NXmw[YFNWmWmdXPld{Bk\WyuII\pZYJqdGm2edMg MX68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF5MEm4PEc,OjFzN{C5PFg9N2F-
Jurkat NG\GcGNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVfRcWNtOSEQvF2= NFfF[3kzPCCq Mn;TVoVlfWOnczDj[YxtKH[rYXLpcIl1gcLi NHXKbZE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUG3NFk5QCd-MkGxO|A6QDh:L3G+
SNT-16 MorNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml7hNUDPxE1? NF33SZMzPCCq NX\KdWJNWmWmdXPld{Bk\WyuII\pZYJqdGm2edMg MnTwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzN{C5PFgoRjJzMUewPVg5RC:jPh?=
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MG 63 (6-TG R) M2nNZ5FJXFNiYYPzZZk> MU\xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVUdiNkOgLFYuXEdiUjmgZ4VtdHN? MkfIQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
NB1643 MkDHdWhVWyCjc4PhfS=> NFzre2RyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTlKxOlQ{KGOnbHzz NE\RVIo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
OHS-50 NVPEdnpoeUiWUzDhd5NigQ>? NIfYfmhyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiT1jTMVUxKGOnbHzz MoHjQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
BT-12 MXjxTHRUKGG|c3H5 M3nyN5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJGJVNTF{IHPlcIx{ MoPmQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
fibroblast MW\xTHRUKGG|c3H5 MkLEdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKGOxboTyc4whUGhid3ns[EB1gXCnIH\pZpJw[myjc4SgZ4VtdHN? NEPITno9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
LAN-5 NFHnb49yUFSVIHHzd4F6 M2\xc5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJGxCVi13IHPlcIx{ MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
DAOY MnzXdWhVWyCjc4PhfS=> NXfvVot{eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhTEGRWTDj[Yxtew>? M4HDUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
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SK-N-SH M3;Se5FJXFNiYYPzZZk> MVTxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDTT{1PNVOKIHPlcIx{ MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
Rh30 M1izcJFJXFNiYYPzZZk> NELEb5lyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiUnizNEBk\Wyucx?= NU\pWIYxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
A673 NIPoOHByUFSVIHHzd4F6 MWLxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDBOlc{KGOnbHzzLS=> MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
BT-37 M1;ZTpFJXFNiYYPzZZk> NHGxd21yUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBDXC1|NzDj[Yxtew>? MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
MG 63 (6-TG R) NYH2dJJoeUiWUzDhd5NigQ>? M2jhdpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJG1IKDZ|IDi2MXRIKFJrIHPlcIx{ NUm5d25pRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
Rh30 M1TySZFJXFNiYYPzZZk> NWTqcGVMeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhWmh|MDDj[Yxtew>? NIHjboM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
fibroblast NWnJRXREeUiWUzDhd5NigQ>? M4jN[ZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJINwdnS{b3ygTIghf2muZDD0fZBmKG[rYoLvZoxie3RiY3XscJM> M3XlWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
U-2 OS NV;yUY5NeUiWUzDhd5NigQ>? NXHMVXY4eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhXS1{IF;TJINmdGy| NV:wSpJRRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
OHS-50 NULGPJpReUiWUzDhd5NigQ>? M3zmbZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJG9JWy13MDDj[Yxtew>? Mn30QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
SK-N-SH MXzxTHRUKGG|c3H5 NVK5VplxeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiT4L0bI9od26jbDCzSEB3cWGkaXzpeJkhe2O{ZXXuJIZweiCVSz3OMXNJKGOnbHzz MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
Rh41 M2nuWJFJXFNiYYPzZZk> NHPYSZhyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBTcDRzIHPlcIx{ MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
RD M3O1UZFJXFNiYYPzZZk> MUDxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDSSEBk\Wyucx?= MmjTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
Daoy MV3xTHRUKGG|c3H5 MWXxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBQenSqb3fvcoFtKDOGII\pZYJqdGm2eTDzZ5Jm\W5iZn;yJGRid3liY3XscJM> M{X5VlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
TC32 Mk\xdWhVWyCjc4PhfS=> MVHxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBQenSqb3fvcoFtKDOGIHPhd5Bie2Vic3Py[YVvKG[xcjDUR|MzKGOnbHzz Mmn1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
TC32 NYjmRmJ1eUiWUzDhd5NigQ>? M1\1cpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KE:{dHjv[49v[WxiM1Sgeoli[mmuaYT5JJNkemWnbjDmc5IhXEN|MjDj[Yxtew>? NXHuVHlDRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
MG 63 (6-TG R) MkLSdWhVWyCjc4PhfS=> MYTxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBQenSqb3fvcoFtKDOGII\pZYJqdGm2eTDzZ5Jm\W5iZn;yJG1IKDZ|IDi2MXRIKFJrIHPlcIx{ NWfUSIZzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
SJ-GBM2 NFfwcGNyUFSVIHHzd4F6 NV[wWYZLeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPKMWdDVTJiY3XscJM> MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
SK-N-MC NEi1e49yUFSVIHHzd4F6 NVTOZ4M6eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPLMW4uVUNiY3XscJM> NVi0epRRRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
NB-EBc1 NILtOJpyUFSVIHHzd4F6 MVrxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVkJvRVLjNUBk\Wyucx?= NIXoPHQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
LAN-5 NVTOcoVReUiWUzDhd5NigQ>? NUi0N5VLeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IFzBUk02KGOnbHzz MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
Rh18 MVTxTHRUKGG|c3H5 MYTxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWmhzODDj[Yxtew>? MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
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SEM M1;JNWZ2dmO2aX;uJIF{e2G7 NWD1b3VtOTBibl2= M{DueFE5KGi{cx?= M3HOSGlvcGmkaYTpc44hd2ZicILveIVie2:vZTDpckBpfW2jbjDTSW0h[2WubIOgZZN{\XO|ZXSgZZMhcW6lcnXhd4UhcW5iYXfndoV{d22nIHHjZ5VufWyjdHnvckBifCBzMDDuUUBi\nSncjCxPEBpenNiYomg[ox2d3Knc3PlcoNmKG2rY4Lvd4NweGmlIH3leIhw\A>? MYi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODN4NUi5Nkc,OzB|NkW4PVI9N2F-
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Assay
Methods Test Index PMID
Western blot phospho-PERK / ATF-4 ; GRP-78 / GADD-34 ; pro-caspase-12 / pro-caspase-3 ; pro-caspase-9 ; p-IκBα / IκBα ; COX-2 / cIAP2 15509775 20335171 24085292
Immunofluorescence Vimentin ; Ubiquitin 19010849
Growth inhibition assay Cell viability 20571067
ELISA IL-8 24085292
In vivo

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]

Protocol (from reference)

Kinase Assay:

[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.

Cell Research:

[5]

  • Cell lines: Human multiple myeloma cells line U266
  • Concentrations: ~10 μM
  • Incubation Time: 2 days
  • Method:

    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.

Animal Research:

[3]

  • Animal Models: Human plasmacytoma xenografts RPMI 8226
  • Dosages: 1 mg/kg
  • Administration: i.v. twice weekly for 4 weeks, then once weekly

Solubility (25°C)

In vitro

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
2% DMSO+30% PEG 300+ddH2O
For best results, use promptly after mixing.

5mg/mL

Chemical Information

Molecular Weight 384.24
Formula

C19H25BN4O4

CAS No. 179324-69-7
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles B(C(CC(C)C)NC(=O)C(CC1=CC=CC=C1)NC(=O)C2=NC=CN=C2)(O)O

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT05383547 Recruiting Drug: Bortezomib Bortezomib|Glomerulonephritis|MN|MPGN|FSGS|IgA Nephropathy Ruijin Hospital June 1 2022 Not Applicable
NCT04915248 Not yet recruiting Drug: Daratumumab|Drug: Bortezomib|Drug: Dexamethasone Plasmablastic Lymphoma Fondazione Italiana Linfomi ONLUS|Janssen-Cilag S.p.A. May 2022 Phase 2
NCT04656951 Recruiting Drug: Daratumumab Multiple Myeloma University of Cologne|Janssen-Cilag G.m.b.H June 1 2021 Phase 2
NCT04570631 Recruiting Drug: Eftozanermin alfa|Drug: Bortezomib|Drug: Dexamethasone Multiple Myeloma AbbVie November 5 2020 Phase 1
NCT03993262 Recruiting Drug: Bortezomib|Drug: Placebo Autoimmune Encephalitis Jena University Hospital May 13 2020 Phase 2

(data from https://clinicaltrials.gov, updated on 2022-08-01)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
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Frequently Asked Questions

Question 1:
On your website, it is mentioned that Bortezomib should be prepared at a concentration of 5 mg/ml in 2% DMSO/30% PEG300/ddH2O for in vivo use. But on the product sheet we received with the compound, it is mentioned: 5mg/ml in 0.5% methylcellulose, 0.2% tween 80. So which is the correct preparation buffer?

Answer:
S1013 Bortezomib in 2% DMSO+30% PEG 300+ddH2O at 5 mg/ml is a clear solution, and it in 0.5% methylcellulose+0.2% Tween 80 is a suspension. Please choose the suitable vehicle according to your administration route. When you prepare the clear solution, please dissolve Bortezomib in DMSO first, make sure it dissolves well, warm it up to 45 degree and/or sonicate if necessary, then add PEG, mix well, and finally add water.

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