Carfilzomib (PR-171)

For research use only. Not for use in humans.

製品コードS2853

CAS No. 868540-17-4

Carfilzomib (PR-171) is an irreversible proteasome inhibitor with IC50 of <5 nM in ANBL-6 cells, displayed preferential in vitro inhibitory potency against the ChT-L activity in the β5 subunit, but little or no effect on the PGPH and T-L activities. Carfilzomib activates prosurvival autophagy and induces cell apoptosis.

サイズ

価格(税別)

10mM (1mL in DMSO)	JPY 81000
5mg	JPY 30200
50mg	JPY 113200
200mg	JPY 196200

最寄りの販売代理店を探す

東京
北海道
東北
北関東
南関東
東海
北信越
近畿
中国
四国
九州

お探しのディーラーが見当たらない場合は直接こちらのメールアドレスまでお問い合わせください：[email protected]

バルク問合せ

代表番号: 03-5615-9297 | 電子メール：[email protected]

文献中Selleckの製品使用例(137)

製品安全説明書

Proteasome阻害剤の選択性比較

生物活性

製品説明

ターゲット

Proteasome ^[1]
(ANBL-6 cells)

5 nM

体外試験

Carfilzomib inhibits proliferation in a variety of cell lines and patient-derived neoplastic cells, including multiple myeloma, and induced intrinsic and extrinsic apoptotic signaling pathways and activation of c-Jun-N-terminal kinase (JNK). Carfilzomib reveals enhanced anti-MM activity compared with bortezomib, overcome resistance to bortezomib and other agents, and acts synergistically with dexamethasone (Dex). Carfilzomib shoes preferential in vitro inhibitory potency against the ChT-L activity in the β5 subunit, with over 80% inhibition at doses of 10 nM. Short exposure to low-dose Carfilzomib leads to preferential binding specificity for the β5 constitutive 20S proteasome and the β5i immunoproteasome subunits. Measurement of caspase activity in ANBL-6 cells pulsed with Carfilzomib reveals substantial increases in caspase-8, caspase-9, and caspase-3 activity after 8 hours, giving a 3.2-, 3.9- and 6.9-fold increase, respectively, over control cells after 8 hours. In carfilzomib pulse-treated cells, the mitochondrial membrane integrity is decreased to 41% (Q1 + Q2), compared with 75% in vehicle-treated control cells. ^[1] In another study, Carfilzomib has also shown preclinical effectiveness against hematological and solid malignancies. ^[2] Carfilzomib directly inhibits osteoclasts formation and bone resorption. ^[3]

細胞データ

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
MM.1S	Ml\SS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	Mnu3NE0yODBibl2=	M4rkVlQ5KGh?	M4LiT2lEPTEEoE5CpFExKG6P	NV\ZWG9uRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWzNVI2PDNpPkK1N\|EzPTR\|PD;hQi=>
NCI-H929	MlnBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NEjVelkxNTFyMDDuUS=>	M3GwRlQ5KGh?	MmTJTWM2OCB;wrCxOEBvVQ>?	M{HCPFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3M{GyOVQ{Lz5{NUOxNlU1OzxxYU6=
SUDHL16	MnHERZBweHSxc3nzJGF{e3OjeR?=	M1LHRVIvPeLCk{OuOUBvVQ>?	NYXvZ2tPPDhiaB?=	NVfZSVB7\W6qYX7j[ZMhfGinIHPlcIwh\GWjdHigZ48ufHKnYYTt[Y51KHerdHigRWN[OTJzNR?=	MXG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTJ\|OUmzOUc,OjV{M{m5N\|U9N2F-
SUDHL14	MkPNRZBweHSxc3nzJGF{e3OjeR?=	NVLTbXFCOi534pETN{42KG6P	M{WwU\|Q5KGh?	MYnlcohidmOnczD0bIUh[2WubDDk[YF1cCClbz30doVifG2nboSge4l1cCCDQ2mxNlE2	NFfDR3g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUKzPVk{PSd-MkWyN\|k6OzV:L3G+
U2932	M3vv[mFxd3C2b4Ppd{BCe3O\|YYm=	NWPpeZlOOi534pETN{42KG6P	NHLydlQ1QCCq	M37oTYVvcGGwY3XzJJRp\SClZXzsJIRm[XSqIHPvMZRz\WG2bXXueEB4cXSqIFHDXVEzOTV?	M{jqSFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MkO5PVM2Lz5{NUKzPVk{PTxxYU6=
P-UMSCC-1	NIjKc25Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NV3hOIx6UUN3ME2xNU4zKG6P	MoXQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7MUWwN\|koRjJ2OUG1NFM6RC:jPh?=
R-UMSCC-1	Mne3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			Mn7ITWM2OD1{Mkm0JI5O	MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlzNUCzPUc,OjR7MUWwN\|k9N2F-
P-Cal33	NV7FSWRiT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			M2mzR2lEPTB;MUeuN{BvVQ>?	NE\xT2o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmxOVA{QSd-MkS5NVUxOzl:L3G+
R-Cal33	NYLy[HJrT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			NV7aWnpMUUN3ME2xNVEzKG6P	MoS0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7MUWwN\|koRjJ2OUG1NFM6RC:jPh?=
Jurkat	MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MlLmNU0yOW6P	MWO0PEBp	MnPmbY5pcWKrdIOgeIhmKGOnbHygdJJwdGmoZYLheIlwdiClbz30doVifG2nboSge4l1cCC4b4Lpco9{fGG2	MoTCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR6MEGxNlgoRjJ2OECxNVI5RC:jPh?=
Jurkat	NWfOeJFKSXCxcITvd4l{KEG\|c4PhfS=>	MkT1PEBvVQ>?	MWOyOE81QCCq	M1juZYlv\HWlZYOgZZBweHSxc3nzMEBk[XOyYYPlJIFkfGm4YYTpc44tKGGwZDDQRXJRKGOuZXH2ZYdmKGOxLYTy[YF1dWWwdDD3bZRpKH[xcnnuc5N1[XR?	MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDhyMUGyPEc,OjR6MEGxNlg9N2F-
UMSCC-22A	NFKxRpdCeG:ydH;zbZMhSXO\|c3H5	NUezSZlPOjByIH7N	NWe5N3RjOjRiaB?=	NWniT3M3cW6mdXPlJJRp\SClZXzsJIFxd3C2b4Ppd{Bkdy22cnXheI1mdnRid3n0bEBQVlhiMEmxNi=>	NYLDZo42RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK5Nlk5ODNpPkKyPVI6QDB\|PD;hQi=>
UMSCC-22B	MV7BdI9xfG:\|aYOgRZN{e2G7	MmXhNlAxKG6P	MmjqNlQhcA>?	MUXpcoR2[2VidHjlJINmdGxiYYDvdJRwe2m\|IHPvMZRz\WG2bXXueEB4cXSqIF;OXEAxQTF{	NF3hVHI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkmyPVgxOyd-MkK5Nlk5ODN:L3G+
1483	M4m5SWFxd3C2b4Ppd{BCe3O\|YYm=	Ml\QNlAxKG6P	NVHCfYlJOjRiaB?=	M1rxZolv\HWlZTD0bIUh[2WubDDhdI9xfG:\|aYOgZ48ufHKnYYTt[Y51KHerdHigU25ZKDB7MUK=	M3vJ[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OUK5PFA{Lz5{MkmyPVgxOzxxYU6=
UMSCC-1	M3THSWFxd3C2b4Ppd{BCe3O\|YYm=	NFn6Xo8zODBibl2=	M3TvT\|I1KGh?	MmnobY5lfWOnIITo[UBk\WyuIHHwc5B1d3OrczDjc{11emWjdH3lcpQhf2m2aDDPUnghODlzMh?=	M{\aTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OUK5PFA{Lz5{MkmyPVgxOzxxYU6=
UMSCC-22A	NIL4[pBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MlfWTWM2OD1\|OD63JOKyKDFwMDDuUS=>	NXyxWIl1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK5Nlk5ODNpPkKyPVI6QDB\|PD;hQi=>
UMSCC-22B	MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			M16x[GlEPTB;M{CuO{DDuSB7LkOgcm0>	M{X4WVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OUK5PFA{Lz5{MkmyPVgxOzxxYU6=
1483	MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			M4j4c2lEPTB;NUCuOUDDuSBzMT65JI5O	MmrJQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ7Mkm4NFMoRjJ{OUK5PFA{RC:jPh?=
UMSCC-1	NXrXd2tIT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			MVTJR\|UxRTN2Lk[gxtEhOi54IH7N	MWW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjl{OUiwN{c,OjJ7Mkm4NFM9N2F-
Cal33	MnTDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			MULJR\|UxRTR7LkOgxtEhQC57IH7N	NIi0WHU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkmyPVgxOyd-MkK5Nlk5ODN:L3G+
PCI-15A	MljhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			NUXQNW03UUN3ME23NE41KMLzIEKyMlYhdk1?	MlfDQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ7Mkm4NFMoRjJ{OUK5PFA{RC:jPh?=
PCI-15B	MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			M4q4WGlEPTB;M{muOUDDuSBzMT6wJI5O	NGDNVXI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkmyPVgxOyd-MkK5Nlk5ODN:L3G+
OSC-19	MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			M3S5emlEPTB;MUiuN{DDuSB2LkKgcm0>	MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjl{OUiwN{c,OjJ7Mkm4NFM9N2F-
SUDHL16	M3jBSWFxd3C2b4Ppd{BCe3O\|YYm=	NX[1WlRXOi5yLUSuNEBvVQ>?	NYf3W2pIPDhiaB?=	M4WzSolv\HWlZYOgZ4VtdCCmZXH0bEBkdy22cnXheI1mdnRid3n0bEBw[mG2b3PsZZg>	MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjRzMUi5PUc,OjJ2MUG4PVk9N2F-
SUDHL16	MWLGeY5kfGmxbjDBd5NigQ>?	MUmyMlUhdk1?	NYLSN2dyOjRiaB?=	MYnhZ5RqfmG2ZYOgTm5MNCCrbnHjeIl3[XSnczDBT3QtKHWyLYLl[5Vt[XSnczDOc5hiNCCjbnSgbY5lfWOnczFOt2gzSS6[IHPvMZRz\WG2bXXueEB4cXSqIH;iZZRw[2yjeB?=	NVHiU2hYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK0NVE5QTlpPkKyOFEyQDl7PD;hQi=>
Granta	NFzFOZZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NVHsVmY4OC12IH7N	M3HXfFQ5KGh?	NFXKWm5qdmS3Y3WgZ4VtdCCmZXH0bEBkdy22cnXheI1mdnRid3n0bEBJSUSFSYO=	MlL5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF5NUCyNlQoRjJzN{WwNlI1RC:jPh?=
SUDHL16	M{XRVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M{jXOlEuPCCwTR?=	M1KwXFM3KGh?	NWnlZ4xUcW6mdXPlJINmdGxiZHXheIgh[29vdILlZZRu\W62IIfpeIghUEGGQ1nz	M171dVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJyMkOzPVc{Lz5{MEKzN\|k4OzxxYU6=
MOLT4	MW\GeY5kfGmxbjDhd5NigQ>?		NHTkWZQyKGi{	M{H2fWlvcGmkaYTpc44hd2ZiY3j5cY91enmyc3nuMYxqc2ViYXP0bZZqfHlib3[gNlBUKHC{b4TlZZNwdWViaX6gbJVu[W5iTV;MWFQh[2WubIOgZYZ1\XJiMTDodkBjgSCFZXzsWIl1\XJvR3zvJIx2dWmwZYPj[Y51KGG\|c3H5MEBKSzVyIE2gNE4xODVzIN88UU4>	M17MPFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7M{S4OFc{Lz5zOUO0PFQ4OzxxYU6=
MESSA	M3PDWGN6fG:2b4jpZ4l1gSCjc4PhfS=>		NFH2T4w4OiCqcoO=	NFT6PFBEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBOTVOVQTDj[YxteyCjc4Pld5Nm\CCjczDj[YxtKH[rYXLpcIl1gSCjZoTldkA4OiCqcoOgZpkhS2WubGTpeIVzNUeubzDseY1qdmW\|Y3XueEBie3OjeTygTWM2OCB;IECuNFE5KM7:TT6=	NWXCdJA1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUmzOFg1PzNpPkG5N\|Q5PDd\|PD;hQi=>
MESSA	MXzDfZRwfG:6aXPpeJkh[XO\|YYm=		M2jSU\|czKGi{cx?=	MWnDfZRwfG:6aXPpeJkh[WejaX7zeEBufWy2aXTyeYchemW\|aYP0ZY5k\SC2cnHud5BwenSncjDlfJBz\XO\|aX7nJIRwgG:{dXLpZ4lvKHKnc3nzeIFvfCCqdX3hckBOTVOVQTDj[YxteyCjc4Pld5Nm\CCjczDj[YxtKH[rYXLpcIl1gSCjZoTldkA4OiCqcoOgZpkhS2WubGTpeIVzNUeubzDseY1qdmW\|Y3XueEBie3OjeTygTWM2OCB;IECuOFE{KM7:TT6=	M4DmfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7M{S4OFc{Lz5zOUO0PFQ4OzxxYU6=
RPMI8226	M3:1[WN6fG:2b4jpZ4l1gSCjc4PhfS=>		MnLsO\|IhcHK\|	NFizSHVEgXSxdH;4bYMh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDSVG1KQDJ{NjDj[YxteyCjZoTldkA4OiCqcoOgZpkhVVSVIHHzd4F6NCCLQ{WwJF0hOC5yMUOxPUDPxE1w	MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDd4N{ixPEc,OjR5Nke4NVg9N2F-
NCI-H929	MlTLR5l1d3SxeHnjbZR6KGG\|c3H5		MVy3NkBpenN?	M4CzOGN6fG:2b4jpZ{Bi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF7DTU1JQTJ7IHPlcIx{KGGodHXyJFczKGi{czDifUBOXFNiYYPzZZktKEmFNUCgQUAxNjB{MUOyJO69VS5?	MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDd4N{ixPEc,OjR5Nke4NVg9N2F-
CCRF-CEM	NUiycVB5SW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		NEnDUHo4OiCqcoO=	NIfZTVVCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFPDVmYuS0WPIHPlcIx{KGGodHXyJFczKGi{czDifUBwgHmudXPp[oVzcW5ibIXtbY5me2OnbnPlJIF{e2G7LDDJR\|UxKD1iMD6wNFYyKM7:TT6=	NEmzd\|k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkKzNVE3Oid-Mk[yN\|EyPjJ:L3G+
RPMI8266	Mnj5RY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		M1\3UVczKGi{cx?=	NGG2fWVCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGLQUWk5OjZ4IHPlcIx{KGGodHXyJFczKGi{czDifUBwgHmudXPp[oVzcW5ibIXtbY5me2OnbnPlJIF{e2G7LDDJR\|UxKD1iMD6wNVM6KM7:TT6=	NXvUe29VRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[yN\|EyPjJpPkK2NlMyOTZ{PD;hQi=>
HCT116	NGfCb4dCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		NEH1flE4OiCqcoO=	NXXTWIExSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDIR3QyOTZiY3XscJMh[W[2ZYKgO\|IhcHK\|IHL5JI95gWy3Y3nm[ZJqdiCudX3pcoV{[2WwY3WgZZN{[XluIFnDOVAhRSByLkCxPVMh\|ryPLh?=	MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjJ\|MUG2Nkc,OjZ{M{GxOlI9N2F-
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MG 63 (6-TG R)	MljCdWhVWyCjc4PhfS=>			NYrlVldjeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF3HJFY{KCh4LWTHJHIqKGOnbHzz	NXuyVJh5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
NB1643	MUnxTHRUKGG\|c3H5			MofBdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKE6EMU[0N{Bk\Wyucx?=	Ml7aQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
OHS-50	M2e5XJFJXFNiYYPzZZk>			M3vBR5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCRSGOtOVAh[2WubIO=	NFjBSng9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
BT-12	MkjwdWhVWyCjc4PhfS=>			NXTpcFJUeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhSlRvMUKgZ4VtdHN?	M3L1dVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
LAN-5	NGTndWpyUFSVIHHzd4F6			NH\rPG5yUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBNSU5vNTDj[Yxtew>?	NFGwUnY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
fibroblast cells	M1f2V5FJXFNiYYPzZZk>			M{TpPJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiClb370do9tKEiqIIfpcIQhfHmyZTDmbYJzd2KuYYP0JINmdGy\|	M4P4d\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
NB-EBc1	NYrLTVg{eUiWUzDhd5NigQ>?			NF2wU2VyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBPSi2HQnOxJINmdGy\|	MWG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SK-N-SH	MluwdWhVWyCjc4PhfS=>			M1PUdpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHNMNU5vU1igZ4VtdHN?	MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Rh41	Mkj5dWhVWyCjc4PhfS=>			M1rlepFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCUaESxJINmdGy\|	MkXQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
A673	NV7OSo9{eUiWUzDhd5NigQ>?			NUfEOHFqeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhSTZ5MzDj[Yxteyl?	NYP5[YtRRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Rh30	M4qyNpFJXFNiYYPzZZk>			M1;Ee5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCUaEOwJINmdGy\|	NGi3[2E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
BT-37	M4HVVpFJXFNiYYPzZZk>			M1vlXpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJGJVNTN5IHPlcIx{	NH6wWWE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
MG 63 (6-TG R)	M4jkfpFJXFNiYYPzZZk>			NG\BWnRyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBOTyB4MzCoOk1VTyCUKTDj[Yxtew>?	MlzyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
Rh30	MXvxTHRUKGG\|c3H5			Ml\RdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgVog{OCClZXzsdy=>	MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
fibroblast cells	M2S3VJFJXFNiYYPzZZk>			NEWwZYtyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBkd262cn;sJGhpKHerbHSgeJlx\SCoaXLyc4Jt[XO2IHPlcIx{	M1ftblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
OHS-50	MkHQdWhVWyCjc4PhfS=>			NVOzeotJeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhV0iVLUWwJINmdGy\|	M2r2UVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SK-N-SH	M2e1UJFJXFNiYYPzZZk>			MoCwdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohV3K2aH;nc45idCB\|RDD2bYFjcWyrdImgd4Nz\WWwIH\vdkBUUy2QLWPIJINmdGy\|	MnjwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
Daoy	NVnmU\|VxeUiWUzDhd5NigQ>?			Ml\YdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohV3K2aH;nc45idCB\|RDD2bYFjcWyrdImgd4Nz\WWwIH\vdkBF[W:7IHPlcIx{	NHryTGg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
TC32	MWfxTHRUKGG\|c3H5			NHnUVY5yUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCRcoToc4dwdmGuIEPEJINie3Cjc3Wgd4Nz\WWwIH\vdkBVSzN{IHPlcIx{	NGfQXFY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
TC32	NV7OTGRZeUiWUzDhd5NigQ>?			NHvyOphyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCRcoToc4dwdmGuIEPEJJZq[WKrbHn0fUB{[3KnZX6g[o9zKFSFM{KgZ4VtdHN?	NGraOnI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
MG 63 (6-TG R)	M3;HXpFJXFNiYYPzZZk>			MYfxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBQenSqb3fvcoFtKDOGII\pZYJqdGm2eTDzZ5Jm\W5iZn;yJG1IKDZ\|IDi2MXRIKFJrIHPlcIx{	M{DRNFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SJ-GBM2	MnTndWhVWyCjc4PhfS=>			MYPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0pvR1LNNkBk\Wyucx?=	MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SK-N-MC	NHjoN\|lyUFSVIHHzd4F6			NFGxc3NyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU1utUk1OSyClZXzsdy=>	NInIWYY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
NB-EBc1	MWjxTHRUKGG\|c3H5			MWnxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVkJvRVLjNUBk\Wyucx?=	MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
LAN-5	M4DOPJFJXFNiYYPzZZk>			MnvodWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEyDTj21JINmdGy\|	Mle0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
Rh18	MkK1dWhVWyCjc4PhfS=>			NYjIZ3F6eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGLoNVgh[2WubIO=	Mmq3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SK-N-MC	MoXvdWhVWyCjc4PhfS=>			M1rJWJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHNMNU5vTVOgZ4VtdHN?	M4rOSFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SJ-GBM2	NVLDNItFeUiWUzDhd5NigQ>?			NWLOdZZoeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhW0pvR1LNNkBk\Wyucx?=	Mn7zQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
TC32	NYLsd2d[eUiWUzDhd5NigQ>?			NIjtfZpyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBVSzN{IHPlcIx{	NXf0NoFYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Rh18	M2nVRZFJXFNiYYPzZZk>			MXXxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDSbFE5KGOnbHzz	MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Saos-2	NFfyeWVyUFSVIHHzd4F6			NEPCUI9yUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBU[W:\|LUKgZ4VtdHN?	MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SJ-GBM2	M{O3V5FJXFNiYYPzZZk>			MUTxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBQenSqb3fvcoFtKDOGII\pZYJqdGm2eTDzZ5Jm\W5iZn;yJHNLNUeETUKgZ4VtdHN?	NF7FXJI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
RD	NFT3WXlyUFSVIHHzd4F6			NXzxTVJneUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiT4L0bI9od26jbDCzSEB3cWGkaXzpeJkhe2O{ZXXuJIZweiCURDDj[Yxtew>?	MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
ANBL-6	NHTKR2lHfW6ldHnvckBie3OjeR?=			MYrJcohq[mm2aX;uJI9nKDJyUzDwdo91\WG\|b33lJIFkfGm4aYT5JIlvKGi3bXHuJGFPSkxvNjDj[YxteyxiSVO1NEA:KDBwMEGg{txONg>?	M1HURVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NkWyNVQ{Lz5{OU[1NlE1OzxxYU6=
MCF7	MX\DfZRwfG:6aXPpeJkh[XO\|YYm=		M3f6cVQ5KGi{cx?=	NYjXfW9pS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hVUOINzDj[YxteyCjZoTldkA1QCCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwJF0hOC5yMESxJO69VS5?	MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODF4NUO0OEc,OzBzNkWzOFQ9N2F-
MDA-MB-231	NG\aOZpEgXSxdH;4bYNqfHliYYPzZZk>		M2HabFQ5KGi{cx?=	NVjsW5J3S3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hVUSDLV3CMVI{OSClZXzsd{Bi\nSncjC0PEBpenNiYomgUXRVKGG\|c3H5MEBKSzVyIE2gNE4xODR2IN88UU4>	MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODF4NUO0OEc,OzBzNkWzOFQ9N2F-
RPMI8226	NE\YfZhEgXSxdH;4bYNqfHliYYPzZZk>		MlH5OFghcHK\|	MoToR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gVnBOUTh{Mk[gZ4VtdHNiYX\0[ZIhPDhiaILzJIJ6KE2WVDDhd5NigSxiSVO1NEA:KDBwMEC2O{DPxE1w	M2e5PFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyMU[1N\|Q1Lz5\|MEG2OVM1PDxxYU6=

他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

アッセイ

Methods	Test Index	PMID
Western blot	pERK / ERK / pSTAT5 / STAT5 / pPI3K / PI3K; PubMed: 24590311 Oncogenesis Western blot analysis for activated (phosphorylated) ERK, Stat5 and PI3K signaling pathways following exposure to carfilzomib, total levels of ERK, Stat5 and PI3K were used as a loading control. caspase-9 / caspase-8; PubMed: 24590311 Oncogenesis Western blot analysis for activated (cleaved) caspase-8 and caspase-9 following exposure to carfilzomib. c-PARP / PARP / caspase-3; PubMed: 22929803 Clin Cancer Res UMSCC-22A, UMSCC-22B, 1483 and UMSCC-1 cells were treated for 24 hours with 0.1% DMSO, or 200 nmol/L carfilzomib or ONX 0912, followed by immunoblotting with anti-PARP, anti-caspase-3, or anti-β-actin. Shown are full-length PARP, cleaved PARP (c-PARP), and the cleaved, active subunits of caspase-3. Similar results were obtained in 3 independent experiments. Bcl-2 / Bcl-Xl / Mcl-1 / Bik / Bim / Bax / Bak; PubMed: 22929803 Clin Cancer Res UMSCC-22A, UMSCC-22B, 1483 and UMSCC-1 cells were treated for 24 hours with 0.1% DMSO, or 100 nmol/L carfilzomib or ONX 0912, followed by immunoblotting for the indicated proteins. In the case of Bik immunoblotting, cells were treated with 200 nmol/L carfilzomib or ONX 0912 to more clearly demonstrate Bik upregulation in 1483 and UMSCC-1 cells. Blots shown are representative of 3 independent experiments. Atg5 / Atg12 / Beclin-1 / LC3-II; PubMed: 22929803 Clin Cancer Res HNSCC cells were treated for 24 hours with 100 nmol/L carfilzomib or ONX 0912, or with 0.1% DMSO. Immunoblots were probed for Beclin-1, Atg5/12 conjugate, LC3-II, or β-actin. Representative blots from 3 independent experiments are shown. Noxa / Bik / Puma / Mcl-1; PubMed: 25548100 Mol Cancer Res SW620 cells were treated with the indicated dosage for 48 h. Expression of Noxa, Bik and/or Puma, c-myc and Mcl-1 proteins was then analyzed by immunoblotting. Tubulin served as control for protein loading. EGFR / HER2 / ER alpha / p-Akt(Ser473) / Akt / p-ERK / ERK / p53; PubMed: 29069787 Oncotarget T47D and MCF7 cells were cultured with the indicated carfilzomib concentrations for 32 or 36 hours, respectively. Western blots of protein lysates were probed with the indicated antibodies. β-actin served as loading control. BDP1 / HER2(Tyr1248) / HER2(Tyr1221/Tyr1222) / PARP1 / caspase-7 / p53 Mut; PubMed: 29069787 Oncotarget BT474 cells were cultured in the presence of the indicated carfilzomib concentrations for 32 hours. Western blots of protein lysates were probed with the indicated antibodies. HLA class I; PubMed: 26323098 Oncotarget Immunofluorescence analysis was performed to confirm the consequence that down-regulation of HLA class I was in a dose- and time-dependent manner.	24590311 22929803 25548100 29069787 26323098
Growth inhibition assay	Cell viability; PubMed: 27655642 Oncotarget Cytotoxic effects of carfilzomib on breast cancer cells in MTT assays. Seven human breast cancer cell lines, MCF7, T-47D, MDA-MB-361, HCC1954, MDA-MB-468, MDA-MB-231, and BT-549 were treated with carfilzomib at 0, 0.001 μM, 0.01 μM, 0.05 μM, 0.1 μM, 1 μM, 10 μM, or 50 μM for 72 h, then subjected to MTT assays. The absorbance of each well was measured at 540 nm and plotted for the cell viability curve. IC50 values of carfilzomib in breast cancer cell lines were listed.	27655642

体内試験

Carfilzomib moderately reduces tumor growth in an in vivo xenograft model. Carfilzomib effectively decreases multiple myeloma cell viability following continual or transient treatment mimicking. Carfilzomib increases trabecular bone volume, decreases bone resorption and enhances bone formation in non-tumor bearing mice. ^[3]

お薦めの試験操作（参考用のみ）

キナーゼ試験：^[1]	- 合併 Enzyme-linked immunosorbent assay for subunit profiling of carfilzomib: ANBL-6 cells (2 × 10⁶/well) are plated in 96-well plates and treated with Carfilzomib doses from 0.001 to 10 μM for 1 hour. Cells are then lysed (20 mM Tris-HCl, 0.5 mM EDTA), and cleared lysates are transferred to polymerase chain reaction (PCR) plates. A standard curve is generated using untreated ANBL-6 cell lysates starting at a concentration of 6 μg protein/μL. The active site probe [biotin-(CH2)4-Leu-Leu-Leu-epoxyketone; 20 μM] is added and incubated at room temperature for 1 hour. Cell lysates are then denatured by adding 1% sodium dodecyl sulfate (SDS) and heating to 100°C, followed by mixing with 20 μL per well streptavidin-sepharose high-performance beads in a 96-well multiscreen DV plate and incubated for 1 hour. These beads are then washed with enzyme-linked immunosorbent assay (ELISA) buffer (PBS, 1% bovine serum albumin, and 0.1% Tween-20), and incubated overnight at 4°C on a plate shaker with antibodies to proteasome subunits. Antibodies used included mouse monoclonal anti-β1, anti-β2, anti-β1i, and anti-β5i, goat polyclonal anti-β2i, and rabbit polyclonal anti-β5 (affinity-purified antiserum against KLH-CWIRVSSDNVADLHDKYS peptide). The beads are washed and incubated for 2 hours with horseradish peroxidase-conjugated secondary goat antirabbit, goat antimouse or rabbit antigoat antibodies. After washing, the beads are developed using the supersignal ELISA picochemiluminescence substrate. Luminescent detection is performed. Raw luminescence is converted to μg/mL by comparison with the standard curve and expressed as the % inhibition relative to vehicle control. Curve fits are generated using the following nonsigmoidal dose-response equation: Y = Bottom + (Top-Bottom)/(1 + 10̂((LogEC50 − X) × HillSlope)), where X is the logarithm of concentration, Y is the % inhibition, and EC50 is the dose showing 50% effect.
細胞試験： ^[1]	- 合併細胞株： WST-1, ANBL-6 cells 濃度： 100 nM 反応時間： 1 hour 実験の流れ： WST-1 is used to determine the effects of proteasome inhibitor Carfilzomib on cell proliferation. The inhibition of proliferation is calculated in relation to parallel control cells that receives vehicle alone. A linear spline function is used to interpolate the median inhibitory concentration (IC50) using XLfit 4 software. The degree of resistance (DOR) is calculated using the formula: DOR = IC50(resistant cells)/IC50(sensitive cells). ANBL-6 cells pulsed with 100 nM carfilzomib are washed and suspended in PBS containing 5 μg/mL of JC-1, which exhibits potential-dependent accumulation in mitochondria. Analysis of the mitochondrial membrane potential-dependent color shift from 525 to 590 nm is carried out on a FacScan, and the data are analyzed with CellQuest software. (参考用のみ)
動物試験：^[4]	- 合併動物モデル： Beige-nude-XID mice 投薬量： 2.0 mg/kg 投与方法： i.v. (参考用のみ)

参考

[4] Dasmahapatra G, et al. Mol Cancer Ther. 2011, 10(9), 1686-1697.

- 合併

溶解度 (25°C)

体外	DMSO	50 mg/mL (69.45 mM)
	Water	Insoluble
	Ethanol	Insoluble
体内	左から（NMPから）右の順に溶剤を製品に加えます(文献ではなく、Selleckの実験によるデータ): 2% DMSO+30% PEG 300+2%Tween 80+ddH2O 混合させたのち直ちに使用することを推奨します。	1mg/mL

* 溶解度測定はSelleck技術部門によって行われており、その他文献に示されている溶解度と差異がある可能性がありますが、同一ロットの生産工程で起きる正常な現象ですからご安心ください。

化学情報 Carfilzomib (PR-171) SDFをダウンロードする

分子量	719.91
化学式	C₄₀H₅₇N₅O₇
CAS No.	868540-17-4
Storage	3 years-20°C powder 2 years-80°C in solvent
別名	N/A
Smiles	CC(C)CC(C(=O)C1(CO1)C)NC(=O)C(CC2=CC=CC=C2)NC(=O)C(CC(C)C)NC(=O)C(CCC3=CC=CC=C3)NC(=O)CN4CCOCC4

投与溶媒組成計算器(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量

mg/kg

動物平均体重

投与体積（動物毎）

動物数

匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO+ % + % Tween 80+ % ddH₂O

計算リセット

計算結果:

投与溶媒濃度： mg/ml；

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL，注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。）

投与溶媒調製方法：μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

便利ツール

モル濃度計算器

求めたい質量、体積または濃度を計算してください。

質量 (mg) = 濃度 (mM) x 体積 (mL) x 分子量 (g/mol)

モル濃度計算器方程式

質量

濃度

体積

分子量
=

×

×

*貯蔵液を準備するとき、常に、オンであるとわかる製品のバッチに特有の分子量を使って、を通してラベルとMSDS/COA（製品ページで利用可能な）。

希釈計算器

貯蔵液を準備するために必要な希釈率を計算してください。Selleck希釈計算器は、以下の方程式に基づきます：

開始濃度 x 開始体積 = 最終濃度 x 最終体積

希釈の計算式

この方程式は、一般に略語を使われます：C1V1 = C2V2 ( 入力出力 )

C1

V1

C2

V2
×

=

×

常に貯蔵液を準備するとき、小びんラベルとMSDS/COA（オンラインで利用できる）で見つかる製品のバッチに特有の分子量を使ってください。

連続希釈計算器方程式

連続希釈剤
初めの濃度：
稀釈倍数：

計算結果

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

分子量計算器

分子量计算器

そのモル質量と元素組成を計算するために、合成物の化学式を入力してください：

チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

臨床試験 (data from https://clinicaltrials.gov, updated on 2021-01-06)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04407858	Recruiting	--	Myeloma\|Heart Failure\|Hypertension	European Georges Pompidou Hospital	May 21 2020	--
NCT03673826	Recruiting	Drug: Carfilzomib\|Drug: Dexamethasone\|Drug: Lenalidomide	Smouldering Myeloma	Stichting Hemato-Oncologie voor Volwassenen Nederland	November 19 2018	Phase 2

技術サポート

ストックの作り方、阻害剤の保管方法、細胞実験や動物実験の際に注意すべき点など、製品を取扱う時に問い合わせが多かった質問に対しては取扱説明書でお答えしています。

Handling Instructions

他に質問がある場合は、お気軽にお問い合わせください。

* 必須
*大学・企業名:
*名前:
*電子メール:
*電話番号:
*内容:

よくある質問（FAQ）

質問1：
How should I prepare solution of Carfilzomib for ongoing in vivo study?
回答：
This compound can be dissolved in 2% DMSO/30% PEG 300/dd H2O at 10 mg/ml as a suspension, and can be dissolved in 2% DMSO/ castor oil at 10 mg/ml as a clear solution.

Proteasomeシグナル伝達経路

Proteasome Inhibitors with Unique Features

Pan Proteasome Inhibitor

Ixazomib (MLN2238) : β5 site, IC50=3.4 nM; β1 site, IC50=31 nM; β2 site, IC50=3500 nM.
Most Potent Proteasome Inhibitor

Bortezomib (PS-341) : 20S proteasome, K_i of 0.6 nM.
Newest Proteasome Inhibitor

Oprozomib (ONX 0912) : Orally bioavailable inhibitor for CT-L activity of 20S proteasome β5/LMP7 with IC50 of 36 nM/82 nM.
Classic Proteasome Inhibitor

ONX-0914 (PR-957) : Selective immunoproteasome inhibitor with minimal cross-reactivity for the constitutive proteasome.

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Bortezomib (PS-341)

Bortezomib (PS-341, Velcade, LDP-341, MLM341, NSC 681239) is a potent 20S proteasome inhibitor with K_i 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.
Ixazomib (MLN2238)

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Features:A first-in-class proteasome inhibitor that has improved pharmacokinetics (PK), pharmacodynamics(PD), and antitumor activity in preclinical studies.
ONX-0914 (PR-957) ^New

ONX-0914 (PR-957) is a potent and selective immunoproteasome inhibitor with minimal cross-reactivity for the constitutive proteasome in a cell-free assay.

Features:The first highly selective, small molecule inhibitor of the immunoproteasome. Potential use in cancer and autoimmune diseases (e.g. rheumatoid arthritis, inflammatory bowel disease, and lupus).
Ixazomib Citrate (MLN9708)

Ixazomib Citrate (MLN9708) immediately hydrolyzed to Ixazomib (MLN2238), the biologically active form, on exposure to aqueous solutions or plasma. Ixazomib (MLN2238) inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with IC50/K_i of 3.4 nM/0.93 nM in cell-free assays, less potent to β1 and little activity to β2. Ixazomib (MLN2238) induces autophagy. Phase 3.

Features:The 1st oral proteasome inhibitor in early stage clinical trials for Multiple Myeloma.

研究分野別

製品類型

Carfilzomib (PR-171)

文献中Selleckの製品使用例(137)

製品安全説明書

Proteasome阻害剤の選択性比較

生物活性

お薦めの試験操作（参考用のみ）

参考

溶解度 (25°C)

化学情報 Carfilzomib (PR-171) SDFをダウンロードする

投与溶媒組成計算器(クリア溶液)

便利ツール

モル濃度計算器

質量 (mg) = 濃度 (mM) x 体積 (mL) x 分子量 (g/mol)

モル濃度計算器方程式

希釈計算器

開始濃度 x 開始体積 = 最終濃度 x 最終体積

希釈の計算式

連続希釈計算器方程式

連続希釈剤

計算結果

分子量计算器

総分子量：g/mol

モル濃度計算器

臨床試験 (data from https://clinicaltrials.gov, updated on 2021-01-06)

技術サポート

よくある質問（FAQ）

Proteasomeシグナル伝達経路

Proteasome Inhibitors with Unique Features

相関Proteasome製品