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]|よく尋ねられる質問

文献中Selleckの製品使用例(165)

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	NFPBcYNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NYm2T4V6OC1zMECgcm0>	NVfJWnNZPDhiaB?=	MVXJR\|UxyqB;wrCxNEBvVQ>?	MlmxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV\|MUK1OFMoRjJ3M{GyOVQ{RC:jPh?=
NCI-H929	M1rOd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M1rsfVAuOTByIH7N	M{PobVQ5KGh?	NHrxUmNKSzVyIE5CpFE1KG6P	NFizN3E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUOxNlU1Oyd-MkWzNVI2PDN:L3G+
SUDHL16	NV;KW3EzSXCxcITvd4l{KEG\|c4PhfS=>	NGfiO\|QzNjYkgKOzMlUhdk1?	MWK0PEBp	NIjLRlZmdmijbnPld{B1cGViY3XscEBl\WG2aDDjc{11emWjdH3lcpQhf2m2aDDBR3kyOjF3	MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTJ\|OUmzOUc,OjV{M{m5N\|U9N2F-
SUDHL14	NH3xO3NCeG:ydH;zbZMhSXO\|c3H5	MkTSNk426oDVMz61JI5O	M2\xXVQ5KGh?	Mk\m[Y5p[W6lZYOgeIhmKGOnbHyg[IVifGhiY3:teJJm[XSvZX70JJdqfGhiQVPZNVIyPQ>?	MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTJ\|OUmzOUc,OjV{M{m5N\|U9N2F-
U2932	MlXLRZBweHSxc3nzJGF{e3OjeR?=	MVWyMlXjiJN\|LkWgcm0>	MmPkOFghcA>?	Mk\Q[Y5p[W6lZYOgeIhmKGOnbHyg[IVifGhiY3:teJJm[XSvZX70JJdqfGhiQVPZNVIyPQ>?	NXm2SGtPRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWyN\|k6OzVpPkK1NlM6QTN3PD;hQi=>
P-UMSCC-1	NGnObJVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MkjETWM2OD1zMT6yJI5O	NX7TZm0{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NVUxOzlpPkK0PVE2ODN7PD;hQi=>
R-UMSCC-1	MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MnnsTWM2OD1{Mkm0JI5O	NHi3SZI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmxOVA{QSd-MkS5NVUxOzl:L3G+
P-Cal33	MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MonhTWM2OD1zNz6zJI5O	NWXGelBGRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NVUxOzlpPkK0PVE2ODN7PD;hQi=>
R-Cal33	NYrzPVV3T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			MWHJR\|UxRTFzMUKgcm0>	MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlzNUCzPUc,OjR7MUWwN\|k9N2F-
Jurkat	NWjPeIdwT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NX7ScXFVOS1zMX7N	Mom2OFghcA>?	NVX0ZWZXcW6qaXLpeJMhfGinIHPlcIwheHKxbHnm[ZJifGmxbjDjc{11emWjdH3lcpQhf2m2aDD2c5Jqdm:\|dHH0	NGXMUno9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEiwNVEzQCd-MkS4NFEyOjh:L3G+
Jurkat	MXHBdI9xfG:\|aYOgRZN{e2G7	MmrIPEBvVQ>?	MlPoNlQwPDhiaB?=	NWjuWWwzcW6mdXPld{BieG:ydH;zbZMtKGOjc4Dhd4Uh[WO2aY\heIlwdixiYX7kJHBCWlBiY3zlZZZi\2ViY3:teJJm[XSvZX70JJdqfGhidn;ybY5we3SjdB?=	MnLWQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR6MEGxNlgoRjJ2OECxNVI5RC:jPh?=
UMSCC-22A	MYDBdI9xfG:\|aYOgRZN{e2G7	NX;FeYxSOjByIH7N	MX6yOEBp	NETncWJqdmS3Y3WgeIhmKGOnbHygZZBweHSxc3nzJINwNXS{ZXH0cYVvfCC5aYToJG9PYCByOUGy	NYDGXWV1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK5Nlk5ODNpPkKyPVI6QDB\|PD;hQi=>
UMSCC-22B	NFLFTJZCeG:ydH;zbZMhSXO\|c3H5	M2TFNVIxOCCwTR?=	NXfI[mJrOjRiaB?=	MUPpcoR2[2VidHjlJINmdGxiYYDvdJRwe2m\|IHPvMZRz\WG2bXXueEB4cXSqIF;OXEAxQTF{	NWXaNYJiRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK5Nlk5ODNpPkKyPVI6QDB\|PD;hQi=>
1483	NI\2VlhCeG:ydH;zbZMhSXO\|c3H5	NV3ROFBOOjByIH7N	MlLsNlQhcA>?	MUTpcoR2[2VidHjlJINmdGxiYYDvdJRwe2m\|IHPvMZRz\WG2bXXueEB4cXSqIF;OXEAxQTF{	NE\yVZQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkmyPVgxOyd-MkK5Nlk5ODN:L3G+
UMSCC-1	MoDrRZBweHSxc3nzJGF{e3OjeR?=	NVPXPYpXOjByIH7N	MlLsNlQhcA>?	MWDpcoR2[2VidHjlJINmdGxiYYDvdJRwe2m\|IHPvMZRz\WG2bXXueEB4cXSqIF;OXEAxQTF{	Mk\lQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ7Mkm4NFMoRjJ{OUK5PFA{RC:jPh?=
UMSCC-22A	MkLFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			MoK5TWM2OD1\|OD63JOKyKDFwMDDuUS=>	MnjBQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ7Mkm4NFMoRjJ{OUK5PFA{RC:jPh?=
UMSCC-22B	MmWyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			NFLBO4dKSzVyPUOwMlchyrFiOT6zJI5O	MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjl{OUiwN{c,OjJ7Mkm4NFM9N2F-
1483	NYq2UlY4T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			M2P0cWlEPTB;NUCuOUDDuSBzMT65JI5O	NUHLT2FJRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK5Nlk5ODNpPkKyPVI6QDB\|PD;hQi=>
UMSCC-1	MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NWOwU\|VKUUN3ME2zOE43KMLzIEKuOkBvVQ>?	NVrPSFZURGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK5Nlk5ODNpPkKyPVI6QDB\|PD;hQi=>
Cal33	MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NX7MRW9yUUN3ME20PU4{KMLzIEiuPUBvVQ>?	NW\id5F[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK5Nlk5ODNpPkKyPVI6QDB\|PD;hQi=>
PCI-15A	NXTJVZBVT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			M2X1T2lEPTB;N{CuOEDDuSB{Mj62JI5O	NGXveHk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkmyPVgxOyd-MkK5Nlk5ODN:L3G+
PCI-15B	M4H3NWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			MlziTWM2OD1\|OT61JOKyKDFzLkCgcm0>	NXvlcY1jRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK5Nlk5ODNpPkKyPVI6QDB\|PD;hQi=>
OSC-19	NV3BWGxrT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			NHXqfHRKSzVyPUG4MlMhyrFiND6yJI5O	M2XWN\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OUK5PFA{Lz5{MkmyPVgxOzxxYU6=
SUDHL16	M4i4[WFxd3C2b4Ppd{BCe3O\|YYm=	NWfSZoNoOi5yLUSuNEBvVQ>?	NE[wPVY1QCCq	Ml3RbY5lfWOnczDj[YxtKGSnYYToJINwNXS{ZXH0cYVvfCC5aYToJI9j[XSxY3zhfC=>	NVHvV3FSRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK0NVE5QTlpPkKyOFEyQDl7PD;hQi=>
SUDHL16	NHX6c5dHfW6ldHnvckBCe3OjeR?=	NHTpWWMzNjVibl2=	M3vBWVI1KGh?	NXPHS5pz[WO2aY\heIV{KEqQSzygbY5i[3SrdnH0[ZMhSUuWLDD1dE1z\We3bHH0[ZMhVm:6YTygZY5lKGmwZIXj[ZMh\|rOKMlGuXEBkdy22cnXheI1mdnRid3n0bEBw[mG2b3PsZZg>	MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjRzMUi5PUc,OjJ2MUG4PVk9N2F-
Granta	M3zUVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MXOwMVQhdk1?	NHTxVow1QCCq	MoDibY5lfWOnIHPlcIwh\GWjdHigZ48ufHKnYYTt[Y51KHerdHigTGFFS0m\|	MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTd3MEKyOEc,OjF5NUCyNlQ9N2F-
SUDHL16	M3rnd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MVKxMVQhdk1?	NUDTeWVUOzZiaB?=	NETGTJZqdmS3Y3WgZ4VtdCCmZXH0bEBkdy22cnXheI1mdnRid3n0bEBJSUSFSYO=	NV7TS4o{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkCyN\|M6PzNpPkKwNlM{QTd\|PD;hQi=>
MOLT4	MUfGeY5kfGmxbjDhd5NigQ>?		MkjKNUBpeg>?	M3;3bmlvcGmkaYTpc44hd2ZiY3j5cY91enmyc3nuMYxqc2ViYXP0bZZqfHlib3[gNlBUKHC{b4TlZZNwdWViaX6gbJVu[W5iTV;MWFQh[2WubIOgZYZ1\XJiMTDodkBjgSCFZXzsWIl1\XJvR3zvJIx2dWmwZYPj[Y51KGG\|c3H5MEBKSzVyIE2gNE4xODVzIN88UU4>	M4LUSVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7M{S4OFc{Lz5zOUO0PFQ4OzxxYU6=
MESSA	NV\XbGI6S3m2b4TvfIlkcXS7IHHzd4F6		NEWwU404OiCqcoO=	NX;WeFBSS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hVUWVU1GgZ4VtdHNiYYPz[ZN{\WRiYYOgZ4VtdCC4aXHibYxqfHliYX\0[ZIhPzJiaILzJIJ6KEOnbHzUbZRmei2JbH:gcJVucW6nc3PlcpQh[XO\|YYmsJGlEPTBiPTCwMlAyQCEQvF2u	MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTN2OES3N{c,OTl\|NEi0O\|M9N2F-
MESSA	NULObmcxS3m2b4TvfIlkcXS7IHHzd4F6		NIO5XHU4OiCqcoO=	MWLDfZRwfG:6aXPpeJkh[WejaX7zeEBufWy2aXTyeYchemW\|aYP0ZY5k\SC2cnHud5BwenSncjDlfJBz\XO\|aX7nJIRwgG:{dXLpZ4lvKHKnc3nzeIFvfCCqdX3hckBOTVOVQTDj[YxteyCjc4Pld5Nm\CCjczDj[YxtKH[rYXLpcIl1gSCjZoTldkA4OiCqcoOgZpkhS2WubGTpeIVzNUeubzDseY1qdmW\|Y3XueEBie3OjeTygTWM2OCB;IECuOFE{KM7:TT6=	M1;PWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7M{S4OFc{Lz5zOUO0PFQ4OzxxYU6=
RPMI8226	MVfDfZRwfG:6aXPpeJkh[XO\|YYm=		NEXXS3A4OiCqcoO=	MYTDfZRwfG:6aXOgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCUUF3JPFIzPiClZXzsd{Bi\nSncjC3NkBpenNiYomgUXRUKGG\|c3H5MEBKSzVyIE2gNE4xOTNzOTFOwG0v	NHjFWnA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEe2O\|gyQCd-MkS3Olc5OTh:L3G+
NCI-H929	NY[0OYpoS3m2b4TvfIlkcXS7IHHzd4F6		M4HZXVczKGi{cx?=	MoPKR5l1d3SxeHnjJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTlPJMWg6OjliY3XscJMh[W[2ZYKgO\|IhcHK\|IHL5JG1VWyCjc4PhfUwhUUN3MDC9JFAvODJzM{Kg{txONg>?	M32yZ\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2N{[3PFE5Lz5{NEe2O\|gyQDxxYU6=
CCRF-CEM	MorkRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		M4G5TVczKGi{cx?=	MUTBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEOFUl[tR2VOKGOnbHzzJIFnfGW{IEeyJIhzeyCkeTDvfJltfWOrZnXybY4hdHWvaX7ld4NmdmOnIHHzd4F6NCCLQ{WwJF0hOC5yME[xJO69VS5?	NEfnb\|Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkKzNVE3Oid-Mk[yN\|EyPjJ:L3G+
RPMI8266	M4HLUWFvfGmycn;sbYZmemG2aY\lJIF{e2G7		NH3sS4o4OiCqcoO=	M1\Lc2FvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iUmDNTVgzPjZiY3XscJMh[W[2ZYKgO\|IhcHK\|IHL5JI95gWy3Y3nm[ZJqdiCudX3pcoV{[2WwY3WgZZN{[XluIFnDOVAhRSByLkCxN\|kh\|ryPLh?=	MUK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjJ\|MUG2Nkc,OjZ{M{GxOlI9N2F-
HCT116	M365PWFvfGmycn;sbYZmemG2aY\lJIF{e2G7		MoT0O\|IhcHK\|	NYrPUVVqSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDIR3QyOTZiY3XscJMh[W[2ZYKgO\|IhcHK\|IHL5JI95gWy3Y3nm[ZJqdiCudX3pcoV{[2WwY3WgZZN{[XluIFnDOVAhRSByLkCxPVMh\|ryPLh?=	Mlm2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ{M{GxOlIoRjJ4MkOxNVYzRC:jPh?=
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MG 63 (6-TG R)	M2qwbJFJXFNiYYPzZZk>			MVPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVUdiNkOgLFYuXEdiUjmgZ4VtdHN?	NH3o[4M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
NB1643	NGDI[5hyUFSVIHHzd4F6			NGLYSGpyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTlKxOlQ{KGOnbHzz	M{G3WlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
OHS-50	MV;xTHRUKGG\|c3H5			NUnVfodQeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF;IV{02OCClZXzsdy=>	M1PBd\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
BT-12	NHvQTZVyUFSVIHHzd4F6			M1TpZpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJGJVNTF{IHPlcIx{	M2\yPVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
LAN-5	NEO0So9yUFSVIHHzd4F6			NH:2dmxyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBNSU5vNTDj[Yxtew>?	MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
fibroblast cells	M2nqb5FJXFNiYYPzZZk>			M2G3epFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiClb370do9tKEiqIIfpcIQhfHmyZTDmbYJzd2KuYYP0JINmdGy\|	Mke4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
NB-EBc1	NYXwPHFQeUiWUzDhd5NigQ>?			MlnIdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgUmIuTUKlMTDj[Yxtew>?	NFjnO\|U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
SK-N-SH	NEHISGNyUFSVIHHzd4F6			M1Xze5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHNMNU5vU1igZ4VtdHN?	NXzhN4d{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Rh41	NYXGc2ZneUiWUzDhd5NigQ>?			MmTDdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFKqNEGgZ4VtdHN?	MoXtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
A673	M3\m[JFJXFNiYYPzZZk>			M3jaOpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJGE3PzNiY3XscJMq	M{TYfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Rh30	MWXxTHRUKGG\|c3H5			M2THN5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCUaEOwJINmdGy\|	MXG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
BT-37	M2m1OpFJXFNiYYPzZZk>			M3nhW5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJGJVNTN5IHPlcIx{	MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
MG 63 (6-TG R)	M4TUVZFJXFNiYYPzZZk>			MnT2dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgUWchPjNiKE[tWGchWiliY3XscJM>	MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Rh30	NIfSPWxyUFSVIHHzd4F6			MWHxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDSbFMxKGOnbHzz	MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
fibroblast cells	NVLYWWdjeUiWUzDhd5NigQ>?			NUW3XXJXeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5Ih[2:wdILvcEBJcCC5aXzkJJR6eGViZnnido9jdGG\|dDDj[Yxtew>?	NIHKVY49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
OHS-50	M3rJTZFJXFNiYYPzZZk>			NGrNfpByUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBQUFNvNUCgZ4VtdHN?	NUnGc4hnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
SK-N-SH	NV31Xpk{eUiWUzDhd5NigQ>?			NUW3V2o4eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiT4L0bI9od26jbDCzSEB3cWGkaXzpeJkhe2O{ZXXuJIZweiCVSz3OMXNJKGOnbHzz	M2PHWFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Daoy	NV\sVWxCeUiWUzDhd5NigQ>?			MmXVdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohV3K2aH;nc45idCB\|RDD2bYFjcWyrdImgd4Nz\WWwIH\vdkBF[W:7IHPlcIx{	M4jRXVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
TC32	NGW4S\|ZyUFSVIHHzd4F6			M1L2NZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KE:{dHjv[49v[WxiM1SgZ4F{eGG\|ZTDzZ5Jm\W5iZn;yJHREOzJiY3XscJM>	NVPJeIxCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
TC32	MWnxTHRUKGG\|c3H5			NXfiVY1QeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiT4L0bI9od26jbDCzSEB3cWGkaXzpeJkhe2O{ZXXuJIZweiCWQ{OyJINmdGy\|	MonSQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
MG 63 (6-TG R)	NFnGW29yUFSVIHHzd4F6			MniydWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohV3K2aH;nc45idCB\|RDD2bYFjcWyrdImgd4Nz\WWwIH\vdkBOTyB4MzCoOk1VTyCUKTDj[Yxtew>?	M{nuS\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SJ-GBM2	MlridWhVWyCjc4PhfS=>			NV\3bVl7eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGPKMWdDVTJiY3XscJM>	MkfEQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SK-N-MC	M1XBZpFJXFNiYYPzZZk>			NXXBO49veUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGPLMW4uVUNiY3XscJM>	NFXab5Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
NB-EBc1	NF7VUolyUFSVIHHzd4F6			MWLxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVkJvRVLjNUBk\Wyucx?=	MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
LAN-5	M4KwcJFJXFNiYYPzZZk>			M2X5U5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCOQV6tOUBk\Wyucx?=	MmXrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
Rh18	NYLnWoZVeUiWUzDhd5NigQ>?			NVjpeFNxeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGLoNVgh[2WubIO=	NHvIfno9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
SK-N-MC	MX\xTHRUKGG\|c3H5			M3;pOJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHNMNU5vTVOgZ4VtdHN?	NIfiZ2g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
SJ-GBM2	M{jLRpFJXFNiYYPzZZk>			NHrTOHdyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBUUi2JQl2yJINmdGy\|	M37lblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
TC32	MYDxTHRUKGG\|c3H5			Mo\wdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgWGM{OiClZXzsdy=>	MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Rh18	MXHxTHRUKGG\|c3H5			MmS3dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgVogyQCClZXzsdy=>	M{HGXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Saos-2	NEDW[lhyUFSVIHHzd4F6			NF3iXYtyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBU[W:\|LUKgZ4VtdHN?	NYPOTYJORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
SJ-GBM2	MnnodWhVWyCjc4PhfS=>			MXfxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBQenSqb3fvcoFtKDOGII\pZYJqdGm2eTDzZ5Jm\W5iZn;yJHNLNUeETUKgZ4VtdHN?	NHXnWYg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
RD	NUPTOpFReUiWUzDhd5NigQ>?			NYPsT5FQeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiT4L0bI9od26jbDCzSEB3cWGkaXzpeJkhe2O{ZXXuJIZweiCURDDj[Yxtew>?	MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
ANBL-6	MUfGeY5kfGmxbjDhd5NigQ>?			NUDNO2s4UW6qaXLpeIlwdiCxZjCyNHMheHKxdHXhd49u\SCjY4Tpeol1gSCrbjDoeY1idiCDTlLMMVYh[2WubIOsJGlEPTBiPTCwMlAyKM7:TT6=	NGrGbo49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OU[1NlE1Oyd-Mkm2OVIyPDN:L3G+
MCF7	NIDrU\|dEgXSxdH;4bYNqfHliYYPzZZk>		NXH3NI1rPDhiaILz	M13vOGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJG1ETjdiY3XscJMh[W[2ZYKgOFghcHK\|IHL5JG1VXCCjc4PhfUwhUUN3MDC9JFAvODB2MTFOwG0v	NHfGeoM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEG2OVM1PCd-M{CxOlU{PDR:L3G+
MDA-MB-231	NULPWYNES3m2b4TvfIlkcXS7IHHzd4F6		M3nxO\|Q5KGi{cx?=	NHLNR49EgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBOTEFvTVKtNlMyKGOnbHzzJIFnfGW{IES4JIhzeyCkeTDNWHQh[XO\|YYmsJGlEPTBiPTCwMlAxPDRizszNMi=>	NHTKcZI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEG2OVM1PCd-M{CxOlU{PDR:L3G+
RPMI8226	MkXKR5l1d3SxeHnjbZR6KGG\|c3H5		NGDhPZA1QCCqcoO=	NUO1UlF3S3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hWlCPSUiyNlYh[2WubIOgZYZ1\XJiNEigbJJ{KGK7IF3UWEBie3OjeTygTWM2OCB;IECuNFA3PyEQvF2u	NFKwV2I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEG2OVM1PCd-M{CxOlU{PDR:L3G+

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SDS/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SDS/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 2022-01-17)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT05041933	Recruiting	Drug: outsourcing of chemotherapy to Hospital at Home	Hematological Diseases	University Hospital Limoges	September 15 2021	--
NCT04811508	Recruiting	--	Relapsed Multiple Myeloma	Centre Hospitalier le Mans	August 4 2020	--

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)

Ixazomib (MLN2238) inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with IC50 and K_i of 3.4 nM and 0.93 nM in cell-free assays, respectively, also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites, with IC50 of 31 and 3500 nM. Ixazomib (MLN2238) induces autophagy. Phase 3.

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

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研究分野別

製品類型

Carfilzomib (PR-171)

文献中Selleckの製品使用例(165)

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 2022-01-17)

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