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Celastrol (NSC 70931)

Name: Celastrol (NSC 70931)
Brand: Selleck Chemicals
SKU: S1290
Rating: 5 (9 reviews)

Catalog No.S1290 Synonyms: Tripterine

For research use only.

Celastrol (NSC 70931, Tripterine) is a potent proteasome inhibitor for the chymotrypsin-like activity of a purified 20S proteasome with IC50 of 2.5 μM. Celastrol induces apoptosis and autophagy via the ROS/JNK signaling pathway. Celastrol inhibits dopaminergic neuronal death of Parkinson's disease through activating mitophagy.

Celastrol (NSC 70931) Chemical Structure

CAS No. 34157-83-0

Selleck's Celastrol (NSC 70931) has been cited by 9 Publications

2 Customer Reviews

Purity & Quality Control

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Proteasome Signaling Pathway Map

Biological Activity

Description

Features

A potent antioxidant and anti-inflammatory drug.

Targets

20S proteasome ^[1]
(Cell-free assay)

2.5 μM

In vitro

Celastrol at 5 μM inhibits the chymotrypsin-like, PGPH-like, and trypsin-like activities of the purified 20S proteasome by 80%, 5%, and <1%, respectively, whereas at 10 μM, it inhibits these three proteasomal activities by ∼90%, 15%, and <1%, respectively. Celastrol significantly inhibits the proteasomal chymotrypsin activity in PC-3 cells in a concentration-dependent manner. Celastrol at 2.5 μM to 5 μM induces caspase-3 activity by 4.7-fold to 5.5-fold in PC-3 cells. Celastrol (5 μM) treated cells, the levels of the proteasome target proteins, IκB-α and Bax, are increased after 1 hour and further increased to its peak for 4 hours to 12 hours. Celastrol (2.5 μM) treatment induces proteasome inhibition by 40%, as shown by the decreased levels of chymotrypsin-like activity and increased accumulation of ubiquitinated proteins in LNCaP cells. Celastrol (2.5 μM) induces apoptosis in the Celastrol-treated LNCaP cells, as shown by increased levels of caspase-3 activity (up to 3.5-fold), PARP cleavage, and apoptotic morphology. ^[1] Celastrol (300 nM) is found to suppress LPS-induced production of TNF-alpha and IL-1beta by human monocytes and macrophages. Celastrol (100 nM) also decreases LPS-induced expression of class II MHC molecules by microglia. Celastrol strongly inhibits LPS and IFN-y-induced NO production with IC50 of 200 nM in macrophage lineage cells. Celastrol strongly inhibits TNF-α and IFN-γ-induced NO production with IC50 of 200 nM in endothelial cells. ^[2] Celastrol (2.5 μM) potentiates the apoptosis induced by TNF and chemotherapeutic agents and inhibits invasion, both regulated by NF-kappaB activation, in KBM-5 cells. Celastrol (2.5 μM) suppresses the expression of TNF induced the expression of gene products involved in antiapoptosis (IAP1, IAP2, Bcl-2, Bcl-XL, c-FLIP, and survivin), proliferation (cyclin D1 and COX-2), invasion (MMP-9), and angiogenesis (VEGF) in KBM-5 cells. Celastrol (5 μM) is found to inhibit the TNF-induced activation of IkappaBalpha kinase, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 nuclear translocation and phosphorylation, and NF-kappaB-mediated reporter gene expression. ^[3] Celastrol inhibits proliferating of RPMI 8226, KATOIII, UM-SCC1, U251MG and MDA-MB-231 cells with IC50 of 0.52 μM, 0.54 μM, 0.76 μM, 0.69 μM and 0.67 μM, respectively. Celastrol (1 μM) inhibits growth of RPMI 8226 with a decrease in the levels of cyclin D1 and cyclin E, but concomitant increase in the levels of p21 and p27. Celastrol induces apoptosis in RPMI-8226 cells indicated by the activation of caspase-8, bid cleavage, caspase-9 activation, caspase-3 activation, PARP cleavage and through the down regulation of anti-apoptototic proteins. Celastrol (1 μM) suppresses Akt pathway and activates JNK kinase in RPMI-8226 cells. ^[4]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID

RAW264.7	M4TaO2FvfGmrbn\sZY1u[XSxcomgZZN{[Xl?		M4XudFI1KGi{cx?=	NY\Vd3hWSW62aXnu[oxidW2jdH;yfUBi[3Srdnn0fUBi\2GrboP0JI1wfXOnIGLBW\|I3PC55IHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4YhVFCVLXnu[JVk\WRiTl:gdJJw\HWldHnvckB1emWjdHXkJFMhcHK\|IHLl[o9z\SCOUGOgZ4hidGynbnflJIF{e2W\|c3XkJIFnfGW{IEK0JIhzeyCkeTDHdolme3NicnXh[4VvfCCjc4PhfUwhUUN3MDC9JFAvOjNizszNMi=>	MlzLQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTF6MEmwO\|YoRjFzOEC5NFc3RC:jPh?=
RAW264.7	MWjBcpRqcW6obHHtcYF1d3K7IHHzd4F6		NWrE[FN7OjRiaILz	NXr4SXZuSW62aXnu[oxidW2jdH;yfUBi[3Srdnn0fUBi\2GrboP0JI1wfXOnIGLBW\|I3PC55IHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4YhVFCVLXnu[JVk\WRiTl[tb4FxeGGEIHHjeIl3[XSrb36geJJm[XSnZDCzJIhzeyCkZX\vdoUhVFCVIHPoZYxt\W6pZTDhd5Nme3OnZDDh[pRmeiB{NDDodpMh[nliU1XBVEBz\XCxcoTldkBo\W6nIHHzd4F6NCCLQ{WwJF0hOC5{NzFOwG0v	NGDhWWE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zMUiwPVA4Pid-MUG4NFkxPzZ:L3G+
RPMI8226	MYfHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>?			MkL0S5Jwf3SqIHnubIljcXSrb36gc4YhcHWvYX6gVnBOUTh{Mk[gZ4VtdHNuIFnDOVAhRSB\|IN88UU4>	MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDF4NEG5O{c,OThzNkSxPVc9N2F-
HeLa	NFjiSFhHfW6ldHnvckBie3OjeR?=			MXHJcohq[mm2aX;uJI9nKFSQRj3hcJBp[S2rbnT1Z4VlKE6ILXvhdJBiSiCjY4TpeoF1cW:wIHnuJIh2dWGwIFjlUIEh[2WubIOgZpkhW0WDUDDy[ZBwenSncjDn[Y5mKGG\|c3H5MEBKSzVyIE2gNE4yPSEQvF2u	NWDnXHU4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUi4OFE6ODZpPkG4PFQyQTB4PD;hQi=>
RAW264.7	MY\GeY5kfGmxbjDhd5NigQ>?			Mn\uTY5pcWKrdHnvckBw\iCOUGOtbY5lfWOnZDDOSk1s[XCyYVKgZYN1cX[jdHnvckBqdiCvb4Xz[UBTSVd{NkSuO{Bk\WyuczDifUBUTUGSIILldI9zfGW{IHflcoUh[XO\|YYmsJGlEPTBiPTCwMlMh\|ryPLh?=	NU[ycHI4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUi4OFE6ODZpPkG4PFQyQTB4PD;hQi=>
SH-SY5Y	NID1TJhHfW6ldHnvckBie3OjeR?=			MWPO[ZVzd3C{b4TlZ5Rqd25iYXfhbY5{fCCkZYThMYFugWyxaXSgdIVxfGmmZTCxMVQzNWmwZIXj[YQhfG:6aXPpeJkhcW5iaIXtZY4hW0hvU2m1XUBk\WyuczDhd5Nme3OnZDDhd{Bt[WO2YYTlJIRmcHmmcn;n[Y5ie2VicnXs[YF{\SxiRVO1NEA:KDBwMEO3OlQh\|ryPLh?=	MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTF\|OEi1PUc,OTlzM{i4OVk9N2F-
HeLa	M{njV2Z2dmO2aX;uJIF{e2G7		NEnwNpczKGi{cx?=	MYHBcZBtcW[rY3H0bY9vKG:oIFjTSlEhfHKjboPjdolxfGmxbnHsJIFkfGm4aYT5JIlvKGi3bXHuJIhm[XRic3jvZ4sucW6mdXPl[EBJ\UyjIHPlcIx{KGG\|c3Xzd4VlKGG\|IHfyZY52dGViZn;ycYF1cW:wIITy[YF1\WRiMTDodkBj\W[xcnWgbIVifCC\|aH;jb{BkcGGubHXu[4UhdWWjc4Xy[YQh[W[2ZYKgNkBpenNid3n0bI92fCC{ZXPveoVzgSC2aX3lJIJ6KGmvbYXuc4N6fG:laHXtbYNidCC\|dHHpcolv\yxiRVO1NEA:KDFwMTFOwG0v	MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTVyMkC1O{c,OTl3MEKwOVc9N2F-
SK-N-SH	MXjDfZRwfG:6aXPpeJkh[XO\|YYm=		MV63NkBpenN?	NHHPfWZEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBUUy2QLWPIJINmdGy\|IHHmeIVzKDd{IHjyd{BjgSCPVGOgZZN{[XluIFPDOVAhRSBzLk[g{txONg>?	MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTVyMkC1O{c,OTl3MEKwOVc9N2F-
HeLa	MnnzSpVv[3Srb36gZZN{[Xl?		NVTTXZRXOyCqcoO=	MkT0RY1xdGmoaXPheIlwdiCxZjDIV2YyKHS{YX7zZ5JqeHSrb37hcEBi[3Srdnn0fUBqdiCqdX3hckBJ\UyjIHPlcIx{KGG\|c3Xzd4VlKGG\|IHfyZY52dGViZn;ycYF1cW:wIIDy[ZRz\WG2ZXSg[o9zKDNiaILzJIJ6KGmvbYXuc4N6fG:laHXtbYNidCC\|dHHpcolv\yxiRVO1NEA:KDJwNjFOwG0v	Ml\WQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTl3MEKwOVcoRjF7NUCyNFU4RC:jPh?=
HeLa	NX3jcYtNS3m2b4TvfIlkcXS7IHHzd4F6		MmGwO\|IhcHK\|	M3ewNWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGhmVGFiY3XscJMh[W[2ZYKgO\|IhcHK\|IHL5JG1VWyCjc4PhfUwhS0N3MDC9JFMh\|ryPLh?=	NH\2SHU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUWwNlA2Pyd-MUm1NFIxPTd:L3G+
HeLa	NFzMXW1HfW6ldHnvckBie3OjeR?=			NUGxOmhHUW6qaXLpeIlwdiCxZjDOSk1s[XCyYVKgZYN1cX[rdImgbY4hcHWvYX6gTIVN[SClZXzsd{BjgSCVRVHQJJJmeG:{dHXyJIF{e2G7LDDJR\|UxKD1iMD6xOUDPxE1w	Ml7FQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjB2Nkm4PFcoRjJyNE[5PFg4RC:jPh?=
LNCAP	MW\BcpRqfHWvb4KgZZN{[Xl?			NXywTW52SW62aYT1cY9zKGGldHn2bZR6KGGpYXnud5QhcHWvYX6gUG5ESVBiY3XscJMtKEmFNUCgQUAzNjVizszNMi=>	MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zODZ{N{W1Okc,OjB4Mke1OVY9N2F-
PC12	M4DPSGN6fG:ycn;0[YN1cX[nIHHzd4F6			MUTDfZRweHKxdHXjeIl3\SCjY4Tpeol1gSCjZ3HpcpN1KHRvQmDIMYlv\HWlZXSgZ4VtdCCmYX3h[4UhcW5icnH0JHBEOTJiY3XscJMh[XO\|ZYPz[YQh[XNiY3XscEB3cWGkaXzpeJktKEmFNUCgQUA{NjF3IN88UU4>	NVHhfmNGRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkC2Nlc2PTZpPkKwOlI4PTV4PD;hQi=>
PC12	NIj1dYlEgXSxcILveIVkfGm4ZTDhd5NigQ>?	NUDRd2w{OS54IIXN		M1\BbWN6fG:ycn;0[YN1cX[nIHHjeIl3cXS7IHHnZYlve3RidD3CVGgucW6mdXPl[EBk\WyuIHThcYFo\SCrbjDyZZQhWENzMjDj[YxteyCjc4Pld5Nm\CCjczDj[YxtKH[rYXLpcIl1gSCjdDCxMlYhfU1?	NFHPb4c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{ME[yO\|U2Pid-MkC2Nlc2PTZ:L3G+
THP1	MW\BdI9xfG:\|aYOgZZN{[Xl?		M{LO[VI1KGi{cx?=	NHnwd\|ZKdmS3Y4Tpc44hd2ZiYYDvdJRwe2m\|IHnuJHRTSUmOLYLld4l{fGGwdDDoeY1idiCWSGCxJINmdGy\|IHHmeIVzKDJ2IHjyd{BjgSCjbn7lfIlvNVZic4ThbY5qdmduIFXDOVAhRSBzNTFOwG0v	MkXRQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjB6NkSzOFIoRjJyOE[0N\|QzRC:jPh?=
293T	NV60b2Q5TnWwY4Tpc44h[XO\|YYm=		MWmzNEBucW6\|	Mn3KTY5pcWKrdHnvckBw\iCOUGOtbY5lfWOnZDDOSk1s[XCyYVKgZYN1cX[jdHnvckBqdiCqdX3hckAzQTOWIHPlcIx{KGmwY4XiZZRm\CCob4KgN\|AhdWmwczDmc4xtd3enZDDifUB1emWjdHXkJJdqfGhiTGDTJIZweiB4IHjyd{BjgSCmdXHsMYx2[2moZYLhd4UhemWyb4L0[ZIh[XO\|YYmsJGlEPTBiPTCwMlE4KM7:TT6=	NV7vd3Z4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGzPVMxODRpPkKxN\|k{ODB2PD;hQi=>
293T	NELJO3NEgXSxdH;4bYNqfHliYYPzZZk>			NXTreZpqS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hOjl\|VDDj[YxteyCjc4Pld5Nm\CCjczDj[YxtKH[rYXLpcIl1gSCkeTDkeYFtNWy3Y3nm[ZJie2VicnXwc5J1\XJiYYPzZZktKEmFNUCgQUAxNjZ5IN88UU4>	MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTN7M{CwOEc,OjF\|OUOwNFQ9N2F-
RAW264	NGfjV\|VHfW6ldHnvckBie3OjeR?=		MXSyOEBpenN?	MWrJcohq[mm2aX;uJI9nKEySUz3pcoR2[2WmIF7PJJBzd2S3Y4Tpc44hcW5ibX;1d4UhWkGZMk[0JINmdGy\|IHHmeIVzKDJ2IHjydy=>	M1v2d\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzM{mzNFA1Lz5{MUO5N\|AxPDxxYU6=
NCI-H460	MkfaR5l1d3SxeHnjbZR6KGG\|c3H5			NGXVZXhEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBPS0lvSES2NEBk\WyuczDh[pRmeiCxdnXycolocHRiaX7jeYJifGmxbjDifUBOXFRiYYPzZZktKEmFNUCgQUAyOi5\|IN88UU4>	MlXFQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7NEK3OlUoRjJzOUSyO\|Y2RC:jPh?=
RAW264.7	NYTRfmJpSW62aXnu[oxidW2jdH;yfUBie3OjeR?=		MnPYNlQhcHK\|	Ml;FRY51cWmwZnzhcY1ifG:{eTDhZ5Rqfmm2eTDpckBud3W\|ZTDSRXczPjRwNzDj[YxteyCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKEySUz3pcoR2[2WmIF7PJJBzd2S3Y4Tpc44h[W[2ZYKgNlQhcHK\|IHL5JGdzcWW\|czDy[YFo\W62IH3leIhw\CxiSVO1NEA:KDFizszNMi=>	NFLPOXc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUm3PFY4Pid-MkG5O\|g3PzZ:L3G+
RAW264.7	NE[wOHlCdnSraX7mcIFudWG2b4L5JIF{e2G7		MXeyOEBpenN?	MWDBcpRqcW6obHHtcYF1d3K7IHHjeIl3cXS7IHnuJI1wfXOnIGLBW\|I3PC55IHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4YhVFCVLXnu[JVk\WRibnn0dolkKG:6aXTlJJBzd2S3Y4Tpc44h[W[2ZYKgNlQhcHK\|IHL5JIdzcWW\|czDhd5NigSxiSVO1NEA:KDFizszNMi=>	MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjB{NECzN{c,OjJyMkSwN\|M9N2F-
RAW264.7	M3P1eWZ2dmO2aX;uJIF{e2G7		NXvk[YpoOThiaILz	NF7OfmJKdmirYnn0bY9vKG:oIFzQV{1{fGmvdXzheIVlKE6Ia3HwdIFDKGGldHn2ZZRqd25idILhcpNn\WO2ZXSgbY4hdW:3c3WgVmFYOjZ2LkegZ4VtdHNiYX\0[ZIhOThiaILzJIJ6KGy3Y3nm[ZJie2VicnXwc5J1\XJiZ3Xu[UBie3OjeTygTWM2OCB;IECuNkDPxE1w	NF\WNYU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkewOVAzOCd-MkK3NFUxOjB:L3G+
spleen adherent cells	MWDBcpRq[XK2aILpeIlkKGG\|c3H5	MVKyNFAhfWd?		MnLZRY51cWG{dHjybZRq[yCnZn\lZ5QhcW5iTHX3bZMhemG2IHHkbpV3[W62LXnu[JVk\WRiYYL0bJJqfGm\|IH3v[IVtKHOybHXlckBi\GincnXueEBk\WyuczDy[ZN1cW23bHH0[YQhf2m2aDDzc45q[2G2ZXSgUZRjKHCxc4SgbZNwdGG2aX;uJIF{e2W\|c3XkJIF{KHKnZIXjeIlwdiCrbjDDR3IzKGW6cILld5Nqd25iYYSgNlAxKHWpLDDpdEB{fGG{dHnu[{Bnem:vIHHyeIhzcXSrczDvcpNmfCCjbnSgZ49vfGmwdXXkJJVvcW62ZYLyeZB1\WRidX70bYw>	NEK2Wo09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{Mki1OFE6Oyd-MkK4OVQyQTN:L3G+
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MCF7	NF;1cFJHfW6ldHnvckBie3OjeR?=		NUXaeYJ4OjRiaILz	M3;yVGNp[W6pZTDpckBE\GN\|NzDlfJBz\XO\|aX;uJIlvKGi3bXHuJG1ETjdiY3XscJMh[XRiNTD0bY1meyCLQ{WwJIFnfGW{IEK0JIhzeyCkeTDX[ZN1\XKwIHLsc5Qh[W6jbInzbZM>	MnnuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5NU[yPVkoRjJ3N{W2Nlk6RC:jPh?=
MCF7	MVLGeY5kfGmxbjDhd5NigQ>?		MYWyOEBpenN?	NYKx[XJxS2ijbnflJIlvKHB{MzDlfJBz\XO\|aX;uJIlvKGi3bXHuJG1ETjdiY3XscJMh[XRiNTD0bY1meyCLQ{WwJIFnfGW{IEK0JIhzeyCkeTDX[ZN1\XKwIHLsc5Qh[W6jbInzbZM>	MoHnQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5NU[yPVkoRjJ3N{W2Nlk6RC:jPh?=
MCF7	NHy0cVBHfW6ldHnvckBie3OjeR?=		M4L2U\|I1KGi{cx?=	Ml3YTY5pcWKrdHnvckBw\iCKU2C5NEBqdiCqdX3hckBOS0Z5IHPlcIx{KGG\|c3Xzd4VlKGG\|IHTpd5J2eHSrb36gc4YhcW62ZYLhZ5Rqd25id3n0bEBE\GN\|NzDheEA2KHSrbXXzJGlEPTBiYX\0[ZIhOjRiaILzJIJ6KGOxLXntcZVvd3C{ZXPpdIl1[XSrb36gZZN{[Xl?	NVnjNpE1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3OVYzQTlpPkK1O\|U3Ojl7PD;hQi=>
MCF7	M3PKcWZ2dmO2aX;uJIF{e2G7		NHjWc5UzPCCqcoO=	M1\iO2lvcGmkaYTpc44hd2ZiSGPQPVAhcW5iaIXtZY4hVUOINzDj[YxteyCjc4Pld5Nm\CCjczDkbZNzfXC2aX;uJI9nKGmwdHXyZYN1cW:wIIfpeIgheDJ\|IHH0JFUhfGmvZYOgTWM2OCCjZoTldkAzPCCqcoOgZpkh[29vaX3teY5weHKnY3nwbZRifGmxbjDhd5NigQ>?	NWHCdmlWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3OVYzQTlpPkK1O\|U3Ojl7PD;hQi=>
SGC7901	M3v5TWFvfGmlYX7j[ZIh[XO\|YYm=		NVvONZNqPDhiaILz	NVPXPYFuSW62aXPhcoNmeiCjY4Tpeol1gSCjZ3HpcpN1KGi3bXHuJHNISzd7MEGgZ4VtdHNiYYPz[ZN{\WRiYYOgZ4VtdCC\|dYL2bZZidCCjZoTldkA1QCCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwJF0hOC5zNTFOwG0v	M3\2RVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEGyPVY3Lz5{NUixNlk3PjxxYU6=
SMMC7721	Mn;WRY51cWOjbnPldkBie3OjeR?=		MVq0PEBpenN?	NGezSYNCdnSrY3HuZ4VzKGGldHn2bZR6KGGpYXnud5QhcHWvYX6gV21OSzd5MkGgZ4VtdHNiYYPz[ZN{\WRiYYOgZ4VtdCC\|dYL2bZZidCCjZoTldkA1QCCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwJF0hOC53ODFOwG0v	M2LvUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEGyPVY3Lz5{NUixNlk3PjxxYU6=
MGC803	NYTQZmRSSW62aXPhcoNmeiCjc4PhfS=>		MWi0PEBpenN?	MkjKRY51cWOjbnPldkBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF3HR\|gxOyClZXzsd{Bie3Onc4Pl[EBieyClZXzsJJN2en[rdnHsJIFnfGW{IES4JIhzeyCkeTDNWHQh[XO\|YYmsJGlEPTBiPTCxMlU2KM7:TT6=	MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPThzMkm2Okc,OjV6MUK5OlY9N2F-
HepG2	Mm\1RY51cWOjbnPldkBie3OjeR?=		NIDqSHc1QCCqcoO=	Mmm4RY51cWOjbnPldkBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFjldGczKGOnbHzzJIF{e2W\|c3XkJIF{KGOnbHygd5Vzfmm4YXygZYZ1\XJiNEigbJJ{KGK7IF3UWEBie3OjeTygTWM2OCB;IESuNFEh\|ryPLh?=	MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPThzMkm2Okc,OjV6MUK5OlY9N2F-
A549	MlTRRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		M2fUNlQ5KGi{cx?=	MlPBRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDwZYNtcXSjeHXsMZJme2m\|dHHueEBpfW2jbjDBOVQ6KGOnbHzzJIF{e2W\|c3XkJIF{KHKnZIXjeIlwdiCrbjDj[YxtKH[rYXLpcIl1gSCjZoTldkA1QCCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwJF0hOi5yMTFOwG0v	NF;qXYk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{[0O\|M3QSd-Mke2OFc{Pjl:L3G+
A549	NHvFdIJCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		NGHpU3Q1QCCqcoO=	NUnnUWViSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDBOVQ6KGOnbHzzJIF{e2W\|c3XkJIF{KHKnZIXjeIlwdiCrbjDj[YxtKH[rYXLpcIl1gSCjZoTldkA1QCCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwJF0hOi5yMjFOwG0v	Mn3IQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjd4NEezOlkoRjJ5NkS3N\|Y6RC:jPh?=
MCF7	MmLiRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		NID1UJA1QCCqcoO=	MYPBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKE2FRkegZ4VtdHNiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJIlvKGOnbHygeoli[mmuaYT5JIFnfGW{IES4JIhzeyCkeTDNWHQh[XO\|YYmsJGlEPTBiPTCyMlE{KM7:TT6=	NGDyNWs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{[0O\|M3QSd-Mke2OFc{Pjl:L3G+
PANC1	M2Dhc2FvfGmycn;sbYZmemG2aY\lJIF{e2G7		NHXucZg1QCCqcoO=	NHLscVFCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGDBUmMyKGOnbHzzJIF{e2W\|c3XkJIF{KHKnZIXjeIlwdiCrbjDj[YxtKH[rYXLpcIl1gSCjZoTldkA1QCCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwJF0hOi52ODFOwG0v	NX3x[nd5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMke2OFc{PjlpPkK3OlQ4OzZ7PD;hQi=>
LNCAP	M3jVW2Z2dmO2aX;uJIF{e2G7	MnO5OUB2VQ>?	M2\ObFI1KGi{cx?=	MX;BcpRi\2:waYP0JIFkfGm4aYT5JIF1KEGUIHnuJIh2dWGwIFzOR2FRKGOnbHzzJIF{e2W\|c3XkJIF{KHO3cIDy[ZN{cW:wIH;mJGRJXC2rbnT1Z4VlKHKnY3XweI9zKHS{YX7zZ5JqeHSrb37hcEBi[3Srdnn0fUBifCB3IIXNJIFnfGW{IEK0JIhzeyCkeTDkeYFtKGy3Y3nm[ZJie2VicnXwc5J1\XJiZ3Xu[UBie3OjeR?=	MUK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzl7NEezNUc,Ojd7OUS3N\|E9N2F-
A549	NFTvbVFIem:5dHigbY5pcWKrdHnvckBie3OjeR?=		NFvCXIY3KGSjeYO=	NWD4cGJQT3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hSTV2OTDj[YxteyCvZXHzeZJm\CCndnXyfUAzKGi{czDveoVzKDZiZHH5d{BjgSCuaY\lJINmdGxiaX3h[4lv\yCkYYPl[EBu\XSqb3SsJGlEPTBiPTCwMlY6KM7:TT6=	M4LRNVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6NkKxPVQ{Lz5{OE[yNVk1OzxxYU6=
HEK293	MXPGeY5kfGmxbjDhd5NigQ>?	NHPhdGwyOCC3TR?=	NGDaNHkzOCCvaX7z	M3OzdmlvcGmkaYTpc44hd2ZiR3HsdIhidyCrboTldoFkfGmxbjD3bZRpKEeIUD3meZNm\CCUR2OxO{ApfW6tbn;3ckBwemmpaX6pJIRmdHSjTjDteZRidnRiZYjwdoV{e2WmIHnuJGhGUzJ7MzDj[YxteyCjc4Pld5Nm\CCjczDpcoNz\WG\|ZTDpckBTT1NzNzDk[Yx1[U5ibYX0ZY51KGyxY3HsbZpifGmxbjDheEBkgXSxcHzhd40h[XRiMUCgeW0hfXBidH:gNlAhdWmwczDifUBkd26ob3PhcEBucWO{b4Pjc5Bq[yCjbnHsfZNqew>?	MnXVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh4MkG5OFMoRjJ6NkKxPVQ{RC:jPh?=
HEK293	M{nieWZ2dmO2aX;uJIF{e2G7	MoTNNVAxKHWP	MYC1JI1qdnN?	NU\PRXZOUW6qaXLpeIlwdiCxZjDHZYxxcGFyIHnueIVz[WO2aX;uJJdqfGhiR1\QMYZ2e2WmIGLHV\|E4KCi3bnvuc5dvKG:{aXfpckkh\GWudHHOJI12fGGwdDDlfJBz\XO\|ZXSgbY4hUEWNMkmzJINmdGy\|IHHzd4V{e2WmIHHzJIlv[3KnYYPlJIlvKFKJU{G3JIRmdHSjTjDteZRidnRibH;jZYxqgmG2aX;uJIF1KGO7dH;wcIF{dSCjdDCxNFAhfU1idYCgeI8hPSCvaX7zJIJ6KGOxbn\vZ4FtKG2rY4Lvd4NweGmlIHHuZYx6e2m\|	MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDZ{MUm0N{c,Ojh4MkG5OFM9N2F-
HEK293	M1Hyc2Z2dmO2aX;uJIF{e2G7	M{[yOlExKHWP	NWLpbmFDPSCvaX7z	M{fTVGlvcGmkaYTpc44hd2ZiR3HsdIhidyCrboTldoFkfGmxbjD3bZRpKEeIUD3meZNm\CCUR2OxO{ApfW6tbn;3ckBwemmpaX6pJIRmdHSjTjDteZRidnRiZYjwdoV{e2WmIHnuJGhGUzJ7MzDj[YxteyCjc4Pld5Nm\CCjczDpcoNz\WG\|ZTDpckBTT1NzNzDk[Yx1[U5ibYX0ZY51KGyxY3HsbZpifGmxbjDheEBkgXSxcHzhd40h[XRiMUCgeW0hfXBidH:gOUBucW6\|IHL5JINwdm[xY3HsJI1q[3Kxc3PvdIlkKGGwYXz5d4l{	NFPQNXY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OE[yNVk1Oyd-Mki2NlE6PDN:L3G+
MIAPaCa2	MkDqRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		M{HsfFczKGi{cx?=	NW\n[2x7SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNTWFR[UOjMjDj[YxteyCjZoTldkA4OiCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwJF0hOC52NjFOwG0v	NF74Ulg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OE[4PFI5OSd-Mki2PFgzQDF:L3G+
SKBR3	NXfjXldbSW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		MYO3NkBpenN?	M2TlZWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iU1vCVlMh[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeTygTWM2OCB;IECuO\|Ih\|ryPLh?=	NE\zdpk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OE[4PFI5OSd-Mki2PFgzQDF:L3G+
SKOV3	NUPDXYs{SW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		M4fOdlczKGi{cx?=	M13XN2FvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iU1vPWlMh[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeTygTWM2OCB;IEGuNVYh\|ryPLh?=	MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDZ6OEK4NUc,Ojh4OEiyPFE9N2F-
MDA-MB-231	NHPIXotCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		MVi3NkBpenN?	NVvMRlN6SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNSGEuVUJvMkOxJINmdGy\|IHHmeIVzKDd{IHjyd{BjgSCPVGSgZZN{[XluIFnDOVAhRSBzLkOyJO69VS5?	NWe4Onh7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki2PFgzQDFpPkK4Olg5OjhzPD;hQi=>
A549	NW\tOnRNSW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		NW\0cXl7PzJiaILz	NXO1e\|Q2SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDBOVQ6KGOnbHzzJIFnfGW{IEeyJIhzeyCkeTDNWHQh[XO\|YYmsJGlEPTBiPTCxMlU3KM7:TT6=	MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDZ6OEK4NUc,Ojh4OEiyPFE9N2F-
BJ	NV3qdWpnS3m2b4TvfIlkcXS7IHHzd4F6		M3LTbVczKGi{cx?=	NXHadWQ1S3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hSkpiY3XscJMh[XO\|ZYPz[YQh[XNicnXkeYN1cW:wIHnuJINmdGxidnnhZoltcXS7IHHmeIVzKDd{IHjyd{BjgSCPVGSgZZN{[XluIFnDOVAhRSB{Lke0JO69VS5?	MWC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDZ6OEK4NUc,Ojh4OEiyPFE9N2F-
NCI-H460	M1fu[WZ2dmO2aX;uJIF{e2G7	MlziNUB2VQ>?	M1LqXFEzKGi{cx?=	NVXNeXROSWO2aY\heIlwdiCxZjDIV2YyKGmwIHj1cYFvKE6FST3IOFYxKGOnbHzzJIF{e2W\|c3XkJIF{KHWycnXneYxifGmxbjDv[kBJW1B{NTDwdo91\WmwIHzleoVteyCjdDCxJJVOKGGodHXyJFEzKGi{czDifUBY\XO2ZYLuJIJtd3RiYX7hcJl{cXN?	NIPvcZU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEezO\|kyPid-Mki3N\|c6OTZ:L3G+
NCI-H460	NI\IdZBHfW6ldHnvckBie3OjeR?=	M3fS[FEhfU1?	MlnJNVIhcHK\|	MYLBZ5RqfmG2aX;uJI9nKEiVRkGgbY4hcHWvYX6gUmNKNUh2NkCgZ4VtdHNiYYPz[ZN{\WRiYYOgeZBz\We3bHH0bY9vKG:oIFjTVFcxKHC{b4TlbY4hdGW4ZXzzJIF1KDFidV2gZYZ1\XJiMUKgbJJ{KGK7IGfld5Rmem5iYnzveEBidmGueYPpdy=>	MknPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh5M{e5NVYoRjJ6N{O3PVE3RC:jPh?=
NCI-H1299	M1q2S2N6fG:2b4jpZ4l1gSCjc4PhfS=>			NILsPJNEgXSxdH;4bYNqfHliaX6gbJVu[W5iTlPJMWgyOjl7IHPlcIx{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDpckBk\WyuII\pZYJqdGm2eTygTWM2OCB;IEGg{txONg>?	M3;ZfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6N{W0OFcxLz5{OEe1OFQ4ODxxYU6=
BCP-ALL	Ml3zR5l1d3SxeHnjbZR6KGG\|c3H5			NILVdGlEgXSxdH;4bYNqfHliaX6gbJVu[W5iQlPQMWFNVCClZXzsd{Bie3Onc4Pl[EBieyC{ZXT1Z5Rqd25iaX6gZ4VtdCC4aXHibYxqfHluIFnDOVAhRSBzIN88UU4>	MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDd3NES3NEc,Ojh5NUS0O\|A9N2F-
T-ALL	MULDfZRwfG:6aXPpeJkh[XO\|YYm=			NUXyZoNYS3m2b4TvfIlkcXS7IHnuJIh2dWGwIGStRWxNKGOnbHzzJIF{e2W\|c3XkJIF{KHKnZIXjeIlwdiCrbjDj[YxtKH[rYXLpcIl1gSxiSVO1NEA:KDFizszNMi=>	M{TTUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6N{W0OFcxLz5{OEe1OFQ4ODxxYU6=
Daudi	MmX6R5l1d3SxeHnjbZR6KGG\|c3H5			MVnDfZRwfG:6aXPpeJkhcW5iaIXtZY4hTGG3ZHmgZ4VtdHNiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJIlvKGOnbHygeoli[mmuaYT5MEBKSzVyIE2gNUDPxE1w	NXXSRpg3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki3OVQ1PzBpPkK4O\|U1PDdyPD;hQi=>
HL60	NH\D[m1EgXSxdH;4bYNqfHliYYPzZZk>			MoDVR5l1d3SxeHnjbZR6KGmwIHj1cYFvKEiONkCgZ4VtdHNiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJIlvKGOnbHygeoli[mmuaYT5MEBKSzVyIE2gNUDPxE1w	NXjSOWdsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki3OVQ1PzBpPkK4O\|U1PDdyPD;hQi=>
TC32	MnvGdWhVWyCjc4PhfS=>			NHjQTlhyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiVFOzNkBk\Wyucx?=	MlrOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
DAOY	M1TiNZFJXFNiYYPzZZk>			NILXPVhyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiRFHPXUBk\Wyucx?=	Mnv5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SJ-GBM2	NH76Z\|ZyUFSVIHHzd4F6			MX3xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0pvR1LNNkBk\Wyucx?=	M{nKcVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
A673	MVHxTHRUKGG\|c3H5			NUjiXItmeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IFG2O\|Mh[2WubIO=	MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SK-N-MC	M2fvUJFJXFNiYYPzZZk>			MUDxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0tvTj3NR{Bk\Wyucx?=	NUDCdFUyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
BT-37	NVjGVlhieUiWUzDhd5NigQ>?			NWrvTYJ{eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IFLUMVM4KGOnbHzz	NHP1SoU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
NB-EBc1	MlPidWhVWyCjc4PhfS=>			NFK0dXNyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTlKtSWJkOSClZXzsdy=>	MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Saos-2	MmC0dWhVWyCjc4PhfS=>			NFLW[4FyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU3Hvd{0zKGOnbHzz	NHnPd4s9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
SK-N-SH	NY\xdlB1eUiWUzDhd5NigQ>?			NXK0XmMzeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGPLMW4uW0hiY3XscJM>	NHi0dm09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
NB1643	M{XkWZFJXFNiYYPzZZk>			Mn6wdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKE6EMU[0N{Bk\Wyucx?=	M3TSOVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
LAN-5	M3;R[ZFJXFNiYYPzZZk>			NGXyVolyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTFHOMVUh[2WubIO=	NH\XXmY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
BT-12	MYTxTHRUKGG\|c3H5			MnvkdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEKWLUGyJINmdGy\|	NYXLe5ZtRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Rh18	MYTxTHRUKGG\|c3H5			M{HuOpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCUaEG4JINmdGy\|	MWC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
OHS-50	MnfsdWhVWyCjc4PhfS=>			NYW3R296eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF;IV{02OCClZXzsdy=>	NVjKNmFsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
RD	NUS2bW9xeUiWUzDhd5NigQ>?			NXHyeoJ7eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGLEJINmdGy\|	M2HI[\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
MG 63 (6-TG R)	M4r2bJFJXFNiYYPzZZk>			M2XIUJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCPRzC2N{ApPi2WRzDSLUBk\Wyucx?=	M2LiOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Rh30	M4jJfZFJXFNiYYPzZZk>			MW\xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWmh\|MDDj[Yxtew>?	MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Rh41	MX;xTHRUKGG\|c3H5			NXrId2FDeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGLoOFEh[2WubIO=	MWm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
NB1643	M1LsbpFJXFNiYYPzZZk>			NELifFJyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBPSjF4NEOgZ4VtdHN?	M1G2TFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
A673	M{fDXJFJXFNiYYPzZZk>			NFTzS4RyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBCPjd\|IHPlcIx{MQ>?	MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SK-N-MC	NG\5NmFyUFSVIHHzd4F6			M1TUc5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHNMNU5vTVOgZ4VtdHN?	M{TTZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
BT-12	MnHLdWhVWyCjc4PhfS=>			M3;ESZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJGJVNTF{IHPlcIx{	MmTkQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
LAN-5	M1fpUpFJXFNiYYPzZZk>			M1HvbJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJGxCVi13IHPlcIx{	NG\u[Y89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
DAOY	M2\tO5FJXFNiYYPzZZk>			MYPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDERW9[KGOnbHzz	NYXEU3FNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
NB-EBc1	MYTxTHRUKGG\|c3H5			MkL5dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgUmIuTUKlMTDj[Yxtew>?	NEDT[4k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
SJ-GBM2	NX;LcFQ6eUiWUzDhd5NigQ>?			Mki0dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgV2ouT0KPMjDj[Yxtew>?	MnHzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
BT-37	MlvmdWhVWyCjc4PhfS=>			M1XENpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJGJVNTN5IHPlcIx{	NEDWUmI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
TC32	M3jJNpFJXFNiYYPzZZk>			MkSwdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgWGM{OiClZXzsdy=>	M4C3SVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
MG 63 (6-TG R)	MX7xTHRUKGG\|c3H5			NGrjW5lyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBOTyB4MzCoOk1VTyCUKTDj[Yxtew>?	M1S0NFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
fibroblast cells	M3m0NpFJXFNiYYPzZZk>			MXjxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDjc451em:uIFjoJJdqdGRidInw[UBncWK{b3LsZZN1KGOnbHzz	Mn20QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
U-2 OS	NX:0ZoVReUiWUzDhd5NigQ>?			NF7VWoZyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBWNTJiT2OgZ4VtdHN?	M3O2Z\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Rh41	NIPvU4RyUFSVIHHzd4F6			M{fq[ZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHJpPDFiY3XscJM>	MoHTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
RD	NXTyOWJueUiWUzDhd5NigQ>?			NWXqRlZteUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhWkRiY3XscJM>	M2raTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Rh18	NVTxUlF4eUiWUzDhd5NigQ>?			MnHGdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgVogyQCClZXzsdy=>	M3jmWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Rh30	MYDxTHRUKGG\|c3H5			M2XhdZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHJpOzBiY3XscJM>	MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Saos-2	MYjxTHRUKGG\|c3H5			Mly2dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgV4Fwey1{IHPlcIx{	NIX2bWg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
OHS-50	NVXjcpRGeUiWUzDhd5NigQ>?			MkHTdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgU2hUNTVyIHPlcIx{	M165e\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SK-N-SH	MUXxTHRUKGG\|c3H5			NFLpfFlyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBUUy2QLWPIJINmdGy\|	MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
HCT116	NH;xR4ZCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		Mm\6OFghcHK\|	MmnBRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCKQ2SxNVYh[2WubIOgZYZ1\XJiNEigbJJ{KGK7IF3UWEBie3OjeTygTWM2OCB;IEWuNlYh\|ryPLh?=	MlzhQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2OE[5OVQoRjJ7NEi2PVU1RC:jPh?=
HepG2	MVHBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		M{LRRVQ5KGi{cx?=	MXXBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEincFeyJINmdGy\|IHHmeIVzKDR6IHjyd{BjgSCPVGSgZZN{[XluIFnDOVAhRSB4LkG3JO69VS5?	NV[xUpc6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0PFY6PTRpPkK5OFg3QTV2PD;hQi=>
A549	NYjKSJJISW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		MUS0PEBpenN?	NGfwXHNCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFG1OFkh[2WubIOgZYZ1\XJiNEigbJJ{KGK7IF3UWEBie3OjeTygTWM2OCB;IE[uOVkh\|ryPLh?=	MkXaQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2OE[5OVQoRjJ7NEi2PVU1RC:jPh?=
MCF7	NUKyN3JISW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		NEXlXI81QCCqcoO=	NYXLT5M{SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNR2Y4KGOnbHzzJIFnfGW{IES4JIhzeyCkeTDNWHQh[XO\|YYmsJGlEPTBiPTC2Mlg1KM7:TT6=	MUK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR6Nkm1OEc,Ojl2OE[5OVQ9N2F-
HEK293	NHLsTIJEgXSxdH;4bYNqfHliYYPzZZk>			MU\DfZRwfG:6aXPpeJkh[WejaX7zeEBJTUt{OUOgZ4VtdHNiKFPPMWFFTDqPQW:wNFcqQyCFQ{WwJIJ6KGOnbHygeoli[mmuaYT5JIF{e2G7IHnuJGROTU1iKEGwKUBHSlNrIH3l[IliKHW\|aX7nJHREKHCuYYTld{wh[nliUnXzZZp2emmwIF[oOVYxNzV7MDmsJGNEPTBiPTCwMlg{PyEQvF2u	MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyzNFE6QDJxJ{7DbGVOSkx:L3G+

Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID

Western blot	HIF-1α ; Akt / p-Akt / p-p70S6K ; PARP / p53 / p21 / cIAP1 / Bcl-xl / Bcl-2 ; IκBα / p-IKKα/β ; iNOS / COX-2 / Arg-1 ; Chk2 / p-Chk2 / Cyclin B1 / Cdc25c / p-Cdc25c	25383959 28388439 29040966 31053160
Immunofluorescence	p21 / Nur77	28388439
Growth inhibition assay	Cell viability	29040966

In vivo

Celastrol (3 mg/kg) results in significant inhibition (up to 70%) of tumor growth in male nude mice bearing PC-3 tumors, associated with increased p27 levels and Bax level. Celastrol (3 mg/kg) results more apoptotic tumor cells with the appearance of various PARP cleavage fragments in tumor of male nude mice bearing PC-3 tumors. Celastrol (3 mg/kg) causes 35% of tumor inhibition, associated with decreased proteasome activity and decreased expression of AR protein in nude mice bearing C4-2B tumors. ^[1] Celastrol (3 mg/kg) is found to suppress strongly joint swelling and other manifestations of adjuvant arthritis in mice. Celastrol (0.2 mg/kg) significantly improves the performance in memory, learning and psychomotor activity tests in rats. ^[2]

Protocol (from reference)

Kinase Assay:^[1]	Inhibition of purified 20S proteasome activity: A purified rabbit 20S proteasome (0.1 μg) is incubated with 40 μM of various fluorogenic peptide substrates in 100 μL assay buffer (20 mM Tris-HCl (pH 7.5)), in the presence of Celastrol at different concentrations or in the solvent DMSO for 2 hours at 37 ℃, followed by measurement of inhibition of each proteasomal activity.
Cell Research:^[4]	Cell lines: RPMI 8226, KATOIII, UM-SCC1, U251MG and MDA-MB-231 cells Concentrations: ~5 μM Incubation Time: 2 hours Method: The anti-proliferative effect of celastrol on various human tumor cell lines is determined by the MTT uptake method. Briefly, 5×10³ cells are incubated with Celastrol in triplicate in a 96-well plate at 37 ℃. MTT solution is then added to each well. After a 2 hours incubation at 37 ℃, extraction buffer (20% SDS, 50% dimethylformamide) is added, cells are incubated overnight at 37 ℃, and the optical density is then measured at 570 nm using a Tecan plate reader.
Animal Research:^[1]	Animal Models: nude mice bearing C4-2B tumors Dosages: 3 mg/kg Administration: Intraperitoneal injection

References

[4] Kannaiyan R, et al. Apoptosis, 2011, 16(10), 1028-1041.

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Solubility (25°C)

In vitro

Chemical Information

Molecular Weight	450.61
Formula	C₂₉H₃₈O₄
CAS No.	34157-83-0
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
Smiles	CC1=C(C(=O)C=C2C1=CC=C3C2(CCC4(C3(CCC5(C4CC(CC5)(C)C(=O)O)C)C)C)C)O

Download Celastrol (NSC 70931) SDF

In vivo Formulation Calculator (Clear solution)

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