Piperlongumine

Name: Piperlongumine
Brand: Selleck Chemicals
SKU: S7551
Rating: 5 (17 reviews)

For research use only.

Catalog No.S7551 Synonyms: PPLGM, Piplartine

17 publications

CAS No. 20069-09-4

Piperlongumine (PPLGM, Piplartine), a natural alkaloid from Piper longum L., increases the level of reactive oxygen species (ROS) and selectively kills cancer cells. It is a direct TrxR1 inhibitor with suppressive activity against gastric cancer and a novel inhibitor of CRM1; also an inhibitor of PI3K/Akt/mTOR in human breast cancer cells.

Selleck's Piperlongumine has been cited by 17 publications

Cancer Cell, 2019, 36(2):179-193

PubMed: 31378681 ( click the link to review the publication )

Cell, 2019, 36(2):179-193

PubMed: 28162770 ( click the link to review the publication )

Cancer Cell, 2018, 33(5):890-904.e5

PubMed: 29657129 ( click the link to review the publication )

Toxicol In Vitro, 2020, 65:104775

PubMed: 31987842 ( click the link to review the publication )

Onco Targets Ther, 2020, 13:5591-5603

PubMed: 32606774 ( click the link to review the publication )

Protein Sci, 2020, 29(6):1366-1372

PubMed: 31495993 ( click the link to review the publication )

Adv Sci (Weinh), 2020, 7(13):2000112

PubMed: 32670759 ( click the link to review the publication )

Cell Rep, 2019, 28(2):512-525.e6

PubMed: 31291585 ( click the link to review the publication )

Cell Death Dis, 2019, 10(8):600

PubMed: 31395855 ( click the link to review the publication )

Biochem Pharmacol, 2019, 163:101-110

PubMed: 30753811 ( click the link to review the publication )

Int J Biol Sci, 2019, 15(4):826-837

PubMed: 30906213 ( click the link to review the publication )

Front Pharmacol, 2019, 10:1180

PubMed: 31680962 ( click the link to review the publication )

Front Pharmacol, 2019, 10:1178

PubMed: 31680961 ( click the link to review the publication )

J Med Virol, 2019, 91(8):1440-1447

PubMed: 30900754 ( click the link to review the publication )

Cell Oncol (Dordr), 2019, 10.1007/s13402-019-00471-x

PubMed: 31493144 ( click the link to review the publication )

Oncotarget, 2016, 7(26):40531-40545

PubMed: 27244895 ( click the link to review the publication )

Oncotarget, 2016, 10.18632/oncotarget.10921

PubMed: 27486766 ( click the link to review the publication )

2 Customer Reviews

a. Cell growth of ARID1A-wildtype RMG1 cells transfected with ARID1A and non-target siRNA for 24 h and treated with piperlongumine for 72 h. b. Apoptosis of RMG1 cells after transfection and treatment as described in a as measured using annexin-V and PI staining. c. Cell growth of RMG1 cells transfected and treated with 5 μM of piperlongumine as described in a, but in the presence or absence of the antioxidant NAC. Cell growth was measured using the WST-1 assay and quantified relative to DMSO treated non-target control. *P < 0.05; **P < 0.01; ***P < 0.001.

Oncotarget, 2016, 7(35):56933-56943. Piperlongumine purchased from Selleck.
MPC cells were treated with the indicated concentrations of PL at 21% and 1% O2 for 24 hours. Total cell lysates were subjected to Western blot with antibodies against cleaved PARP, cleaved caspase 3, and caspase 3. β-tubulin was used as a loading control. A representative image (n=3) is shown.

Oncotarget, 2016, 7(26):40531-40545. Piperlongumine purchased from Selleck.

Purity & Quality Control

Choose Selective ROS Inhibitors

Biological Activity

Description

Targets

reactive oxygen species (ROS) ^[1]

TrxR1 ^[5]

CRM1 ^[6]

PI3K/Akt/mTOR ^[7]

In vitro

Piperlongumine is a known ROS inducer which could induce pancreatic cancer cell death in cell culture^[1] As a thromboxane A(2) receptor antagonist, Piperlongumine inhibits platelet aggregation. ^[2] Piperlongumine also promotes autophagy via inhibition of Akt/mTOR signalling and mediates cancer cell death. ^[3]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
ZR75-30	M2DFbGN6fG:2b4jpZ4l1gSCjc4PhfS=>		NYHuPJVuPzJiaILz	M3uycGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJHpTPzVvM{CgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigSxiSVO1NF02Njh4zszN	M3LJclxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUO3NVg3Lz5{NEmzO\|E5PjxxYU6=
HCT116	MYDDfZRwfG:6aXPpeJkh[XO\|YYm=		MmXlO\|IhcHK\|	MXXDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDIR3QyOTZiY3XscJMh[W[2ZYKgO\|IhcHK\|IHL5JG1VXCCjc4PhfUwhUUN3ME22MlA1\|ryP	NHXZZpY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmzO\|E5Pid-MkS5N\|cyQDZ:L3G+
MDA-MB-231	NGm0c2REgXSxdH;4bYNqfHliYYPzZZk>		NU\5cZNTPzJiaILz	NILQUohEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBOTEFvTVKtNlMyKGOnbHzzJIFnfGW{IEeyJIhzeyCkeTDNWHQh[XO\|YYmsJGlEPTB;OD60Ou69VQ>?	MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDl\|N{G4Okc,OjR7M{exPFY9N2F-
A549	MUHDfZRwfG:6aXPpeJkh[XO\|YYm=		NWjtfpo2PzJiaILz	NUfrXY9CS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hSTV2OTDj[YxteyCjZoTldkA4OiCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwQVIzNjh3zszN	MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDl\|N{G4Okc,OjR7M{exPFY9N2F-
WI38	M3zrU2N6fG:2b4jpZ4l1gSCjc4PhfS=>		M4\WZ\|czKGi{cx?=	MnO5R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gW2k{QCClZXzsd{Bi\nSncjC3NkBpenNiYomgUXRVKGG\|c3H5MEBKSzVyPUK2Mlc5\|ryP	M{T5WVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUO3NVg3Lz5{NEmzO\|E5PjxxYU6=
MRC5	NXnaTZd6S3m2b4TvfIlkcXS7IHHzd4F6		NIG1UWY4OiCqcoO=	Mo\0R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gUXJEPSClZXzsd{Bi\nSncjC3NkBpenNiYomgUXRVKGG\|c3H5MEBKSzVyPUO1MlA1\|ryP	MofHQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7M{exPFYoRjJ2OUO3NVg3RC:jPh?=
PANC1	MULDfZRwfG:6aXPpeJkh[XO\|YYm=		M2PuV\|I1KGi{cx?=	MmPtR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gVGFPSzFiY3XscJMh[XO\|ZYPz[YQh[XNicnXkeYN1cW:wIHnuJINmdGxidnnhZoltcXS7IHHmeIVzKDJ2IHjyd{BjgSCPVGSgdoVlfWO2aX;uJIF{e2G7LDDJR\|UxRTNwMt88US=>	NELydpc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUOwOVcyQCd-MkWzNFU4OTh:L3G+
HaCaT	Mnz6R5l1d3SxeHnjbZR6KGG\|c3H5		NI\PbYUzPCCqcoO=	MkjoR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gTIFE[VRiY3XscJMh[XO\|ZYPz[YQh[XNicnXkeYN1cW:wIHnuJINmdGxidnnhZoltcXS7IHHmeIVzKDJ2IHjyd{BjgSCPVGSgdoVlfWO2aX;uJIF{e2G7LDDJR\|UxRTF4zszN	MorjQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV\|MEW3NVgoRjJ3M{C1O\|E5RC:jPh?=
RAW264.7	MkXWRY51cWmwZnzhcY1ifG:{eTDhd5NigQ>?			NYj5eIhPSW62aXnu[oxidW2jdH;yfUBi[3Srdnn0fUBqdiCvb4Xz[UBTSVd{NkSuO{Bk\WyuczDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oIFzQV{1qdmS3Y3XkJG5QKHC{b3T1Z5Rqd25uIFnDOVA:O87:TR?=	MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTR3M{iwPUc,OjV2NUO4NFk9N2F-
MA9.3	MkW1R5l1d3SxeHnjbZR6KGG\|c3H5		MUW0PEBpenN?	MXTDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDNRVkvOyClZXzsd{Bi\nSncjC0PEBpenNiYomgUXRVKGG\|c3H5MEBKSzVyPUNOwG0>	Mn;uQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV2NkS4PFcoRjJ3NE[0PFg4RC:jPh?=
SK-MEL-2	NWLw[I4ySW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		M1[3d\|czKGi{cx?=	NITFb4lCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGPLMW1GVC1{IHPlcIx{KGGodHXyJFczKGi{czDifUBOXFRiYYPzZZktKEWFNUC9OE4{Qc7:TR?=	NXryZnZYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4NlY{QThpPkK1PFI3Ozl6PD;hQi=>
HaCaT	MULBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		M2H4eFczKGi{cx?=	Mn\4RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCKYVPhWEBk\WyuczDh[pRmeiB5MjDodpMh[nliTWTUJIF{e2G7LDDFR\|UxRTRwNEdOwG0>	MkLRQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6Mk[zPVgoRjJ3OEK2N\|k5RC:jPh?=
A375	NFG3PJZCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		M1OzblczKGi{cx?=	NETXdHlCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFGzO\|Uh[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeTygSWM2OD14LkG3{txO	NG\2XVc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUiyOlM6QCd-MkW4NlY{QTh:L3G+
HCT116	MkLMRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		M3\IU\|czKGi{cx?=	NXXVN3hGSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDIR3QyOTZiY3XscJMh[W[2ZYKgO\|IhcHK\|IHL5JG1VXCCjc4PhfUwhTUN3ME2xNU42\|ryP	NXTWOYZTRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4NlY{QThpPkK1PFI3Ozl6PD;hQi=>
A549	M{PpUmFvfGmycn;sbYZmemG2aY\lJIF{e2G7		M{XIdlczKGi{cx?=	NFLr[nJCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFG1OFkh[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeTygSWM2OD1zMj6y{txO	MlnQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6Mk[zPVgoRjJ3OEK2N\|k5RC:jPh?=
HFF1	M{jzO2FvfGmycn;sbYZmemG2aY\lJIF{e2G7		MUO3NkBpenN?	NFi0TnRCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JGhHTjFiY3XscJMh[W[2ZYKgO\|IhcHK\|IHL5JG1VXCCjc4PhfUwhTUN3ME2xN{4y\|ryP	NWG1WHBzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4NlY{QThpPkK1PFI3Ozl6PD;hQi=>
MCF10A	NH;kOGdCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		MV:3NkBpenN?	NGWyTIZCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF3DSlExSSClZXzsd{Bi\nSncjC3NkBpenNiYomgUXRVKGG\|c3H5MEBGSzVyPUG4MlHPxE1?	NX\MTIJVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4NlY{QThpPkK1PFI3Ozl6PD;hQi=>
A549	NVvkcmRXTnWwY4Tpc44h[XO\|YYm=		NX;XO5dEOyCqcoO=	NVTKb5Y2UW6mdXP0bY9vKG:oIGLPV{Bxem:mdXP0bY9vKGmwIHj1cYFvKEF3NEmgZ4VtdHNiYX\0[ZIhOyCqcoOgZpkhTEiHIIP0ZYlvcW6pLXLhd4VlKG[udX;y[ZNk\W6lZTDhd5NigQ>?	MknSQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6Mk[zPVgoRjJ3OEK2N\|k5RC:jPh?=
A549	NE\oZpVHfW6ldHnvckBie3OjeR?=		NHTjO\|c{KGi{cx?=	NUHCSo05UW6mdXP0bY9vKG:oIGLPV{Bxem:mdXP0bY9vKGmwIHj1cYFvKEF3NEmgZ4VtdHNiYX\0[ZIhOyCqcoOgZpkhSVCIIIP0ZYlvcW6pLXLhd4VlKG[udX;y[ZNk\W6lZTDhd5NigQ>?	M2XOOVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEK2N\|k5Lz5{NUiyOlM6QDxxYU6=
A549	M2[5eWZ2dmO2aX;uJIF{e2G7	NF61TVEyOCC3TR?=	NWLTNoVCPCCqcoO=	MkHUVoVlfWO2aX;uJIlvKHSxdHHsJGdUUCCuZY\lcEBqdiCqdX3hckBCPTR7IHPlcIx{KGG2IEGwJJVOKGGodHXyJFQhcHK\|IHL5JIx2dWmwZYPj[Y5k\SCjc4PhfS=>	M{TJW\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEK2N\|k5Lz5{NUiyOlM6QDxxYU6=
A549	MUjGeY5kfGmxbjDhd5NigQ>?	Mn3hNVAhfU1?	MYK0JIhzew>?	MXrS[YR2[3Srb36gbY4hemWmdXPl[EBIW0hibHX2[YwhcW5iaIXtZY4hSTV2OTDj[YxteyCjdDCxNEB2VSCjZoTldkA1KGi{czDifUBtfW2rbnXzZ4Vv[2ViYYPzZZk>	MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh{NkO5PEc,OjV6Mk[zPVg9N2F-
HT1080	M33ocmN6fG:2b4jpZ4l1gSCjc4PhfS=>		Mon5O\|IhcHK\|	NYjCfGM2S3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hUFRzMEiwJINmdGy\|IHHzd4V{e2WmIHHzJINmdGxidnnhZoltcXS7IHHmeIVzKDd{IHjyd{BjgSC{ZYPhfpVzcW5icnXkeYN1cW:wIHHzd4F6NCCLQ{WwQVMvPDQQvF2=	M4Hm[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NUm5OVMxLz5{NkW5PVU{ODxxYU6=
GBM10	M4HGU2N6fG:2b4jpZ4l1gSCjc4PhfS=>		NVHEZWF[PzJiaILz	NXfZOWpXS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hT0KPMUCgZ4VtdHNiYYPz[ZN{\WRiYYOgZ4VtdCC4aXHibYxqfHliYX\0[ZIhPzJiaILzJIJ6KHKnc3H6eZJqdiC{ZXT1Z5Rqd25iYYPzZZktKEmFNUC9N{45Oc7:TR?=	MmD4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ3OUm1N\|AoRjJ4NUm5OVMxRC:jPh?=
SF188	NHTq[HBEgXSxdH;4bYNqfHliYYPzZZk>		M3LGXVczKGi{cx?=	NWDkdo5RS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hW0ZzOEigZ4VtdHNiYYPz[ZN{\WRiYYOgZ4VtdCC4aXHibYxqfHliYX\0[ZIhPzJiaILzJIJ6KHKnc3H6eZJqdiC{ZXT1Z5Rqd25iYYPzZZktKEmFNUC9N{46\|ryP	NFXvXWY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkW5PVU{OCd-Mk[1PVk2OzB:L3G+
SKBR3	NIHEWGFEgXSxdH;4bYNqfHliYYPzZZk>		MkS1O\|IhcHK\|	NEjCbYREgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBUU0KUMzDj[YxteyCjc4Pld5Nm\CCjczDj[YxtKH[rYXLpcIl1gSCjZoTldkA4OiCqcoOgZpkhemW\|YYr1dolvKHKnZIXjeIlwdiCjc4PhfUwhUUN3ME20MlA1\|ryP	NF:2TFk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkW5PVU{OCd-Mk[1PVk2OzB:L3G+
T98G	MX\DfZRwfG:6aXPpeJkh[XO\|YYm=		NVf5T4VkPzJiaILz	M2C4W2N6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJHQ6QEdiY3XscJMh[XO\|ZYPz[YQh[XNiY3XscEB3cWGkaXzpeJkh[W[2ZYKgO\|IhcHK\|IHL5JJJme2G8dYLpckBz\WS3Y4Tpc44h[XO\|YYmsJGlEPTB;ND65Nu69VQ>?	NHnGPI89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkW5PVU{OCd-Mk[1PVk2OzB:L3G+
HT-29	NGHNPXREgXSxdH;4bYNqfHliYYPzZZk>		MWe3NkBpenN?	M2rofWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGhVNTJ7IHPlcIx{KGG\|c3Xzd4VlKGG\|IHPlcIwhfmmjYnnsbZR6KGGodHXyJFczKGi{czDifUBz\XOjeoXybY4hemWmdXP0bY9vKGG\|c3H5MEBKSzVyPUWuOFnPxE1?	NFrMfo49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkW5PVU{OCd-Mk[1PVk2OzB:L3G+
MCF7	MlrGR5l1d3SxeHnjbZR6KGG\|c3H5		MUS3NkBpenN?	MV7DfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDNR2Y4KGOnbHzzJIF{e2W\|c3XkJIF{KGOnbHygeoli[mmuaYT5JIFnfGW{IEeyJIhzeyCkeTDy[ZNignW{aX6gdoVlfWO2aX;uJIF{e2G7LDDJR\|UxRTZwMUVOwG0>	NWHGfoRlRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[1PVk2OzBpPkK2OVk6PTNyPD;hQi=>
A549	NXzoT4dCS3m2b4TvfIlkcXS7IHHzd4F6		NHfSWGg4OiCqcoO=	M37nPGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGE2PDliY3XscJMh[XO\|ZYPz[YQh[XNiY3XscEB3cWGkaXzpeJkh[W[2ZYKgO\|IhcHK\|IHL5JJJme2G8dYLpckBz\WS3Y4Tpc44h[XO\|YYmsJGlEPTB;Nj61OO69VQ>?	Ml6xQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ3OUm1N\|AoRjJ4NUm5OVMxRC:jPh?=
MV4-11	NHLYXmZCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		M2rBclczKGi{cx?=	MnTERY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCPVkStNVEh[2WubIOgZYZ1\XJiN{KgbJJ{KGmwIIDy[ZNmdmOnIH;mJHNCUEFiYomgUXRVKGG\|c3H5MEBKSzVyPUCuNlg6Oc7:TR?=	MmmzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjd3MEW4OFgoRjJ5NUC1PFQ5RC:jPh?=
CMK	MUTBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		MWK3NkBpenN?	MlPNRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDBdoEuSyC{ZYPpd5RidnRiaIXtZY4hS02NIHPlcIx{KGGodHXyJFczKGi{czDpckBxemW\|ZX7j[UBw\iCVQVjBJIJ6KE2WVDDhd5NigSxiSVO1NF0xNjR{MUlOwG0>	MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzVyNUi0PEc,Ojd3MEW4OFg9N2F-
CMY	MYHBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		Mk\oO\|IhcHK\|	M{fWZWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iQ13ZJINmdGy\|IHHmeIVzKDd{IHjyd{BqdiCycnXz[Y5k\SCxZjDTRWhCKGK7IF3UWEBie3OjeTygTWM2OD1yLkS0NlTPxE1?	MkHIQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjd3MEW4OFgoRjJ5NUC1PFQ5RC:jPh?=
HL60	MmXhRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		M2fRbFczKGi{cx?=	M2XjVmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iSFy2NEBk\WyuczDh[pRmeiB5MjDodpMhcW5icILld4Vv[2Vib3[gV2FJSSCkeTDNWHQh[XO\|YYmsJGlEPTB;MD61Nlkz\|ryP	MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzVyNUi0PEc,Ojd3MEW4OFg9N2F-
CMK	M1LNe2FvfGmycn;sbYZmemG2aY\lJIF{e2G7		MXK3NkBpenN?	NGjQRWRCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFPNT{Bk\WyuczDh[pRmeiB5MjDodpMhcW5icILld4Vv[2Vib3[gV2FJSSCkeTDNWHQh[XO\|YYmsJGlEPTB;MD62NVI4\|ryP	NV3KRo1GRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMke1NFU5PDhpPkK3OVA2QDR6PD;hQi=>
U937	MYDBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		MnfXO\|IhcHK\|	M2HtRmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgdFU{KG63bHygbJVu[W5iVUmzO{Bk\WyuczDh[pRmeiB5MjDodpMhcW5icILld4Vv[2Vib3[gV2FJSSCkeTDNWHQh[XO\|YYmsJGlEPTB;MD63OlfPxE1?	MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzVyNUi0PEc,Ojd3MEW4OFg9N2F-
MOLM13	NUXlc4pqSW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		MkX5O\|IhcHK\|	MnnTRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCPT1zNNVMh[2WubIOgbIFz[m:{aX7nJJdqdGRidInw[UBxPTNxRlzUN{1KXERibYX0ZY51KGGodHXyJFczKGi{czDpckBxemW\|ZX7j[UBw\iCVQVjBJIJ6KE2WVDDhd5NigSxiSVO1NF0xNjl\|NEZOwG0>	NX7YR4l3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMke1NFU5PDhpPkK3OVA2QDR6PD;hQi=>
CMS	MWPBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		MVe3NkBpenN?	M3vuU2FvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iQ13TJINmdGy\|IHHmeIVzKDd{IHjyd{BqdiCycnXz[Y5k\SCxZjDTRWhCKGK7IF3UWEBie3OjeTygTWM2OD1zLkCzO:69VQ>?	MnrDQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjd3MEW4OFgoRjJ5NUC1PFQ5RC:jPh?=
OCI-AML3	MX;BcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		MXi3NkBpenN?	M4fYSWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iT1PJMWFOVDNiY3XscJMh[W[2ZYKgO\|IhcHK\|IHnuJJBz\XOnbnPlJI9nKFODSFGgZpkhVVSWIHHzd4F6NCCLQ{WwQVEvOTB7zszN	MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzVyNUi0PEc,Ojd3MEW4OFg9N2F-
HL60	MlTMRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		NFT5ZYs4OiCqcoO=	MnT6RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDBdoEuSyC{ZYPpd5RidnRiaIXtZY4hUEx4MDDj[YxteyCjZoTldkA4OiCqcoOgbY4heHKnc3XuZ4Uhd2ZiU1HIRUBjgSCPVGSgZZN{[XluIFnDOVA:OS5zMklOwG0>	NFnpZ249[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{WwOVg1QCd-Mke1NFU5PDh:L3G+
MV4-11	MVXBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		NWHKdZByPzJiaILz	MoPxRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCPVkStNVEh[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeTygTWM2OD1zLkSzPe69VQ>?	MlPqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjd3MEW4OFgoRjJ5NUC1PFQ5RC:jPh?=
CMY	M{LqXGFvfGmycn;sbYZmemG2aY\lJIF{e2G7		NEPt[mM4OiCqcoO=	MUXBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEOPWTDj[YxteyCjZoTldkA4OiCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwQVEvPjMQvF2=	NF3KRlE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{WwOVg1QCd-Mke1NFU5PDh:L3G+
HL60	NGjxeVlCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		M3\RSVczKGi{cx?=	M3;wbWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iSFy2NEBk\WyuczDh[pRmeiB5MjDodpMh[nliTWTUJIF{e2G7LDDJR\|UxRTFwN{e4{txO	MmL2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjd3MEW4OFgoRjJ5NUC1PFQ5RC:jPh?=
MOLM13	MVzBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		NETrPWg4OiCqcoO=	M1vYTWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTV;MUVE{KGOnbHzzJIhiemKxcnnu[{B4cWymIIT5dIUheDV\|L1\MWFMuUVSGIH31eIFvfCCjZoTldkA4OiCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwQVEvQDN6zszN	NEKzdW09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{WwOVg1QCd-Mke1NFU5PDh:L3G+
OCI-AML3	NHixVGRCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		M2jMOVczKGi{cx?=	MVHBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKE:FST3BUWw{KGOnbHzzJIFnfGW{IEeyJIhzeyCkeTDNWHQh[XO\|YYmsJGlEPTB;MT64OljPxE1?	MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzVyNUi0PEc,Ojd3MEW4OFg9N2F-
CMK	NXH4cmFYSW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		NVzJZoIxPzJiaILz	NIq1eVdCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JGFz[S2FIILld4l{fGGwdDDoeY1idiCFTVugZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigSxiSVO1NF0yNjlzMd88US=>	NWn4RldoRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMke1NFU5PDhpPkK3OVA2QDR6PD;hQi=>
U937	Mmf1RY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		NWHNfHJNPzJiaILz	NECzZpRCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JJA2OyCwdXzsJIh2dWGwIGW5N\|ch[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeTygTWM2OD1{LkG3OO69VQ>?	NYjVUXJXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMke1NFU5PDhpPkK3OVA2QDR6PD;hQi=>
HL60	NITiZ3dCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		NYfid2hGPzJiaILz	MlP1RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDBdoEuSyC{ZYPpd5RidnRiaIXtZY4hUEx4MDDj[YxteyCjZoTldkA4OiCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwQVIvOjYQvF2=	MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzVyNUi0PEc,Ojd3MEW4OFg9N2F-
CMK	M33jSWFvfGmycn;sbYZmemG2aY\lJIF{e2G7		MYW3NkBpenN?	NX6wWXltSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDDUWsh[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeTygTWM2OD1{LkixOe69VQ>?	NFGwU2E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{WwOVg1QCd-Mke1NFU5PDh:L3G+
CMS	M4P3TmFvfGmycn;sbYZmemG2aY\lJIF{e2G7		MWG3NkBpenN?	NGK5TIVCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFPNV{Bk\WyuczDh[pRmeiB5MjDodpMh[nliTWTUJIF{e2G7LDDJR\|UxRTNwMEm3{txO	Mn;sQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjd3MEW4OFgoRjJ5NUC1PFQ5RC:jPh?=
U937	M3PPWGFxd3C2b4Ppd{Bie3OjeR?=	NGSzOGQzKHWP	M4T6V\|I1KGi{cx?=	MVnJcoR2[3Srb36gc4Yh[XCxcITvd4l{KGmwIIC1N{BvfWyuIHj1cYFvKFV7M{egZ4VtdHNiYYPz[ZN{\WRiYYOgZ4F{eGG\|ZTCzJINt\WG4YXflJIF1KDJidV2gZYZ1\XJiMkSgbJJ{KGmwIIDy[ZNmdmOnIH;mJHNCUEFiYomgW4V{fGW{bjDicI91KGGwYXz5d4l{	MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzVyNUi0PEc,Ojd3MEW4OFg9N2F-
U937	NGTPfHNCeG:ydH;zbZMh[XO\|YYm=	MmfBNkB2VQ>?	Mn3yNlQhcHK\|	NEjle3RKdmS3Y4Tpc44hd2ZiYYDvdJRwe2m\|IHnuJJA2OyCwdXzsJIh2dWGwIGW5N\|ch[2WubIOgZZN{\XO\|ZXSgZZMhWEGUUD2xJINt\WG4YXflJIF1KDJidV2gZYZ1\XJiMkSgbJJ{KGmwIIDy[ZNmdmOnIH;mJHNCUEFiYomgW4V{fGW{bjDicI91KGGwYXz5d4l{	MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzVyNUi0PEc,Ojd3MEW4OFg9N2F-
U937	MlizR4VtdCCmZXH0bEBie3OjeR?=	MX[xJJRwKDRidV2=	NInyboQzPCCqcoO=	MmK5TY5lfWO2aX;uJI9nKGOnbHyg[IVifGhiaX6gdFU{KG63bHygbJVu[W5iVUmzO{Bk\WyuczDheEAyKHSxIESgeW0h[W[2ZYKgNlQhcHK\|IHL5JIFvdmW6aX6gWk1HUVSFL2DJJJN1[WmwaX7nJIJie2WmIH\sc5ch[3m2b33leJJ6	MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzVyNUi0PEc,Ojd3MEW4OFg9N2F-
U937	MYnDfZRwfG:6aXPpeJkh[XO\|YYm=	NWH6dIRtOC53IITvJFUhfU1?	MkTtNlQhcHK\|	M2K2VmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KHB3MzDueYxtKGi3bXHuJHU6OzdiY3XscJMh[XO\|ZYPz[YQh[XNiZHXjdoVie2ViaX6gZ4VtdCC4aXHibYxqfHliYYSgNE42KHSxIEWgeW0h[W[2ZYKgNlQhcHK\|IHnuJJBz\XOnbnPlJI9nKFODSFGgZpkhVVSWIHHzd4F6	NHW4R3Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{WwOVg1QCd-Mke1NFU5PDh:L3G+
U937	MVPGeY5kfGmxbjDhd5NigQ>?	MVSyJJVO	NHPOVYYzOCCqcoO=	MorUTY5lfWO2aX;uJI9nKESQQTDkZY1i\2ViaX6gdFU{KG63bHygbJVu[W5iVUmzO{Bk\WyuczDheEAzKHWPIHHmeIVzKDJyIHjyd{BqdiCycnXz[Y5k\SCxZjDTRWhCKGK7IGPZRnIh\2:uZDDzeIFqdmmwZzDiZZNm\CCjbHvhcIlv\SClb33leEBie3OjeR?=	M2rzR\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5NUC1PFQ5Lz5{N{WwOVg1QDxxYU6=
MCF7	M4jNOWFvfGmycn;sbYZmemG2aY\lJIF{e2G7		NFrPfYo1QCCqcoO=	NI\idG1CdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBqdiCqdX3hckBOS0Z5IHPlcIx{KGG\|c3Xzd4VlKGG\|IHPlcIwhfmmjYnnsbZR6KGGodHXyJFQ5KGi{czDifUBidGGvYYLCcJVmKGG\|c3H5MEBKSzVyPUGuNu69VQ>?	NIfDRnM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{[4PVczQCd-Mke2PFk4Ojh:L3G+
Jurkat	NXHTR\|hISW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		MnjlOFghcHK\|	M1HlRmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIlvKGi3bXHuJGp2emujdDDj[YxteyCjc4Pld5Nm\CCjczDj[YxtKH[rYXLpcIl1gSCjZoTldkA1QCCqcoOgZpkh[WyjbXHyRox2\SCjc4PhfUwhUUN3ME2xMlTPxE1?	NFn3bmw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{[4PVczQCd-Mke2PFk4Ojh:L3G+
Jurkat	Ml7kR5l1d3SxeHnjbZR6KGG\|c3H5		MYCyOEBpenN?	MV;DfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDKeZJs[XRiY3XscJMh[W[2ZYKgNlQhcHK\|IHL5JG1VXCCjc4PhfUwhUUN3ME21{txO	Mmf6QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjd4OEm3NlgoRjJ5Nki5O\|I5RC:jPh?=
MCF7	NFXxT2pEgXSxdH;4bYNqfHliYYPzZZk>		MoHFNlQhcHK\|	MkTpR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gUWNHPyClZXzsd{Bi\nSncjCyOEBpenNiYomgUXRVKGG\|c3H5MEBKSzVyPUlOwG0>	M1z1TVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5Nki5O\|I5Lz5{N{[4PVczQDxxYU6=
MCF7	NUPtUYF4SXCxcITvd4l{KGG\|c3H5	MVGxNEB2VQ>?	M1;BXlQ5KGi{cx?=	NXzDWoZWUW6mdXP0bY9vKG:oIHHwc5B1d3OrczDpckBpfW2jbjDNR2Y4KGOnbHzzJIF{e2W\|c3XkJIF{KGSxd37y[Yd2dGG2aX;uJI9nKEKlbEKg[ZhxemW\|c3nvckBifCBzMDD1UUBi\nSncjC0PEBpenNiYomgW4V{fGW{bjDicI91KG2ndHjv[C=>	NVrCd5hsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMke2PFk4OjhpPkK3Olg6PzJ6PD;hQi=>
MCF7	MV\BdI9xfG:\|aYOgZZN{[Xl?	M1HURVExKHWP	NWX2bnVCPzJiaILz	MnjVTY5lfWO2aX;uJI9nKGGyb4D0c5NqeyCrbjDoeY1idiCPQ1[3JINmdGy\|IHHzd4V{e2WmIHHzJIRwf26{ZXf1cIF1cW:wIH;mJG1kdC1zIHX4dJJme3Orb36gZZQhOTBidV2gZYZ1\XJiN{KgbJJ{KGK7IGfld5Rmem5iYnzveEBu\XSqb3S=	NIPudWQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{[4PVczQCd-Mke2PFk4Ojh:L3G+
MCF7	M2fLTWZ2dmO2aX;uJIF{e2G7	NUTlSYljOjBidV2=	M1X1VVE3KGi{cx?=	MlvuSIl{enWydHnvckBw\iCvaXPyc5R2[nWuZTDu[ZR4d3KtIHnuJIh2dWGwIF3DSlch[2WubIOgZZQhOjBidV2gZYZ1\XJiMU[gbJJ{KGK7IHntcZVvd2[udX;y[ZNk\W6lZTDhcoFtgXOrcx?=	NYDJdGtuRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMke2PFk4OjhpPkK3Olg6PzJ6PD;hQi=>
MCF7	MWfGeY5kfGmxbjDhd5NigQ>?	NYTMeIhHOTBidV2=	NWntWHl7OTZiaILz	M{nydmlv\HWldHnvckBw\iCvaXPyc5R2[nWuZTDk[ZBwdHmvZYLpfoF1cW:wIHnuJIh2dWGwIF3DSlch[2WubIOgZZQhOTBidV2gZYZ1\XJiMU[gbJJ{KGK7IHntcZVvd2[udX;y[ZNk\W6lZTDhcoFtgXOrcx?=	MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzZ6OUeyPEc,Ojd4OEm3Nlg9N2F-
MCF7	M4Xs[WZ2dmO2aX;uJIF{e2G7	M33vbVEhfG9iMkCgeW0>	MXi0PEBpenN?	MmL4TY5lfWO2aX;uJI9nKHKnYXP0bZZmKG:6eXflckB{eGWlaXXzJIdmdmW{YYTpc44hcW5iaIXtZY4hVUOINzDj[YxteyCjc4Pld5Nm\CCjczDk[YNz\WG\|ZTDpckBk\WyuII\pZYJqdGm2eTDheEAyKHSxIEKwJJVOKGmwIIDy[ZNmdmOnIH;mJJRzd2yxeDDh[pRmeiB2ODDodpMh[nliYXzhcYFzSmy3ZTDhd5NigQ>?	M1XvdFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5Nki5O\|I5Lz5{N{[4PVczQDxxYU6=
MCF7	M{D1T2Z2dmO2aX;uJIF{e2G7	NEjmTZo2KHSxIEKwJJVO	MVK0JIhzew>?	MVXJcoR2[3Srb36gc4YhfHWkdXzpckBl\XCxbInt[ZJqgmG2aX;uJIlvKGi3bXHuJG1ETjdiY3XscJMh[XRiNTD0c{AzOCC3TTDh[pRmeiB2IHjyd{BjgSCZZYP0[ZJvKGKub4SgcYV1cG:m	NYq4NYl4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMke2PFk4OjhpPkK3Olg6PzJ6PD;hQi=>
Jurkat	MWPGeY5kfGmxbjDhd5NigQ>?	NXy3dnNWPSC2bzCyNEB2VQ>?	NEfrdHY1KGi{cx?=	NF7m[pBKdmS3Y4Tpc44hd2ZidIXieYxqdiCmZYDvcJlu\XKrenH0bY9vKGmwIHj1cYFvKEq3cnvheEBk\WyuczDheEA2KHSxIEKwJJVOKGGodHXyJFQhcHK\|IHL5JHdme3Sncn6gZoxwfCCvZYToc4Q>	MlvuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjd4OEm3NlgoRjJ5Nki5O\|I5RC:jPh?=
A549	NYfmT\|hHTnWwY4Tpc44h[XO\|YYm=		Ml3XNlQhcHK\|	MYrJcohq[mm2aX;uJI9nKE6ILXvhdJBiSiCrbjDoeY1idiCDNUS5JINmdGy\|IHHmeIVzKDJ2IHjyd{BjgSCudXPp[oVz[XOnIILldI9zfGW{IHflcoUh[XO\|YYmsJGlEPTB;MT63Ou69VQ>?	MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzhzMEW5OEc,Ojd6MUC1PVQ9N2F-
HepG2	NULjcWlTS3m2b4TvfIlkcXS7IHHzd4F6		NHvGOIc4OiCqcoO=	MVXDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDI[ZBIOiClZXzsd{Bie3Onc4Pl[EBieyCpcn;3eIghcW6qaXLpeIlwdiCjZoTldkA4OiCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwQVgvQc7:TR?=	NELPe5c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEG1PVQyPSd-MkixOVk1OTV:L3G+
HCT116	MXzDfZRwfG:6aXPpeJkh[XO\|YYm=		NWG4N5VYPzJiaILz	NUe4d\|gyS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hUEOWMUG2JINmdGy\|IHHzd4V{e2WmIHHzJIdzd3e2aDDpcohq[mm2aX;uJIFnfGW{IEeyJIhzeyCkeTDNWHQh[XO\|YYmsJGlEPTB;OT6y{txO	MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDF3OUSxOUc,OjhzNUm0NVU9N2F-
A549	M4TVR2N6fG:2b4jpZ4l1gSCjc4PhfS=>		M3jXdFczKGi{cx?=	M4DNXWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGE2PDliY3XscJMh[XO\|ZYPz[YQh[XNiZ4Lve5RpKGmwaHnibZRqd25iYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigSxiSVO1NF0yOM7:TR?=	MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDF3OUSxOUc,OjhzNUm0NVU9N2F-
MRC5	MnXSR5l1d3SxeHnjbZR6KGG\|c3H5		M3XJOlczKGi{cx?=	MUfDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDNVmM2KGOnbHzzJIFnfGW{IEeyJIhzeyCkeTDNWHQh[XO\|YYmsJGlEPTB;M{hOwG0>	MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDF3OUSxOUc,OjhzNUm0NVU9N2F-
A549	NXLpeZhnSW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		NFewcJo4OiCqcoO=	MYjBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEF3NEmgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigSxiSVO1NF03Njh2zszN	NEfGNnI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OESzOFc3PCd-Mki0N\|Q4PjR:L3G+
Saos2	M4TtTmFvfGmycn;sbYZmemG2aY\lJIF{e2G7		NH3rfWI4OiCqcoO=	MUfBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKFOjb4OyJINmdGy\|IHHmeIVzKDd{IHjyd{BjgSCPVGSgZZN{[XluIFnDOVA:Py5\|Md88US=>	NEmxb3o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OESzOFc3PCd-Mki0N\|Q4PjR:L3G+
HCT116	MULBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		NWr3TpdSPzJiaILz	M2fQSmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iSFPUNVE3KGOnbHzzJIFnfGW{IEeyJIhzeyCkeTDNWHQh[XO\|YYmsJGlEPTB;Nz6zOO69VQ>?	M{m1S\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6NEO0O\|Y1Lz5{OESzOFc3PDxxYU6=
U2OS	Mn3sRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		NHvZblc4OiCqcoO=	NHP5V\|ZCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGWyU3Mh[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeTygTWM2OD17LkS5{txO	NFe5fmM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OESzOFc3PCd-Mki0N\|Q4PjR:L3G+
MDA-MB-231	MVvBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		M3HhcVczKGi{cx?=	M2K4OWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTVTBMW1DNTJ\|MTDj[YxteyCjZoTldkA4OiCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwQVExNjcQvF2=	NWHMTWozRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki0N\|Q4PjRpPkK4OFM1PzZ2PD;hQi=>
SKHEP1	MW\BcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		MoHEO\|IhcHK\|	MmnJRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCVS1jFVFEh[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeTygTWM2OD1zMz6z{txO	MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDR\|NEe2OEc,Ojh2M{S3OlQ9N2F-
HCT116	MX7GeY5kfGmxbjDhd5NigQ>?	MWqxNEB2VQ>?	Mnm0NUBpeg>?	NETWXodKdmS3Y4Tpc44hd2ZicnXhZ5RqfmVib4j5[4VvKHOyZXPp[ZMh\2WwZYLheIlwdiCrbjDoeY1idiCKQ2SxNVYh[2WubIOgZZQhOTBidV2gZYZ1\XJiMTDodkBjgSCGQ1\IMWRCKGS7ZT3iZZNm\CCobIXvdoV{[2WwY3WgcYlkem:\|Y3;wbYMh[W6jbInzbZM>	NGnQfoI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OESzOFc3PCd-Mki0N\|Q4PjR:L3G+
HCT116	M{PMUmNmdGxiY4njcIUh[XO\|YYm=	MYqxJJRwKDVidV2=	M3XNOFI1KGi{cx?=	NGflUWlE\WyuIHP5Z4xmKGG{cnXzeEBqdiCqdX3hckBJS1RzMU[gZ4VtdHNiYYPz[ZN{\WRiYYOgZYNkfW23bHH0bY9vKGG2IGOgdIhie2ViMTD0c{A2KHWPIHHmeIVzKDJ2IHjyd{BjgSCycn;wbYRqfW1iaX;kbYRmKHO2YXnubY5oKGKjc3XkJIZtd3diY4n0c41mfHKrYzDt[ZRpd2R?	MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDR\|NEe2OEc,Ojh2M{S3OlQ9N2F-
HCT116	NYDXVWprS2WubDDjfYNt\SCjc4PhfS=>	MlLaNUB1dyB3IIXN	MVeyOEBpenN?	M1;uWmNmdGxiY4njcIUh[XK{ZYP0JIlvKGi3bXHuJGhEXDFzNjDj[YxteyCjc4Pld5Nm\CCjczDhZ4N2dXWuYYTpc44h[XRiR{CvS\|EheGijc3WgZZQhOSC2bzC1JJVOKGGodHXyJFI1KGi{czDifUBxem:yaXTpeY0hcW:maXTlJJN1[WmwaX7nJIJie2WmIH\sc5ch[3m2b33leJJq[yCvZYToc4Q>	M{[0S\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6NEO0O\|Y1Lz5{OESzOFc3PDxxYU6=
HCT116	NVXLN2xpS2WubDDjfYNt\SCjc4PhfS=>	M2DQXFEhfG9iNTD1US=>	NX7KPVhXOjRiaILz	M2LaOWNmdGxiY4njcIUh[XK{ZYP0JIlvKGi3bXHuJGhEXDFzNjDj[YxteyCmZXPy[YF{\SCrbjDwc5B2dGG2aX;uJIF1KEdyL1exJJBp[XOnIHH0JFEhfG9iNTD1UUBi\nSncjCyOEBpenNiYomgdJJweGmmaYXtJIlw\GmmZTDzeIFqdmmwZzDiZZNm\CCobH;3JIN6fG:vZYTybYMhdWW2aH;k	MlzoQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh2M{S3OlQoRjJ6NEO0O\|Y1RC:jPh?=
HT-29	NFvWXIFCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		M2TZcVczKGi{cx?=	NX7LRmFsSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDIWE0zQSClZXzsd{Bi\nSncjC3NkBpenNiYomgUXRVKGG\|c3H5MEBKSzVyPUKuOlXPxE1?	NIP1PJo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OE[4OlkyOSd-Mki2PFY6OTF:L3G+
HCT8	NFT2VYxCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		MlPlO\|IhcHK\|	M3Sz[mFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iSFPUPEBk\WyuczDh[pRmeiB5MjDodpMh[nliTWTUJIF{e2G7LDDJR\|UxRTRwMd88US=>	M132SFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6Nki2PVEyLz5{OE[4OlkyOTxxYU6=
HCT116	M3nnfGFvfGmycn;sbYZmemG2aY\lJIF{e2G7		NVTnXHhMPzJiaILz	MX\BcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEiFVEGxOkBk\WyuczDh[pRmeiB5MjDodpMh[nliTWTUJIF{e2G7LDDJR\|UxRThwMUROwG0>	NY\D[nhORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki2PFY6OTFpPkK4Olg3QTFzPD;hQi=>
CCD-841	MY\DfZRwfG:6aXPpeJkh[XO\|YYm=		NVTpfoxoPzJiaILz	MoPtR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gR2NFNTh2MTDj[YxteyCjc4Pld5Nm\CCjczDy[YR2[3Srb36gbY4h[2WubDD2bYFjcWyrdImgZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeTygTWM2OD12ND6zNu69VQ>?	MkfxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh4OE[5NVEoRjJ6Nki2PVEyRC:jPh?=
HCT116	M1X6cmFvfGmycn;sbYZmemG2aY\lJIF{e2G7	NH\RWYYyOCC3TR?=	NVTLNGFCPzJiaILz	M3TvWWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iSFPUNVE3KGOnbHzzJIF1KDFyIIXNJIFnfGW{IEeyJIhzeyCkeTDNWHQh[XO\|YYm=	MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDZ6NkmxNUc,Ojh4OE[5NVE9N2F-
A549	NITDO4dCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=	NUXTem9xOTBidV2=	NXnBb\|d{PzJiaILz	NEnudnhCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFG1OFkh[2WubIOgZZQhOTBidV2gZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeR?=	M2fFVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6Nki2PVEyLz5{OE[4OlkyOTxxYU6=
K562	MknhRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?	MXOxNEB2VQ>?	NWHyR2FGPzJiaILz	MmXiRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCNNU[yJINmdGy\|IHH0JFExKHWPIHHmeIVzKDd{IHjyd{BjgSCPVGSgZZN{[Xl?	NXOw[HN7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki2PFY6OTFpPkK4Olg3QTFzPD;hQi=>
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RAW264.7	NEXoW\|NHfW6ldHnvckBie3OjeR?=	MWqxNEB2VQ>?	MlrDNE42KGi{cx?=	M3W3WGlvcGmkaYTpc44hd2ZiTVHQT{9PTmujcIDhRkBqdiCLQ2KgcY92e2ViUlHXNlY1NjdiY3XscJMh[XO\|ZYPz[YQh[XNicnXkeYN1cW:wIHnuJGxRWy2rbnT1Z4VlKFSQRnHsdIhiKHC{b3T1Z5Rqd25iYYSgNVAhfU1icILleJJm[XSnZDDmc5IhOC53IHjyd{Bnd2yub4fl[EBjgSCOUGOgZ4hidGynbnflJIFv\CCvZXHzeZJm\CCjZoTldkAzPCCqcoOgZpkhTUyLU1GgdoVt[XSrdnWgeI8h[2:wdILvcC=>	NYO5OG9{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{C3PFAxQDhpPkOwO\|gxODh6PD;hQi=>
RAW264.7	NFywdFZHfW6ldHnvckBie3OjeR?=	MkOxNVAhfU1?	MXewMlUhcHK\|	NUXROoJWUW6qaXLpeIlwdiCxZjDNRXBMN06Ia3HwdIFDKGmwIFnDVkBud3W\|ZTDSRXczPjRwNzDj[YxteyCjc4Pld5Nm\CCjczDy[YR2[3Srb36gbY4hVFCVLXnu[JVk\WRiSVy2JJBzd2S3Y4Tpc44h[XRiMUCgeW0heHKndILlZZRm\CCob4KgNE42KGi{czDmc4xtd3enZDDifUBNWFNiY3jhcIxmdmenIHHu[EBu\WG\|dYLl[EBi\nSncjCyOEBpenNiYomgSWxKW0FicnXsZZRqfmVidH:gZ49vfHKxbB?=	MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODd6MEC4PEc,OzB5OECwPFg9N2F-
BHK21	MYrDfZRwfG:6aXPpeJkh[XO\|YYm=		NYrxcFhuPDhiaILz	M2G2O2N6fG:2b4jpZ4l1gSCjZ3HpcpN1KEKKS{KxJINmdGy\|IHHzd4V{e2WmIHHzJJJm\HWldHnvckBqdiClZXzsJJZq[WKrbHn0fUBi\nSncjC0PEBpenNiYomgUXRVKGG\|c3H5MEBESzVyPUSwMlE1\|ryP	NXLmfJZZRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{GwNFk6ODhpPkOxNFA6QTB6PD;hQi=>
SH-SY5Y	MlHLR5l1d3SxeHnjbZR6KGG\|c3H5		NH3GZ4Y4OiCqcoO=	NHe2WphEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBUUC2VWUXZJINmdGy\|IHHzd4V{e2WmIHHzJJJm\HWldHnvckBqdiClZXzsJJZq[WKrbHn0fUBqdmO3YnH0[YQh\m:{IEeyJIhzeyCkeTDNWHQh[XO\|YYmsJGlEPTB;NT65OO69VQ>?	M3TWVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNzNECwO\|A5Lz5\|MUSwNFcxQDxxYU6=
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SH-SY5Y	MWrGeY5kfGmxbjDhd5NigQ>?		NEeyU5gyPSCvaX7z	M2n5R2lvcGmkaYTpc44hd2ZiVIL4VkBqdiCqdX3hckBUUC2VWUXZJINmdGy\|IIXzbY5oKESWTlKgZZMhe3Wkc4TyZZRmKHC{ZXnuZ5Vj[XSnZDDmc5IhOTVibXnud{Bnd2yub4fl[EBjgSC\|dXLzeJJifGViYXTkbZRqd25iYX7kJI1m[XO3cnXkJIZweiB{MDDtbY5{KGK7IFXscI1idie\|IH3leIhw\CxiSVO1NF01PS56ON88US=>	M1fYU\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNzNECwO\|A5Lz5\|MUSwNFcxQDxxYU6=

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	CDK2 / Cyclin E / Cyclin A ; PubMed: 27634873 Oncotarget NCI-H929 cells were treated with 4 μM piperlongumine for 12, 24, or 48 h; cyclins and CDK2 levels were then measured Bax / Bcl-2 ; PubMed: 27634873 Oncotarget NCI-H929 cells were treated with 4 μM piperlongumine for 12 or 24 h and Bcl-2 and Bax levels were measured. Quantitative analysis was performed using Image J software, with normalization to GAPDH expression. Survivin / p21 / p27 ; PubMed: 27634873 Oncotarget NCI-H929 cells were treated with 4 μM piperlongumine for different amounts of time. Survivin, p21, and p27 levels were then measured. p-STAT3 / STAT3 / p-JAK2 / JAK2 / c-myc ; PubMed: 27634873 Oncotarget NCI-H929 cells were treated with 4 μM piperlongumine for different amounts of time, and STAT3, p-STAT3, p-JAK2, JAK2 and c-myc levels were then measured. Hexokinase 1 / Hexokinase 2 ; PubMed: 30906213 Int J Biol Sci Piperlongumine regulates glycolysis in NSCLC cells. NSCLC cells, including H23 (A), HCC827 (B) and H1975 (C) were treated with different concentrations of piperlongumine for 24 h. Western blotting was performed to detect HK2 expression (left). The levels of glucose consumption (middle) and lactate production (right) were examined in these cells. Columns, mean of the number of colonies as determined from three independent experiments; bars, standard deviation; asterisk, significant (p<0.05, p<0.01, **p<0.001) suppression of HK2 expression or glycolysis by piperlongumine compared with DMSO treated group. PL, Piperlongumine. p-AKT / AKT / p-S6 / S6 ; PubMed: 30906213 Int J Biol Sci HCC827 (left), H1975 (middle) and H23 cells were treated with piperlongumine for 24 h, western blot was conducted to detect the target proteins as indicated.	27634873 30906213
Growth inhibition assay	Cell viability; PubMed: 25193861 Oncotarget Piperlongumine induces death in HNC cells but not normal cells. Cytotoxicity was assessed by MTT assay	25193861

In vivo

Piperlongumine (50 mg/kg i.p.) causes in vivo growth inhibition of tumor cells without leading to major changes in the biochemical, hematological and histopathological parameters. ^[4]

Protocol

Cell Research: ^[3]	- Collapse Cell lines: MCF-7 and 786-O cells Concentrations: ~10 μM Incubation Time: 48 hours Method: MCF-7 and 786-O cells are incubated with various PL concentrations for 48h. Cell proliferation is analysed by CellTiter Blue assay. Effective doses (ED) are calculated using XLift, Microsoft Excel add-in. (Only for Reference)
Animal Research: ^[4]	- Collapse Animal Models: Mice transplanted with sarcoma 180 tumors Dosages: ~50 mg/kg Administration: i.p. (Only for Reference)

References

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Solubility (25°C)

In vitro	DMSO	16 mg/mL warmed (50.41 mM)
	Ethanol	6 mg/mL warmed (18.9 mM)
	Water	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 2% DMSO+40% PEG 300+2% Tween 80+ddH2O For best results, use promptly after mixing.	5mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download Piperlongumine SDF

Molecular Weight	317.34
Formula	C₁₇H₁₉NO₅
CAS No.	20069-09-4
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	PPLGM, Piplartine
Smiles	COC1=CC(=CC(=C1OC)OC)C=CC(=O)N2CCC=CC2=O

In vivo Formulation Calculator (Clear solution)

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

Dosage

mg/kg

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

% DMSO+ % + % Tween 80+ % ddH₂O

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Calculation results:

Working concentration： mg/ml；

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

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

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

Bio Calculators

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration _(start) x Volume _(start) = Concentration _(final) x Volume _(final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

Serial Dilutions
Concertration (start):
Dilution-folds:

Computed Result

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):

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

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

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Piperlongumine