Nutlin-3

For research use only. Not for use in humans.

目录号：S1061

CAS No. 890090-75-2

Nutlin-3是一种有效的，选择性Mdm2(它自身和p53的环指依赖性泛素蛋白连接酶)拮抗剂，无细胞试验中IC50为90 nM；可稳定p53缺陷细胞中的p73。

规格

价格

库存

购买数量

10mM (1mL in DMSO)	RMB 1515.15	现货
5mg	RMB 900.36	现货
25mg	RMB 3026.07	现货
50mg	RMB 5298.93	现货
100mg	RMB 7939.67	现货
200mg	RMB 13243.23	现货
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客户使用Selleck生产的Nutlin-3发表文献77篇：

Nat Biotechnol, 2022, 10.1038/s41587-021-01172-3

PubMed: 35165384 ( click the link to review the publication )

Nat Cell Biol, 2021, 23(6):595-607

PubMed: 34108663 ( click the link to review the publication )

Cell Stem Cell, 2018, 23(4):544-556

PubMed: 30244867 ( click the link to review the publication )

Nat Biotechnol, 2017, 35(6):577-582

PubMed: 28459450 ( click the link to review the publication )

J Exp Clin Cancer Res, 2022, 41(1):79

PubMed: 35227287 ( click the link to review the publication )

Cell Biosci, 2022, 12(1):20

PubMed: 35216629 ( click the link to review the publication )

Hum Cell, 2022, 10.1007/s13577-022-00671-y

PubMed: 35118583 ( click the link to review the publication )

Sci Adv, 2021, 7(32)eabf7561

PubMed: 34348895 ( click the link to review the publication )

Nat Commun, 2021, 12(1):3481

PubMed: 34108482 ( click the link to review the publication )

Cell Death Differ, 2021, 10.1038/s41418-021-00886-w

PubMed: 34642466 ( click the link to review the publication )

Elife, 2021, 10e61630

PubMed: 33459596 ( click the link to review the publication )

Cancer Lett, 2021, S0304-3835(21)00481-X

PubMed: 34562520 ( click the link to review the publication )

Cell Death Dis, 2021, 12(7):640

PubMed: 34162828 ( click the link to review the publication )

Cell Death Dis, 2021, 12(1):1

PubMed: 33414393 ( click the link to review the publication )

Eur J Med Chem, 2021, 217:113359

PubMed: 33725632 ( click the link to review the publication )

Dis Model Mech, 2021, dmm.049001

PubMed: 34569598 ( click the link to review the publication )

Cancer Immunol Immunother, 2021, 10.1007/s00262-021-02940-5

PubMed: 33866408 ( click the link to review the publication )

Sci Rep, 2021, 11(1):14253

PubMed: 34244565 ( click the link to review the publication )

J Biol Chem, 2021, S0021-9258(21)00730-4

PubMed: 34216619 ( click the link to review the publication )

J Biol Chem, 2021, S0021-9258(21)00965-0

PubMed: 34481841 ( click the link to review the publication )

Hum Cell, 2021, 10.1007/s13577-021-00639-4

PubMed: 34731453 ( click the link to review the publication )

Hum Cell, 2021, 10.1007/s13577-021-00579-z

PubMed: 34304386 ( click the link to review the publication )

Hum Cell, 2021, 34(6):1911-1918

PubMed: 34383271 ( click the link to review the publication )

Clin Cancer Res, 2020, 26(1):122-134

PubMed: 31767563 ( click the link to review the publication )
Cell Rep, 2020, 30(2):497-509

PubMed: 31940492 ( click the link to review the publication )

Eur J Cancer, 2020, 126:93-103

PubMed: 31927215 ( click the link to review the publication )

Cancers (Basel), 2020, 12(11)E3205

PubMed: 33143299 ( click the link to review the publication )

Cancers (Basel), 2020, 20;12(2) pii: E493

PubMed: 32093281 ( click the link to review the publication )

Cancer Sci, 2020, 112(1):133-143

PubMed: 33067904 ( click the link to review the publication )

Virology, 2020, 539:1-10

PubMed: 31605941 ( click the link to review the publication )

BMC Cancer, 2020, 20(1):617

PubMed: 32615946 ( click the link to review the publication )

Leuk Lymphoma, 2020, 1-10

PubMed: 32558607 ( click the link to review the publication )

Hum Cell, 2020, 10.1007/s13577-020-00420-z

PubMed: 32870449 ( click the link to review the publication )

Cell Death Differ, 2020, 10.1038/s41418-020-0590-4

PubMed: 32694652 ( click the link to review the publication )

Cell Rep, 2020, 32(1):107845

PubMed: 32640215 ( click the link to review the publication )

Cell Mol Gastroenterol Hepatol, 2020, S2352-345X(20)30179-X

PubMed: 33161156 ( click the link to review the publication )

Clin Transl Med, 2020, 10.1002/ctm2.41

PubMed: 32508052 ( click the link to review the publication )

Cell Rep, 2019, 29(5):1249-1260

PubMed: 31665637 ( click the link to review the publication )

Cell Death Differ, 2019, 10.1038/s41418-019-0338-1

PubMed: 31065106 ( click the link to review the publication )

Oncogene, 2019, 38(14):2501-2515

PubMed: 30532073 ( click the link to review the publication )

EBioMedicine, 2019, 45:251-260

PubMed: 31201144 ( click the link to review the publication )

Cell Death Dis, 2019, 10(10):737

PubMed: 31570706 ( click the link to review the publication )

Oncologist, 2019, 24(7):989-996

PubMed: 31019022 ( click the link to review the publication )

Oncogenesis, 2019, 8(12):67

PubMed: 31732712 ( click the link to review the publication )

J Cell Mol Med, 2019, 23(7):4545-4558

PubMed: 31062473 ( click the link to review the publication )

Mol Immunol, 2019, 108:68-74

PubMed: 30784764 ( click the link to review the publication )

Oncol Rep, 2019, 41(2):1075-1082

PubMed: 30535478 ( click the link to review the publication )

Nat Commun, 2018, 9(1):2494

PubMed: 29950602 ( click the link to review the publication )
Sci Adv, 2018, 4(12):eaat5077

PubMed: 30585287 ( click the link to review the publication )

Cell Rep, 2018, 22(12):3206-3216

PubMed: 29562177 ( click the link to review the publication )

EBioMedicine, 2018, 36:252-265

PubMed: 30274821 ( click the link to review the publication )

Cell Death Dis, 2018, 9(2):168

PubMed: 29416011 ( click the link to review the publication )

Oncogenesis, 2018, 7(3):33

PubMed: 29593251 ( click the link to review the publication )

J Cell Physiol, 2018, 233(9):7424-7434

PubMed: 29663367 ( click the link to review the publication )

EMBO J, 2017, 36(23):3483-3500

PubMed: 29046333 ( click the link to review the publication )

Leukemia, 2017, 31(6):1296-1305

PubMed: 27885271 ( click the link to review the publication )

Cell Death Dis, 2017, 8(10):e3130

PubMed: 29048401 ( click the link to review the publication )

Sci Rep, 2017, 7(1):16652

PubMed: 29192272 ( click the link to review the publication )

FEBS Lett, 2017, 591(18):2905-2918

PubMed: 28670683 ( click the link to review the publication )

Journal of Functional Foods, 2017, 31:217-228

PubMed: None ( click the link to review the publication )

Oncotarget, 2017, 8(25):41422-41431

PubMed: 28507282 ( click the link to review the publication )

Mol Cell, 2016, 63(3):526-38

PubMed: 27453044 ( click the link to review the publication )

PLoS Genet, 2016, 12(9):e1006279

PubMed: 27588951 ( click the link to review the publication )

Med Oncol, 2016, 33(10):113

PubMed: 27586146 ( click the link to review the publication )

Hepatology, 2015, 62(5):1497-510

PubMed: 26173433 ( click the link to review the publication )

Mol Ther, 2015, 23(5):857-65

PubMed: 25648263 ( click the link to review the publication )

Sci Rep, 2015, 5:8202

PubMed: 25644037 ( click the link to review the publication )

Int J Cancer, 2014, 10.1002/ijc.29194

PubMed: 25196217 ( click the link to review the publication )

Int J Oncol, 2014, 45(2):675-82

PubMed: 24867259 ( click the link to review the publication )

Int J Oncol, 2014, 44(3):761-8

PubMed: 24366007 ( click the link to review the publication )

PLoS One, 2014, 9(9):e108758

PubMed: 25268132 ( click the link to review the publication )

Universidade de Lisboa, 2014, Matias

PubMed: ( click the link to review the publication )
J Thorac Oncol, 2014, 9(9):1305-15

PubMed: 25122426 ( click the link to review the publication )

Assay Drug Dev Technol, 2014, 12(9-10):514-26

PubMed: 25506801 ( click the link to review the publication )

Transl Oncol, 2013, 6(6):685-96

PubMed: 24466371 ( click the link to review the publication )

Cell Death Dis, 2012, 3:e294

PubMed: 22476102 ( click the link to review the publication )

Cell Death Dis, 2011, 2:e243

PubMed: 22170099 ( click the link to review the publication )

产品安全说明书

Mdm2抑制剂选择性比较

生物活性

产品描述

Nutlin-3是一种有效的，选择性Mdm2(它自身和p53的环指依赖性泛素蛋白连接酶)拮抗剂，无细胞试验中IC50为90 nM；可稳定p53缺陷细胞中的p73。

靶点

Mdm2 ^[5]
(Cell-free assay)

180 nM

体外研究

Nutlin-3有效抑制MDM2-p53相互作用，IC50 为 90 nM, 导致p53通路激活。Nutlin-3 处理含野生型p53的细胞，如HCT116, RKO 和SJSA-1,诱导MDM2 和p21表达, 且具有有效的抗增殖活性，IC50 为~1.5 μM, 但是作用于含突变型p53的细胞系 SW480和 MDA-MB-435没有效果。10 μM Nutlin-3处理 SJSA-1细胞48小时，显著诱导caspase依赖的细胞凋亡，凋亡达~45%。虽然Nutlin-3也抑制人皮肤 (1043SK) 和小鼠胚胎 (NIH/3T3) 的生长和活力，IC50分别为2.2 μM 和1.3 μM, 10 μM Nutlin-3处理一周后仍保留细胞活力，而3 μM Nutlin-3 处理SJSA-1细胞后，细胞则无活力。^[1] Nutlin-3 不诱导p53在关键丝氨酸残基的磷酸化，在特定DNA结合序列没有区别，且与基因毒性药物Doxorubicin和Etoposide诱导的磷酸化p53相比，使p53靶点基因转活，说明 p53 在关键丝氨酸残基的磷酸化对转录激活和凋亡是非必需的。^[2] 虽然与MDM2相比，Nutlin-3 与MDMX 结合的效率低一点, Nutlin-3作用于视网膜母细胞瘤细胞(Weri1)，能抑制MDMX–p53相互作用，且诱导 p53通路，IC50为0.7 μM。^[3] 30 μM Nutlin-3作用于无野生型p53的细胞，也扰乱内源性p73-HDM2 相互作用，且增强p73稳定性和促凋亡活性, 导致细胞生长受抑制，和诱导凋亡。^[4]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
SMMC-7721	M13pfmZ2dmO2aX;uJGF{e2G7	NGTlOVcyOCEQvF2=	NYLxcnVnOzZiaB?=	MYHEUXNQ	M2OyVIRwf25vcnXneYxifGW\|IITo[UBxem:2ZXnuJIV5eHKnc4Ppc44hdGW4ZXygc4YheGixc4Doc{1U\XJ\|OUKtdFU{	NFfGbmQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEK4OlMyOid-MkSyPFY{OTJ:L3G+
HuH-7	MXTBdI9xfG:\|aYOgRZN{[Xl?	NHnLWmkzOCEQvF2=	M3LMW\|Q5KGh?	MoHpSG1UVw>?	NULMSXVwcW6mdXPld{BieG:ydH;zbZM>	MUK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDJ6NkOxNkc,OjR{OE[zNVI9N2F-
SMMC-7721	NEjDdlRCeG:ydH;zbZMhSXO\|YYm=	NGHMSnQzOCEQvF2=	NXPOXpc5PDhiaB?=	Moj6SG1UVw>?	NGGzV5ZqdmS3Y3XzJIFxd3C2b4Ppdy=>	NVvrNYtSRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSyPFY{OTJpPkK0Nlg3OzF{PD;hQi=>
HuH-7	NIXifIlE\WyuIG\pZYJqdGm2eTDBd5NigQ>?	NUDoU4dlOS5{NT2yNEDPxE1?	M4nrWVI1NzR6L{eyJIg>	M4Hi[GROW09?	Mn;SbY5pcWKrdIOgZ4VtdCCycn;sbYZmemG2aX;uJIRwe2ViYX7kJJRqdWViZHXw[Y5l\W62bIm=	MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDJ6NkOxNkc,OjR{OE[zNVI9N2F-
SMMC-7721	NWLBZZlDS2WubDDWbYFjcWyrdImgRZN{[Xl?	MXKxMlI2NTJyIN88US=>	NUnRXoI6OjRxNEivO\|IhcA>?	MlPoSG1UVw>?	M3HUXolvcGmkaYTzJINmdGxicILvcIln\XKjdHnvckBld3OnIHHu[EB1cW2nIHTldIVv\GWwdHz5	NULjTJNkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSyPFY{OTJpPkK0Nlg3OzF{PD;hQi=>
RKO	MnT5SpVv[3Srb36gRZN{[Xl?	MojKNlAh\|ryP	MkPQNlQhcA>?		MYTpcoR2[2W\|IFjPMVEh\XiycnXzd4lwdiCjdDD0bIUhdGW4ZXygc4YhfHKjboPjdolxfGmxbh?=	M4\aPFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{[2NFA4Lz5{NEO2OlAxPzxxYU6=
U2OS	MV7GeY5kfGmxbjDBd5NigQ>?	M1XXe\|IxKM7:TR?=	MYSyOEBp		M2\ke4lv\HWlZYOgTG8uOSCneIDy[ZN{cW:wIHH0JJRp\SCuZY\lcEBw\iC2cnHud4NzcXC2aX;u	M2PFVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{[2NFA4Lz5{NEO2OlAxPzxxYU6=
RKO	NX;lOWtoTnWwY4Tpc44hSXO\|YYm=	MoDCNlAh\|ryP	NEPiNWwzPCCq		M2XHTYlv[3KnYYPld{B1cGVibHX2[Yx{KG:oIITo[UBJVy1zIIDyc5RmcW5iYYOge4VtdCCjczD0bIUheDV\|IIDyc5RmcW5?	NGHseYo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEO2OlAxPyd-MkSzOlYxODd:L3G+
U2OS	NF\6Z4lHfW6ldHnvckBCe3OjeR?=	MWeyNEDPxE1?	NGPqW4QzPCCq		NUTOW2s1cW6lcnXhd4V{KHSqZTDs[ZZmdHNib3[geIhmKEiRLUGgdJJwfGWrbjDhd{B4\WyuIHHzJJRp\SCyNUOgdJJwfGWrbh?=	NV7HPHVSRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzOlYxODdpPkK0N\|Y3ODB5PD;hQi=>
MOLM	MlvWSpVv[3Srb36gRZN{[Xl?	MWmxNEDPxE1?	MYCyOEBp		M4DYTpVxemWpdXzheIV{KHSqZTDTU2NUNTFiZYjwdoV{e2mxbh?=	NEfXZVQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NES3N\|U3Oid-MkS0O\|M2PjJ:L3G+
OCI	NWPGW4lOTnWwY4Tpc44hSXO\|YYm=	MoHrNVAh\|ryP	NFy1Z3UzPCCq		MYH1dJJm\3WuYYTld{B1cGViU1;DV{0yKGW6cILld5Nqd25?	MlX1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR2N{O1OlIoRjJ2NEezOVYzRC:jPh?=
BeWo	MmLiRZBweHSxc3nzJGF{e2G7	M3vIWFMxKML3TR?=	M{PCUFI1KGh?		MnyybY5kemWjc3XzJIFxd3C2b4Ppdy=>	MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDR7OEG1OEc,OjR2OUixOVQ9N2F-
BeWo	NITGNGJHfW6ldHnvckBCe3OjeR?=	NGPx[VE{OCEEtV2=	NHTUR4MzPCCq		NHXuRmVqdmO{ZXHz[ZMheDV\|LDDN[I0zNCCyMkGgZY5lKFC3bXGgZZQhfGinIIDyc5RmcW5ibHX2[Yw>	NUfZSZhnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS0PVgyPTRpPkK0OFk5OTV2PD;hQi=>
MOML13	MnvXSpVv[3Srb36gRZN{[Xl?	NWLJW4tROTEQvF2=	MXGyM\|QhcA>?		NHnsUJBqdmO{ZXHz[ZMhfGinIHzleoVtKG:oIIC1Ny=>	MmC2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR4NUm3OFkoRjJ2NkW5O\|Q6RC:jPh?=
AML3	MWrGeY5kfGmxbjDBd5NigQ>?	NEDPOG0yOM7:TR?=	MYmyM\|QhcA>?		M1jsRYlv[3KnYYPld{B1cGVibHX2[Ywhd2ZicEWz	MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDZ3OUe0PUc,OjR4NUm3OFk9N2F-
AML2	NXnwNm9uTnWwY4Tpc44hSXO\|YYm=	MXWxNO69VQ>?	MV:yM\|QhcA>?		M4LnO4lv[3KnYYPld{B1cGVibHX2[Ywhd2ZicEWz	NHW2PFc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NE[1PVc1QSd-MkS2OVk4PDl:L3G+
MOML13	NGPveVlCeG:ydH;zbZMhSXO\|YYm=	M2\WTlIwOTBizszN	NEDVdFIzPC92ODDo		MmjRbY5lfWOnczDhdI9xfG:\|aYO=	MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDZ3OUe0PUc,OjR4NUm3OFk9N2F-
AML2	Mle2RZBweHSxc3nzJGF{e2G7	NIH4TYwzNzFyIN88US=>	M{XZflI1NzR6IHi=		M{\3TYlv\HWlZYOgZZBweHSxc3nz	NYf6cXl6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS2OVk4PDlpPkK0OlU6PzR7PD;hQi=>
U2OS	MmDkSpVv[3Srb36gRZN{[Xl?	MWqyNEDPxE1?	NUnFTIRGOjRiaB?=		MYrpcoNz\WG\|ZYOgeIhmKG2UTlGgcIV3\Wy\|IH;mxsBDS0x{QUGsJGJEVFiOwrDhcoRDS0yZ	NUGyemdvRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS4OlczPTlpPkK0PFY4OjV7PD;hQi=>
Hep3B	NVf5[5FqSXCxcITvd4l{KEG\|c3H5				NGDreHlqdmS3Y3XzJIFxd3C2b4Ppdy=>	NUTDdWNsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS4PFQ5ODlpPkK0PFg1QDB7PD;hQi=>
Huh-7	MVnBdI9xfG:\|aYOgRZN{[Xl?				M{KwZYlv\HWlZYOgZZBweHSxc3nz	NVnCXJdRRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS4PFQ5ODlpPkK0PFg1QDB7PD;hQi=>
SMMC7721	MXnBdI9xfG:\|aYOgRZN{[Xl?				NGi2N5ZqdmS3Y3XzJIFxd3C2b4Ppdy=>	M2\MVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OEi0PFA6Lz5{NEi4OFgxQTxxYU6=
HepG2	NXvXWlFUSXCxcITvd4l{KEG\|c3H5				NX35WlVscW6mdXPld{BieG:ydH;zbZM>	NFfr[I49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEi4OFgxQSd-MkS4PFQ5ODl:L3G+
Hep3B	NFr4OWVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=		NIDMPHA4OiCq	MlP1SG1UVw>?	MlPzTWM2OD1{MD6xPEDDuSBzLki0JO69VQ>?	NHXBUJM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEi4OFgxQSd-MkS4PFQ5ODl:L3G+
Huh-7	M{\rXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		MWO3NkBp	MYXEUXNQ	NE\iNWFKSzVyPUOzMlk3KMLzIEOuPUDPxE1?	NVzQVG9xRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS4PFQ5ODlpPkK0PFg1QDB7PD;hQi=>
SMMC7721/Ac	M4LkTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		MoTLO\|IhcA>?	NFq5[YFFVVOR	MXHJR\|UxRTV3LkKxJOKyKDVwMEOg{txO	MlPXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR6OES4NFkoRjJ2OEi0PFA6RC:jPh?=
SMMC7721	Mo\aS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		NGPIUFQ4OiCq	MYPEUXNQ	NYDqbm5MUUN3ME2zNU4zQCEEsTC0MlIh\|ryP	M1rDcVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OEi0PFA6Lz5{NEi4OFgxQTxxYU6=
HepG2/As	Mn3KS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		MUC3NkBp	NI\5XFBFVVOR	NIOwN\|hKSzVyPU[4MlE{KMLzIEmuOkDPxE1?	NXTPVIMxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS4PFQ5ODlpPkK0PFg1QDB7PD;hQi=>
HepG2	NVLDWohUT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		M3PyNFczKGh?	MlHOSG1UVw>?	MmLZTWM2OD1\|NT64OkDDuSB{Lkmg{txO	MkXtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR6OES4NFkoRjJ2OEi0PFA6RC:jPh?=
MOLM-13	MoHCSpVv[3Srb36gRZN{[Xl?	MUK2xsDPxE1?	MmTSOkBp	MVzEUXNQ	NGm3[lZmdmijbnPld{B1cGViYXPleJlt[XSrb36gc4YhcGm\|dH;u[UBJOkJiYX7kJIhm[XRic3jvZ4sheHKxdHXpcpMhUHOyMkegZY5lKEi\|cEmw	NWKzdIxiRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS4PFUxQDJpPkK0PFg2ODh{PD;hQi=>
MOLM-13	MWrGeY5kfGmxbjDBd5NigQ>?	MoCwOuKh\|ryP	M{LjUFAuQCCq	MXvEUXNQ	MnzkbY5kemWjc3XzJJRp\SCuZY\lcJMhd2ZicEWzMEBOTE1{LDDwNlEh[W6mIHHj[ZR6dGG2ZXSgdFU{	NUfsOJYyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS4PFUxQDJpPkK0PFg2ODh{PD;hQi=>
115	M1zZVWZ2dmO2aX;uJGF{e2G7	NX\FS\|dwPSEQvF2=	MUi0PEBp	NHzYS3JFVVOR	MVTpcoR2[2W\|IIC1N{1l\XCnbnTlcpQhe2WwZYPj[Y5k\cLi	MnvwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjVyNke3PFcoRjJ3ME[3O\|g4RC:jPh?=
A498	MV7GeY5kfGmxbjDBd5NigQ>?	NUi3SIw5PSEQvF2=	NXrvTXMyPDhiaB?=	M1q3ZmROW09?	M2niSIlv\HWlZYOgdFU{NWSncHXu[IVvfCC\|ZX7ld4NmdmOnwrC=	MnnPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjVyNke3PFcoRjJ3ME[3O\|g4RC:jPh?=
Caki-2	Mn\iSpVv[3Srb36gRZN{[Xl?	NUHyPVdKPSEQvF2=	M130UlQ5KGh?	MlG1SG1UVw>?	M2fGPIlv\HWlZYOgdFU{NWSncHXu[IVvfCC\|ZX7ld4NmdmOnwrC=	MlvmQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjVyNke3PFcoRjJ3ME[3O\|g4RC:jPh?=
ACHN	MXvGeY5kfGmxbjDBd5NigQ>?	MoXMOUDPxE1?	NFTa[3Y1QCCq	MXTEUXNQ	NX3DNGRzcW6mdXPld{BxPTNvZHXw[Y5l\W62IIPlcoV{[2WwY3ZCpC=>	M{m1[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3ME[3O\|g4Lz5{NUC2O\|c5PzxxYU6=
115	M1nsPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NEXxRXU2KM7:TR?=	MUG0PEBp	NG\PPYRFVVOR	M2LSeolv\HWlZYOgZ4VtdCCleXPs[UBienKnc4VCpC=>	NVe4UWhJRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWwOlc4QDdpPkK1NFY4Pzh5PD;hQi=>
A498	MnTRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M2nvS\|Uh\|ryP	NETwemU1QCCq	MYDEUXNQ	NGPWUlhqdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0xsA>	M4\sNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3ME[3O\|g4Lz5{NUC2O\|c5PzxxYU6=
Caki-2	NXfYRVZwT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NWi2PJU2PSEQvF2=	NUPiNGxMPDhiaB?=	NEjvdpVFVVOR	MVLpcoR2[2W\|IHPlcIwh[3mlbHWgZZJz\XO2wrC=	MkL6QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjVyNke3PFcoRjJ3ME[3O\|g4RC:jPh?=
ACHN	NUTD[mNjT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MorSOUDPxE1?	MUm0PEBp	NUXRRYNtTE2VTx?=	MYDpcoR2[2W\|IHPlcIwh[3mlbHWgZZJz\XO2wrC=	MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTB4N{e4O{c,OjVyNke3PFc9N2F-
115	MUjGeY5kfGmxbjDBd5NigQ>?	M2jOWVAvPS9zL{Wg{txO	M1:1NlQ5KGh?	MX3EUXNQ	M4O0fIxm[WS\|IITvJIlv[3KnYYPl[EBmgHC{ZYPzbY9vKG:oIIC1N{BidmRic3;t[UBxPTNidHHy[4V1KGenbnXzPkBOTE1{LDDhcoQheDJz	NHL3bIo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUC2O\|c5Pyd-MkWwOlc4QDd:L3G+
A498	NYDBcYQxTnWwY4Tpc44hSXO\|YYm=	M2fSdVAvPS9zL{Wg{txO	MmrkOFghcA>?	NGnpT4tFVVOR	NXXq[5JJdGWjZIOgeI8hcW6lcnXhd4VlKGW6cILld5Nqd25ib3[gdFU{KGGwZDDzc41mKHB3MzD0ZZJo\XRiZ3Xu[ZM7KE2GTUKsJIFv\CCyMkG=	NIP2SYM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUC2O\|c5Pyd-MkWwOlc4QDd:L3G+
Caki-2	MUHGeY5kfGmxbjDBd5NigQ>?	MUewMlUwOS93IN88US=>	NUDadJJGPDhiaB?=	M2HFPGROW09?	NHr2NoVt\WGmczD0c{BqdmO{ZXHz[YQh\XiycnXzd4lwdiCxZjDwOVMh[W6mIIPvcYUheDV\|IIThdodmfCCpZX7ld\|ohVUSPMjygZY5lKHB{MR?=	MnHsQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjVyNke3PFcoRjJ3ME[3O\|g4RC:jPh?=
ACHN	MoLESpVv[3Srb36gRZN{[Xl?	NGXWWI4xNjVxMT:1JO69VQ>?	MVy0PEBp	M1PVT2ROW09?	MlPucIVi\HNidH:gbY5kemWjc3XkJIV5eHKnc4Ppc44hd2ZicEWzJIFv\CC\|b33lJJA2OyC2YYLn[ZQh\2WwZYO6JG1FVTJuIHHu[EBxOjF?	MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTB4N{e4O{c,OjVyNke3PFc9N2F-
117	NGLDcZVE\WyuIG\pZYJqdGm2eTDBd5NigQ>?	MoHFNE42NTFyIN88US=>	NIHoN\|MxNTZiZB?=	MYDEUXNQ	M1;rT4lvcGmkaYTzJJBzd2yrZnXyZZRqd25iaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XJ?	NXzPNW9uRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWwOlc4QDdpPkK1NFY4Pzh5PD;hQi=>
115	MlnsR4VtdCCYaXHibYxqfHliQYPzZZk>	NF2wU40xNjVvMUCg{txO	MVqwMVYh\A>?	NGT1OGJFVVOR	NXHZd5h2cW6qaXLpeJMheHKxbHnm[ZJifGmxbjDpckBiKGSxc3Wt[IVx\W6mZX70JI1idm6nch?=	Mof0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjVyNke3PFcoRjJ3ME[3O\|g4RC:jPh?=
A498	NHq5XIlE\WyuIG\pZYJqdGm2eTDBd5NigQ>?	NIf2dlExNjVvMUCg{txO	MoP4NE03KGR?	MoLxSG1UVw>?	NFjWUVJqdmirYnn0d{Bxem:uaX\ldoF1cW:wIHnuJIEh\G:\|ZT3k[ZBmdmSnboSgcYFvdmW{	NEHtXWk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUC2O\|c5Pyd-MkWwOlc4QDd:L3G+
Caki-2	MXrD[YxtKF[rYXLpcIl1gSCDc4PhfS=>	MUSwMlUuOTBizszN	M{TnUlAuPiCm	M3zENmROW09?	NIfWcWhqdmirYnn0d{Bxem:uaX\ldoF1cW:wIHnuJIEh\G:\|ZT3k[ZBmdmSnboSgcYFvdmW{	NUe5b\|ZjRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWwOlc4QDdpPkK1NFY4Pzh5PD;hQi=>
ACHN	NF3QdHVE\WyuIG\pZYJqdGm2eTDBd5NigQ>?	MXOwMlUuOTBizszN	NXXyRWVTOC14IHS=	M1jUVGROW09?	NFjjVotqdmirYnn0d{Bxem:uaX\ldoF1cW:wIHnuJIEh\G:\|ZT3k[ZBmdmSnboSgcYFvdmW{	M3fwUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3ME[3O\|g4Lz5{NUC2O\|c5PzxxYU6=
MCF7	MX\GeY5kfGmxbjDBd5NigQ>?	NFvhXmkzNjViwsXN	Mlv5OFghcA>?	NFf6TG5FVVOR	MVLk[YNz\WG\|ZYOgeIhmKGixbX;sc4dwfXNiRGPCJJJmeGGrcjDmdoVyfWWwY3nldy=>	MmL4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjVyOEW5NFIoRjJ3MEi1PVAzRC:jPh?=
MCF7	NVHpNVZVS2WubDDWbYFjcWyrdImgRZN{[Xl?	MnfBNk42KML3TR?=	NWLTfIt[PSCm	M3flcmROW09?	MXTz[Y5{cXSrenXzJG1ETjdidH:gVGFTWCCrbnjpZol1cW:w	NYDBe5oxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWwPFU6ODJpPkK1NFg2QTB{PD;hQi=>
RAW 264.7	NGnNUlBHfW6ldHnvckBCe3OjeR?=	MmS1NVDDqM7:TR?=	MYGzNEBucW5?		NUT6dmRCcW6qaXLpeJMhVFCVLXnu[JVk\WRiTl:gdJJw\HWldHnvcuKh	Mn\EQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjVzN{K1OFcoRjJ3MUeyOVQ4RC:jPh?=
RAW 264.7	MoLSSpVv[3Srb36gRZN{[Xl?	MlTCNVDDqM7:TR?=	NXjtfotwOzBibXnu		M1PVUJJm\HWlZYOgeIhmKEySUz3heYdu\W62ZXSgeIhmKE6ILd86RkBtfWOrZnXyZZNmKHKncH;yeIVzKGenbnWgZYN1cX[rdIm=	MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTF5MkW0O{c,OjVzN{K1OFc9N2F-
RAW 264.7	NYXEVHNKTnWwY4Tpc44hSXO\|YYm=	NV;tUmltOTEEoN88US=>	NYThOIVMOzBibXnu		M1fnRpBz\X[nboTzJJRp\SCyNUOgdoVlfWO2aX;uJIlvKHKnc4DvcpNmKHSxIFzQVy=>	NVTPfmpLRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWxO\|I2PDdpPkK1NVczPTR5PD;hQi=>
SUM102PT	NFruOpRHfW6ldHnvckBCe3OjeR?=	M3zPdFExyqEQvF2=	M1rCOFI1KGh?	NEf0XWdFVVOR	NE\Kb4NqdmirYnn0d{AhXEeILd8yN{1qdmS3Y3XkJGVRUEJ{wrDtVm5CKGGwZDDwdo91\WmwIHX4dJJme3Orb36=	MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTJ3N{eyPUc,OjV{NUe3Nlk9N2F-
SK-BR-7	NYrDbXN4TnWwY4Tpc44hSXO\|YYm=	NYjKRoFDOTEEoN88US=>	NEfhPZAzPCCq	NH3zdnVFVVOR	MnThbY5pcWKrdIOgJHRITi4QskOtbY5lfWOnZDDFVGhDOsLibWLORUBidmRicILveIVqdiCneIDy[ZN{cW:w	M4TCRlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MkW3O\|I6Lz5{NUK1O\|czQTxxYU6=
MCF-10CA1a	MV7GeY5kfGmxbjDBd5NigQ>?	MXyxNOKh\|ryP	MV6yOEBp	NEnN[GJFVVOR	M3nOeolvcGmkaYTzJEBVT0ZvzsKzMYlv\HWlZXSgSXBJSjMEoH3SUmEh[W6mIIDyc5RmcW5iZYjwdoV{e2mxbh?=	MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTJ3N{eyPUc,OjV{NUe3Nlk9N2F-
MCF-10CA1a	MlHCSpVv[3Srb36gRZN{[Xl?	M13ITVExyqEQvF2=	MkW0NlQhcA>?	MXLEUXNQ	NVjSR29u\GWlcnXhd4V{KHSqZTDUS2Yu\|rJ\|LXnu[JVk\WRibWLORUBt\X[nbIOgc4ZOVVB{LNMgUW1RQSxiYX7kxsBqdnSnZ4LpcuKh\|rMEoEO=	M120TlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MkW3O\|I6Lz5{NUK1O\|czQTxxYU6=
MCF-10A1	MlTESpVv[3Srb36gRZN{[Xl?	NH:xdYIyOMLizszN	M1u5R\|I1NzR6IHi=	M1LmXGROW09?	M2XsZ4lvcGmkaYTzJI1q\3KjdHnvckBw\iCwb4LtZYwh[nKnYYP0JIVxcXSqZXzpZYzDqA>?	M{HpOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MkW3O\|I6Lz5{NUK1O\|czQTxxYU6=
MCF-10CA1a	NY\ENXF4TnWwY4Tpc44hSXO\|YYm=	NWDrdGhvOTEEoN88US=>	NVvaOndiPDhiaB?=	MofLSG1UVw>?	NYLEU3NScW6qaXLpeJMh[mG\|YXygbY53[XOrb36gZY5lKHKnZIXj[YQhXEeILd8yN{1qdmS3Y3XkJIlvfmG\|aX;uJJRwKGKjc3HsJIxmfmWucx?=	MnvIQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV{NUe3NlkoRjJ3MkW3O\|I6RC:jPh?=
HCT116	NUnnVmc3TnWwY4Tpc44hSXO\|YYm=	NFHEeoYyOCEEtV2=	MVKyOEBp		NUmyb5Q5[2G3c3XzJIEheDV\|LXTldIVv\GWwdDD0[ZRz[XCub3nkJGcyNWG{cnXzeEBqdiCmaYDsc4llKEiFVEGxOkBkdG:wZYOgSFMh[W6mIFS4	MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTN6MEC1OUc,OjV\|OECwOVU9N2F-
A2780	MVPGeY5kfGmxbjDBd5NigQ>?	NIfGVVUyOMLizszN	M3T1cVIycMLi	NYLD[Xh6TE2VTx?=	NYnicZdI\GWlcnXhd4V{KHSqZTDGc5hOOSCuZY\lcJM>	NFH5R2c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUSyOlU1QCd-MkW0NlY2PDh:L3G+
NCI-H23	NUnKWXUxTnWwY4Tpc44hSXO\|YYm=	M3PhSlExyqEQvF2=	M{TaWFIycMLi	MVzEUXNQ	M1LCdoRm[3KnYYPld{B1cGViRn;4UVEhdGW4ZXzz	M17jV\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NEK2OVQ5Lz5{NUSyOlU1QDxxYU6=
A2780	M2XGfWZ2dmO2aX;uJGF{e2G7	MXKxNOKh\|ryP	MXOyNYjDqA>?	MX\EUXNQ	NXnYb\|Y2cW6lcnXhd4V{KHB3MzDwdo91\WmwIHzleoVtew>?	NVzDN3V[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW0NlY2PDhpPkK1OFI3PTR6PD;hQi=>
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SW620	NVTTVXZDS3m2b4TvfIlkcXS7IHHzd4F6		MoOyO\|IhcHK\|		NVjLb3hpS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hW1d4MkCgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KFOUQjDhd5NigSxiSVO1NEA:KDBwM{ig{txONg>?	Mmj4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVkyOzN2Lze+R4hGVUKOPD;hQi=>
A549	NIPPNHhEgXSxdH;4bYNqfHliYYPzZZk>		NIm1PVM4OiCqcoO=		M3vMb2N6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGE2PDliY3XscJMh[W[2ZYKgO\|IhcHK\|IHL5JHNTSiCjc4PhfUwhUUN3MDC9JFAvPDFizszNMi=>	MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPVE{OzRxJ{7DbGVOSkx:L3G+
SJSA1	NWHqUnZES3m2b4TvfIlkcXS7IHHzd4F6		NEfoR5o4OiCqcoO=		M1L5bWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJHNLW0FzIHPlcIx{KGGodHXyJFczKGi{czDifUBUWkJiYYPzZZktKEmFNUCgQUAyNjhzIN88UU4>	NX[0[FM4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTlzM{O0M{c,S2iHTVLMQE9iRg>?
HCT116	NFnmfWtEgXSxdH;4bYNqfHliYYPzZZk>		NFG1RoU4OiCqcoO=		NF;x[ZpEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBJS1RzMU[gZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KFOUQjDhd5NigSxiSVO1NEA:KDRwNkOg{txONg>?	MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPVE{OzRxJ{7DbGVOSkx:L3G+
PC3	NYLmZ\|JvS3m2b4TvfIlkcXS7IHHzd4F6		NFT6PY04OiCqcoO=		NYPae49US3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hWEN\|IHPlcIx{KGGodHXyJFczKGi{czDifUBUWkJiYYPzZZktKEmFNUCgQUA3NjN5IN88UU4>	NIrVWYo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQTF\|M{SvK\|5EcEWPQly8M4E,

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	MDM2 / p53 / ALKBH2 / p21 / PUMA; PubMed: 23258843 Neuro Oncol CCF-STTG1 cells were treated with the MDM2 antagonist nutlin-3 (0–8 µM) for 24h before cell lysates were collected for western blotting. RRM1 / RRM2 / p53R2 / p21 / p53 / pS6 / S6; PubMed: 28507282 Oncotarget (A) Rh18 cells were treated with different concentrations of nutlin-3 as indicated for 24 hr. Total proteins were extracted for immunoblotting of RRM1, RRM2, γH2AX, p21, p53R2, p53, S6, pS6-235/6 and 4E-BP1. (B) Rh30 cells were treated with different concentrations of nutlin-3 as indicated for 24 hr. Total proteins were extracted for immunoblotting of RRM1, RRM2, γH2AX, p21, p53R2, p53, S6, pS6-235/6 and 4E-BP1. GAPDH and Actin served as loading controls.	23258843 28507282
Immunofluorescence	Lamin A / Lamin C / p16 / H3K9me3; PubMed: 30728349 Cell Death Dis c Immunofluorescence images of nuclear deformation and p16 expression after Nutlin-3 treatment for different time period. HCT p53+/− cells were treated with Nutlin-3 (1 μM) for different time (24, 48 h). After treatment, cells were subjected to immunofluorescence staining for Lamin A/C (Red), p16 (Green), and counterstained with DAPI (Blue). dImmunofluorescence images of nuclear deformation and decreased expression of H3K9me3 in HCT p53+/− cells (left). Counting of histone H3K9me3-positive cells (middle) and signal intensities (right) on the basis of IF staining. HCT p53+/− cells were treated with Nutlin-3 (1 μM) for different time (24, 48 h). After treatment, cells were IF stained with Lamin A/C (Red), H3K9me3 (Green), and counterstained with DAPI (Blue). *P < 0.05. Merlin / cyclin D1 / p53 / MDM2; PubMed: 30274821 EBioMedicine The changes in the subcellular localization of proteins in response to Nutlin-3. Nuclear merlin was indicated with white arrows. Scale bar = 50 μm. p53; PubMed: 24286312 BMB Rep The subcellular localization of p53 was detected under immunofluorescence microscope (1,000×). The cells were treated as indicated and stained for p53 (red). Nuclei were counterstained with DAPI (blue).	30728349 30274821 24286312
Growth inhibition assay	Cell viability; PubMed: 29286113 Mol Med Rep Inhibitory effect of nutlin-3 for the cell proliferation after cultivate cells at different concentration for three times (24, 48 and 72 h), respectively.	29286113

体内研究

Nutlin-3 按200 mg/kg 剂量口服处理，每天两次，持续3周，显著抑制SJAS-1移植瘤生长，抑制达90%, 而Doxorubicin抑制81%肿瘤生长。^[1]

激酶实验： ^[1]	- 合并 Biacore 研究: 在Biacore S51上进行竞争性实验。衍生一系列S传感器芯片CM5，用于固定 PentaHis抗体，为了捕获 His-标记的p53。捕获的水平为~200反应单位(1 反应单位对应于1 pg 蛋白/ mm²)。MDM2蛋白浓度一直维持在300 nM。Nutlin-3 溶于DMSO，浓度为10 mM，然后进一步稀释，在每个MDM2实验样本中产生系列浓度的Nutlin-3。在电泳缓冲液(10 mM Hepes,0.15 M NaCl, 2% DMSO)中25^oC下进行实验。在Nutlin-3存在时，计算MDM2-p53结合情况，作为结合百分数，使用Microsoft Excel计算IC50。
细胞实验： ^[1]	- 合并 Cell lines: HCT116, RKO, SJSA-1, SW480, 和 MDA-MB-435 Concentrations: 溶于DMSO,终浓度为~ 30 μM Incubation Time: 8, 24, 和 48 小时 Method: 使用不同浓度Nutlin-3处理细胞8, 24和 48 小时。通过实时PCR分析p21 和MDM2基因转录水平,通过Western Blotting分析蛋白水平。通过MTT实验测定细胞活力。通过末端脱氧核苷酸转移酶调节的脱氧尿苷三磷酸缺口末端标记法（TUNEL）染色，使用流式细胞仪和荧光显微镜测定细胞凋亡。 (Only for Reference)
动物实验： ^[1]	- 合并 Animal Models: 皮下注射 SJSA-1细胞的雌性无胸腺Nu/Nu-nuBR裸鼠 Dosages: 200 mg/kg Administration: 口服处理，每天两次 (Only for Reference)

参考文献

- 合并

溶解度 (25°C)

体外	DMSO	100 mg/mL (171.96 mM)
	Ethanol	30 mg/mL (51.59 mM)
	Water	Insoluble

* 溶解度检测是由Selleck技术部门检测的，可能会和文献中提供的溶解度有所差异，这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据 Download Nutlin-3 SDF

分子量	581.5
化学式	C₃₀H₃₀Cl₂N₄O₄
CAS号	890090-75-2
储存条件	3年-20°C 粉状 2年-80°C 溶于溶剂
别名	N/A

动物体内配方计算器 (澄清溶液)

第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量）

给药剂量

mg/kg

动物平均体重

每只动物给药体积

动物数量

只

第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系Selleck为您提供正确的澄清溶液配方）

% DMSO+ % + % Tween 80+ % ddH₂O

计算重置

计算结果:

工作液浓度： mg/ml；

DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；

体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL ddH₂O，混匀澄清。

注意：1. 首先保证母液是澄清的；
2. 一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。

计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为:

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

质量

浓度

体积

分子量
=

×

×

*在配置溶液时，请务必参考Selleck产品标签上、SDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。

稀释计算器

用本工具协助配置特定浓度的溶液，使用的计算公式为：

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入输出 )

C1

V1

C2

V2
×

=

×

在配置溶液时，请务必参考Selleck产品标签上、SDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。.

连续稀释计算器方程

连续稀释
初始浓度:
稀释倍数:

计算结果

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):

分子量计算器

通过输入化合物的化学式来计算其分子量：

注：化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量	浓度	体积	分子量
=	×	×
计算

技术支持

在订购、运输、储存和使用我们的产品的任何阶段，您遇到的任何问题，均可以通过拨打我们的热线电话400-668-6834，或者技术支持邮箱tech@selleck.cn，直接联系到我们。我们会在24小时内尽快联系您。

操作手册

如果有其他问题，请给我们留言。

常见问题及建议解决方法

问题 1：
Is this a racemic mixture of Nutlin-3a and Nutlin-3b or just the Nutlin-3a enantiomer?
回答：
It is a racemate.

研究领域

产品类型

定制您的化合物库

Nutlin-3

客户使用Selleck生产的Nutlin-3发表文献77篇：

产品安全说明书

Mdm2抑制剂选择性比较

生物活性

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

参考文献

溶解度 (25°C)

化学数据 Download Nutlin-3 SDF

动物体内配方计算器 (澄清溶液)

计算器

摩尔浓度计算器

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

稀释计算器

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

连续稀释计算器方程

连续稀释

计算结果

分子量计算器

总分子量：g/mol

摩尔浓度计算器

技术支持

常见问题及建议解决方法

Mdm2 Signaling Pathway Map

相关Mdm2产品