Alvespimycin (17-DMAG) HCl

Name: Alvespimycin (17-DMAG) HCl
Brand: Selleck Chemicals
SKU: S1142
Rating: 5 (50 reviews)

For research use only.

Catalog No.S1142 Synonyms: NSC 707545,BMS 826476 HCl,KOS 1022

50 publications

Alvespimycin (17-DMAG) HCl Chemical Structure

CAS No. 467214-21-7

Alvespimycin (17-DMAG, NSC 707545, BMS 826476, KOS 1022) HCl is a potent HSP90 inhibitor with IC50 of 62 nM in a cell-free assay. Phase 2.

Selleck's Alvespimycin (17-DMAG) HCl has been cited by 50 publications

Sci Adv, 2021, 7(7)eabd2645

PubMed: 33579708 ( click the link to review the publication )

J Virol, 2021, JVI0059421

PubMed: 34037421 ( click the link to review the publication )

Transl Oncol, 2021, 14(1):100982

PubMed: 33395748 ( click the link to review the publication )

Nat Commun, 2020, 22;11(1):1935

PubMed: 32321921 ( click the link to review the publication )

Aging Cell, 2020, e13269

PubMed: 33145977 ( click the link to review the publication )

Cancers (Basel), 2020, 12(11)E3335

PubMed: 33187254 ( click the link to review the publication )

Cancers (Basel), 2020, 12(9)E2630

PubMed: 32942617 ( click the link to review the publication )

J Mol Cell Biol, 2020, 24;12(3):216-229

PubMed: 31408169 ( click the link to review the publication )

Hum Mutat, 2020, 10.1002/humu.24147

PubMed: 33252173 ( click the link to review the publication )

Front Oncol, 2020, 10:117

PubMed: 32117764 ( click the link to review the publication )

Life Sci, 2020, 15;249:117532

PubMed: 32151689 ( click the link to review the publication )

J Bioenerg Biomembr, 2020, 15

PubMed: 32291605 ( click the link to review the publication )

Theranostics, 2020, 10(18):8415-8429

PubMed: 32724478 ( click the link to review the publication )

Yonsei Med J, 2020, 61(7):587-596

PubMed: 32608202 ( click the link to review the publication )

Nat Commun, 2019, 10(1):3562

PubMed: 31395886 ( click the link to review the publication )

Mol Cancer Ther, 2019, 18(11):2097-2110

PubMed: 31395684 ( click the link to review the publication )

Mol Pharm, 2019, 16(5):2069-2082

PubMed: 30916978 ( click the link to review the publication )

Nan Fang Yi Ke Da Xue Xue Bao, 2019, 39(2):169-174

PubMed: 30890504 ( click the link to review the publication )

Hepatology, 2019, 69(2):573-586

PubMed: 29356025 ( click the link to review the publication )

Nat Commun, 2018, 9(1):4296

PubMed: 30327466 ( click the link to review the publication )

Nat Commun, 2018, 9(1):672

PubMed: 29445180 ( click the link to review the publication )

Mol Syst Biol, 2018, 14(3):e7858

PubMed: 29507054 ( click the link to review the publication )

Biomed Pharmacother, 2018, 105:1026-1032

PubMed: 30021337 ( click the link to review the publication )

Nat Commun, 2017, 8(1):422

PubMed: 28871086 ( click the link to review the publication )
Mol Cancer Ther, 2017,

PubMed: 28619760 ( click the link to review the publication )

Int J Biol Sci, 2017, 13(4):505-517

PubMed: 28529458 ( click the link to review the publication )

Experimental Cell Research, 2017, 353(1):46-53

PubMed: 28279658 ( click the link to review the publication )

Am J Transl Res, 2017, 9(11):4945-4953

PubMed: 29218092 ( click the link to review the publication )

Cell Death Dis, 2016, 7(6):e2290

PubMed: 27362807 ( click the link to review the publication )

Sci Rep, 2016, 6:19004

PubMed: 26743233 ( click the link to review the publication )

Sci Rep, 2016, 6:38072

PubMed: 27909289 ( click the link to review the publication )

J Biol Chem, 2016,

PubMed: 27489107 ( click the link to review the publication )

Cell Stress Chaperones, 2016, 21(2):339-48

PubMed: 26786409 ( click the link to review the publication )

Medicinal Chemistry Research, 2016, 10.1007/s00044-016-1553-7

PubMed: ( click the link to review the publication )

Viruses, 2016, 8(11)

PubMed: 27801778 ( click the link to review the publication )

Oncotarget, 2016, 7(1):433-45

PubMed: 26595521 ( click the link to review the publication )

Molecules, 2015, 20(1):1643-60

PubMed: 25608045 ( click the link to review the publication )

Immunopharmacol Immunotoxicol, 2015, 8:1-10

PubMed: 26642940 ( click the link to review the publication )

Oncotarget, 2015, 6(14):12128-40

PubMed: 25900240 ( click the link to review the publication )

PLoS One, 2014, 9(12):e114000

PubMed: 25486409 ( click the link to review the publication )

Oncotarget, 2014, 5(13):4920-8

PubMed: 24952482 ( click the link to review the publication )

Zhongguo Fei Ai Za Zhi, 2014, 17(11):778-82

PubMed: 25404267 ( 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 )

Hepatology, 2013, 57(1):70-80

PubMed: 22898980 ( click the link to review the publication )

Mol Oncol, 2013, 7(6):1093-102

PubMed: 23993685 ( click the link to review the publication )

FEBS J, 2013, 10.1111/febs.12672

PubMed: 24304935 ( click the link to review the publication )

PLoS One, 2013, 8(4):e59315

PubMed: 23565147 ( click the link to review the publication )

Tumour Biol, 2013, 35(4):3229-35

PubMed: 24293393 ( click the link to review the publication )
J Thorac Oncol, 2012, 7(7):1078-85

PubMed: 22592212 ( click the link to review the publication )

Eukaryot Cell, 2012, 11(11):1324-32

PubMed: 22822234 ( click the link to review the publication )

Purity & Quality Control

Choose Selective HSP (HSP90) Inhibitors

Biological Activity

Description

Alvespimycin (17-DMAG, NSC 707545, BMS 826476, KOS 1022) HCl is a potent HSP90 inhibitor with IC50 of 62 nM in a cell-free assay. Phase 2.

Features

A synthetic derivative Geldanamycin, with lower hepatotoxicity than parent antibiotic & higher potency and bioavailability than the similar derivative 17-AAG.

Targets

HSP90 ^[1]
(Cell-free assay)

62 nM

In vitro

17-DMAG displays ~2 times potency against human Hsp90 than 17-AAG, with IC50 of 62 nM versus 119 nM. In SKBR3 and SKOV3 cells which over-express Hsp90 client protein Her2, 17-DMAG causes down-regulation of Her2 with EC50 of 8 nM and 46 nM, respectively, as well as induction of Hsp70 with EC50 of 4 nM and 14 nM, respectively, leading to significant cytotoxicity with GI50 of 29 nM and 32 nM, respectively, consistent with Hsp90 inhibition. ^[1] 17-DMAG in combination with vorinostat synergistically induces apoptosis of the cultured MCL cells as well as primary MCL cells, more potently than either agent alone, by markedly attenuating the levels of cyclin D1 and CDK4, as well as of c-Myc, c-RAF and Akt. ^[3] In contrast to 17-AAG which is only active for IKKβ in chronic lymphocytic leukemia (CLL) cells, 17-DMAG treatment effectively leads to depletion of the Hsp90 client protein, resulting in diminished NF-κB p50/p65 DNA binding, decreased NF-κB target gene transcription, and caspase-dependent apoptosis. By targeting the NF-κB family, 17-DMAG selectively mediates dose- and time-dependent cytotoxicity against CLL cells, but not normal T cells or NK cells important for immune surveillance. ^[5]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
SKBr3	MmrRR5l1d3SxeHnjbZR6KGG\|c3H5			M3HjS2N6fG:2b4jpZ4l1gSCjZ3HpcpN1KFONQoKzJINmdGy\|LDDJR\|UxRTBwMEK0{txONg>?	NFT2VXU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zNkG2OVM2PCd-MU[xOlU{PTR:L3G+
SKBR3	M2rrOmZ2dmO2aX;uJIF{e2G7			MUDVdJJm\3WuYYTpc44hd2ZiSIPwO\|AhcW5iU1vCVlMh[2WubIOsJGVEPTB;MD6wNFTPxE1w	NVjydnNqRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMU[4OVQxPjZpPkG2PFU1ODZ4PD;hQi=>
SKBR3	M3;4UWZ2dmO2aX;uJIF{e2G7			M4nBS2Rm\3KjZHH0bY9vKG:oIFjldlIhcW5iU1vCVlMh[2WubIOsJGVEPTB;MD6wNFjPxE1w	MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPjh3NEC2Okc,OTZ6NUSwOlY9N2F-
SKOV3	MVfGeY5kfGmxbjDhd5NigQ>?			NWXxd\|ZsXXC{ZXf1cIF1cW:wIH;mJGh{eDdyIHnuJHNMV1Z\|IHPlcIx{NCCHQ{WwQVAvODF2zszNMi=>	NEPGc\|g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zNki1OFA3Pid-MU[4OVQxPjZ:L3G+
SKOV3	NUPQR\|Y2TnWwY4Tpc44h[XO\|YYm=			NUDkfpFITGWpcnHkZZRqd25ib3[gTIVzOiCrbjDTT29XOyClZXzsd{whTUN3ME2wMlA1Ps7:TT6=	MmP5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTZ6NUSwOlYoRjF4OEW0NFY3RC:jPh?=
AGS	MnrBSpVv[3Srb36gZZN{[Xl?		MlzENVYhcHK\|	M4HCdWlvcGmkaYTpc44hd2ZiSFnGNUBi[3SrdnH0bY9vKGmwIHj1cYFvKEGJUzDj[YxteyCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKGi7cH;4bYEucW6mdXPl[EBtfWOrZnXyZZNmKGW6cILld5Nqd25iYX\0[ZIhOTZiaILzJIJ6KHKncH;yeIVzKGG\|c3H5MEBKSzVyPUCuNFM3\|ryPLh?=	M4TCflxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF5NUizPVUxLz5zN{W4N\|k2ODxxYU6=
Hep3B	MXfGeY5kfGmxbjDhd5NigQ>?		NGiwPGwyPiCqcoO=	M1jXR2lvcGmkaYTpc44hd2ZiSFnGNUBi[3SrdnH0bY9vKGmwIHj1cYFvKEincEPCJINmdGy\|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiaInwc5hq[S2rbnT1Z4VlKGy3Y3nm[ZJie2ViZYjwdoV{e2mxbjDh[pRmeiBzNjDodpMh[nlicnXwc5J1\XJiYYPzZZktKEmFNUC9NE4xPjIQvF2u	NEjn[mg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zN{W4N\|k2OCd-MUe1PFM6PTB:L3G+
AGS	M4DDN2Z2dmO2aX;uJIF{e2G7		NEjPUZYzPCCqcoO=	NFT2VXRXcWGkaXzpeJkhd2ZiaIXtZY4hSUeVIHPlcIx{KHWwZHXyJI5wem2xeHnjJINwdmSrdHnvcpMh[W[2ZYKgNlQhcHK\|IHL5JG1VXCCjc4PhfUwhUUN3ME2xOu69VS5?	M3\MTVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF5NUizPVUxLz5zN{W4N\|k2ODxxYU6=
NCI-H526	M4jpN2Z2dmO2aX;uJIF{e2G7	M1;1U\|EhfU1?	Mk\vNlQhcHK\|	MYPCbY5lcW6pIHHm[olvcXS7IITvJGhUWDlyIHnuJIh2dWGwIF7DTU1JPTJ4IHPlcIx{KGG2IEGgeW0h[W[2ZYKgNlQhcHK\|IHL5JIZtfW:{ZYPj[Y5k\SCyb3zhdol7[XSrb36gZZN{[Xl?	Mnn1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTd4MEO1OFAoRjF5NkCzOVQxRC:jPh?=
NCI-H526	NGW1OmRHfW6ldHnvckBie3OjeR?=	M4HJZVEhfU1?	Mlq0PVYhcHK\|	M1T4OGlvcGmkaYTpc44hd2ZiSGPQPVAudWWmaXH0[YQheHKxbHnm[ZJifGmxbjDv[kBpfW2jbjDOR2kuUDV{NjDj[YxteyCjdDCxJJVOKGGodHXyJFk3KGi{czDifUB{fWyob4Loc4RidWmwZTDCJIF{e2G7	MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPzZyM{W0NEc,OTd4MEO1OFA9N2F-
AGS	NHq4eWFHfW6ldHnvckBie3OjeR?=			NHHOXVNKdmirYnn0bY9vKG:oIHj5dI95cWFvaX7keYNm\CCKSV[xJIFkfGm4YYTpc44hcW5iaIXtZY4hSUeVIHPlcIx{KGK7IILldI9zfGW{IHflcoUh[XO\|YYmsJGlEPTB;MD6wNFM3\|ryPLh?=	NV\oSI5rRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUizOVk3OzFpPkG4N\|U6PjNzPD;hQi=>
HeLa	M2DDc2Z2dmO2aX;uJIF{e2G7			MlPjTY5pcWKrdHnvckBw\iCWTl[tZYxxcGFvaX7keYNm\CCQRj3rZZBx[UJiYXP0bZZifGmxbjDpckBpfW2jbjDI[WxiKGOnbHzzMEBKSzVyPUCuNVXPxE1w	NETWcYE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEO1PVY{OSd-MUizOVk3OzF:L3G+
HeLa	MUHDfZRwfG:6aXPpeJkh[XO\|YYm=			NWrlbZZGS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hUGWOYTDj[YxteyCkeTDNWHQh[XO\|YYmsJGlEPTB;Mj6wOu69VS5?	M{DsVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6M{W5OlMyLz5zOEO1PVY{OTxxYU6=
AGS	NHP4dppEgXSxdH;4bYNqfHliYYPzZZk>			NGLUNZpEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBCT1NiY3XscJMh[nliTWTUJIF{e2G7LDDJR\|UxRTF4zszNMi=>	NUK4SZBWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUizOVk3OzFpPkG4N\|U6PjNzPD;hQi=>
A2058	MmDYR5l1d3SxeHnjbZR6KGG\|c3H5			MUfDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDBNlA2QCClZXzsd{BjgSCPVGSgZZN{[XluIFnDOVA:OC5yMEKx{txONg>?	MnHYQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh7Mkm0PFYoRjF6OUK5OFg3RC:jPh?=
MDA-MB-231	M{TVb2Z2dmO2aX;uJIF{e2G7			MX7Jcohq[mm2aX;uJI9nKEi\|cEmwJIlvKGi3bXHuJG1FSS2PQj2yN\|Eh[2WubIOgZZN{\XO\|ZXSgZZMhcGW{MjDk[Ydz[WSjdHnvckwhUUN3ME2wMlAxPDYQvF2u	M1[y[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6OUK5OFg3Lz5zOEmyPVQ5PjxxYU6=
MDA-MB-231	MWfDfZRwfG:6aXPpeJkh[XO\|YYm=			M3q5WGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJG1FSS2PQj2yN\|Eh[2WubIOgZpkhVVSWIHHzd4F6NCCLQ{WwQVAvODB3ON88UU4>	M4jmelxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6OUK5OFg3Lz5zOEmyPVQ5PjxxYU6=
A2058	NWC1WpZpTnWwY4Tpc44h[XO\|YYm=			MmLKTY5pcWKrdHnvckBw\iCKc4C5NEBqdiCqdX3hckBCOjB3ODDj[YxteyxiRVO1NF0xNjByN{pOwG0v	MkfuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh7Mkm0PFYoRjF6OUK5OFg3RC:jPh?=
MDA-MB-231	NYXFZWJzTnWwY4Tpc44h[XO\|YYm=			NYf2UGpGUW6qaXLpeIlwdiCxZjDId5A6OCCrbjDoeY1idiCPRFGtUWIuOjNzIHPlcIx{KGG\|c3Xzd4VlKGG\|IFHreEBl\We{YXTheIlwdixiSVO1NF0xNjBzN{dOwG0v	NXfNcXM6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUi5Nlk1QDZpPkG4PVI6PDh4PD;hQi=>
A2058	M2PWRmZ2dmO2aX;uJIF{e2G7			M3PuUmlvcGmkaYTpc44hd2ZiSIPwPVAhcW5iaIXtZY4hSTJyNUigZ4VtdHNiYYPz[ZN{\WRiYYOgRYt1KGSnZ4Lh[IF1cW:wLDDJR\|UxRTBwMEK0N:69VS5?	MlrkQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh7Mkm0PFYoRjF6OUK5OFg3RC:jPh?=
HuH7	MkjyRY51cX[rcnHsJIF{e2G7		MVKzJIRigXN?	MnuzRY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTIVx[XSrdHnzJGMhfmm{dYOg[4Vvd3S7cHWgNYIhS2:wMTDpcoZm[3SnZDDpckBpfW2jbjDIeWg4KGOnbHzzJIF{e2W\|c3XkJIF{KEeDUFTIJHJPSSCxcjCxPHMhelKQQTDs[ZZmdCCjZoTldkA{KGSjeYOgZpkheVKWLWDDVkBidmGueYPpd{whTUN3ME2wMlAxOTMQvF2u	M4TWNVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6OUO2NVkyLz5zOEmzOlE6OTxxYU6=
HuH7	Mnr6RY51cX[rcnHsJIF{e2G7		MUCzJIRigXN?	M33PfmFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGhmeGG2aYTpd{BEKH[rcoXzJIdmdm:2eYDlJFFjKEOxbkGgbY5n\WO2ZXSgbY4hcHWvYX6gTJVJPyClZXzsd{Bie3Onc4Pl[EBieyCJQWDETEBTVkFib4KgNVhUKHKUTlGgcIV3\WxiYX\0[ZIhOyCmYYnzJJNmdGWldHXkJJdqfGhiNECgcm0hUEOYLUe5OkBidmRiOECwJI5OKGKxY3XwdoV3cXJiYomgdXJVNVCFUjDhcoFtgXOrczygSWM2OD1yLkCwN\|HPxE1w	M3vSPVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6OUO2NVkyLz5zOEmzOlE6OTxxYU6=
SKBR3	NYfKfZYxTnWwY4Tpc44h[XO\|YYm=			M{LLSWJqdmSrbnegZYZncW6rdImgeI8hUHOyOUCgbY4hcHWvYX6gV2tDWjNiY3XscJMtKEmFNUC9NE4xOjUQvF2u	NXLW[4hXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUmwNVc2PjJpPkG5NFE4PTZ{PD;hQi=>
Hep3B	Mn\JSpVv[3Srb36gZZN{[Xl?		NXTaO5NpOzBibXnudy=>	M2jBPWlvcGmkaYTpc44hd2ZiaInwc5hq[S2rbnT1Z4VlKEiLRkHhcJBp[SCycn;0[YlvKGGlY4XteYxifGmxbjDpckBpfW2jbjDI[ZA{SiClZXzsd{B1emWjdHXkJIZweiB\|MDDtbY5{KG2nYYP1doVlKGGodHXyJFEzKGi{czDifUBY\XO2ZYLuJIJtd3RiYX7hcJl{cXNuIFnDOVA:OC5yNUey{txONg>?	M3;1V\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7MEeyNlE1Lz5zOUC3NlIyPDxxYU6=
Hep3B	MY\GeY5kfGmxbjDhd5NigQ>?		MkP2NVYhcHK\|	NUXwPIVOUW6qaXLpeIlwdiCxZjDofZBwgGmjLXnu[JVk\WRiVlXHSkBxem:2ZXnuJJNm[3KndHnvckBqdiCqdX3hckBJ\XB\|QjDj[YxteyCjZoTldkAyPiCqcoOgZpkhTUyLU1GsJGlEPTB;MD6wO\|k2\|ryPLh?=	NHWwZpQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUC3NlIyPCd-MUmwO\|IzOTR:L3G+
HCT116	NGLjW\|dEgXSxdH;4bYNqfHliYYPzZZk>		MX63NkBpenN?	M1fW[mN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGhEXDFzNjDj[YxteyCjZoTldkA4OiCqcoOsJGlEPTB;MD6wOVfPxE1w	MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTJ\|MUi2OEc,OTl{M{G4OlQ9N2F-
SKBR3	M365PWN6fG:2b4jpZ4l1gSCjc4PhfS=>		NICy[WY4OiCqcoO=	NFnnNWREgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBUU0KUMzDj[YxteyCjZoTldkA4OiCqcoOsJGlEPTB;MD6wOVjPxE1w	MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTJ\|MUi2OEc,OTl{M{G4OlQ9N2F-
MCF7	M2\YNWN6fG:2b4jpZ4l1gSCjc4PhfS=>		MnPGO\|IhcHK\|	MVXDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDNR2Y4KGOnbHzzJIFnfGW{IEeyJIhzeyxiSVO1NF0xNjB5Md88UU4>	NETyc5g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUKzNVg3PCd-MUmyN\|E5PjR:L3G+
SKOV3	MmHTR5l1d3SxeHnjbZR6KGG\|c3H5		MWS3NkBpenN?	NE\JVJREgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBUU0:YMzDj[YxteyCjZoTldkA4OiCqcoOsJGlEPTB;MD6xNlLPxE1w	NUj0XIhQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUmyN\|E5PjRpPkG5NlMyQDZ2PD;hQi=>
SKBR3	NEj0TINEgXSxdH;4bYNqfHliYYPzZZk>		M{XUcFczKGi{cx?=	M4rET2N6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJHNMSlJ\|IHPlcIx{KGGodHXyJFczKGi{czDpckBxemW\|ZX7j[UBw\iCQUV:xJIlvcGmkaYTvdkBlcWOxdX3hdo9tNCCLQ{WwQVAvOjQQvF2u	Mn;HQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTl{M{G4OlQoRjF7MkOxPFY1RC:jPh?=
MCF7	M1XrO2N6fG:2b4jpZ4l1gSCjc4PhfS=>		NVnXV5dRPzJiaILz	Moe1R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gUWNHPyClZXzsd{Bi\nSncjC3NkBpenNiaX6gdJJme2WwY3Wgc4YhVlGRMTDpcohq[mm2b4Kg[Ilkd3WvYYLvcEwhUUN3ME2wMlg3Os7:TT6=	MXK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTJ\|MUi2OEc,OTl{M{G4OlQ9N2F-
NCI-H596	NWnHVlg5S3m2b4TvfIlkcXS7IHHzd4F6		MUG3NkBpenN?	MWXDfZRwfG:6aXPpeJkh[WejaX7zeEBPWTBzLXTl[olkcWWwdDDoeY1idiCQQ1mtTFU6PiClZXzsd{Bi\nSncjC3NkBpenNuIFnDOVA:OS5zzszNMi=>	NUfRSJc2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUmyN\|E5PjRpPkG5NlMyQDZ2PD;hQi=>
MDA468	MonzR5l1d3SxeHnjbZR6KGG\|c3H5		MnTtO\|IhcHK\|	M3nOcGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KE6TMEGt[IVncWOrZX70JIh2dWGwIF3ERVQ3QCClZXzsd{Bi\nSncjC3NkBpenNuIFnDOVA:OS54zszNMi=>	NXXtNGpCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUmyN\|E5PjRpPkG5NlMyQDZ2PD;hQi=>
SKBR3	NGTTSWFEgXSxdH;4bYNqfHliYYPzZZk>		MkLaO\|IhcHK\|	MnLVR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gV2tDWjNiY3XscJMh[W[2ZYKgO\|IhcHK\|IHL5JINmdGy2aYTldk1odG9iYYPzZZktKEmFNUC9NE4xOjUQvF2u	MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTRyNUWyPEc,OTl2MEW1Nlg9N2F-
A549	NH3kbFNEgXSxdH;4bYNqfHliYYPzZZk>		MnzNO\|IhcHK\|	M{DPT2N6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGE2PDliY3XscJMh[W[2ZYKgO\|IhcHK\|IHL5JINmdGy2aYTldk1odG9iYYPzZZktKEmFNUC9NE4xPjkQvF2u	MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTRyNUWyPEc,OTl2MEW1Nlg9N2F-
SKOV3	Ml3rR5l1d3SxeHnjbZR6KGG\|c3H5		MkLKO\|IhcHK\|	MmfqR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gV2tQXjNiY3XscJMh[W[2ZYKgO\|IhcHK\|IHL5JINmdGy2aYTldk1odG9iYYPzZZktKEmFNUC9NE4zOs7:TT6=	NXuyNYlYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUm0NFU2OjhpPkG5OFA2PTJ6PD;hQi=>
MCF7	NWLmSIl5S3m2b4TvfIlkcXS7IHHzd4F6		NH7o[WI4OiCqcoO=	NYrhR5hlS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hVUOINzDj[YxteyCjZoTldkA4OiCqcoOgZpkh[2WubITpeIVzNWeubzDhd5NigSxiSVO1NF0xNjJ\|zszNMi=>	NIfpWJY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUSwOVUzQCd-MUm0NFU2Ojh:L3G+
CCRF-CEM	Mly3R5l1d3SxeHnjbZR6KGG\|c3H5		NI\UWnM4OiCqcoO=	MmXuR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gR2NTTi2FRV2gZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KGOnbHz0bZRmei17NjDhdZVmd3W\|IH;u[UB{d2y3dHnvckBie3OjeTygTWM2OD1yLkW0{txONg>?	MontQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTl2MEW1NlgoRjF7NEC1OVI5RC:jPh?=
CCRF-CEM	NHv0XpZEgXSxdH;4bYNqfHliYYPzZZk>		NUjLNmVVPzJiaILz	NX\OfndkS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4heGGlbHn0ZZhmdC2{ZYPpd5RidnRiQ1PSSk1ETU1iY3XscJMh[W[2ZYKgO\|IhcHK\|IHL5JINmdGy2aYTldk06PiCjcYXlc5V{KG:wZTDzc4x2fGmxbjDhd5NigSxiSVO1NF0zNjYQvF2u	NXro[mNuRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUm0NFU2OjhpPkG5OFA2PTJ6PD;hQi=>
Hep3B	NYjZdoVyTnWwY4Tpc44h[XO\|YYm=		NHLmS2c{OCCvaX7z	MU\Jcohq[mm2aX;uJI9nKGi7cH;4bYEucW6mdXPl[EBJUUZzYXzwbIEheHKxdHXpckBi[2O3bYXsZZRqd25iaX6gbJVu[W5iSHXwN2Ih[2WubIOgeJJm[XSnZDDmc5IhOzBibXnud{Bu\WG\|dYLl[EBi\nSncjCxNkBpenNiYomgW4V{fGW{bjDicI91KGGwYXz5d4l{NCCLQ{WwQVAvODV5zszNMi=>	Mo\LQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjB2Nkm4PFcoRjJyNE[5PFg4RC:jPh?=
Hep3B	NFj3cpZHfW6ldHnvckBie3OjeR?=		M1Hvc\|E3KGi{cx?=	MYDJcohq[mm2aX;uJI9nKGi7cH;4bYEucW6mdXPl[EBXTUeIIIDyc5RmcW5ic3XjdoV1cW:wIHnuJIh2dWGwIFjldFNDKGOnbHzzJIFnfGW{IEG2JIhzeyCkeTDFUGlUSSxiSVO1NF0xNjB5Od88UU4>	NIi0PIo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MES2PVg5Pyd-MkC0Olk5QDd:L3G+
HCT116	MXLDfZRwfG:6aXPpeJkh[XO\|YYm=			NGfuNHBEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBJS1RzMU[gZ4VtdHNiYomgRYxidWG{IHLseYUh[XO\|YYmsJGlEPTB;MD6wOe69VS5?	MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zODZ4MkWzOEc,OjB4NkK1N\|Q9N2F-
NCI-H1299	M{DqRWZ2dmO2aX;uJIF{e2G7		NIXvRnQzPCCqcoO=	NFnMbJdKdmirYnn0bY9vKG:oIHj1cYFvKEiVUEmwJIlvKGi3bXHuJG5EUS2KMUK5PUBk\WyuczDhd5Nme3OnZDDhd{BCc3RiZHXndoFl[XSrb36gZYZ1\XJiMkSgbJJ{KGK7IHz1cYlv\XhiYYPzZZktKEmFNUC9NE4y\|ryPLh?=	MWW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTR\|OEW0NUc,OjF2M{i1OFE9N2F-
LN229-Lux	NED3XpRHfW6ldHnvckBie3OjeR?=	Mnv6Nk42KHSxIEGwJJVO	MWGxJIhz	M1jtOWlvcGmkaYTpc44hd2ZibIXjbYZmemG\|ZTDhZ5Rqfmm2eTDpckBpfW2jbjDMUlIzQS2OdYigZ4VtdHNiYYSgNk42KHSxIEGwJJVOKGmwY4XiZZRm\CCob4KgNUBpeiC3bnTldkBvd3Kvb4jpZUBnd2yub4fl[EBjgSB{NDDodpMhfW6mZYKgbJlxd3irYTDifUBz\XCxcoTldkBo\W6nIHHzd4F6	NV2wNok2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK3OFYzPzRpPkKyO\|Q3Ojd2PD;hQi=>
MCF7	M1fqcmFvfGmycn;sbYZmemG2aY\lJIF{e2G7		MWG0PEBpenN?	Mki5RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCPQ1[3JINmdGy\|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiY3XscEB3cWGkaXzpeJkh[W[2ZYKgOFghcHK\|IHL5JG1VXCCjc4PhfUwhUUN3ME2wMlM6\|ryPLh?=	NIjPPIg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEW4NlQ4Pyd-MkS1PFI1Pzd:L3G+
HCT116	NVvDeXFYSW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		NEjtWZQ1QCCqcoO=	MUPBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEiFVEGxOkBk\WyuczDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oIHPlcIwhfmmjYnnsbZR6KGGodHXyJFQ5KGi{czDifUBOXFRiYYPzZZktKEmFNUC9NE44QM7:TT6=	MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDV6MkS3O{c,OjR3OEK0O\|c9N2F-
SKBR3	NVjmdVE3SW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		MYG0PEBpenN?	M4jQd2FvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iU1vCVlMh[2WubIOgZZN{\XO\|ZXSgZZMhcW6qaXLpeIlwdiCxZjDj[YxtKH[rYXLpcIl1gSCjZoTldkA1QCCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwQVEvOzUQvF2u	M3[3TlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NUiyOFc4Lz5{NEW4NlQ4PzxxYU6=
A231	MVrBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		MUW0PEBpenN?	NXvVO\|lISW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDBNlMyKGOnbHzzJIFnfGW{IES4JIhzeyCkeTDNWHQh[XO\|YYmsJGlEPTB;MD6xO:69VS5?	M3X0OFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2N{[zNlYyLz5{NEe2N\|I3OTxxYU6=
MCF7	MXfBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		NGK3TY01QCCqcoO=	MlfMRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCPQ1[3JINmdGy\|IHHmeIVzKDR6IHjyd{BjgSCPVGSgZZN{[XluIFnDOVA:OC56zszNMi=>	NGXSPJk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEe2N\|I3OSd-MkS3OlMzPjF:L3G+
HCT116	MXzBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		MWC0PEBpenN?	M4DMeGFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iSFPUNVE3KGOnbHzzJIFnfGW{IES4JIhzeyCkeTDNWHQh[XO\|YYmsJGlEPTB;MT6yNe69VS5?	NFL1Z\|c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEe2N\|I3OSd-MkS3OlMzPjF:L3G+
SKBR3	MXnBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		NUP0b5p3PDhiaILz	MomxRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCVS1LSN{Bk\WyuczDh[pRmeiB2ODDodpMh[nliTWTUJIF{e2G7LDDJR\|UxRTNwMUJOwG0v	NFL0eJo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEe2N\|I3OSd-MkS3OlMzPjF:L3G+
NCI-H1299	NVrIc2RGTnWwY4Tpc44h[XO\|YYm=		M3rRZVEzKGi{cx?=	MoqwVoVlfWO2aX;uJIlvKG:6eXflckBkd26\|dX3weIlwdiC{YYTlJIlvKGi3bXHuJG5EUS2KMUK5PUBk\WyuczDpcoN2[mG2ZXSg[o9zKDF{IHjydy=>	MmXMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV\|OEO5NVUoRjJ3M{izPVE2RC:jPh?=
PC9	NH:wNm5EgXSxdH;4bYNqfHliYYPzZZk>		MYG3NkBpenN?	M3fzXmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KEiJRj3pcoR2[2WmIHXycI91cW6rYj3y[ZNqe3SjboSgbJVu[W5iUFO5JINmdGy\|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiY3XscEBoem:5dHigZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeTygTWM2OD1yLkCx{txONg>?	NIKyNHg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{Nki0OFY5QSd-Mk[4OFQ3QDl:L3G+
Ma1	M{C5bGN6fG:2b4jpZ4l1gSCjc4PhfS=>		NWLxWnpVPzJiaILz	NIH5ZnpEgXSxdH;4bYNqfHliYXfhbY5{fCCKR1[tbY5lfWOnZDDldoxwfGmwaXKtdoV{cXO2YX70JIh2dWGwIF3hNUBk\WyuczDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oIHPlcIwh\3Kxd4ToJIFnfGW{IEeyJIhzeyCkeTDNWHQh[XO\|YYmsJGlEPTB;MD6wNe69VS5?	MkjqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ6NES2PFkoRjJ4OES0Olg6RC:jPh?=
SKBR3	Mn6wSpVv[3Srb36gZZN{[Xl?			MVjJcohq[mm2aX;uJI9nKEi\|cEmwJIlvKGi3bXHuJHNMSlJ\|IHPlcIx{NCCLQ{WwQVAvODJ2zszNMi=>	M2jSblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4OES0Olg6Lz5{Nki0OFY5QTxxYU6=
HeLa	NGGwRY9HfW6ldHnvckBie3OjeR?=	MlLpNVAhfU1?	NHXOZpc3KGi{cx?=	MYXJcohq[mm2aX;uJI9nKEiVUEmwJIlvKGi3bXHuJGhmVGFiY3XscJMh[XO\|ZYPz[YQh[XNiaX7keYN1cW:wIH;mJINpczFiZHXndoFl[XSrb36gZZQhOTBidV2gZYZ1\XJiNjDodpMh[nliV3XzeIVzdiCkbH;0JI1mfGixZB?=	MlrqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh6MU[0OFkoRjJ6OEG2OFQ6RC:jPh?=
HeLa	MkOwSpVv[3Srb36gZZN{[Xl?	NIexXHcyOCC3TR?=	MYe2JIhzew>?	MlPpTY5pcWKrdHnvckBw\iCKU2C5NEBqdiCqdX3hckBJ\UyjIHPlcIx{KGG\|c3Xzd4VlKGG\|IHnu[JVkfGmxbjDv[kBCc3RiZHXndoFl[XSrb36gZZQhOTBidV2gZYZ1\XJiNjDodpMh[nliV3XzeIVzdiCkbH;0JI1mfGixZB?=	MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDhzNkS0PUc,Ojh6MU[0OFk9N2F-
HeLa	MmLjSpVv[3Srb36gZZN{[Xl?	NX20WWNYOTBidV2=	NGm4eFM3KGi{cx?=	MYPJcohq[mm2aX;uJI9nKEiVUEmwJIlvKGi3bXHuJGhmVGFiY3XscJMh[XO\|ZYPz[YQh[XNiaX7keYN1cW:wIH;mJGhUWDdyIIDyc5RmcW5iZYjwdoV{e2mxbjDheEAyOCC3TTDh[pRmeiB4IHjyd{BjgSCZZYP0[ZJvKGKub4SgcYV1cG:m	NEfDR\|g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEixOlQ1QSd-Mki4NVY1PDl:L3G+
PC3	MlfESpVv[3Srb36gZZN{[Xl?	NXjwWmlbOTBidV2=	M3XHdlYhcHK\|	MVjJcohq[mm2aX;uJI9nKEiVUEmwJIlvKGi3bXHuJHBEOyClZXzsd{Bie3Onc4Pl[EBieyCrbnT1Z5Rqd25ib3[gZ4hsOSCmZXfyZYRifGmxbjDheEAyOCC3TTDh[pRmeiB4IHjyd{BjgSCZZYP0[ZJvKGKub4SgcYV1cG:m	NUK2SmZNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki4NVY1PDlpPkK4PFE3PDR7PD;hQi=>
PC3	NX3iZ5c3TnWwY4Tpc44h[XO\|YYm=	NGLJZYYyOCC3TR?=	NXHHOodKPiCqcoO=	MXXJcohq[mm2aX;uJI9nKEiVUEmwJIlvKGi3bXHuJHBEOyClZXzsd{Bie3Onc4Pl[EBieyCrbnT1Z5Rqd25ib3[gRYt1KGSnZ4Lh[IF1cW:wIHH0JFExKHWPIHHmeIVzKDZiaILzJIJ6KFenc4Tldo4h[myxdDDt[ZRpd2R?	MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDhzNkS0PUc,Ojh6MU[0OFk9N2F-
PC3	MV7GeY5kfGmxbjDhd5NigQ>?	NIHMSGgyOCC3TR?=	M1ryWVYhcHK\|	Mni1TY5pcWKrdHnvckBw\iCKU2C5NEBqdiCqdX3hckBRSzNiY3XscJMh[XO\|ZYPz[YQh[XNiaX7keYN1cW:wIH;mJGhUWDdyIIDyc5RmcW5iZYjwdoV{e2mxbjDheEAyOCC3TTDh[pRmeiB4IHjyd{BjgSCZZYP0[ZJvKGKub4SgcYV1cG:m	MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDhzNkS0PUc,Ojh6MU[0OFk9N2F-

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	HSP90 / HSP70 ; PubMed: 28915605 Oncotarget Western blot analysis showing dose-dependent elevation of Hsp70 and HSP90 levels in AGS cells by 17-DMAG. p-Akt / Survivin / MMP2 ; PubMed: 28915605 Oncotarget Western blot analysis showing the dose-dependent reduction of the expression of HSP90 client proteins, such as p-Akt, survivin, and MMP2 by 17-DMAG. PARP / Cleaved caspase-3 / Cleaved caspase-8 / Cleaved caspase-9 / PUMA ; PubMed: 28915605 Oncotarget (C-D) 17-DMAG effects on the expression of apoptotic proteins (PARP, c-caspase 3, c-caspase-8, c-caspase-9, and PUMA) in AGS cells. Western blot analyses indicate that 17-DMAG significantly increased the expression of apoptotic proteins in AGS cells in a dose- (C) and time- (D) dependent manner (P < 0.05). p-ALK / ALK / p-Akt / Akt / p-ERK / ERK ; PubMed: 26219569 BMC Cancer Modulation of ALK signaling in parental and 17-DMAG-resistant cells. Cells were treated with the indicated concentrations of 17-DMAG or AUY922 for 6 h. The molecules of ALK-related signaling activity were detected by western blot analysis. α-Tax / α-IKKα / α-IKKβ/ α-NEMO / α-TBK1 / α-p65 / α-p50 ; PubMed: 24109220 J Virol C8166, MT-2, and MT-4 cells were treated with 17-DMAG as indicated, and cell lysates were subjected to immunoblotting with the indicated antibodies.	28915605 26219569 24109220
Growth inhibition assay	Cell proliferation ; PubMed: 28915605 Oncotarget Proliferation assay of AGS cells treated with graded concentrations of 17-DMAG for 24 h or 48 h. 17-DMAG resulted in significant dose- and time-dependent reduction of AGS cell proliferation (P < 0.05)	28915605

In vivo

17-DMAG treatment at 5 mg/kg or 25 mg/kg thrice per week significantly reduces tumor growth of TMK-1 xenografts, by significantly reducing vessel area and numbers of proliferating tumor cells in sections. ^[2] Consistent the inhibition of FAK signaling in vivo, 17-DMAG treatment at 25 mg/kg three times a week significantly suppresses tumor growth, and metastasis of ME180 and SiHa xenografts in mice. ^[4] Administration of 17-DMAG at 10 mg/kg for 16 days significantly decreases the white blood cell count and prolongs the survival in a TCL1-SCID transplant mouse model. ^[5]

Protocol

Kinase Assay:^[1]	- Collapse Fluorescence polarization (FP)-based competition binding assay: This assay utilizes a boron difluoride dipyrromethene (BODIPY) labeled geldanamycin analogue (BODIPY-AG) as a probe and measured fluorescence polarization upon binding of the probe to a protein. Native human Hsp90 protein (α + β isoforms) is isolated from HeLa cells. BODIPY-AG solution is freshly prepared in FP assay buffer (20 mM HEPES-KOH, pH 7.3, 1.0 mM EDTA, 100 mM KCl, 5.0 mM MgCl₂, 0.01% NP-40, 0.1 mg/mL fresh bovine γ-globulin (BGG), 1.0 mM fresh DTT, and protease inhibitor from stock solution in DMSO. Competition curves are obtained by mixing 10 μL each of a solution containing BODIPY-AG and Hsp90, and a serial dilution of 17-DMAG freshly prepared in FP assay buffer from stock solution in DMSO. Final concentrations are 10 nM BODIPY-AG, 40 or 60 nM Hsp90, varying concentration of 17-DMAG (0.10 nM-10 μM), and ≤0.25% DMSO in a 384-well microplate. After 3 hours incubation at 30 °C, fluorescence anisotropy (γ_Ex = 485 nm, γ_Em = 535 nm) is measured on an EnVision 2100 multilabel plate reader. IC50 value of 17-DMAG is obtained from the competition curves.
Cell Research:^[5]	- Collapse Cell lines: Chronic lymphocytic leukemia (CLL) Concentrations: Dissolved in DMSO, final concentrations ~1 μM Incubation Time: 24, or 48 hours Method: Cells are exposed to various concentrations of 17-DMAG for 24, or 48 hours. For the assessment of cytotoxicity, MTT reagent is then added, and plates are incubated for an additional 24 hours before spectrophotometric measurement. Apoptosis is determined by staining with annexin V-fluorescein isothiocyanate and propidium iodide (PI). (Only for Reference)
Animal Research:^[5]	- Collapse Animal Models: SCID mice engrafted with TCL1 leukemia cells Dosages: 10 mg/kg Administration: Intraperitoneal injection 5 times per week (Only for Reference)

References

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Solubility (25°C)

In vitro	DMSO	131 mg/mL (200.54 mM)
	Water	Insoluble
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 1% DMSO+30% polyethylene glycol+1% Tween 80 For best results, use promptly after mixing.	30 mg/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 Alvespimycin (17-DMAG) HCl SDF

Molecular Weight	653.21
Formula	C₃₂H₄₈N₄O₈•HCl
CAS No.	467214-21-7
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	NSC 707545,BMS 826476 HCl,KOS 1022
Smiles	CC1CC(C(C(C=C(C(C(C=CC=C(C(=O)NC2=CC(=O)C(=C(C1)C2=O)NCCN(C)C)C)OC)OC(=O)N)C)C)O)OC.Cl

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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.

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The Serial Dilution Calculator Equation

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Computed Result

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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2021-05-17)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT00780000	Terminated	Drug: Alvespimycin	Breast Cancer	Bristol-Myers Squibb	April 2008	Phase 2
NCT00248521	Unknown status	Drug: alvespimycin hydrochloride	Unspecified Adult Solid Tumor Protocol Specific	Institute of Cancer Research United Kingdom\|National Cancer Institute (NCI)	October 2005	Phase 1

Tech Support

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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HSP (HSP90) Signaling Pathway Map

HSP (HSP90) Inhibitors with Unique Features

Selective HSP90 Inhibitor

NVP-BEP800 : HSP90β-selective, IC50=58 nM.
Most Potent HSP90 Inhibitor

KW-2478 : HSP90, IC50=3.8 nM.
HSP90 Inhibitor in Clinical Trial

17-AAG (Tanespimycin) : Phase III for Gastrointestinal Stromal Tumors.
Newest HSP90 Inhibitor

XL888 : ATP-competitive inhibitor of HSP90 with IC50 of 24 nM.

Related HSP (HSP90) Products

PU-H71 ^New

PU-H71 (NSC 750424) is a potent and selective inhibitor of HSP90 with IC50 of 51 nM. Phase 1.
KNK437 ^New

KNK437 is a pan-HSP inhibitor, which inhibits the synthesis of inducible HSPs, including HSP105, HSP72, and HSP40.
VER155008 ^New

VER155008 (C07) is a potent Hsp70 family inhibitor with IC50 of 0.5 μM, 2.6 μM, and 2.6 μM in cell-free assays for HSP70, HSC70, and GRP78 (HSPA5, Bip), respectively, >100-fold selectivity over HSP90. VER155008 inhibits autophagy and causes reduced levels of HSP90 client proteins.
Tanespimycin (17-AAG)

Tanespimycin (17-AAG, CP127374, NSC-330507, KOS 953) is a potent HSP90 inhibitor with IC50 of 5 nM in a cell-free assay, having a 100-fold higher binding affinity for HSP90 derived from tumour cells than HSP90 from normal cells. Tanespimycin (17-AAG) induces apoptosis, necrosis, autophagy and mitophagy. Phase 3.

Features:Displays very low toxicity toward normal cells.
Luminespib (NVP-AUY922)

Luminespib (AUY-922, NVP-AUY922, VER-52296) is a highly potent HSP90 inhibitor for HSP90α/β with IC50 of 13 nM /21 nM in cell-free assays, weaker potency against the HSP90 family members GRP94 and TRAP-1, exhibits the tightest binding of any small-molecule HSP90 ligand. Luminespib (AUY-922, NVP-AUY922) effectively downregulates and destabilizes the IGF-1Rβ protein and results in growth inhibition, autophagy and apoptosis. Phase 2.
Ganetespib (STA-9090)

Ganetespib (STA-9090) is an HSP90 inhibitor with IC50 of 4 nM in OSA 8 cells, induces apoptosis of OSA cells while normal osteoblasts are not affected; active metabolite of STA-1474. Phase 3.
Geldanamycin (NSC 122750)

Geldanamycin (NSC 122750) is a natural existing HSP90 inhibitor with K_d of 1.2 μM, specifically disrupts glucocorticoid receptor (GR)/HSP association. Geldanamycin attenuates virus infection-induced ALI (acute lung injury)/ARDS (acute respiratory distress syndrome) by reducing the host's inflammatory responses.
HSP990 (NVP-HSP990)

HSP990 (NVP-HSP990) is a novel, potent and selective HSP90 inhibitor for HSP90α/β with IC50 of 0.6 nM/0.8 nM. NVP-HSP990 induces cell cycle arrest and apoptosis.

Features:NVP-HSP990 is an orally available HSP90 inhibitor and is structurally distinct from other clinical HSP90 inhibitors.
Elesclomol (STA-4783)

Elesclomol (STA-4783) is a novel potent oxidative stress inducer that elicits pro-apoptosis events among tumor cells. Phase 3.
Onalespib (AT13387)

Onalespib (AT13387) is a selective potent Hsp90 inhibitor with IC50 of 18 nM in A375 cells, displays a long duration of anti-tumor activity. Phase 2.

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Alvespimycin (17-DMAG) HCl