Torin 1

Name: Torin 1
Brand: Selleck Chemicals
SKU: S2827
Rating: 5 (135 reviews)

For research use only.

Catalog No.S2827

135 publications

CAS No. 1222998-36-8

Torin 1 is a potent inhibitor of mTORC1/2 with IC50 of 2 nM/10 nM in cell-free assays; exhibits 1000-fold selectivity for mTOR than PI3K.

Selleck's Torin 1 has been cited by 135 publications

Nature, 2020, 10.1038/s41586-020-03056-z

PubMed: 33328639 ( click the link to review the publication )

Cell, 2020, S0092-8674(20)31627-5

PubMed: 33338421 ( click the link to review the publication )

Cell, 2020, 25;181(7):1596-1611.e27.

PubMed: 32559461 ( click the link to review the publication )

Nat Biotechnol, 2020, 38(5):638-648

PubMed: 32249828 ( click the link to review the publication )

Cell, 2019, 177(4):896-909

PubMed: 31030999 ( click the link to review the publication )

Nat Immunol, 2018, 19(12):1330-1340

PubMed: 30420624 ( click the link to review the publication )

Cell Metab, 2018, 28(3):369-382

PubMed: 30043754 ( click the link to review the publication )

Nature, 2017, 1;546(7656):168-172.

PubMed: 28538732 ( click the link to review the publication )

Cancer Discov, 2016, 6(7):727-39

PubMed: 27231123 ( click the link to review the publication )

EMBO Rep, 2021, e51329

PubMed: 33480074 ( click the link to review the publication )

Cell Signal, 2021, 80:109912

PubMed: 33388443 ( click the link to review the publication )

Nat Cell Biol, 2020, 22(10):1170-1179

PubMed: 32989246 ( click the link to review the publication )

Sci Transl Med, 2020, 12(548):eaay5691

PubMed: 32554707 ( click the link to review the publication )

Mol Cell, 2020, S1097-2765(20)30786-3

PubMed: 33271062 ( click the link to review the publication )

Nat Commun, 2020, 11(1):5842

PubMed: 33203880 ( click the link to review the publication )

Nat Commun, 2020, 24;11(1):479

PubMed: 31980602 ( click the link to review the publication )

Autophagy, 2020, 15:1-13

PubMed: 32264736 ( click the link to review the publication )

Dev Cell, 2020, 55(3):298-313.e10

PubMed: 33171110 ( click the link to review the publication )

Cell Rep, 2020, 30(5):1400-1416

PubMed: 32023458 ( click the link to review the publication )

Cell Rep, 2020, 30(6):1835-1847

PubMed: 32049014 ( click the link to review the publication )

Cell Death Differ, 2020, 10.1038/s41418-020-00646-2

PubMed: 33100324 ( click the link to review the publication )

Cancers (Basel), 2020, 12(12)E3766

PubMed: 33327544 ( click the link to review the publication )

PLoS Pathog, 2020, 9;16(6):e1008568

PubMed: 32516328 ( click the link to review the publication )

Cell Death Dis, 2020, 8;5:e1214

PubMed: 24810050 ( click the link to review the publication )
Br J Cancer, 2020, 22

PubMed: 32439931 ( click the link to review the publication )

Mol Nutr Food Res, 2020, 1;e1901231

PubMed: 32476238 ( click the link to review the publication )

Am J Cancer Res, 2020, 10(12):4488-4497

PubMed: 33415013 ( click the link to review the publication )

J Immunol, 2020, ji2000244

PubMed: 32989095 ( click the link to review the publication )

Mol Cancer Res, 2020, 10.1158/1541-7786

PubMed: 32169890 ( click the link to review the publication )

Int J Mol Sci, 2020, 24;21(6) pii: E2240

PubMed: 32213867 ( click the link to review the publication )

Exp Cell Res, 2020, 10.1016/j.yexcr.2020.111981

PubMed: 32234375 ( click the link to review the publication )

Exp Eye Res, 2020, 203:108421

PubMed: 33359326 ( click the link to review the publication )

J Clin Invest, 2020, 137585

PubMed: 32673292 ( click the link to review the publication )

Emerg Microbes Infect, 2020, 9(1):1748-1760

PubMed: 32691695 ( click the link to review the publication )

J Biol Chem, 2020, jbc.RA120.13703

PubMed: 32683324 ( click the link to review the publication )

bioRxiv, 2020, 2020.10.09.334128

PubMed: 33052348 ( click the link to review the publication )

Oxid Med Cell Longev, 2020, 2020:1364147

PubMed: 32724488 ( click the link to review the publication )

J Cell Physiol, 2020, 10.1002/jcp.30172

PubMed: 33230821 ( click the link to review the publication )

Nat Metab, 2020, 2(1):41-49

PubMed: 31993556 ( click the link to review the publication )

Cancer Res, 2020, 80(3):444-457

PubMed: 31722999 ( click the link to review the publication )

Mol Cell, 2019, 73(4):788-802

PubMed: 30704899 ( click the link to review the publication )

Nat Commun, 2019, 10(1):4741

PubMed: 31628323 ( click the link to review the publication )

Nat Commun, 2019, 10(1):1693

PubMed: 30979895 ( click the link to review the publication )

Nat Commun, 2019, 10(1):5681

PubMed: 31831743 ( click the link to review the publication )

Autophagy, 2019, 15(3):493-509

PubMed: 30304977 ( click the link to review the publication )

Autophagy, 2019, 1-13

PubMed: 30957628 ( click the link to review the publication )

Autophagy, 2019, 10.1080/15548627.2019.1703353

PubMed: 31847700 ( click the link to review the publication )

Autophagy, 2019, 10.1080/15548627.2019.1628536

PubMed: 31203721 ( click the link to review the publication )
Proc Natl Acad Sci U S A, 2019, 10.1073/pnas.1911393116

PubMed: 31732667 ( click the link to review the publication )

Cell Rep, 2019, 29(3):589-602

PubMed: 31618629 ( click the link to review the publication )

Cell Rep, 2019, 27(7):2075-2091.e5

PubMed: 31091447 ( click the link to review the publication )

Cell Mol Immunol, 2019, 10.1038/s41423-019-0281-6

PubMed: 31467416 ( click the link to review the publication )

Oncogene, 2019, 38(10):1639-1650

PubMed: 30337688 ( click the link to review the publication )

Oncogene, 2019, 10.1038/s41388-019-1085-y

PubMed: 31685947 ( click the link to review the publication )

Oncogene, 2019, 38(2):209-227

PubMed: 30087437 ( click the link to review the publication )

EBioMedicine, 2019, 40:151-162

PubMed: 30711516 ( click the link to review the publication )

Cell Death Dis, 2019, 10(6):399

PubMed: 31113939 ( click the link to review the publication )

Lab Invest, 2019, 99(5):648-658

PubMed: 30679758 ( click the link to review the publication )

Biochem Pharmacol, 2019, 162:191-201

PubMed: 30471247 ( click the link to review the publication )

J Biol Chem, 2019, 294(10):3760-3771

PubMed: 30617181 ( click the link to review the publication )

Life Sci, 2019, 232:116665

PubMed: 31323273 ( click the link to review the publication )

Biochem Biophys Res Commun, 2019, 519(4):909-915

PubMed: 31563324 ( click the link to review the publication )

Nat Commun, 2018, 9(1):4831

PubMed: 30446646 ( click the link to review the publication )

Nat Commun, 2018, 9(1):5426

PubMed: 30575721 ( click the link to review the publication )

Nat Commun, 2018, 9(1):2819

PubMed: 30026551 ( click the link to review the publication )

J Pathol, 2018, 245(2):235-248

PubMed: 29570219 ( click the link to review the publication )

PLoS Genet, 2018, 14(5):e1007369

PubMed: 29750810 ( click the link to review the publication )

Development, 2018, 145(18)

PubMed: 30126904 ( click the link to review the publication )

Lung Cancer, 2018, 120:34-45

PubMed: 29748013 ( click the link to review the publication )

Mol Cancer Res, 2018, 16(4):599-609

PubMed: 29330285 ( click the link to review the publication )

Exp Cell Res, 2018, 363(1):84-94

PubMed: 29289595 ( click the link to review the publication )

Braz J Med Biol Res, 2018, 51(6):e7080

PubMed: 29694502 ( click the link to review the publication )
Cell Res, 2017, 27(2):184-201

PubMed: 27934868 ( click the link to review the publication )

Mol Cell, 2017, 67(6):907-921

PubMed: 28844862 ( click the link to review the publication )

Mol Cell, 2017, 65(6):1029-1043

PubMed: 28306502 ( click the link to review the publication )

Nat Commun, 2017, 8:15045

PubMed: 28429794 ( click the link to review the publication )

Nat Commun, 2017, 8;8:15617

PubMed: 28593995 ( click the link to review the publication )

Autophagy, 2017, 13(8):1364-1385

PubMed: 28598230 ( click the link to review the publication )

Autophagy, 2017, 13(4):686-702

PubMed: 28121484 ( click the link to review the publication )

J Cell Biol, 2017, 216(6):1567-1577

PubMed: 28442534 ( click the link to review the publication )

PLoS Pathog, 2017, 13(3):e1006249

PubMed: 28249048 ( click the link to review the publication )

Cell Death Dis, 2017, 8(8):e2970

PubMed: 28771229 ( click the link to review the publication )

Sci Rep, 2017, 7(1):1994

PubMed: 28515443 ( click the link to review the publication )

Sci Rep, 2017, 7(1):13832

PubMed: 29062139 ( click the link to review the publication )

J Biol Chem, 2017, 292(35):14544-14555

PubMed: 28684424 ( click the link to review the publication )

Am J Physiol Cell Physiol, 2017, 313(5):C501-C515

PubMed: 28794108 ( click the link to review the publication )

J Agric Food Chem, 2017, 65(31):6625-6637

PubMed: 28697598 ( click the link to review the publication )

Radiat Res, 2017, 187(3):382-396

PubMed: 28327001 ( click the link to review the publication )

Oncotarget, 2017, 8(65):109848-109856

PubMed: 29312653 ( click the link to review the publication )

Oncotarget, 2017, 8(55):93688-93703

PubMed: 29212182 ( click the link to review the publication )

Oncotarget, 2017, 8(52):89527-89538

PubMed: 29163768 ( click the link to review the publication )

Oncotarget, 2017, 8(65):109848-109856

PubMed: 29312653 ( click the link to review the publication )

Oncotarget, 2017, 8(27):44550-44566

PubMed: 28562352 ( click the link to review the publication )

Protein Cell, 2016, 7(12):878-887

PubMed: 27909983 ( click the link to review the publication )

Aging (Albany NY), 2016, 8(12):3535-3551

PubMed: 28077803 ( click the link to review the publication )

Stem Cells Transl Med, 2016, 5(5):580-90

PubMed: 27025692 ( click the link to review the publication )
ACS Chem Biol, 2016, 11(5):1428-37

PubMed: 26938669 ( click the link to review the publication )

Mol Biol Cell, 2016, 27(2):321-33

PubMed: 26582390 ( click the link to review the publication )

J Biol Chem, 2016, 291(33):17467-77

PubMed: 27339899 ( click the link to review the publication )

J Cell Physiol, 2016, 10.1002/jcp.25456

PubMed: 27301841 ( click the link to review the publication )

Front Plant Sci, 2016, 7:1746

PubMed: 27917191 ( click the link to review the publication )

BMC Musculoskelet Disord, 2016, 17:150

PubMed: 27052304 ( click the link to review the publication )

Oncotarget, 2016, 7(5):5521-37

PubMed: 26575168 ( click the link to review the publication )

Oncotarget, 2016, 7(34):55690-55703

PubMed: 27494886 ( click the link to review the publication )

Oncotarget, 2016, 7(36):57525-57544

PubMed: 27438153 ( click the link to review the publication )

J Clin Invest, 2015, 125(3):1174-88

PubMed: 25664849 ( click the link to review the publication )

Elife, 2015, 4

PubMed: 25846574 ( click the link to review the publication )

J Med Chem, 2015, 58(16):6559-73

PubMed: 26237138 ( click the link to review the publication )

Cell Commun Signal, 2015, 13:15

PubMed: 25849580 ( click the link to review the publication )

J Cell Physiol, 2015, 230(5):1064-74

PubMed: 25283437 ( click the link to review the publication )

Mol Cancer Res, 2015, 13(2):223-30

PubMed: 25582703 ( click the link to review the publication )

J Virol, 2015, 89(1):626-42

PubMed: 25339775 ( click the link to review the publication )

Sci Rep, 2015, 5:13891

PubMed: 26403635 ( click the link to review the publication )

J Biol Chem, 2015, 10.1074/jbc.M114.621706

PubMed: 25878248 ( click the link to review the publication )

J Biol Chem, 2015, 290(9):5592-605

PubMed: ( click the link to review the publication )

J Biol Chem, 2015, 290(9):5592-605

PubMed: 25561726 ( click the link to review the publication )

Cell Signal, 2015, 27(8):1557-68

PubMed: 25936523 ( click the link to review the publication )

BMC Cancer, 2015, 15:855

PubMed: 26542945 ( click the link to review the publication )

PLoS One, 2015, 10(8):e0135614

PubMed: 26267903 ( click the link to review the publication )

Oncotarget, 2015, 6(27):23238-48

PubMed: 26177051 ( click the link to review the publication )
PLoS Pathog, 2014, 10(6):e1004196

PubMed: 24945378 ( click the link to review the publication )

Cell Death Dis, 2014, 5:e1214

PubMed: 24810050 ( click the link to review the publication )

Am J Pathol, 2014, 184(1):214-29

PubMed: 24215913 ( click the link to review the publication )

J Biol Chem, 2014, 289(43):29739-49

PubMed: 25164809 ( click the link to review the publication )

J Biol Chem, 2014, 289(25):17830-42

PubMed: 24798333 ( click the link to review the publication )

Mol Cell Biol, 2014, 34(24):4474-84

PubMed: 25288641 ( click the link to review the publication )

Biochem Biophys Res Commun, 2014, 10.1016/j.bbrc.2014.05.047

PubMed: 24858682 ( click the link to review the publication )

Oncotarget, 2014, 5(24):12715-27

PubMed: 25587030 ( click the link to review the publication )

Oncotarget, 2014, 5(16):6816-31

PubMed: 25149175 ( click the link to review the publication )

Oncotarget, 2014, 5(18):8737-49

PubMed: 25228590 ( click the link to review the publication )

Blood, 2013, 121(18):3619-30

PubMed: 23444404 ( click the link to review the publication )

Trends Microbiol, 2013, 21(6):286-95

PubMed: 23608036 ( click the link to review the publication )

Genes Dev, 2013, 27(10):1115-31

PubMed: 23699409 ( click the link to review the publication )

PLoS One, 2013, 8(11):e80070

PubMed: 24244612 ( click the link to review the publication )

EMBO Mol Med, 2011, 3(4):189-200

PubMed: 21412983 ( click the link to review the publication )

Purity & Quality Control

Choose Selective mTOR Inhibitors

Biological Activity

Description

Torin 1 is a potent inhibitor of mTORC1/2 with IC50 of 2 nM/10 nM in cell-free assays; exhibits 1000-fold selectivity for mTOR than PI3K.

Targets

mTORC1 ^[1] (Cell-free assay)	mTOR ^[2] (Cell-free assay)	DNA-PK ^[2] (Cell-free assay)	mTORC2 ^[1] (Cell-free assay)	p110γ ^[2] (Cell-free assay)	View More
2 nM	4.32 nM	6.34 nM	10 nM	171 nM	View More

In vitro

Torin1 inhibits phosphorylation of mTORC1 and mTORC2 substrates in cells at concentrations of 2 and 10 nM, respectively. Moreover, Torin1 exhibits 1000-fold selectivity for mTOR over PI3K (EC50 = 1800 nM) and exhibits 100-fold binding selectivity relative to 450 other protein kinases. ^[1] ^[2] Torin1 causes cell cycle arrest through a rapamycin-resistant mechanism that is also independent of mTORC2. Torin1 disrupts mTORC1-dependent phenotypes more completely than rapamycin. Rapamycin-resistant functions of mTORC1 are required for cap-dependent translation. ^[1] In a recent study, it is reported Torin1 increases neurotensin secretion and gene expression through activation of the MEK/ERK/c-Jun pathway in the human endocrine cell line BON. ^[3]

Cell Data

Cell Lines	Assay Type	Activity Description	PMID
ETK-1	M1raVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MVHJR\|UxRTBwMECwN\|A3KM7:TR?=	Mmm0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
OCUB-M	MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NGnXRVJKSzVyPUCuNFAyQTRizszN	NFn4UHA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
DOHH-2	MnqyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MYTJR\|UxRTBwMECyNlUh\|ryP	NVnqeHRGRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
NOS-1	MoDHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M4r4WWlEPTB;MD6wNFI1OiEQvF2=	NYPlNYI1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
L-363	MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M2ixemlEPTB;MD6wNFI5PCEQvF2=	NWnMfWR4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
RL95-2	NHzWWmJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MljqTWM2OD1yLkCwN\|Ih\|ryP	M4jLZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzPTZ2NUmvK\|5USU6JRWK8M4E,
BL-70	MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NH3ROYdKSzVyPUCuNFA{OzdizszN	M2ixbFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzPTZ2NUmvK\|5USU6JRWK8M4E,
TGBC1TKB	NYnPN\|dNT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NXz4NmlNUUN3ME2wMlAxOzd7IN88US=>	NIT6eZY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
697	Mk\wS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MUXJR\|UxRTBwMEC2N\|Qh\|ryP	MmPHQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
RPMI-8226	MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NGHMbm5KSzVyPUCuNFA3PTFizszN	MoLyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
BL-41	NVrxTZpQT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NHG0cXhKSzVyPUCuNFA3QTZizszN	MYi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlU3PDV7Lze+V2FPT0WUPD;hQi=>
MRK-nu-1	Mnn5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MnP6TWM2OD1yLkCwO\|A4KM7:TR?=	NWDEO2NTRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
EW-1	NGL0[ZZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NX7ifYp[UUN3ME2wMlAxPzR7IN88US=>	NE[zb4Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
EVSA-T	M13TWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NH3PZZBKSzVyPUCuNFA5QTJizszN	M1;0b\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzPTZ2NUmvK\|5USU6JRWK8M4E,
HUTU-80	MlfTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NGPrRlRKSzVyPUCuNFA6OjlizszN	Mn;nQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
VA-ES-BJ	M4fJd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NVvtTWhLUUN3ME2wMlAxQTh2IN88US=>	NYHHeolIRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
GCIY	MlS1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MmWxTWM2OD1yLkCxNFA4KM7:TR?=	M2HoPFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzPTZ2NUmvK\|5USU6JRWK8M4E,
ES6	MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	Ml6xTWM2OD1yLkCxNFg{KM7:TR?=	NUnYRmpRRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
NALM-6	NHPOWndIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MVTJR\|UxRTBwMEGxNFIh\|ryP	MW[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlU3PDV7Lze+V2FPT0WUPD;hQi=>
LB996-RCC	MmT5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MkHaTWM2OD1yLkCxNVM4KM7:TR?=	NEnoXJg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
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KALS-1	M{Dwb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M3zBTWlEPTB;MD6wNVE6QCEQvF2=	MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlU3PDV7Lze+V2FPT0WUPD;hQi=>
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KU812	NYTBTmp1T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NWnlOJA3UUN3ME2wMlAyOjl4IN88US=>	NGe3d209[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
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KS-1	NIjzXGZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MWnJR\|UxRTBwMEGzPVIh\|ryP	MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlU3PDV7Lze+V2FPT0WUPD;hQi=>
no-11	M172Z2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NEnYUmxKSzVyPUCuNFE{QTVizszN	MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlU3PDV7Lze+V2FPT0WUPD;hQi=>
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HT-144	MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MYPJR\|UxRTBwMEG0OVEh\|ryP	NFjHVmE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
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GB-1	MmO5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NYLOPIVFUUN3ME2wMlAyPTV\|IN88US=>	MoDuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
KE-37	MnXKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M3TDUGlEPTB;MD6wNVU4OyEQvF2=	NUTEbG9qRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
no-10	NF3pZnNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	M2nEWGlEPTB;MD6wNVU5PCEQvF2=	M4TTXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzPTZ2NUmvK\|5USU6JRWK8M4E,
MOLT-16	NY\pcotyT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MYDJR\|UxRTBwMEG2NlIh\|ryP	NVXMUpdQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
HEL	MkjOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M{jhc2lEPTB;MD6wNVY1KM7:TR?=	NIfFcHY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
NCI-H1355	NVvlWJo4T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NXTJeHRUUUN3ME2wMlAyPjR4IN88US=>	NWe1XVc1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
IST-MEL1	NUTpOYppT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MnS3TWM2OD1yLkCxO\|c1KM7:TR?=	NUDNOlBQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
MHH-PREB-1	M4HONWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MkLMTWM2OD1yLkCxPFE5KM7:TR?=	MmW3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
ES8	M1rpRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	Ml72TWM2OD1yLkCxPFQ1KM7:TR?=	NWrUNWdiRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
LC-2-ad	NIHnOodIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NGewc3pKSzVyPUCuNFIyOzdizszN	MliwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
LAMA-84	MkHVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NUDQ[m1yUUN3ME2wMlAzOTZ5IN88US=>	MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlU3PDV7Lze+V2FPT0WUPD;hQi=>
BV-173	Mn73S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	Ml3GTWM2OD1yLkCyNlA{KM7:TR?=	M2OzOVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzPTZ2NUmvK\|5USU6JRWK8M4E,
SW872	MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MUfJR\|UxRTBwMEKyOFch\|ryP	MnjCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
SK-UT-1	NY\PVnlVT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NWfreGNOUUN3ME2wMlAzOjZzIN88US=>	MoLGQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
OS-RC-2	M3LWSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NVXvTph5UUN3ME2wMlAzOzJ\|IN88US=>	NVvubpdIRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
NCI-H747	M17YTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NV7QUnBMUUN3ME2wMlAzOzNizszN	M2\nblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzPTZ2NUmvK\|5USU6JRWK8M4E,
MZ2-MEL	M4L5cWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MmfwTWM2OD1yLkCyN\|M4KM7:TR?=	M1S0bFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzPTZ2NUmvK\|5USU6JRWK8M4E,
TE-11	M3y2fmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MoKxTWM2OD1yLkCyN\|czKM7:TR?=	NVXmSJdORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
KURAMOCHI	MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NEf2UFJKSzVyPUCuNFI1OTRizszN	MkDmQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
HD-MY-Z	MmPZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M1;TTGlEPTB;MD6wNlQzPiEQvF2=	M4\MO\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzPTZ2NUmvK\|5USU6JRWK8M4E,
GI-1	M1\Jd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NGXJbldKSzVyPUCuNFI1PjlizszN	NGXpU5Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
LB1047-RCC	MnzqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MomzTWM2OD1yLkCyOFg5KM7:TR?=	MnPDQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
TE-12	NFnsVHdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NID2fI9KSzVyPUCuNFI2PSEQvF2=	MnXhQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
MZ7-mel	Mn7JS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M1ju[2lEPTB;MD6wNlYxQSEQvF2=	NFrPVXo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
MMAC-SF	Ml[0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NFrSUXBKSzVyPUCuNFI3OzNizszN	M2DsPVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzPTZ2NUmvK\|5USU6JRWK8M4E,
A101D	MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MYjJR\|UxRTBwMEK2OUDPxE1?	NXL0cGRVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
GR-ST	MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MXzJR\|UxRTBwMEK2OVUh\|ryP	MmD0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
MC116	MmPQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NIW2dZpKSzVyPUCuNFI3QCEQvF2=	NYjqepZvRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
Ramos-2G6-4C10	MlfJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NYLXXHgyUUN3ME2wMlAzPzVizszN	NGroRnY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
ATN-1	MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MW\JR\|UxRTBwMEK3PFkh\|ryP	MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlU3PDV7Lze+V2FPT0WUPD;hQi=>
MFH-ino	MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NWPt[GlLUUN3ME2wMlAzQDF{IN88US=>	MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlU3PDV7Lze+V2FPT0WUPD;hQi=>
DEL	MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NHzaVFhKSzVyPUCuNFI5OTVizszN	MlHYQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
OCI-AML2	NX\GSHJvT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	M1rqcGlEPTB;MD6wNlg4OSEQvF2=	NFXJUYg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
LXF-289	MnK5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MYjJR\|UxRTBwMEK4O\|Ih\|ryP	Mmj3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
IA-LM	MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NXTucZBIUUN3ME2wMlAzQTF5IN88US=>	MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlU3PDV7Lze+V2FPT0WUPD;hQi=>
EoL-1-cell	MlrMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NYSwVY5JUUN3ME2wMlAzQTl4IN88US=>	NG\vSWc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
OVCAR-4	NFHOb2VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NYXTVHRHUUN3ME2wMlA{ODl2IN88US=>	M33EOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzPTZ2NUmvK\|5USU6JRWK8M4E,
ES1	MnTBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M1f2c2lEPTB;MD6wN\|A6PyEQvF2=	MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlU3PDV7Lze+V2FPT0WUPD;hQi=>
CESS	NGL0fHpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MXHJR\|UxRTBwMEOwPVkh\|ryP	NXrSW40{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
GAK	MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MUjJR\|UxRTBwMEOxPFYh\|ryP	Mnr0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
NTERA-S-cl-D1	MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NUPxblFmUUN3ME2wMlA{OjJ4IN88US=>	Mn60QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
TE-10	Mn;2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	Ml\1TWM2OD1yLkCzN\|EyKM7:TR?=	M{\qOVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzPTZ2NUmvK\|5USU6JRWK8M4E,
CCRF-CEM	MljyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NFy5VmNKSzVyPUCuNFM{PzFizszN	MlOyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
NMC-G1	NYjCPXBET3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NFj6d2RKSzVyPUCuNFM1PDhizszN	MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlU3PDV7Lze+V2FPT0WUPD;hQi=>
HOP-62	NIHpSVNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	M1\QcGlEPTB;MD6wN\|U2PiEQvF2=	MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlU3PDV7Lze+V2FPT0WUPD;hQi=>
SH-4	MkjaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NHK2WpVKSzVyPUCuNFM2QDJizszN	NIXr[HY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
NCI-H1648	MmntS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NUfvN\|N5UUN3ME2wMlA{PjJ{IN88US=>	NEjxXVQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
EB-3	NHKw[mdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MkKwTWM2OD1yLkCzOlQ{KM7:TR?=	MkPXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
BB65-RCC	M2H0Z2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MWrJR\|UxRTBwMEO2PVEh\|ryP	M4nJOVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzPTZ2NUmvK\|5USU6JRWK8M4E,
BE-13	M3zTXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NF;vcHRKSzVyPUCuNFM4PTlizszN	NWLOTI9LRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
CP67-MEL	M1fvWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NFvYT4xKSzVyPUCuNFM4PTlizszN	NXTkeo5TRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
SW954	MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MXXJR\|UxRTBwMEO3PUDPxE1?	MWC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlU3PDV7Lze+V2FPT0WUPD;hQi=>
TE-5	MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MV\JR\|UxRTBwMEO4OVQh\|ryP	MlLUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
HCE-4	MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NVWzTpJrUUN3ME2wMlA{QDV3IN88US=>	NYfFW203RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
LC-1F	MlXyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NXuwZXk3UUN3ME2wMlA{QTh7IN88US=>	NEjhS5E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
TK10	MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MWLJR\|UxRTBwMESwNVkh\|ryP	MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlU3PDV7Lze+V2FPT0WUPD;hQi=>
SJSA-1	MoL4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NWLZV4cyUUN3ME2wMlA1OTh6IN88US=>	M2nHN\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzPTZ2NUmvK\|5USU6JRWK8M4E,
Daudi	NG\T[FZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NHTZbIVKSzVyPUCuNFQzOjVizszN	NVvyU4tQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
SW982	MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MofqTWM2OD1yLkC0NlQ3KM7:TR?=	M2C1OlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzPTZ2NUmvK\|5USU6JRWK8M4E,
SF126	MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NWPMUIF1UUN3ME2wMlA1OzZzIN88US=>	MljFQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
TE-15	MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NYfFRoJNUUN3ME2wMlA1PDN3IN88US=>	NGnrfJU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
COLO-684	NFT6Z\|ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NWD5SG9iUUN3ME2wMlA1PTZzIN88US=>	NX7J[IlKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
8-MG-BA	NXPESJRsT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MWjJR\|UxRTBwMES2Nlkh\|ryP	MmXrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
NB13	MniwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NWfIWm5QUUN3ME2wMlA1Pzd4IN88US=>	Mlj4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
HCC1599	MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NF3K[Y9KSzVyPUCuNFQ5PzlizszN	MWO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlU3PDV7Lze+V2FPT0WUPD;hQi=>
SK-PN-DW	MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NUKwb4d1UUN3ME2wMlA1QTR7IN88US=>	MmHrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
ALL-PO	NH;ke3FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	M2Wy[GlEPTB;MD6wOFk2PiEQvF2=	MkPyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
NB6	MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MYDJR\|UxRTBwMEWyO\|Eh\|ryP	NVTJXWtlRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
IST-SL2	NU\QdVdXT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MkX1TWM2OD1yLkC1N\|YzKM7:TR?=	Mm\TQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
BB30-HNC	MmHsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NYrRO49PUUN3ME2wMlA2PzNizszN	M1XkRVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzPTZ2NUmvK\|5USU6JRWK8M4E,
SW962	MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M2rJPWlEPTB;MD6wOVc3OyEQvF2=	MkXQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
TGBC24TKB	NYfMd451T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NVW1c3JnUUN3ME2wMlA2Pzl7IN88US=>	MmfmQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
KINGS-1	M33ScGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NWXVNoJHUUN3ME2wMlA2QDB\|IN88US=>	NHPT[WM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
HC-1	MnTyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NX3ySnRJUUN3ME2wMlA2QDJ5IN88US=>	NHzrRWo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
RS4-11	NVvsVHh{T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NVz0PHN6UUN3ME2wMlA2QTN6IN88US=>	NWmzfFBRRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
LS-123	M{nOcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NUPFT4hKUUN3ME2wMlA2QTR{IN88US=>	MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlU3PDV7Lze+V2FPT0WUPD;hQi=>
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NCI-H2081	M3\afWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M{G2XGlEPTB;ND6yPVE4PCEQvF2=	MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlU3PDV7Lze+V2FPT0WUPD;hQi=>
D-247MG	NUD4e4hST3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NX\6R3J6UUN3ME20MlQ{OTlzIN88US=>	M4rs[\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzPTZ2NUmvK\|5USU6JRWK8M4E,
P31-FUJ	MkfkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M3X3XGlEPTB;ND60OVAyQSEQvF2=	M1nRSFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzPTZ2NUmvK\|5USU6JRWK8M4E,
DMS-79	M4DWRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MlP6TWM2OD12LkmzNVg{KM7:TR?=	M1S2RlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzPTZ2NUmvK\|5USU6JRWK8M4E,
KASUMI-1	MkHoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M3PudWlEPTB;ND65O\|UxQSEQvF2=	NX;Zc5VtRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
JVM-3	Mn\BS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NIf6T49KSzVyPUWuNlUxOTRizszN	M37NcFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzPTZ2NUmvK\|5USU6JRWK8M4E,
LAN-6	NEPmSHRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NInJWIJKSzVyPUWuOVE4OzZizszN	NXPp[FNiRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
DJM-1	NV7oT\|M6T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MUfJR\|UxRTVwNU[wNlkh\|ryP	MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlU3PDV7Lze+V2FPT0WUPD;hQi=>
JVM-2	M4jEVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M3fDWWlEPTB;NT62O\|A6OiEQvF2=	NULaTlZSRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
U-87-MG	MkPZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M1[wbmlEPTB;NT64PVk3PCEQvF2=	Mn7VQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
SHP-77	MnraS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NWq0[Yx5UUN3ME21Mlk1QTJ6IN88US=>	NHHweY49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
RPMI-8866	MnvCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MYXJR\|UxRTZwMkewNVMh\|ryP	NHnVeoU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
ES7	NHzxdZdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MULJR\|UxRTZwM{m5NlQh\|ryP	M4fkUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzPTZ2NUmvK\|5USU6JRWK8M4E,
WSU-NHL	MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MkDhTWM2OD14LkWxOlA6KM7:TR?=	NWDUcVdORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
CAS-1	NU\qdJM2T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MlXlTWM2OD15LkC5O\|Q6KM7:TR?=	MWG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlU3PDV7Lze+V2FPT0WUPD;hQi=>
MHH-NB-11	NF65W2pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	M2WyU2lEPTB;OD6yN\|E2OiEQvF2=	NYXtbHN2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
ES5	NUnGcZk{T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	M2PCVWlEPTB;OT61NlI5PiEQvF2=	MoDrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
HDLM-2	M{mwU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MmmxTWM2OD17Lkm1PVAzKM7:TR?=	M1\JcVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzPTZ2NUmvK\|5USU6JRWK8M4E,
NCI-H2171	NIXNU4FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MYPJR\|UxRTFyLkW5Nlch\|ryP	NXz6UJRVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
LNCaP-Clone-FGC	NHHKS41Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MmK0TWM2OD1zMT6zO\|E5KM7:TR?=	NVHybolpRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
NCI-H1395	Mln4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NWfxe5FsUUN3ME2xNk4zPjl7IN88US=>	MW[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlU3PDV7Lze+V2FPT0WUPD;hQi=>
NCI-H1436	MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NInQWFBKSzVyPUGzMlMyQTVizszN	MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlU3PDV7Lze+V2FPT0WUPD;hQi=>
RCC10RGB	NIjTcpdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MmHrTWM2OD1zMz6zNlIyKM7:TR?=	MmfKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI2PjR3OT:nQnNCVkeHUkyvZV4>
SW684	MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M3y4dGlEPTB;MUOuPVc6PyEQvF2=	NHWwSlA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
NCI-H1650	NH;HTIJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NH\zS4RKSzVyPUG1MlA1PDdizszN	MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlU3PDV7Lze+V2FPT0WUPD;hQi=>
EW-13	Mo\mS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NFnqcINKSzVyPUG1MlIxOjFizszN	NF7rfoY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
EC-GI-10	M1Lw[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M3vsN2lEPTB;MUWuPFY1PCEQvF2=	NGnVcoY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
CHP-126	NWPaPYtqT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MXLJR\|UxRTF5LkG5NVgh\|ryP	NVTUVZNWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
NCI-H226	NYDFWFNiT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NI\oR2NKSzVyPUG4MlA1ODNizszN	NHXUbHY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
NCI-H1838	M4P6[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NGe2c2RKSzVyPUKwMlE5PDhizszN	MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlU3PDV7Lze+V2FPT0WUPD;hQi=>
EW-11	M4H5OGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NUn2[pBwUUN3ME2yOE4zPzF6IN88US=>	NW\3dmd7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
EB2	NETx[FFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MWHJR\|UxRTNzLkWzNVgh\|ryP	NETueWM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
D-502MG	NUi4WVZzT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	M3;ubGlEPTB;NEOuPVIzQSEQvF2=	NVe0VFJ1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
U-698-M	NX35SYU3T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MUfJR\|UxRTR6Lki2O\|Eh\|ryP	NHq2RVA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjV4NEW5M{c,W0GQR1XSQE9iRg>?
ES3	MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	Ml3zTWM2OD12OT6zPFk{KM7:TR?=	NUnsRYYxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ3NkS1PU8oRlODTlfFVlww[T5?
PC3	NXXoNIZMTnWwY4Tpc44h[XO\|YYm=	NEPQZlBKdmirYnn0bY9vKG:oIGDJN2tidHCqYTDpckBpfW2jbjDQR\|Mh[2WubIOg[ZhxemW\|c3nu[{BCc3RzIGO0O\|NFKG23dHHueEBie3Onc4Pl[EBieyCyaH;zdIhwenmuYYTpc44hd2ZiQXv0JHRpejNyODDifUBqdW23bn;icI91fGmwZzygSWM2OCB;IEGuPEDPxE1w	MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTN{MkW2Okc,OjF\|MkK1OlY9N2F-
TC32	MoXsdWhVWyCjc4PhfS=>	NUT5fGlXeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGTDN\|Ih[2WubIO=	MYC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
A673	MnHEdWhVWyCjc4PhfS=>	NV7sb\|F[eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IFG2O\|Mh[2WubIO=	NISyRoQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
BT-37	MnfQdWhVWyCjc4PhfS=>	NWL2Roc5eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IFLUMVM4KGOnbHzz	NIC5TYY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
OHS-50	MYDxTHRUKGG\|c3H5	MoLQdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKE:KUz21NEBk\Wyucx?=	M4f4cFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Rh41	MWjxTHRUKGG\|c3H5	NW\zelNkeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGLoOFEh[2WubIO=	NVXScnNyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
SJ-GBM2	Mn;idWhVWyCjc4PhfS=>	MYnxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0pvR1LNNkBk\Wyucx?=	M1HuW\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SK-N-MC	M4nmUZFJXFNiYYPzZZk>	NHzZXGRyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU1utUk1OSyClZXzsdy=>	MkXsQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
NB-EBc1	MUXxTHRUKGG\|c3H5	M1rqe5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCQQj3FRoMyKGOnbHzz	MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SK-N-MC	MVrxTHRUKGG\|c3H5	M{HuR5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHNMNU5vTVOgZ4VtdHN?	M37rN\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
TC32	M2\F[pFJXFNiYYPzZZk>	Mn3mdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgWGM{OiClZXzsdy=>	MnjMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	ATF4 / p-S6K(T389) / S6K / p-eIF2α(S51) / eIF2α / 4EBP1 / eIF3b; PubMed: 28494858 Cell Rep 4E-BPs are required for mTOR control of ATF4. 4E-BP1/2 wild-type (WT), double knockout (DKO), or DKO MEFs stably expressing 4ebp1 (DKO + 4ebp1) were treated with vehicle (DMSO) or 250 nM Torin 1 for 4 hr. Cell extracts were analyzed by immunoblotting for the indicated proteins. LC3 / p62 / PARP / pAKT(S473) / p4EBP1(S65) / pS6K1(T389) / pS6(S235/236); PubMed: 24126619 Int J Oncol Cells were treated with increasing doses of the mTOR inhibitors, torin 1 (A) and rapamycin (B), in RPMI-1640 containing 10% FBS for 2 days. LC3 processing, p62 accumulation, PARP cleavage, AKT phosphorylation and mTOR pathway activity (indicated by phosphorylation of 4E-BP, S6K1 and S6) were analyzed by western blotting of total cell lysates. GAPDH was the control for protein loading. p-mTOR(S2481) / mTOR / rictor / Sin1 / p-Akt S473 / p-Akt T450 / p-Akt T308 / p-S6K1 T389 / S6K1; PubMed: 21965657 J Biol Chem mTOR kinase activity controls abundance of SIN1. MDA-MB-435 cells were incubated with specific mTOR inhibitor (0.5 μm TORIN) for 24 or 48 h and analyzed. Vinculin / p-S6; PubMed: 28757207 Mol Cell A375 cells were treated with Torin1 for 48 h and localization of proteins was visualized by confocal microscopy. Scale bar, 50 μm. Focal adhesion size was measured by Fiji program.	28494858 24126619 21965657 28757207
Immunofluorescence	lipin-1; PubMed: 28347999 FASEB J Inhibition of mTOR activity promoted the nuclear translocation of lipin-1. After treatment with or without torin 1 for 4 h, cells expressing HA-lipin-1 were fixed and stained with a rabbit HA antibody followed by Alexa 594–conjugated goat anti-rabbit secondary antibody. Nuclei were stained with DAPI. Scale bars, 20 μM.	28347999
Growth inhibition assay	Cell viability; PubMed: 28757207 Mol Cell Cancer cell lines were grown in complete media with/without mTOR inhibitor, Torin1 (250 nM). Media and Torin1 were replaced every 2 days and cells were counted at the indicated time points. Data are the means ± SD of three separate experiments performed in triplicate.	28757207

In vivo

Torin1 is efficacious at a dose of 20 mg/kg in a U87MG xenograft model and demonstrates good pharmacodynamic inhibition of downstream effectors of mTOR in tumor and peripheral tissues. ^[2]

Protocol

Kinase Assay:^[1]	- Collapse mTORC1 and mTORC2 in Vitro Kinase Assays: To produce soluble mTORC1, HEK-293T cell lines that stably express N-terminally FLAG-tagged Raptor are generated using vesicular stomatitis virus G-pseudotyped MSCV retrovirus. For mTORC2, similar HeLa cells that stably express N-terminally FLAG-tagged Protor-1 are generated. Both complexes are purified by lysing cells in 50 mm HEPES, pH 7.4, 10 mm sodium pyrophosphate, 10 mm sodium β-glycerophosphate, 100 mm NaCl, 2 mm EDTA, 0.3% CHAPS. Cells are lysed at 4 °C for 30 min, and the insoluble fraction is removed by microcentrifugation at 13,000 rpm for 10 min. Supernatants are incubated with FLAG-M2 monoclonal antibody-agarose for 1 h and then washed three times with lysis buffer and once with lysis buffer containing a final concentration of 0.5 M NaCl. Purified mTORC1 is eluted with 100 μg/mL 3×FLAG peptide in 50 mm HEPES, pH 7.4, 100 mm NaCl. Eluate can be aliquoted and stored at -80 °C. Substrates S6K1 and Akt1 are purified. Kinase assays are performed for 20 min at 30 °C in a final volume of 20 μL consisting of the kinase buffer (25 mm HEPES, pH 7.4, 50 mm KCl, 10 mm MgCl₂, 500 μm ATP) and 150 ng of inactive S6K1 or Akt1 as substrates. Reactions are stopped by the addition of 80 μL of sample buffer and boiled for 5 min. Samples are subsequently analyzed by SDS-PAGE and immunoblotting.
Cell Research:^[1]	- Collapse Cell lines: MEFs Concentrations: ~250 nM Incubation Time: 4 days Method: Cell viability is assessed with the CellTiter-Glo Luminescent Cell Viability Assay. On Day 0, 96-well plates are seeded with 500 cells per well and grown overnight. On Day 1, cells are treated with the appropriate compounds and subsequently analyzed on Days 3-5. For analysis, plates are incubated for 60 min at room temperature; 50 μL of CellTiter-Glo reagent is added to each well, and plates are mixed on an orbital shaker for 12 min. Luminescence is quantified on a standard plate luminometer. (Only for Reference)
Animal Research:^[2]	- Collapse Animal Models: U87MG xenograft model Dosages: 20 mg/kg Administration: Administered via i.p. once daily (Only for Reference)

References

[4] Dowling RJ, et al, Science, 2010, 328(5982), 1172-1176.

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Solubility (25°C)

In vitro	DMSO	2 mg/mL (3.29 mM)
	Water	Insoluble
	Ethanol	Insoluble

* 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 Torin 1 SDF

Molecular Weight	607.62
Formula	C₃₅H₂₈F₃N₅O₂
CAS No.	1222998-36-8
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	N/A
Smiles	CCC(=O)N1CCN(CC1)C2=C(C=C(C=C2)N3C(=O)C=CC4=CN=C5C=CC(=CC5=C43)C6=CC7=CC=CC=C7N=C6)C(F)(F)F

In vivo Formulation Calculator (Clear solution)

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

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Step 2: Enter the in vivo formulation (Different batches have different solubility ratios, please contact Selleck to provide you with the correct ratio)

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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)

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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 )

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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):
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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

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

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Molarity Calculator

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.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

Frequently Asked Questions

Question 1:
How to re-constitute the inhibitor for i.p. administration?
Answer:
S2827 Torin 1 can be dissolved in 5% DMSO/30% PEG 300/ddH2O at 0.25 mg/ml clearly, and in 10% DMSO/corn oil at 0.5 mg/ml, it is also a clear solution.

mTOR Signaling Pathway Map

mTOR Inhibitors with Unique Features

Selective mTOR inhibitor

Rapamycin (Sirolimus) : mTORC1-selective, IC50=~0.1 nM.
Most Potent mTOR Inhibitor

Rapamycin (Sirolimus) : mTOR, IC50=~0.1 nM.
FDA-approved mTOR Inhibitor

Temsirolimus (CCI-779, NSC 683864) : Approved by FDA for Renal Cell Carcinoma (RCC).
Newest mTOR Inhibitor

XL388 ^New : Highly potent, selective, ATP-competitive inhibitor of mTOR with IC50 of 9.9 nM, 1000-fold selectivity over the closely related PI3K kinases.

Related mTOR Products

MHY1485 ^New

MHY1485 is a potent, and cell-permeable mTOR activator, and also potently inhibits autophagy.
CHIR-99021 (CT99021) ^New

CHIR-99021 (CT99021) is a GSK-3α and GSK-3β inhibitor with IC50 of 10 nM and 6.7 nM, respectively. CHIR99201 does not exhibit cross-reactivity against cyclin-dependent kinases (CDKs) and shows a 350-fold selectivity toward GSK-3β compared to CDKs. CHIR99021 functions as a Wnt/β-catenin activator and induces autophagy.
Dorsomorphin (Compound C) ^New

Dorsomorphin (Compound C, BML-275) is a potent, reversible, selective AMPK inhibitor with K_i of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. Dorsomorphin selectively inhibits the BMP type I receptors ALK2, ALK3 and ALK6. Dorsomorphin is used in promoting specific cell differentiation and inducing cancer cell line autophagy.
Rapamycin (Sirolimus)

Rapamycin (Sirolimus, AY 22989, NSC-2260804) is a specific mTOR inhibitor with IC50 of ~0.1 nM HEK293 cells.
Everolimus (RAD001)

Everolimus (RAD001) is an mTOR inhibitor of FKBP12 with IC50 of 1.6-2.4 nM in a cell-free assay. Everolimus induces cell apoptosis and autophagy and inhibits tumor cells proliferation.
AZD8055

AZD8055 is a novel ATP-competitive mTOR inhibitor with IC50 of 0.8 nM in MDA-MB-468 cells with excellent selectivity (∼1,000-fold) against PI3K isoforms and ATM/DNA-PK. AZD8055 induces caspase-dependent apoptosis and also induces autophagy. Phase 1.

Features:First drug to inhibit both types of mTOR protein.
Temsirolimus (CCI-779)

Temsirolimus (CCI-779, NSC 683864) is a specific mTOR inhibitor with IC50 of 1.76 μM in a cell-free assay. Temsirolimus induces autophagy and apoptosis.
Sapanisertib (MLN0128)

Sapanisertib (MLN0128, INK 128, TAK-228) is a potent and selective mTOR inhibitor with IC50 of 1 nM in cell-free assays; >200-fold less potent to class I PI3K isoforms, superior in blocking mTORC1/2 and sensitive to pro-invasion genes (vs Rapamycin). Phase 1.
Tacrolimus (FK506)

Tacrolimus (FK506, FR900506, Fujimycin, Prograf) is a 23-membered macrolide lactone, it reduces peptidyl-prolyl isomerase activity in T cells by binding to the immunophilin FKBP12 (FK506 binding protein) creating a new complex. Tacrolimus also inhibits the phosphatase activity of calcineurin. Tacrolimus induces vascular endothelial autophagy.
KU-0063794

KU-0063794 is a potent and highly specific dual-mTOR inhibitor of mTORC1 and mTORC2 with IC50 of ~10 nM in cell-free assays; no effect on PI3Ks.

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Torin 1