Mirdametinib (PD0325901)

Name: Mirdametinib (PD0325901)
Brand: Selleck Chemicals
SKU: S1036
Rating: 5 (607 reviews)

For research use only.

Licensed by Pfizer Catalog No.S1036

607 publications

Mirdametinib (PD0325901) Chemical Structure

CAS No. 391210-10-9

Mirdametinib (PD0325901) is a selective and non ATP-competitive MEK inhibitor with IC50 of 0.33 nM in cell-free assays, roughly 500-fold more potent than CI-1040 on phosphorylation of ERK1 and ERK2. Phase 2.

Selleck's Mirdametinib (PD0325901) has been cited by 607 publications

Nature, 2021, 10.1038/s41586-020-03085-8

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Cell Stem Cell, 2021, S1934-5909(21)00169-7

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Cell Stem Cell, 2021, S1934-5909(21)00181-8

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Cell Res, 2021, 1-13

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Nature, 2020, 588(7838):509-514

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Cell, 2020, 30;181(3):621-636.e22.

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Cell, 2020, S0092-8674(20)31394-5

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Nat Genet, 2020, 10.1038/s41588-020-00744-4

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Nat Genet, 2020, 52(3):264-272

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Cell Stem Cell, 2020, S1934-5909(20)30541-5

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Cell, 2019, 179(3):687-702

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Nat Med, 2019, 25(1):130-140

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Nature, 2018, 553(7686):96-100

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Cell, 2018, 174(2):406-421

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Nat Methods, 2018, 15(3):213-220

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Cancer Discov, 2018, 8(5):568-581

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Cell Stem Cell, 2018, 23(3):382-395

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Cancer Cell, 2018, 33(6):985-1003

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Cell Stem Cell, 2017, 20(5):720-731

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Cell Stem Cell, 2017, 20(4):462-477

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Cancer Cell, 2017, 32(6):748-760

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Nature, 2016, 17;539(7629):452-455.

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Cancer Cell, 2016, 12;30(3):499-500

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Nature, 2015, 10.1038/nature14413

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Nature, 2015, 517(7534):391-5

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Cell, 2015, 160(1-2):161-76

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Cell, 2012, 21;151(5):937-50.

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Nat Methods , 2011, 8(6):487-93

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Mol Cell, 2021, S1097-2765(20)30989-8

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Sci Adv, 2021, 7(7)eabd7605

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Genome Biol, 2021, 22(1):176

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J Cell Biol, 2021, 220(1)e202002026

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Protein Cell, 2021, 10.1007/s13238-021-00837-8

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Stem Cell Reports, 2021, 16(1):29-38

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Cancer Lett, 2021, 510:37-47

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Sci Signal, 2021, 14(683)eabd9943

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Cancers (Basel), 2021, 13(6)1205

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Angiogenesis, 2021, 10.1007/s10456-021-09772-y

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Int J Mol Sci, 2021, 22(6)3028

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Phytomedicine, 2021, 80:153387

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Genes Brain Behav, 2021, e12727

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Exp Cell Res, 2021, S0014-4827(21)00024-0

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Stem Cells Dev, 2021, 10.1089/scd.2021.0020

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Adv Biol Regul, 2021, S2212-4926(20)30091-9

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Stem Cell Reports, 2021, 16(2):354-369

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Cancers (Basel), 2021, 13(4)621

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PLoS Pathog, 2021, 17(2):e1009303

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Cell Calcium, 2021, 95:102367

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Cell Rep, 2021, 34(8):108772

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Pharmaceuticals (Basel), 2021, 14(7)614

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Oncotarget, 2021, 12(9):878-890

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Cell Res, 2020, 30(1):21-33

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J Clin Invest, 2020, 139807

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Nucleic Acids Res, 2020, 48(20):11452-11467

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Genes Dev, 2020, 1;34(9-10):637-649

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Mol Syst Biol, 2020, 16(10):e9518

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Aging Cell, 2020, 19(9):e13210

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Elife, 2020, 9e60541

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Stem Cell Res, 2020, 49:102097

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Cancers (Basel), 2020, 27;12(5)pii: E1087

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Cancers (Basel), 2020, 12(10)E2951

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Br J Cancer, 2020, 10.1038/s41416-020-0952-1

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FASEB J, 2020, 34(5):7178-7191

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FASEB J, 2020, 10.1096/fj.202001021R

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Cancer Discov, 2020, 4;CD-20-0329

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Cancer Discov, 2020, CD-20-0706

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Mol Cancer Ther, 2020, 10.1158/1535-7163.MCT-19-1017

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FEBS J, 2020, 287(1):122-144

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Int J Biol Sci, 2020, 16(15):3085-3099

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Biol Reprod, 2020, ioaa216

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Toxicol In Vitro, 2020, 5;66:104852

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Transl Oncol, 2020, 13(4):100751

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J Neurosci Methods, 2020, 330:108486

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Biochem Biophys Res Commun, 2020, 23;S0006-291X(20)30951-7

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Oral Dis, 2020, 10.1111/odi.13638

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Mol Biol Rep, 2020, 10.1007/s11033-020-05969-4

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J Vis Exp, 2020, (156)

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Nucleic Acids Res, 2020, 10.1093

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Elife, 2020, 9:e56008

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Theriogenology, 2020, 146:58-70

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Theriogenology, 2020, 146:120-132

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Neurooncol Adv, 2020, 2(1):vdaa067

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J Biomed Res, 2020, 35(1):36-46

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Int J Immunopathol Pharmacol, 2020, Dec;34:2058738420909041

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Sci Rep, 2020, 10(1):13124

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Cell Rep, 2020, 30(2):510-524

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Front Cell Dev Biol, 2020, 8:482

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Genome Res, 2019, 29(10):1622-1634

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Proc Natl Acad Sci U S A, 2019, 116(26):12986-12995

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PLoS Biol, 2019, 17(3):e3000178

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Haematologica, 2019, 10.3324/haematol.2019.223024

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Cell Syst, 2019, 8(5):427-445

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Kidney Int, 2019, 96(4):927-941

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Cell Rep, 2019, 29(3):573-588

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Pigment Cell Melanoma Res, 2019, 32(6):829-841

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Cell Chem Biol, 2019, 26(3):366-377

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Exp Mol Med, 2019, 51(11):135

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Front Immunol, 2019, 10:2020

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Cancer Discov, 2019, 10.1158/2159-8290.CD-19-0209

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Aging (Albany NY), 2019, 11(22):10513-10531

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Carcinogenesis, 2019, 10.1093/carcin/bgz200

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Am J Cancer Res, 2019, 9(6):1282-1292

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PLoS One, 2019, 14(3):e0211134

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Theriogenology, 2019, 10.1016/j.theriogenology.2019.11.022

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SLAS Technol, 2019, 24(1):28-40

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Blood Adv, 2019, 3(21):3214-3227

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Nat Cell Biol, 2018, 20(4):400-412

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Nat Biomed Eng, 2018, 2(8):578-588

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Cell Commun Signal, 2015, 13:26

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EMBO Mol Med, 2015, 7(9):1104-18

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Oncotarget, 2015, 6(34):36400-17

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Oncotarget, 2015,

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Oncotarget, 2015, 6(35):38061-78

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Cell Biology International Reports, 2015, 10.1002/cbi3.10019

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Oncotarget, 2015, 6(5):2951-65

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Oncotarget, 2015, 6(35):38061-78

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Proc Natl Acad Sci USA, 2014, 111(29):10678-83

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Oncogene, 2014, 33(12):1590-600

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Development, 2014, 141(21):4127-38

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Mol Cancer Ther, 2014, 13(8):2073-80

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Hum Reprod, 2014, 29(5):997-1010

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J Immunol, 2014, 192(4):1351-5

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J Biol Chem, 2014, 10.1074/jbc.M114.580076

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Cell Signal, 2014, 26(10):2276-2283

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Stem Cells Dev, 2014, 23(17):2030-45

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Biol Reprod, 2014, 91(4):88

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Pancreas, 2014, 43(1):88-92

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PLoS One, 2014, 9(10):e111146

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PLoS One, 2014, 9(4):e92304

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PLoS One, 2014, 9(1):e85089

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Blood, 2013, 122,215045

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Proc Natl Acad Sci USA, 2013, 110(10):4015-20

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Purity & Quality Control

Choose Selective MEK Inhibitors

Biological Activity

Description

Targets

MEK ^[1]
(Cell-free assay)

0.33 nM

In vitro

PD0325901 shows higher permeability than CI-1040, another MEK inhibitor. PD0325901 should be able to achieve higher systemic exposures than CI-1040. ^[1] PD0325901 is exquisitely specific and highly potent against purified MEK, revealing a K_i^app of 1 nM against activated MEK1 and MEK2. ^[2] PD0325901 is roughly 500-fold more potent than CI-1040 with respect to its cellular effects on phosphorylation of ERK1 and ERK2, displaying subnanomolar activity. ^[2] PD0325901 prevents the growth of melanoma cell lines. PD0325901 inhibits the growth of TPC-1 cells and K2 cells with GI50 of 11 nM and 6.3 nM, respectively. ^[3] PD0325901 significantly prevents the the growth of PTC cells harboring a BRAF mutation at very low concentration (10 nM) and only moderately increases the growth of the PTC cells carrying the RET/PTC1 rearrangement at the same concentration. PD0325901 effectively inhibits the phosphorylation of ERK1/2 in multiple PTC cell lines. ^[3]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
A549	MlrnTY5pcWKrdHnvckBw\iCPRVuxJIlvKGi3bXHu	NWD2T45JOTBidV2=	M3q3OlEhcHJ?	M3y2O2lvcGmkaYTpc44hd2ZiTVXLNUBqdiCqdX3hckBCPTR7IHPlcIx{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDpckBxTXKtMT:yJIxmfmWuIHH0JFExKHWPIHHmeIVzKDFiaIKgZpkhX2W\|dHXyckBjdG:2dHnu[{BidmGueYPpdy=>	NIS1NoY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUe2OlY{Oyd-MkW3OlY3OzN:L3G+
PANC1	MYfJcohq[mm2aX;uJI9nKE2HS{GgbY4hcHWvYX6=	NVG2TIt3OTBidV2=	MXGxJIhz	NVrTNY9EUW6qaXLpeIlwdiCxZjDNSWsyKGmwIHj1cYFvKFCDTlOxJINmdGy\|IHHzd4V{e2WmIHHzJJJm\HWldHnvckBqdiCyRYLrNU8zKGyndnXsJIF1KDFyIIXNJIFnfGW{IEGgbJIh[nliV3XzeIVzdiCkbH;0eIlv\yCjbnHsfZNqew>?	M3nWNVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{[2OlM{Lz5{NUe2OlY{OzxxYU6=
A549	MVvJcohq[mm2aX;uJI9nKE2Ha{GvNkBqdiCqdX3hci=>		NVjyW5BbPzVibXnudy=>	M4PvPWlvcGmkaYTpc44hd2ZiTVXrNU8zKGmwIHj1cYFvKEF3NEmgZ4VtdHNiYYPz[ZN{\WRiYYOg[IVkemWjc3WgbY4hTVKNIIDoc5NxcG:{eXzheIlwdiCjZoTldkA4PSCvaX7zJIJ6KFenc4Tldo4h[myxdITpcoch[W6jbInzbZM>	Mnu1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN\|OUi0OVMoRjJ\|M{m4OFU{RC:jPh?=
CCD-1070sk	MVXJcohq[mm2aX;uJI9nKE2Ha{GvNkBqdiCqdX3hci=>		MXK3OUBucW6\|	MkHVTY5pcWKrdHnvckBw\iCPRXuxM\|IhcW5iaIXtZY4hS0OGLUGwO\|B{cyClZXzsd{Bie3Onc4Pl[EBieyCmZXPy[YF{\SCrbjDFVmsheGixc4Doc5J6dGG2aX;uJIFnfGW{IEe1JI1qdnNiYomgW4V{fGW{bjDicI91fGmwZzDhcoFtgXOrcx?=	MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzN7OES1N{c,OjN\|OUi0OVM9N2F-
A375	MmXHTY5pcWKrdHnvckBw\iCPRXuxM\|IhcW5iaIXtZY4>		Ml\NO\|UhdWmwcx?=	MVjJcohq[mm2aX;uJI9nKE2Ha{GvNkBqdiCqdX3hckBCOzd3IHPlcIx{KGG\|c3Xzd4VlKGG\|IHTlZ5Jm[XOnIHnuJGVTUyCyaH;zdIhwenmuYYTpc44h[W[2ZYKgO\|UhdWmwczDifUBY\XO2ZYLuJIJtd3S2aX7nJIFv[Wy7c3nz	NULReYVTRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOzPVg1PTNpPkKzN\|k5PDV\|PD;hQi=>
MCF7	NVvSRYdzUW6qaXLpeIlwdiCxZjDNSYsyNzJiaX6gbJVu[W5?		NYi4ToFWPzVibXnudy=>	NEXKZ4NKdmirYnn0bY9vKG:oIF3Fb\|EwOiCrbjDoeY1idiCPQ1[3JINmdGy\|IHHzd4V{e2WmIHHzJIRm[3KnYYPlJIlvKEWUSzDwbI9{eGixconsZZRqd25iYX\0[ZIhPzVibXnud{BjgSCZZYP0[ZJvKGKub4T0bY5oKGGwYXz5d4l{	NFnQWVQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{O5PFQ2Oyd-MkOzPVg1PTN:L3G+
NIH/3T3	NHflNVFKdmirYnn0bY9vKG:oIF3FT\|EwVUWNMjDpckBud3W\|ZR?=		M4DrOlc2KG2rboO=	MVnJcohq[mm2aX;uJI9nKE2HS{GvUWVMOiCrbjDtc5V{\SCQSVivN3Q{KGOnbHzzJIF{e2W\|c3XkJIF{KGSnY4LlZZNmKGmwIFXST{BxcG:\|cHjvdplt[XSrb36gZYZ1\XJiN{WgcYlveyCkeTDX[ZN1\XKwIHLsc5R1cW6pIHHuZYx6e2m\|	NFfkS5c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{O5PFQ2Oyd-MkOzPVg1PTN:L3G+
HT-29	MY\Jcohq[mm2aX;uJI9nKE2HSzDpckBpfW2jbh?=			M4\2c2lvcGmkaYTpc44hd2ZiTVXLJIlvKGi3bXHuJGhVNTJ7IHPlcIx{KHinbn;ndoFnfGWmIHnuJGJCVEJxYzDueU9vfSCvb4Xz[UB1fW2xcjDhd5Nme3OnZDDhd{BxcG:\|cHjvdplt[XSnZDDFVmshdGW4ZXygZZQhdWG6aX31cUB1d2yncnHicIUh\G:\|ZTDh[I1qdmm\|dHXy[YQh[XNicH:=	M3ryVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzM{G2NlE5Lz5{MUOxOlIyQDxxYU6=
HT-29	NYC2bndWUW6qaXLpeIlwdiCxZjDNSWshcW5iaIXtZY4>			MoOzTY5pcWKrdHnvckBw\iCPRVugbY4hcHWvYX6gTHQuOjliY3XscJMhgGWwb3fyZYZ1\WRiaX6gRmFNSi:lIH71M452KG2xdYPlJIJz[WmwIHHzd4V{e2WmIHHzJJBpd3OyaH;yfYxifGWmIFXST{Bt\X[nbDDheEBu[XirbYXtJJRwdGW{YXLs[UBld3OnIHHkcYlvcXO2ZYLl[EBieyCybx?=	MoX0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF\|MU[yNVgoRjJzM{G2NlE5RC:jPh?=
HeLa	MVLDc45k\W62cnH0bY9vNWSncHXu[IVvfCCrbnjpZol1cW:wIH;mJGVTUzFuIFXST\|IheGixc4Doc5J6dGG2aX;uJIlvKEWJRj3zeIlufWyjdHXk			M{TxR2NwdmOnboTyZZRqd25vZHXw[Y5l\W62IHnubIljcXSrb36gc4YhTVKNMTygSXJMOiCyaH;zdIhwenmuYYTpc44hcW5iRVfGMZN1cW23bHH0[YQhUGWOYTDj[Yxtew>?	MnvTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTd6NUCyNVQoRjF5OEWwNlE1RC:jPh?=
HeLa	NH3UW4tEd26lZX70doF1cW:wLXTldIVv\GWwdDDpcohq[mm2aX;uJI9nKEWUS{WgdIhwe3Cqb4L5cIF1cW:wIIPobYZ1KGmwIFXHSk1{fGmvdXzheIVl			MXzDc45k\W62cnH0bY9vNWSncHXu[IVvfCCrbnjpZol1cW:wIH;mJGVTUzVicHjvd5Bpd3K7bHH0bY9vKHOqaX\0JIlvKEWJRj3zeIlufWyjdHXkJGhmVGFiY3XscJM>	M3iwd\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF5OEWwNlE1Lz5zN{i1NFIyPDxxYU6=
rhabdomyosarcoma	M3;sW2lv\HWldHnvckBw\iCPRVuxM\|IheGixc4Doc5J6dGG2aX;uJIlvKGi3bXHu	M2\qd\|AvPCC2bzCxNEB2VQ>?	M2HlSFEhcHJ?	MVTJcoR2[3Srb36gc4YhVUWNMT:yJJBpd3OyaH;yfYxifGmxbjDpckBpfW2jbjDybIFj\G:veX;zZZJkd22jIHPlcIx{KGmwZnXjeIVlKHerdHigSXY4OSCEQ{C4JGdWPDd3MUK3JIF1KDBwNDD0c{AyOCC3TTDwdoUufHKnYYTl[EBnd3JiMTDodkBnd2yub4fl[EBjgSC4aYLhcEBqdm[nY4Tpc44hdWWjc4Xy[YQh[W[2ZYKgNlQhcHK\|IHL5JJdme3Sncn6gZoxwfHSrbnegZY5idHm\|aYO=	MofkQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjd{OEixPFYoRjJ5Mki4NVg3RC:jPh?=
rhabdomyosarcoma	MVXJcohq[mm2aX;uJI9nKE2HS{GgdIhwe3Cqb4L5cIF1cW:wIHnuJIh2dWGw	MXuwMlQhfG9iMUCgeW0>	MUexJIhz	NH\1UFVKdmirYnn0bY9vKG:oIF3FT\|EheGixc4Doc5J6dGG2aX;uJIlvKGi3bXHuJJJp[WKmb335c5NiemOxbXGgZ4VtdHNiaX7m[YN1\WRid3n0bEBGXjdzIFLDNFghT1V2N{WxNlch[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBGWktzL{KgdIhwe3Cqb4L5cIF1cW:wIHH0JFAvPCC2bzCxNEB2VSCycnWteJJm[XSnZDDmc5IhOSCqcjDmc4xtd3enZDDifUB3cXKjbDDpcoZm[3Srb36gcYVie3W{ZXSgZYZ1\XJiMkSgbJJ{KGK7IIfld5Rmem5iYnzveJRqdmd?	NVH6O4pzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkeyPFgyQDZpPkK3Nlg5OTh4PD;hQi=>
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HCC2998	NF[0PWNIem:5dHigbY5pcWKrdHnvckBie3OjeR?=			NWHPPWVHUW6qaXLpeIlwdiCxZjDoeY1idiCKQ1OyPVk5KGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVAhRSByLkCzN\|Y3KM7:TT6=	NXfC[454RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTB5M{[xM{c,W0GQR1XSQE9iRg>?
HO-1-N-1	M4TzNGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7			M4nyO2lvcGmkaYTpc44hd2ZiaIXtZY4hUE9vMT3OMVEh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NEA:KDBwMEO0OFMh\|ryPLh?=	NYrmPIRMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTB5M{[xM{c,W0GQR1XSQE9iRg>?
SW756	NUnqRnpVT3Kxd4ToJIlvcGmkaYTpc44h[XO\|YYm=			NYHub3lTUW6qaXLpeIlwdiCxZjDoeY1idiCVV{e1OkBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwJF0hOC5yM{S0OUDPxE1w	M1[1SVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUxPzN4MT:nQnNCVkeHUkyvZV4>
NCI-H1437	NI\mT25Iem:5dHigbY5pcWKrdHnvckBie3OjeR?=			Ml3xTY5pcWKrdHnvckBw\iCqdX3hckBPS0lvSEG0N\|ch[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NEA:KDBwMEO0OFkh\|ryPLh?=	NHPUZnQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2ODd\|NkGvK\|5USU6JRWK8M4E,
NCI-H747	NEfidYJIem:5dHigbY5pcWKrdHnvckBie3OjeR?=			MVrJcohq[mm2aX;uJI9nKGi3bXHuJG5EUS2KN{S3JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUCgQUAxNjB\|NEm4JO69VS5?	MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NFc{PjFxJ{7TRW5ITVJ:L3G+
SK-MEL-2	MVXHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>?			NVq2Zot{UW6qaXLpeIlwdiCxZjDoeY1idiCVSz3NSWwuOiClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR\|UxKD1iMD6wN\|UzKM7:TT6=	MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NFc{PjFxJ{7TRW5ITVJ:L3G+
MZ2-MEL	MnW0S5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?			NGjQOXFKdmirYnn0bY9vKG:oIHj1cYFvKE2cMj3NSWwh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NEA:KDBwMEO1OlUh\|ryPLh?=	NEixfYk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2ODd\|NkGvK\|5USU6JRWK8M4E,
PSN1	MXvHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>?			M1jENGlvcGmkaYTpc44hd2ZiaIXtZY4hWFOQMTDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG\|c3H5MEBKSzVyIE2gNE4xOzh2NTFOwG0v	NWXTOWRXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTB5M{[xM{c,W0GQR1XSQE9iRg>?
CAL-39	M2XrWGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7			MW\Jcohq[mm2aX;uJI9nKGi3bXHuJGNCVC1\|OTDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG\|c3H5MEBKSzVyIE2gNE4xOzlyNDFOwG0v	NGPKfmM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2ODd\|NkGvK\|5USU6JRWK8M4E,
LOXIMVI	MYTHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>?			M{jqemlvcGmkaYTpc44hd2ZiaIXtZY4hVE:[SV3WTUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwJF0hOC5yM{mzPUDPxE1w	MnrTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVA4OzZzLze+V2FPT0WUPD;hQi=>
COLO-792	NXPUTI11T3Kxd4ToJIlvcGmkaYTpc44h[XO\|YYm=			MUnJcohq[mm2aX;uJI9nKGi3bXHuJGNQVE9vN{myJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUCgQUAxNjB2M{G1JO69VS5?	M1q4TFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUxPzN4MT:nQnNCVkeHUkyvZV4>
CAL-27	NEjHUnpIem:5dHigbY5pcWKrdHnvckBie3OjeR?=			MYPJcohq[mm2aX;uJI9nKGi3bXHuJGNCVC1{NzDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG\|c3H5MEBKSzVyIE2gNE4xPDR7MTFOwG0v	MXK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NFc{PjFxJ{7TRW5ITVJ:L3G+
AsPC-1	NWPiOI5rT3Kxd4ToJIlvcGmkaYTpc44h[XO\|YYm=			MkjuTY5pcWKrdHnvckBw\iCqdX3hckBCe1CFLUGgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3MDC9JFAvODR3Mkig{txONg>?	M{L3blxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUxPzN4MT:nQnNCVkeHUkyvZV4>
NCI-H2291	NXPDO2hHT3Kxd4ToJIlvcGmkaYTpc44h[XO\|YYm=			NGH3NZpKdmirYnn0bY9vKG:oIHj1cYFvKE6FST3INlI6OSClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR\|UxKD1iMD6wOFY1PiEQvF2u	MkfUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVA4OzZzLze+V2FPT0WUPD;hQi=>
RCM-1	MoLPS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?			NETJW\|FKdmirYnn0bY9vKG:oIHj1cYFvKFKFTT2xJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUCgQUAxNjB2Nki1JO69VS5?	NVnoc283RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTB5M{[xM{c,W0GQR1XSQE9iRg>?
NCI-H292	MoTQS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?			M2LKdmlvcGmkaYTpc44hd2ZiaIXtZY4hVkOLLViyPVIh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NEA:KDBwMES3N\|kh\|ryPLh?=	M17kZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUxPzN4MT:nQnNCVkeHUkyvZV4>
WM-115	MUnHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>?			M{PSXmlvcGmkaYTpc44hd2ZiaIXtZY4hX01vMUG1JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUCgQUAxNjB2OEWg{txONg>?	NIL2SoE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2ODd\|NkGvK\|5USU6JRWK8M4E,
RT-112	NH63T5lIem:5dHigbY5pcWKrdHnvckBie3OjeR?=			MU\Jcohq[mm2aX;uJI9nKGi3bXHuJHJVNTFzMjDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG\|c3H5MEBKSzVyIE2gNE4xPDh6MjFOwG0v	M1voOFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUxPzN4MT:nQnNCVkeHUkyvZV4>
HT-29	MnjpS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?			MXjJcohq[mm2aX;uJI9nKGi3bXHuJGhVNTJ7IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO\|YYmsJGlEPTBiPTCwMlA2ODR7IN88UU4>	MlPoQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVA4OzZzLze+V2FPT0WUPD;hQi=>
RKO	NFe2NFJIem:5dHigbY5pcWKrdHnvckBie3OjeR?=			M2LPfWlvcGmkaYTpc44hd2ZiaIXtZY4hWkuRIHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO\|YYmsJGlEPTBiPTCwMlA2OjB{IN88UU4>	NWnwNmsxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTB5M{[xM{c,W0GQR1XSQE9iRg>?
KY821	MYDHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>?			NWfvb\|NuUW6qaXLpeIlwdiCxZjDoeY1idiCNWUiyNUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwJF0hOC5yNUOzJO69VS5?	M3LWelxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUxPzN4MT:nQnNCVkeHUkyvZV4>
LB1047-RCC	MY\Hdo94fGhiaX7obYJqfGmxbjDhd5NigQ>?			M{e4NWlvcGmkaYTpc44hd2ZiaIXtZY4hVEJzMES3MXJESyClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR\|UxKD1iMD6wOVk3PSEQvF2u	NHTybI49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2ODd\|NkGvK\|5USU6JRWK8M4E,
SW1116	Ml[zS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?			M4HjWGlvcGmkaYTpc44hd2ZiaIXtZY4hW1dzMUG2JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUCgQUAxNjB4MES5JO69VS5?	NGf1e4k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2ODd\|NkGvK\|5USU6JRWK8M4E,
P12-ICHIKAWA	NHW1ZnVIem:5dHigbY5pcWKrdHnvckBie3OjeR?=			M4LwRmlvcGmkaYTpc44hd2ZiaIXtZY4hWDF{LVnDTGlMSVeDIHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO\|YYmsJGlEPTBiPTCwMlA3OjJ5IN88UU4>	M4PjcVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUxPzN4MT:nQnNCVkeHUkyvZV4>
HCC70	NEXiXVZIem:5dHigbY5pcWKrdHnvckBie3OjeR?=			NYjDe3JGUW6qaXLpeIlwdiCxZjDoeY1idiCKQ1O3NEBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwJF0hOC5yNkOwNUDPxE1w	MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NFc{PjFxJ{7TRW5ITVJ:L3G+
MIA-PaCa-2	M4\Wfmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7			NFnmWYpKdmirYnn0bY9vKG:oIHj1cYFvKE2LQT3QZWNiNTJiY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OCB;IECuNFY{PTNizszNMi=>	MlP3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVA4OzZzLze+V2FPT0WUPD;hQi=>
LoVo	NEfKT4xIem:5dHigbY5pcWKrdHnvckBie3OjeR?=			NVLnNIs1UW6qaXLpeIlwdiCxZjDoeY1idiCOb2\vJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUCgQUAxNjB4NUK5JO69VS5?	NH62UJE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2ODd\|NkGvK\|5USU6JRWK8M4E,
LB2241-RCC	MWDHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>?			Mn33TY5pcWKrdHnvckBw\iCqdX3hckBNSjJ{NEGtVmNEKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVAhRSByLkC2OVUzKM7:TT6=	NHXweJo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2ODd\|NkGvK\|5USU6JRWK8M4E,
GAK	MXrHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>?			NIniNGRKdmirYnn0bY9vKG:oIHj1cYFvKEeDSzDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG\|c3H5MEBKSzVyIE2gNE4xPjZ6NzFOwG0v	MkHrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVA4OzZzLze+V2FPT0WUPD;hQi=>
RD	MYLHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>?			Moi5TY5pcWKrdHnvckBw\iCqdX3hckBTTCClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR\|UxKD1iMD6wOlcyKM7:TT6=	MmnSQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVA4OzZzLze+V2FPT0WUPD;hQi=>
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LB771-HNC	NVfhVVF6T3Kxd4ToJIlvcGmkaYTpc44h[XO\|YYm=			NIXZVXZKdmirYnn0bY9vKG:oIHj1cYFvKEyEN{exMWhPSyClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR\|UxKD1iM{iuOFc1OyEQvF2u	M1LPfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUxPzN4MT:nQnNCVkeHUkyvZV4>
UMC-11	NXPRd3NrT3Kxd4ToJIlvcGmkaYTpc44h[XO\|YYm=			NEjXW4pKdmirYnn0bY9vKG:oIHj1cYFvKFWPQz2xNUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwJF0hPTJwM{GyOEDPxE1w	NEXBV4c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2ODd\|NkGvK\|5USU6JRWK8M4E,

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Assay

Methods	Test Index	PMID
Western blot	p-ERK / p-AKT / Cyclin D1 / p27; PubMed: 22573716 Cancer Res parental or MEK inhibitor-resistant clonal populations (1182, 1183, and 1187) were treated with increasing doses of PD0325901 for 24 hours and subjected to immunoblot analysis using the indicated antibodies. p-p70S6K(T389) / p4EBP1(S65) / pS6(S235); PubMed: 27699948 Cancer Sci Sensitive (MKN-45, OKAJIMA, HSC-57, GUS, NUGC-4, OCUM-1, SNU-719, and IM95) and resistant (SH-10-TC, MKN-1, HSC-39, NCI-N87, H-111-TC, KE-97, SNU-484, and TMK-1) cell lines were treated with DMSO or PD0325901 (0.1 or 1 μM) for 24 h and then subjected to Western blotting using antibodies against pERK, pAKT, p-p70S6K, p4EBP1, pS6, and GAPDH. cleaved PARP; PubMed: 22573716 Cancer Res NF1-deficient U251 or LN229 GBM cells were treated with PD0325901 for 4 days and subjected to immunoblot analysis using the indicated antibodies. DR5; PubMed: 25867065 Oncogene The indicated cancer cell lines were exposed to the given concentrations of the inhibitors as indicated for 16 h.	22573716 27699948 25867065
Immunofluorescence	Fibronectin / Actin / pFAK; PubMed: 28187762 BMC Cancer Representative immunofluorescence images of FNMA by GBM-3 cells treated either with DMSO (b) or PD0325901 (c). Fibronectin is depicted in green and DAPI (blue) was used as counterstain. PD0325901 did not appear to induce FNMA by GBM-3 cells. Rhodamine-phalloidin staining of actin in DMSO-treated (d) or PD0325901-treated GBM-3 cells (e). Note significant cell shape change and actin fiber organization. Scale bar in (e) is 5 μm. Triple stain for actin (red), p-FAK (green) and DAPI (blue) in DMSO-treated (f) and PD0325901-treated (g) GBM-3 cells. PD0325901 appears to induce the localization of p-FAK at sites of cell-ECM attachment. Thirty-micron thick z-stack of DMSO (h) and PD0325901-treated (i) collected by confocal microscopy of multicellular aggregates of GBM-3. Note marked change in actin organization from cortical to stress fibers. Scale bar in (i) is 30 μm. ZO-1; PubMed: 25394671 EMBO Rep 16HBE cells were fixed and stained for ZO-1 and DNA. Scale bar, 20 μm.	28187762 25394671

In vivo

The improved potency of PD0325901 relative to CI-1040 is evident. A single oral dose of PD0325901 (25 mg/kg) inhibits phosphorylation of ERK by more than 50% at 24 hours post-dosing. In contrast, CI-1040 at a much higher dose (150 mg/kg) only inhibit pERK levels for roughly 8 hours, returning to control levels by 24 hours after treatment. ^[2] Therefore, the dose required to produce a 70% incidence of complete tumor responses (C26 model) is 25 mg/kg/day versus 900 mg/kg/day for PD0325901 and CI-1040, respectively. Anticancer activity of PD 0325901 has been demonstrated for a broad spectrum of human tumor xenografts. ^[2] After 1 week of oral administration of PD0325901 (20–25 mg/kg/day) in mice, no tumor growth is detected in mice inoculated with PTC cells bearing a BRAF mutation. ^[3] For PTC with the RET/PTC1 rearrangement, the average tumor volume of the orthotopic tumor is decreased by 58% as compared with controls. In conclusion, PTC cells carrying a BRAF mutation are more sensitive to PD0325901 than are PTC cells carrying the RET/PTC1 rearrangement. ^[3]

Protocol

Kinase Assay: ^[1]	- Collapse In vitro cascade assay: Incorporation of ³²P into myelin basic protein (MBP) is assayed in the presence of a glutathione S-transferase fusion protein containing p44MAP kinase (GST-MAPK) and a glutathione S-transferase protein containing p45MEK (GST-MEK). The assay solution contained 20 mM HEPES, pH 7.4, 10 mM MgCl₂, 1 mM MnCl₂, 1 mM EGTA, 50 mM [gamma-³²P]ATP, 10 mg GST-MEK, 0.5 mg GST-MAPK and 40 mg MBP in a final volume of 100 mL. Reactions are stopped after 20 minutes by addition of trichloroacetic acid and filtered through a GF/C filter mat. ³²P retained on the filter mat is determined using a 1205 Betaplate. PD0325901 is assessed at various dose ranges in order to determine dose response curves.
Cell Research: ^[3]	- Collapse Cell lines: PTC cells Concentrations: 0.1 nM- 1 μM Incubation Time: 48 hours Method: PTC cells (1 × 10⁴) are seeded in 24-well plates with 1 mL of medium for 4 days in a 37 °C incubator. MEK inhibitor PD0325901 at varying concentrations is added to the cells in triplicate on day 0. MTT dissolved in 0.8% NaCl solution at 5 mg/mL is added to each well (0.2 mL) on day 2 to test GI50 or every day for cell growth curves. The cells are incubated at 37 °C for 3 hours with MTT. The liquid is then aspirated from the wells and discarded. Stained cells are dissolved in 0.5 mL of DMSO and their absorption at 570 nm is measured using a Synergy HT multidetection microplate reader. For GI50, cell growth is calculated as 100 × (T − T₀)/(C − T₀), where T is the optical density of the wells treated with inhibitors after a 48-hour period, T₀ is the optical density at time zero, and C is the control optical density with DMSO only. (Only for Reference)
Animal Research: ^[3]	- Collapse Animal Models: Ncr-nu/nu mice bearing PTC cells Dosages: 20-25 mg/kg Administration: Oral gavage (Only for Reference)

References

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Solubility (25°C)

In vitro	DMSO	96 mg/mL (199.09 mM)
	Ethanol	40 mg/mL (82.95 mM)
	Water	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 5%DMSO+40%PEG300+5%Tween80+50%ddH2O For best results, use promptly after mixing.	5mg/mL

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

Chemical Information Download Mirdametinib (PD0325901) SDF

Molecular Weight	482.19
Formula	C₁₆H₁₄F₃IN₂O₄
CAS No.	391210-10-9
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	N/A
Smiles	C1=CC(=C(C=C1I)F)NC2=C(C=CC(=C2F)F)C(=O)NOCC(CO)O

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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
NCT02510001	Completed	Drug: PF-02341066\|Drug: PD-0325901\|Drug: Binimetinib	Solid Tumor\|Colorectal Cancer	University of Oxford\|Queen''s University Belfast\|Oxford University Hospitals NHS Trust\|Velindre NHS Trust\|University Hospital Antwerp\|Hospital Vall d''Hebron\|Saint Antoine University Hospital\|European Georges Pompidou Hospital\|Pfizer\|University of Turin Italy\|Belfast Health and Social Care Trust\|Beaumont Hospital\|European Commission\|Array BioPharma\|University of Paris 5 - Rene Descartes	November 2014	Phase 1
NCT02096471	Completed	Drug: PD-0325901	Neurofibromatosis Type 1 and Growing or Symptomatic Inoperable PN	University of Alabama at Birmingham	June 2014	Phase 2
NCT02022982	Active not recruiting	Drug: Palbociclib\|Drug: PD-0325901	KRAS Mutant Non-Small Cell Lung Cancer\|Solid Tumors	Dana-Farber Cancer Institute	January 2014	Phase 1\|Phase 2
NCT01347866	Terminated	Drug: PF-05212384\|Drug: PD-0325901\|Drug: irinotecan	Advanced Cancer	Pfizer	October 2011	Phase 1
NCT00174369	Terminated	Drug: PD-0325901	Carcinoma Non-Small-Cell Lung	Pfizer	November 2005	Phase 2

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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Frequently Asked Questions

Question 1:
Whether the inhibitor PD0325901 interacts with other targets other than MEK?
Answer:
PD0325901 has very high selectivity to MEK. In addition, it can also inhibits VEGF activity according to the reference: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2713590/

MEK Signaling Pathway Map

MEK Inhibitors with Unique Features

Selective MEK Inhibitor

Selumetinib (AZD6244) : MEK1-selective, IC50=14 nM.
FDA-approved MEK Inhibitor

Trametinib (GSK1120212) : Approved by FDA against BRAF V600E mutated metastatic melanoma.
Newest MEK Inhibitor

Binimetinib (MEK162, ARRY-162, ARRY-438162) : Potent inhibitor of MEK1/2 with IC50 of 12 nM.
Classic MEK Inhibitor

SL-327 : Water soluble MEK1/2 inhibitor, which can cross the blood-brain barrier.

Related MEK Products

Cobimetinib (GDC-0973) ^New

Cobimetinib (GDC-0973, RG7420) is a potent and highly selective MEK1 inhibitor with IC50 of 4.2 nM, showing more than 100-fold selectively for MEK1 over MEK2 and showed no significant inhibition when tested against a panel of more than 100 of serine-threonine and tyrosine kinases. Cobimetinib induces apoptosis. Phase 3.
BI-847325 ^New

BI-847325 is an orally bioavailable, and selective dual MEK/Aurora kinase inhibitor with IC50 of 3 nM, 25 nM, 15 nM, 25 nM, and 4 nM for Xenopus laevis Aurora B, human Aurora A and Aurora C, as well as human MEK1 and MEK2, respectively. Phase 1.
GDC-0623 ^New

GDC-0623 (G-868) is a potent and ATP-uncompetitive MEK1 inhibitor with K_i of 0.13 nM. Phase 1.
Trametinib (GSK1120212)

Trametinib (GSK1120212, JTP-74057, Mekinist) is a highly specific and potent MEK1/2 inhibitor with IC50 of 0.92 nM/1.8 nM in cell-free assays, no inhibition of the kinase activities of c-Raf, B-Raf, ERK1/2. Trametinib activates autophagy and induces apoptosis.

Features:More potent than PD0325901 or AZD6244.
Selumetinib (AZD6244)

Selumetinib (AZD6244, ARRY-142886) is a potent, highly selective MEK inhibitor with IC50 of 14 nM for MEK1 and Kd value of 530 nM for MEK2. It also inhibits ERK1/2 phosphorylation with IC50 of 10 nM, no inhibition to p38α, MKK6, EGFR, ErbB2, ERK2, B-Raf, etc. Selumetinib suppresses cell proliferation, migration and trigger apoptosis. Phase 3.

Features:First MEK inhibitor being tested in Phase II clinical trials.
U0126-EtOH

U0126-EtOH is a highly selective inhibitor of MEK1/2 with IC50 of 0.07 μM/0.06 μM in cell-free assays, 100-fold higher affinity for ΔN3-S218E/S222D MEK than PD98059. U0126 inhibits autophagy and mitophagy with antiviral activity.

Features:A chemically synthesized and highly selective inhibitor of both MEK1 and MEK2.
PD98059

PD98059 is a non-ATP competitive MEK inhibitor with IC50 of 2 μM in a cell-free assay, specifically inhibits MEK-1-mediated activation of MAPK; does not directly inhibit ERK1 or ERK2. PD98059 is a ligand for the aryl hydrocarbon receptor (AHR) and functions as an AHR antagonist.

Features:Does not inhibit c-Raf phosphorylated MEK1.
PD184352 (CI-1040)

PD184352 (CI-1040) is an ATP non-competitive MEK1/2 inhibitor with IC50 of 17 nM in cell-based assays, 100-fold more selective for MEK1/2 than MEK5. PD184352 (CI-1040) selectively induces apoptosis. Phase 2.

Features:First MEK inhibitor to begin clinical development.
Binimetinib (MEK162)

Binimetinib (MEK162, ARRY-162, ARRY-438162) is a potent inhibitor of MEK1/2 with IC50 of 12 nM in a cell-free assay. Binimetinib induces G1 cell cycle arrest and apoptosis in human NSCLC cell lines and induces autophagy. Phase 3.
Refametinib (RDEA119)

Refametinib (RDEA119, Bay 86-9766) is a potent, ATP non-competitive and highly selective inhibitor of MEK1 and MEK2 with IC50 of 19 nM and 47 nM, respectively.

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Mirdametinib (PD0325901)