I-BET151 (GSK1210151A)

Name: I-BET151 (GSK1210151A)
Brand: Selleck Chemicals
SKU: S2780
Rating: 5 (32 reviews)

For research use only.

Catalog No.S2780

32 publications

I-BET151 (GSK1210151A) Chemical Structure

CAS No. 1300031-49-5

I-BET151 (GSK1210151A) is a novel selective BET inhibitor for BRD2, BRD3 and BRD4 with IC50 of 0.5 μM, 0.25 μM, and 0.79 μM in cell-free assays, respectively.

Selleck's I-BET151 (GSK1210151A) has been cited by 32 publications

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

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

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

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

Cancer Cell, 2018, 34(6):922-938

PubMed: 30537514 ( click the link to review the publication )

Cancer Cell, 2018, 33(3):401-416

PubMed: 29533782 ( click the link to review the publication )

Cancer Discov, 2017, 7(3):302-321

PubMed: 28108460 ( click the link to review the publication )

J Clin Endocrinol Metab, 2021, dgaa986

PubMed: 33417713 ( click the link to review the publication )

Genome Biol, 2020, 21(1):269

PubMed: 33143730 ( click the link to review the publication )

Nat Commun, 2020, 14;11(1):1833

PubMed: 32286255 ( click the link to review the publication )

Int J Cancer, 2020, 10.1002/ijc.33000

PubMed: 32249419 ( click the link to review the publication )

Genomics Inform, 2020, 18(4):e37

PubMed: 33412753 ( click the link to review the publication )

J Mol Cell Biol, 2020, 11;12(5):359-371

PubMed: 31565729 ( click the link to review the publication )

Aging (Albany NY), 2020, 12(5):4547-4557

PubMed: 32163373 ( click the link to review the publication )

Cytotherapy, 2020, S1465-3249(20)30929-4

PubMed: 33246884 ( click the link to review the publication )

Int J Oncol, 2020, 56(6):1429-1441

PubMed: 32236593 ( click the link to review the publication )

Genome Med, 2020, 12(1):63

PubMed: 32669118 ( click the link to review the publication )

Clin Transl Med, 2020, 10(6):e181

PubMed: 33135348 ( click the link to review the publication )

EBioMedicine, 2019, 43:201-210

PubMed: 30975544 ( click the link to review the publication )

Epigenetics, 2019, 10.1080/15592294.2019.1656156

PubMed: 31423932 ( click the link to review the publication )

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

PubMed: 31015631 ( click the link to review the publication )

Mol Cell, 2018, 72(2):341-354

PubMed: 30270106 ( click the link to review the publication )

Nat Commun, 2018, 9(1):5378

PubMed: 30568163 ( click the link to review the publication )

Cancer Res, 2018, 78(2):572-583

PubMed: 29180474 ( click the link to review the publication )

J Immunol, 2018, 201(9):2744-2752

PubMed: 30249811 ( click the link to review the publication )

Sci Rep, 2018, 8(1):3521

PubMed: 29476067 ( click the link to review the publication )
Front Pharmacol, 2018, 9:1166

PubMed: 30386240 ( click the link to review the publication )

Cell Tissue Res, 2018, 374(3):577-585

PubMed: 30182276 ( click the link to review the publication )

Nat Commun, 2017, 8:14802

PubMed: 28378740 ( click the link to review the publication )

Nucleic Acids Res, 2017, 45(14):8403-8410

PubMed: 28854735 ( click the link to review the publication )

Mol Cancer Res, 2017, 15(9):1221-1229

PubMed: 28592703 ( click the link to review the publication )

Theranostics, 2016, 6(2):219-30

PubMed: 26877780 ( click the link to review the publication )

J Hematol Oncol, 2016, 9(1):134

PubMed: 27903272 ( click the link to review the publication )

Oncotarget, 2016, 7(3):2545-54

PubMed: 26575423 ( click the link to review the publication )

Purity & Quality Control

Choose Selective Epigenetic Reader Domain Inhibitors

Biological Activity

Description

I-BET151 (GSK1210151A) is a novel selective BET inhibitor for BRD2, BRD3 and BRD4 with IC50 of 0.5 μM, 0.25 μM, and 0.79 μM in cell-free assays, respectively.

Features

Optimized to retain excellent BET target potency and selectivity while enhancing the in vivo pharmacokinetics and terminal half-life to enable prolonged in vivo studies.

Targets

BRD3 ^[1] (Cell-free assay)	BRD2 ^[1] (Cell-free assay)	BRD4 ^[1] (Cell-free assay)
0.25 μM	0.5 μM	0.79 μM

In vitro

I-BET151 exhibits potent selectivity over an extensive range of diverse protein types such as COX-2, P450, Aurora B, GSK3β, PI3K-γ, GPCR, ion channels, and transporters. Similar to I-BET762 (GSK525762A), I-BET151 displays potent binding affinity to BRD2, BRD3 and BRD4 with K_D of 0.02-0.1 μM, and significantly inhibits lipopolysaccharide-stimulated IL-6 cytokine production in human peripheral blood mononuclear cells (PBMC) and whole blood (WB) as well as rat WB with IC50 of 0.16 μM, 1.26 μM, and 1.26 μM, respectively. I-BET151 (0.5 or 5 μM) inhibits the binding of BETs (BRD2, BRD3, BRD4, and BRD9) but not the binding of 23 other bromodomain proteins in HL60 nuclear extract to acetylated histone peptides. I-BET151 has potent efficacy against cell lines harboring different MLL-fusions such as MV4;11, RS4;11, MOLM13, and NOMO1 cells with IC50 of 15-192 nM. Consistently, I-BET151 completely ablates the colony-forming potential of MLL-fusion-driven leukaemias (MOLM13) but not leukaemias driven by tyrosine kinase activation (K562). I-BET151 also displays potent efficacy in both liquid culture and clonogenic assays using primary murine progenitors transformed with either MLL-ENL or MLL-AF9. I-BET151 treatment significantly induces apoptosis and prominent G0/G1 arrest in MLL-fusion cell lines driven by distinct MLL fusions (MOLM13 and MV4;11 containing MLL-AF9 and MLL-AF4, respectively) but not the K562 cells, probably due to the inhibition of transcription of BCL2, C-MYC and CDK6 by blocking the recruitment of BRD3/4, PAFc and SEC components into transcriptional start site (TSS). ^[1]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
MV4;11	M2\nUYN6fG:2b4jpZ4l1gSCjc4PhfS=>	Ml;UglExOCEQvF2=		M1rWRmROW09?	NFv4VJpKSzVyPUK2JI5O	MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTl4NEO0NEc,OjF7NkSzOFA9N2F-
RS4;11	MmXUZ5l1d3SxeHnjbZR6KGG\|c3H5	NF3TbHF,OTByIN88US=>		MXrEUXNQ	M1m1cWlEPTB;MUmyJI5O	NH7mNW89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUm2OFM1OCd-MkG5OlQ{PDB:L3G+
MOLM13	MlzNZ5l1d3SxeHnjbZR6KGG\|c3H5	MV7+NVAxKM7:TR?=		NYi4XZlZTE2VTx?=	MVfJR\|UxRTF{MDDuUS=>	MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTl4NEO0NEc,OjF7NkSzOFA9N2F-
NOMO1	MVrjfZRwfG:6aXPpeJkh[XO\|YYm=	NGr6XY5,OTByIN88US=>		MmHFSG1UVw>?	NFP5cotKSzVyPUG1JI5O	MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTl4NEO0NEc,OjF7NkSzOFA9N2F-
HEL	M{f3PIN6fG:2b4jpZ4l1gSCjc4PhfS=>	NGfMUJh,OTByIN88US=>		NGLRPZNFVVOR	MYPJR\|UxRTFizszN	M37lRVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOU[0N\|QxLz5{MUm2OFM1ODxxYU6=
K562	MknXZ5l1d3SxeHnjbZR6KGG\|c3H5	MnnmglExOCEQvF2=		MmXVSG1UVw>?	MlOyTWM2OD5zMECg{txO	MkntQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7NkSzOFAoRjJzOU[0N\|QxRC:jPh?=
MEG01	NEjyVGFkgXSxdH;4bYNqfHliYYPzZZk>	MlL6glExOCEQvF2=		NWnvXnpFTE2VTx?=	NWqwPJBkUUN3ME2yOUDPxE1?	MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTl4NEO0NEc,OjF7NkSzOFA9N2F-
HL60	M3f0OoN6fG:2b4jpZ4l1gSCjc4PhfS=>	MWP+NVAxKM7:TR?=		NIfVcGRFVVOR	NVfYWo5XUUN3ME24PVAhdk1?	M{XXdFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOU[0N\|QxLz5{MUm2OFM1ODxxYU6=
MV4;11	NEXyVIxCeG:ydH;zbZMh[XO\|YYm=	MlnWglExOCEQvF2=		M{PDeWROW09?	MVnpcoR2[2W\|IHHwc5B1d3Orcx?=	MkLCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7NkSzOFAoRjJzOU[0N\|QxRC:jPh?=
MOLM13	MmfSRZBweHSxc3nzJIF{e2G7	NVzMZWZ{hjFyMDFOwG0>		NYPsTI01TE2VTx?=	MkfwbY5lfWOnczDhdI9xfG:\|aYO=	M4[3clxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOU[0N\|QxLz5{MUm2OFM1ODxxYU6=
MV4;11	MUHGeY5kfGmxbjDhd5NigQ>?			MWHEUXNQ	NH7zdIJl\WO{ZXHz[ZMhfGinIILlZ5J2cXSvZX70JI9nKEKUREOvOEBidmRiaX3wZYlz\WRicnXjdpVqfG2nboSgc4YhS0SNOTDhcoQhWEGIMTD0c{B1cGVidILhcpNkemmydHnvcoFtKHO2YYL0JJNqfGV?	MljuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7NkSzOFAoRjJzOU[0N\|QxRC:jPh?=
PBMC	MkP1SpVv[3Srb36gZZN{[Xl?			M4HteGROW09?	MWfpcohq[mm2czDJUE03KHerdHigdGlEPTBib3[gOk44	Ml2xQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ2M{exNVUoRjJ{NEO3NVE2RC:jPh?=
A2	MV\GeY5kfGmxbjDhd5NigQ>?	Mn3aglExKM7:TR?=		NHTue3hFVVOR	M1i4RZJm[WO2aY\heIV{KGyjdHXueEBJUVZvMR?=	NWHI[IxYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOyOVUzOThpPkKzNlU2OjF6PD;hQi=>
A72	NVXNPYZkTnWwY4Tpc44h[XO\|YYm=	M2LiV54yOCEQvF2=		NV;XSlFsTE2VTx?=	NUi1[pJlemWjY4TpeoF1\XNibHH0[Y51KEiLVj2x	MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzJ3NUKxPEc,OjN{NUWyNVg9N2F-
BC1	M4j1c2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MnTwglEh\|ryP		NFrlSIVFVVOR	MmfYTWM2OD1{MkCgcm0>	NFXETm89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e5NlQ1QCd-MkO3PVI1PDh:L3G+
BC3	M3XTTGdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	NWHFSYNEhjFizszN		NUWwe2cxTE2VTx?=	M{jpbGlEPTB;NE[wJI5O	M3GwN\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|N{myOFQ5Lz5{M{e5NlQ1QDxxYU6=
BCBL1	M17JN2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7	NH:1TYZ,OSEQvF2=		M1\5UmROW09?	MlvxTWM2OD1\|M{Cgcm0>	M4ruT\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|N{myOFQ5Lz5{M{e5NlQ1QDxxYU6=
BJAB	NVj3ZphUT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NXLUUIE{hjFizszN		MWXEUXNQ	MV3JR\|UxRTl5MDDuUS=>	NHr2RoM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e5NlQ1QCd-MkO3PVI1PDh:L3G+
Namalwa	MnfPS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NIDsWpF,OSEQvF2=		NFz1eHhFVVOR	MYPJR\|UxRTl5MDDuUS=>	M2rwblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|N{myOFQ5Lz5{M{e5NlQ1QDxxYU6=
Jurkat	MUDHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NGXVZnJ,OSEQvF2=		NEjRTlhFVVOR	M{TVWmlEPTB;MUKyNEBvVQ>?	M{DrOVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|N{myOFQ5Lz5{M{e5NlQ1QDxxYU6=
MM1S	M{P1WWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MV3+NUDPxE1?		MYjEUXNQ	MmLwTWM2OD15NkCgcm0>	Ml;oQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN5OUK0OFgoRjJ\|N{myOFQ5RC:jPh?=
U266	MX\Hdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	MXn+NUDPxE1?		M2K0Z2ROW09?	NHXT[lVKSzVyPUm1NEBvVQ>?	NXqzVpg3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO3PVI1PDhpPkKzO\|kzPDR6PD;hQi=>
UM-PEL-1	NX:0e3BFT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NYr1UmdlhjFizszN		NX3VUHZyTE2VTx?=	M3j1[mlEPTB;MkGwJI5O	NYTjTG5TRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO3PVI1PDhpPkKzO\|kzPDR6PD;hQi=>
UM-PEL-3	M4DYTmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	NXH2[nI6hjFizszN		MlO0SG1UVw>?	NVvFZ4x3UUN3ME2xPFAhdk1?	M4f3W\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|N{myOFQ5Lz5{M{e5NlQ1QDxxYU6=
BC1	NHLG[2NHfW6ldHnvckBie3OjeR?=	M37wfVUxOCCwTR?=		MWrEUXNQ	NVLsZYpZcW6mdXPld{Bk\WyuLXP5Z4xmKGG{cnXzeC=>	MUG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzd7MkS0PEc,OjN5OUK0OFg9N2F-
BC3	NETrPIlHfW6ldHnvckBie3OjeR?=	NW\VfWF6PTByIH7N		NEnqcnhFVVOR	NWfEV\|JmcW6mdXPld{Bk\WyuLXP5Z4xmKGG{cnXzeC=>	Mn7XQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN5OUK0OFgoRjJ\|N{myOFQ5RC:jPh?=
BC1	NXv2dmhmTnWwY4Tpc44h[XO\|YYm=	MXK4NFAhdk1?		M4r5cWROW09?	MX;y[YR2[2W\|IHOtUZlkKHC{b4TlbY4hdGW4ZXzz	MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzd7MkS0PEc,OjN5OUK0OFg9N2F-
BC3	MmrKSpVv[3Srb36gZZN{[Xl?	NH;s[I45ODBibl2=		NFPGUZZFVVOR	MmDGdoVlfWOnczDjMW16[yCycn;0[YlvKGyndnXsdy=>	NVzEcG1URGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO3PVI1PDhpPkKzO\|kzPDR6PD;hQi=>
H929	Mm\XSpVv[3Srb36gZZN{[Xl?	M3vqdZ4yKM7:TR?=		MUTEUXNQ	MWXpcoR2[2W\|IHPlcIwh[3mlbHWgZZJz\XO2	MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN\|NUS5PUc,OjR\|M{W0PVk9N2F-
KMS12PE	MXPGeY5kfGmxbjDhd5NigQ>?	MoLoglEh\|ryP		MmXRSG1UVw>?	M3vYbolv\HWlZYOgZ4VtdCCleXPs[UBienKnc4S=	MoPVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR\|M{W0PVkoRjJ2M{O1OFk6RC:jPh?=
KMS12BM	NEXvVJNHfW6ldHnvckBie3OjeR?=	NFP1e\|Z,OSEQvF2=		NXfEV\|NLTE2VTx?=	MUXpcoR2[2W\|IHPlcIwh[3mlbHWgZZJz\XO2	M1;IO\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{O1OFk6Lz5{NEOzOVQ6QTxxYU6=
KMS18	MkDYSpVv[3Srb36gZZN{[Xl?	MVn+NUDPxE1?		MonTSG1UVw>?	M3HKVIlv\HWlZYOgZ4VtdCCleXPs[UBienKnc4S=	MWC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN\|NUS5PUc,OjR\|M{W0PVk9N2F-
KMS11	MUDGeY5kfGmxbjDhd5NigQ>?	MnTQglEh\|ryP		Mkm4SG1UVw>?	Ml3LbY5lfWOnczDj[YxtKGO7Y3zlJIFzemW\|dB?=	M{Lze\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{O1OFk6Lz5{NEOzOVQ6QTxxYU6=
RPMI8226	M3;mdWZ2dmO2aX;uJIF{e2G7	NYX1UJl2hjFizszN		Mn;4SG1UVw>?	MkHFbY5lfWOnczDj[YxtKGO7Y3zlJIFzemW\|dB?=	MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN\|NUS5PUc,OjR\|M{W0PVk9N2F-
H929	MnvyRZBweHSxc3nzJIF{e2G7	MljDglEh\|ryP		M160e2ROW09?	MmLobY5lfWOnczDj[YxtKGGyb4D0c5Nqew>?	NInCUZo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEOzOVQ6QSd-MkSzN\|U1QTl:L3G+
KMS12PE	M{T1T2Fxd3C2b4Ppd{Bie3OjeR?=	NW[0TopwhjFizszN		MUDEUXNQ	NVnyXo1XcW6mdXPld{Bk\WyuIHHwc5B1d3Orcx?=	MmTNQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR\|M{W0PVkoRjJ2M{O1OFk6RC:jPh?=
KMS12BM	MY\BdI9xfG:\|aYOgZZN{[Xl?	MUP+NUDPxE1?		MX7EUXNQ	NETQOFNqdmS3Y3XzJINmdGxiYYDvdJRwe2m\|	NEToRoQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEOzOVQ6QSd-MkSzN\|U1QTl:L3G+
KMS18	MVPBdI9xfG:\|aYOgZZN{[Xl?	MXv+NUDPxE1?		NGTDZXhFVVOR	M4[z[Ylv\HWlZYOgZ4VtdCCjcH;weI9{cXN?	NH\QSHQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEOzOVQ6QSd-MkSzN\|U1QTl:L3G+
KMS11	NXH4fmdLSXCxcITvd4l{KGG\|c3H5	M17ud54yKM7:TR?=		Mnf1SG1UVw>?	NEfYOXdqdmS3Y3XzJINmdGxiYYDvdJRwe2m\|	NYTNS2E2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzN\|U1QTlpPkK0N\|M2PDl7PD;hQi=>
RPMI8226	MWfBdI9xfG:\|aYOgZZN{[Xl?	Mm\rglEh\|ryP		MWfEUXNQ	NFvkcYJqdmS3Y3XzJINmdGxiYYDvdJRwe2m\|	MlrHQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR\|M{W0PVkoRjJ2M{O1OFk6RC:jPh?=
U87MG	M1XDO2Z2dmO2aX;uJIF{e2G7	NYXtSZdUhjFyIN88US=>		NVjrWpRbTE2VTx?=	Mn7OdoVlfWOnczDVPFdOTyClZXzseYxieiCDVGCge4l1cCCLQ{WwJI9nKDFwMEWg{txO	NIizTYE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NES5OlM5OSd-MkS0PVY{QDF:L3G+
A172	MWfGeY5kfGmxbjDhd5NigQ>?	NETWXZB,OTBizszN		NVjNV5k4TE2VTx?=	NVfiOI9WemWmdXPld{Bk\WyudXzhdkBCXFBid3n0bEBKSzVyIH;mJFEvOjhizszN	NW\ONpNYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS0PVY{QDFpPkK0OFk3OzhzPD;hQi=>
SW1783	NI\jRnhHfW6ldHnvckBie3OjeR?=	MX\+NVAh\|ryP		MVHEUXNQ	MYTy[YR2[2W\|IHPlcIx2dGG{IFHUVEB4cXSqIFnDOVAhd2ZiMj62PEDPxE1?	MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDR7NkO4NUc,OjR2OU[zPFE9N2F-
U87MG	M1jEO2Z2dmO2aX;uJIF{e2G7	M3rieZ4yOCEQvF2=		MVzEUXNQ	MX3pcoNz\WG\|ZYOgdJJweG:{dHnvckBw\iClZXzsd{BqdiC2aHWgS\|EwWyC2cnHud4l1cW:w	Ml75QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR2OU[zPFEoRjJ2NEm2N\|gyRC:jPh?=
RAW267.4	NGXOZ\|RHfW6ldHnvckBie3OjeR?=	NXyzO283OSEQvF2=		NGnBTYhFVVOR	M{LF[pJm\HWlZYOgTWwuPiCycn;keYN1cW:wIHnu[JVk\WRiYomgUHBU	M2T4bVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OEW5NFA5Lz5{NEi1PVAxQDxxYU6=
RAW267.4	MV;GeY5kfGmxbjDhd5NigQ>?	M3HidVEh\|ryP		MXLEUXNQ	M1zDeJJm\HWlZYOgeIhmKGG\|c3;jbYF1cW:wIHLleJdm\W5iQmLEOEBidmRiYXPleJlt[XSnZDDwOlU>	M1HLW\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OEW5NFA5Lz5{NEi1PVAxQDxxYU6=
Me007	M4DXTmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	NIKycJd,OTByIN88US=>		M1vESWROW09?	MXHpcohq[mm2czD0bIUh\3Kxd4To	Mkn2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7ME[xN\|coRjJ2OUC2NVM4RC:jPh?=
SK-Mel-28	M{SyfWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	NEjCTXZ,OTByIN88US=>		NVXhS4R2TE2VTx?=	NXPDR\|VXcW6qaXLpeJMhfGinIHfyc5d1cA>?	M2T3elxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
Mel-RMU	Ml;mS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	M3fy[p4yODBizszN		MnL3SG1UVw>?	MWfpcohq[mm2czD0bIUh\3Kxd4To	M1:4[\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
Mel-JD	M{fvXGdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	M2HCVp4yODBizszN		M2D3NWROW09?	NGjT[GxqdmirYnn0d{B1cGViZ4Lve5Rp	MoHQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7ME[xN\|coRjJ2OUC2NVM4RC:jPh?=
Mel-RM	MlnlS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NHTDPZd,OTByIN88US=>		MlLxSG1UVw>?	MYnpcohq[mm2czD0bIUh\3Kxd4To	MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
Me007	NWnKWYhnSXCxcITvd4l{KGG\|c3H5	NIP0Wml,OTByIN88US=>		M{fDcWROW09?	NXTkcpo2cW6mdXPld{BieG:ydH;zbZM>	M{jVOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
SK-Mel-28	NYjsXpo{SXCxcITvd4l{KGG\|c3H5	MUP+NVAxKM7:TR?=		NX;xfGl5TE2VTx?=	M13zeIlv\HWlZYOgZZBweHSxc3nz	MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
Mel-RMU	NGniSoZCeG:ydH;zbZMh[XO\|YYm=	NX;m[WY{hjFyMDFOwG0>		M2G2SWROW09?	NHK1e\|NqdmS3Y3XzJIFxd3C2b4Ppdy=>	NWPNcnRXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
Mel-JD	M2rXXGFxd3C2b4Ppd{Bie3OjeR?=	MmiwglExOCEQvF2=		NIS4bYZFVVOR	MVPpcoR2[2W\|IHHwc5B1d3Orcx?=	M{PpZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
Mel-RM	NX7hSHJ7SXCxcITvd4l{KGG\|c3H5	MlzWglExOCEQvF2=		NW[3fmNoTE2VTx?=	NVe0XIE4cW6mdXPld{BieG:ydH;zbZM>	NWn1R3Y6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
Me007	MnvuSpVv[3Srb36gZZN{[Xl?	MXuxNEDPxE1?		M1H1d2ROW09?	MX;pcoR2[2W\|IHPlcIwh[3mlbHWgZZJz\XO2IHL5JJVxemWpdXzheIlwdiCxZjDwNlE>	NIrDUos9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
SK-Mel-28	MlnZSpVv[3Srb36gZZN{[Xl?	NVrFW4IxOTBizszN		M4HSZ2ROW09?	NV2xfWZtcW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeEBjgSC3cILl[5Vt[XSrb36gc4YheDJz	MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
Mel-RMU	M2PUN2Z2dmO2aX;uJIF{e2G7	NFS1VXMyOCEQvF2=		NGCzb5ZFVVOR	M2nBe4lv\HWlZYOgZ4VtdCCleXPs[UBienKnc4SgZpkhfXC{ZXf1cIF1cW:wIH;mJJAzOQ>?	NXjRbZd4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
Mel-JD	MUPGeY5kfGmxbjDhd5NigQ>?	MnyzNVAh\|ryP		NX2zU5FwTE2VTx?=	NWLU[HFNcW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeEBjgSC3cILl[5Vt[XSrb36gc4YheDJz	NVy3[YxyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
Mel-RM	MWnGeY5kfGmxbjDhd5NigQ>?	M3;OUlExKM7:TR?=		M2HRZWROW09?	NELSWVRqdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0JIJ6KHWycnXneYxifGmxbjDv[kBxOjF?	NWDBSHU1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
Me007	MknrSpVv[3Srb36gZZN{[Xl?	M1;IWFExKM7:TR?=		NWHMWop6TE2VTx?=	MUH1dJJm\3WuYYTld{Bxem:jcH;weI91cWNiYX7kJINmdGxiY4njcIUh[XK{ZYP0JIdmdmW\|	MkL0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7ME[xN\|coRjJ2OUC2NVM4RC:jPh?=
SK-Mel-28	M176bWZ2dmO2aX;uJIF{e2G7	Ml\RNVAh\|ryP		MlTmSG1UVw>?	NHPyUHR2eHKnZ4XsZZRmeyCycn;hdI9xfG:2aXOgZY5lKGOnbHygZ5lkdGViYYLy[ZN1KGenbnXz	MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
Mel-RMU	NVe3XmJETnWwY4Tpc44h[XO\|YYm=	M3HlclExKM7:TR?=		NH3XbZJFVVOR	NFPY[oJ2eHKnZ4XsZZRmeyCycn;hdI9xfG:2aXOgZY5lKGOnbHygZ5lkdGViYYLy[ZN1KGenbnXz	NF;LNHk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
Mel-JD	NEDWRpRHfW6ldHnvckBie3OjeR?=	NHfGOncyOCEQvF2=		M4rESmROW09?	MVf1dJJm\3WuYYTld{Bxem:jcH;weI91cWNiYX7kJINmdGxiY4njcIUh[XK{ZYP0JIdmdmW\|	MkHNQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7ME[xN\|coRjJ2OUC2NVM4RC:jPh?=
Mel-RM	MknvSpVv[3Srb36gZZN{[Xl?	MVOxNEDPxE1?		NEGw[XVFVVOR	MYf1dJJm\3WuYYTld{Bxem:jcH;weI91cWNiYX7kJINmdGxiY4njcIUh[XK{ZYP0JIdmdmW\|	NXm1[FM3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
HepG2	NWnu[mdsTnWwY4Tpc44h[XO\|YYm=		NWLWRodKOThiaILz		NHPUdZhWeHKnZ4XsZZRqd25ib3[gRZBwSTFiZYjwdoV{e2mxbjDpckBpfW2jbjDI[ZBIOiClZXzsd{Bie3Onc4Pl[EBieyClb37j[Y51emG2aX;uJJJmeXWrcnXkJJRwKGmwY4LlZZNmKDdyJTDv[kBtfWOrZnXyZZNmKGGldHn2bZR6KGGodHXyJFE5KGi{czDifUBtfWOrZnXyZZNmKHKncH;yeIVzKGenbnWgZZN{[XluIFXDNVcxKD1iMD6wPUDPxE1w	MlXyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ\|OE[1NlkoRjJ{M{i2OVI6RC:jPh?=
Raji	NF;Oe5dHfW6ldHnvckBie3OjeR?=		MW[0JIhzew>?		NG\pdW5KdmirYnn0bY9vKG:oIFLSSFQhcW5iaIXtZY4hWmGsaTDj[YxteyCjc4Pld5Nm\CCjczDy[YR2[3Srb36gc4YhVVmFIHX4dJJme3Orb36gZYZ1\XJiNDDodpMtKEmFNUCgQUAxNjF\|IN88UU4>	NITCOIQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwNFc2QCd-MkS5NFA4PTh:L3G+
MV4-11	MU\Hdo94fGhiaX7obYJqfGmxbjDhd5NigQ>?		MU[3NkBpenN?		NXHuPIRXT3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hVVZ2LUGxJINmdGy\|IHHmeIVzKDd{IHjyd{BjgSCVUlKgZZN{[XluIFnDOVAhRSByLkGxPUDPxE1w	NX3DdFNiRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW1OVk1OjhpPkK1OVU6PDJ6PD;hQi=>
MM1S	M4HVd2dzd3e2aDDpcohq[mm2aX;uJIF{e2G7		NGjBdos4OiCqcoO=		M4i4Xmdzd3e2aDDpcohq[mm2aX;uJI9nKGi3bXHuJG1OOVNiY3XscJMh[W[2ZYKgO\|IhcHK\|IHL5JHNTSiCjc4PhfUwhUUN3MDC9JFAvOjl7IN88UU4>	NF;4SYk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUW1PVQzQCd-MkW1OVk1Ojh:L3G+
HT-29	NFPiZVVIem:5dHigbY5pcWKrdHnvckBie3OjeR?=		NEjkNFU4OiCqcoO=		NX7MPZlzT3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hUFRvMkmgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KFOUQjDhd5NigSxiSVO1NEA:KDBwOUS1JO69VS5?	NYjSSIVkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW1OVk1OjhpPkK1OVU6PDJ6PD;hQi=>
Rosetta2 DE3	MYXGeY5kfGmxbjDhd5NigQ>?		NXPaZ4VyOzBibXnudy=>		MX3EbZNxdGGlZX3lcpQhd2ZiRlHNMYxi[mWuZXSgXmJCOjR6IH\yc40hSlKGNDDCSFEhMDR2IITvJFE3QCCjbXnuc{Bi[2mmIILld4llfWW\|KTCoeY5sdm:5bjDvdolocW5rIHX4dJJme3OnZDDpckBTd3OndIThNkBFTTNiY3XscJMh[W[2ZYKgN\|AhdWmwczDifUBndHWxcnXzZ4Vv[2VicH;sZZJqgmG2aX;uJIF{e2G7LDDJR\|UxKD1iMD6wN\|E4KM7:TT6=	NWPPVlh2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wPFAxPjRpPkK2NFgxODZ2PD;hQi=>
MV4-11	NH3zVnFEgXSxdH;4bYNqfHliYYPzZZk>		NFfkeYk1KGSjeYO=		NYf6b4lUS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hVVZ2LUGxJINmdGy\|IHjhdoJwemmwZzDNUGwyKG[3c3nvckBo\W6nIHHzd4V{e2WmIHHzJIdzd3e2aDDpcohq[mm2aX;uJIFnfGW{IESg[IF6eyCkeTDD[YxtXGm2ZYKtS4xwKGy3bXnu[ZNk\W62IHHzd4F6NCCLQ{WwJF0hOC5zNkKg{txONg>?	M1XkXFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MEiwNFY1Lz5{NkC4NFA3PDxxYU6=
Rosetta2 DE3	NUfVO45xTnWwY4Tpc44h[XO\|YYm=		M1zye\|MxKG2rboO=		M1\Od2Rqe3CuYXPlcYVvfCCxZjDGRW0udGGkZXzl[EBbSkF{NEig[pJwdSCEUlS0JGJFOiBqM{OzJJRwKDR4MDDhcYlvdyCjY3nkJJJme2mmdXXzLUApfW6tbn;3ckBwemmpaX6pJIV5eHKnc4Pl[EBqdiCUb4PleJRiOiCGRUOgZ4VtdHNiYX\0[ZIhOzBibXnud{BjgSCobIXvdoV{[2WwY3WgdI9t[XKrenH0bY9vKGG\|c3H5MEBKSzVyIE2gNE4zOjZizszNMi=>	MonyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyOECwOlQoRjJ4MEiwNFY1RC:jPh?=
MOLM13	NFfsZmdEgXSxdH;4bYNqfHliYYPzZZk>		NYnE[ZJPPCCmYYnz		NYLDU\|drS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hVU:OTUGzJINmdGy\|IHjhdoJwemmwZzDNUGwyKG[3c3nvckBo\W6nIHHzd4V{e2WmIHHzJIdzd3e2aDDpcohq[mm2aX;uJIFnfGW{IESg[IF6eyCkeTDD[YxtXGm2ZYKtS4xwKGy3bXnu[ZNk\W62IHHzd4F6NCCLQ{WwJF0hOC5{Mkig{txONg>?	MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjB6MEC2OEc,OjZyOECwOlQ9N2F-
Rosetta2 DE3	M17MV2Z2dmO2aX;uJIF{e2G7		MmLuN\|AhdWmwcx?=		M2fNWmlvcGmkaYTpc44hd2ZiRlHNMYxi[mWuZXSgXmJCOjR6IHLpcoRqdmdidH:gdoVkd22kaX7hcpQhcHWvYX6gUk11\XKvaX7hcEBJcXN4LYTh[4dm\CCEUlS0JIJzd22xZH;tZYlvKDFiKES0JJRwKDF4ODDy[ZNq\HWnczmg[ZhxemW\|c3XkJIlvKFKxc3X0eIEzKESHMzDj[YxteyCjZoTldkA{OCCvaX7zJIJ6KE[ub4Xy[ZNk\W6lZTDwc4xiemm8YYTpc44h[XO\|YYmsJGlEPTBiPTCwMlA{OTdizszNMi=>	MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDR4M{S4O{c,Ojh2NkO0PFc9N2F-
MV4-11	MknNS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?		MWe0JIRigXN?		MXvHdo94fGhiaX7obYJqfGmxbjDv[kBpfW2jbjDNWlQuOTFiY3XscJMh[W[2ZYKgOEBl[Xm\|IHL5JHdUXC16IHHzd4F6NCCLQ{WwJF0hOC5zNkKg{txONg>?	M1;GblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6NE[zOFg4Lz5{OES2N\|Q5PzxxYU6=
Rosetta2 DE3	MnPxSpVv[3Srb36gZZN{[Xl?		MU[zNEBucW6\|		NG[5SWRKdmirYnn0bY9vKG:oIF\BUU1t[WKnbHXkJHpDSTJ2ODDibY5lcW6pIITvJJJm[2:vYnnuZY51KGi3bXHuJG4ufGW{bXnuZYwhUGm\|Nj30ZYdo\WRiQmLEOEBjem:vb3TvcYFqdiB{IDizN\|MhfG9iNE[wJJJme2mmdXXzLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHHmeIVzKDNyIH3pcpMh[nliRnzveZJme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfUwhUUN3MDC9JFAvOjJ4IN88UU4>	MmXEQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh2NkO0PFcoRjJ6NE[zOFg4RC:jPh?=
MOLM13	M1Hz[Wdzd3e2aDDpcohq[mm2aX;uJIF{e2G7		NWC5cZpwPCCmYYnz		NHfaXohIem:5dHigbY5pcWKrdHnvckBw\iCqdX3hckBOV0yPMUOgZ4VtdHNiYX\0[ZIhPCCmYYnzJIJ6KFeVVD24JIF{e2G7LDDJR\|UxKD1iMD6yNlgh\|ryPLh?=	MUK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDR4M{S4O{c,Ojh2NkO0PFc9N2F-
Rosetta2 DE3	MVXGeY5kfGmxbjDhd5NigQ>?				MUPCbY5lcW6pIHHm[olvcXS7IITvJIJqd3SrbonsZZRm\CCEUlSzJGJFOSBqMkSgeI8hOTR2IHHtbY5wKGGlaXSgdoV{cWS3ZYOpJEh2dmuwb4fuJI9zcWerbjmg[ZhxemW\|c3XkJIlvKFKxc3X0eIEzKESHMzDj[YxteyCkeTDibY8udGG7ZYKgbY51\XKoZYLvcYV1enlibXX0bI9lNCCNZDC9JFAvODJ7ODFOwG0v	M4PPOVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MEiwNFY1Lz5{NkC4NFA3PDxxYU6=
Rosetta2 DE3	NV7ZXpB{TnWwY4Tpc44h[XO\|YYm=				NXzOZpZJSmmwZHnu[{Bi\m[rbnn0fUB1dyCkaX;0bY56dGG2ZXSgRnJFOyCEREKgLFMxPiC2bzC0NVch[W2rbn:gZYNq\CC{ZYPp[JVmeyliKIXub45wf25ib4Lp[4lvMSCneIDy[ZN{\WRiaX6gVo9{\XS2YUKgSGU{KGOnbHzzJIJ6KGKrbz3sZZlmeiCrboTldoZmem:vZYTyfUBu\XSqb3SsJGtlKD1iMD6wOFA2KM7:TT6=	M4XXN\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MEiwNFY1Lz5{NkC4NFA3PDxxYU6=
Rosetta2 DE3	MVXGeY5kfGmxbjDhd5NigQ>?				MYjCbY5lcW6pIHHm[olvcXS7IITvJIJqd3SrbonsZZRm\CCEUlS0JGJFOSBqNESgeI8hOTZ6IHHtbY5wKGGlaXSgdoV{cWS3ZYOpJEh2dmuwb4fuJI9zcWerbjmg[ZhxemW\|c3XkJIlvKFKxc3X0eIEzKESHMzDj[YxteyCkeTDibY8udGG7ZYKgbY51\XKoZYLvcYV1enlibXX0bI9lNCCNZDC9JFAvODV{ODFOwG0v	M4nkV\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MEiwNFY1Lz5{NkC4NFA3PDxxYU6=
Rosetta2 DE3	NEfkUHFHfW6ldHnvckBie3OjeR?=				NV[4cmtJSmmwZHnu[{Bi\m[rbnn0fUB1dyCkaX;0bY56dGG2ZXSgRnJFOiCEREGgLFczKHSxIEKwOUBidWmwbzDhZ4llKHKnc3nkeYV{MSBqdX7rco94diCxcnnnbY4qKGW6cILld5Nm\CCrbjDSc5NmfHSjMjDESVMh[2WubIOgZpkh[mmxLXzhfYVzKGmwdHXy[oVzd22ndIL5JI1mfGixZDygT4QhRSByLkC1OFgh\|ryPLh?=	MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjB6MEC2OEc,OjZyOECwOlQ9N2F-
Rosetta2 DE3	Mn3MSpVv[3Srb36gZZN{[Xl?				Mn7vRolv\GmwZzDh[oZqdmm2eTD0c{BjcW:2aX75cIF1\WRiQmLENkBDTDJiKEO0PUB1dyB2NkCgZY1qdm9iYXPp[EBz\XOrZIXld{khMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHL5JIJqdy2uYYnldkBqdnSncn\ldo9u\XS{eTDt[ZRpd2RuIFvkJF0hOC5yN{CzJO69VS5?	NV3VeJpORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wPFAxPjRpPkK2NFgxODZ2PD;hQi=>
Rosetta2 DE3	NIfVR21HfW6ldHnvckBie3OjeR?=				Mk\YRolv\GmwZzDh[oZqdmm2eTD0c{BjcW:2aX75cIF1\WRiQmLEOEBDTDJiKEOzN{B1dyB2NkCgZY1qdm9iYXPp[EBz\XOrZIXld{khMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHL5JIJqdy2uYYnldkBqdnSncn\ldo9u\XS{eTDt[ZRpd2RuIFvkJF0hOC5{MUWg{txONg>?	NWT3bVcyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wPFAxPjRpPkK2NFgxODZ2PD;hQi=>
Rosetta2 DE3	NWLwc2o4TnWwY4Tpc44h[XO\|YYm=				NVzkWHF7SmmwZHnu[{Bi\m[rbnn0fUB1dyCkaX;0bY56dGG2ZXSgR3JGSkKSIDixNFQ{KHSxIEGxOVkh[W2rbn:gZYNq\CC{ZYPp[JVmeyliKIXub45wf25ib4Lp[4lvMSCneIDy[ZN{\WRiaX6gVo9{\XS2YUKgSGU{KGOnbHzzJIJ6KGKrbz3sZZlmeiCrboTldoZmem:vZYTyfUBu\XSqb3SsJGtlKD1iMz6wPFQh\|ryPLh?=	MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjB6MEC2OEc,OjZyOECwOlQ9N2F-
Rosetta2 DE3	M4Dhc2Z2dmO2aX;uJIF{e2G7		NEiwTXQ{OCCvaX7z		MVHEbZNxdGGlZX3lcpQhd2ZiRlHNMYxi[mWuZXSgXmJCOjR6IH\yc40hSlKGMzDCSFEhMDJ2IITvJFE1PCCjbXnuc{Bi[2mmIILld4llfWW\|KTCoeY5sdm:5bjDvdolocW5rIHX4dJJme3OnZDDpckBTd3OndIThNkBFTTNiY3XscJMh[W[2ZYKgN\|AhdWmwczDifUBndHWxcnXzZ4Vv[2VicH;sZZJqgmG2aX;uJIF{e2G7LDDLbUA:KDBwMEC3NkDPxE1w	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjB6MEC2OEc,OjZyOECwOlQ9N2F-
Rosetta2 DE3	MVjGeY5kfGmxbjDhd5NigQ>?		M33QXlMxKG2rboO=		MXPEbZNxdGGlZX3lcpQhd2ZiRlHNMYxi[mWuZXSgXmJCOjR6IH\yc40hSlKGNDDCSFEhMDR2IITvJFE3QCCjbXnuc{Bi[2mmIILld4llfWW\|KTCoeY5sdm:5bjDvdolocW5rIHX4dJJme3OnZDDpckBTd3OndIThNkBFTTNiY3XscJMh[W[2ZYKgN\|AhdWmwczDifUBndHWxcnXzZ4Vv[2VicH;sZZJqgmG2aX;uJIF{e2G7LDDLbUA:KDBwMEC5JO69VS5?	M{XpcFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MEiwNFY1Lz5{NkC4NFA3PDxxYU6=
Rosetta2 DE3	NHi5WXVHfW6ldHnvckBie3OjeR?=		Mn\6N\|AhdWmwcx?=		MlTWSIl{eGyjY3Xt[Y51KG:oIF\BUU1t[WKnbHXkJHpDSTJ2ODDmdo9uKEKUREKgRmQyKCh5MjD0c{AzODViYX3pco8h[WOrZDDy[ZNq\HWnczmgLJVvc26xd36gc5Jq\2mwKTDlfJBz\XO\|ZXSgbY4hWm:\|ZYT0ZVIhTEV\|IHPlcIx{KGGodHXyJFMxKG2rboOgZpkh\my3b4Lld4NmdmOnIIDvcIFzcXqjdHnvckBie3OjeTygT4khRSByLkCwPUDPxE1w	MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjB6MEC2OEc,OjZyOECwOlQ9N2F-
Rosetta2 DE3	NY\4OmJjTnWwY4Tpc44h[XO\|YYm=		NW\WWGprOzBibXnudy=>		NHLhdJZFcXOybHHj[Y1mdnRib3[gSmFONWyjYnXs[YQhYkKDMkS4JIZzd21iQmLEN{BDTDJiKEOwOkB1dyB2MUegZY1qdm9iYXPp[EBz\XOrZIXld{khMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHHmeIVzKDNyIH3pcpMh[nliZnz1c5Jme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfUwhU2liPTCwMlAzOjNizszNMi=>	NFTnO5g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkC4NFA3PCd-Mk[wPFAxPjR:L3G+
Rosetta2 DE3	MkHVSpVv[3Srb36gZZN{[Xl?		NUS5[GZxOzBibXnudy=>		M{Ky[WRqe3CuYXPlcYVvfCCxZjDGRW0udGGkZXzl[EBbSkF{NEig[pJwdSCEUlSyJGJFOiBqM{S5JJRwKDR4MDDhcYlvdyCjY3nkJJJme2mmdXXzLUApfW6tbn;3ckBwemmpaX6pJIV5eHKnc4Pl[EBqdiCUb4PleJRiOiCGRUOgZ4VtdHNiYX\0[ZIhOzBibXnud{BjgSCobIXvdoV{[2WwY3WgdI9t[XKrenH0bY9vKGG\|c3H5MEBMcSB;IECuNFQ6PiEQvF2u	M3TqfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MEiwNFY1Lz5{NkC4NFA3PDxxYU6=
Rosetta2 DE3	MlfPSpVv[3Srb36gZZN{[Xl?		MVKzNEBucW6\|		NIjuTGhFcXOybHHj[Y1mdnRib3[gSmFONWyjYnXs[YQhYkKDMkS4JIZzd21iQmLEOEBDTDJiKEOzN{B1dyB2NkCgZY1qdm9iYXPp[EBz\XOrZIXld{khMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHHmeIVzKDNyIH3pcpMh[nliZnz1c5Jme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfUwhU2liPTCwMlA4PDhizszNMi=>	NGXUbWo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkC4NFA3PCd-Mk[wPFAxPjR:L3G+
Rosetta2 DE3	NY[3fW5STnWwY4Tpc44h[XO\|YYm=		M{\GVVMxKG2rboO=		NFXpfpRKdmirYnn0bY9vKG:oIF\BUU1t[WKnbHXkJHpDSTJ2ODDibY5lcW6pIITvJJJm[2:vYnnuZY51KGi3bXHuJG4ufGW{bXnuZYwhUGm\|Nj30ZYdo\WRiQmLEOEBjem:vb3TvcYFqdiBzIDi0OEB1dyBzNkigdoV{cWS3ZYOpJIV5eHKnc4Pl[EBqdiCUb4PleJRiOiCGRUOgZ4VtdHNiYX\0[ZIhOzBibXnud{BjgSCIbH;1doV{[2WwY3WgdI9t[XKrenH0bY9vKGG\|c3H5MEBMcSB;IECuNFA6KM7:TT6=	NIrMd5U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OES2N\|Q5Pyd-Mki0OlM1QDd:L3G+
Rosetta2 DE3	MXvGeY5kfGmxbjDhd5NigQ>?		NV:3ZlNrOzBibXnudy=>		NVnFSZhNUW6qaXLpeIlwdiCxZjDGRW0udGGkZXzl[EBbSkF{NEigZolv\GmwZzD0c{Bz\WOxbXLpcoFvfCCqdX3hckBPNXSncn3pcoFtKEirc{[teIFo\2WmIFLSSFQh[nKxbX;kc41icW5iMjCoN\|M{KHSxIES2NEBz\XOrZIXld{kh\XiycnXzd4VlKGmwIGLvd4V1fGF{IFTFN{Bk\WyuczDh[pRmeiB\|MDDtbY5{KGK7IF\sc5Vz\XOlZX7j[UBxd2yjcnn6ZZRqd25iYYPzZZktKEurIE2gNE4xPzR6IN88UU4>	NUGwVWY1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki0OlM1QDdpPkK4OFY{PDh5PD;hQi=>
THP1	M{TOTWFvfGmrbn\sZY1u[XSxcomgZZN{[Xl?				MnXkRY51cWmwZnzhcY1ifG:{eTDhZ5Rqfmm2eTDpckBpfW2jbjDUTHAyKGOnbHzz	NFjWe3c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkO4OlUzQSd-MkKzPFY2Ojl:L3G+
HT-29	NFHlcoRHfW6ldHnvckBie3OjeR?=	NV\XcZFKOC5\|MUK1JJVOKHSxIEWgeW0>	MmTMNlQhcHK\|		MX7Jcohq[mm2aX;uJI9nKEKURESgbY4hcHWvYX6gTHQuOjliY3XscJMh[XO\|ZYPz[YQh[XNicnXkeYN1cW:wIHnuJIMuVXmlIIDyc5RmcW5iZYjwdoV{e2mxbjDheEAxNjNzMkWgeW0hfG9iNTD1UUB2VSCjZoTldkAzPCCqcoOgZpkhX2W\|dHXyckBjdG:2dHnu[{Bu\XSqb3S=	MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTV3OUSyPEc,OjV3NUm0Nlg9N2F-
MV4-11	NHu2XGlHfW6ldHnvckBie3OjeR?=				NUXTN5QxUW6qaXLpeIlwdiCxZjDCVmQ1KGmwIHj1cYFvKE2YND2xNUBk\WyuczDhd5Nme3OnZDDhd{Bld3ewcnXneYxifGmxbjDv[kBDS0x{IGLORUBmgHC{ZYPzbY9vKGK7IGLORU1{\XFiYX7hcJl{cXN?	NVTaSmxxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkmyOVk4PTFpPkK5NlU6PzVzPD;hQi=>
MV4-11	NFTxSIlHfW6ldHnvckBie3OjeR?=				MknkTY5pcWKrdHnvckBw\iCEUlS0JIlvKGi3bXHuJG1XPC1zMTDj[YxteyCjc4Pld5Nm\CCjczDkc5dvemWpdXzheIlwdiCxZjDjUXlEKFKQQTDlfJBz\XO\|aX;uJIJ6KFKQQT3z[ZEh[W6jbInzbZM>	MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTJ3OUe1NUc,Ojl{NUm3OVE9N2F-
U-2 OS	MWTxTHRUKGG\|c3H5				M1HmcZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCXLUKgU3Mh[2WubIO=	MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
A673	M1Tt[JFJXFNiYYPzZZk>				NIDkTmhyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiQU[3N{Bk\Wyucx?=	NVG1eY4xRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
DAOY	M{exfpFJXFNiYYPzZZk>				M175cpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCGQV;ZJINmdGy\|	NV7hNJVVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
BT-37	NYK0e5FyeUiWUzDhd5NigQ>?				MkK3dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEKWLUO3JINmdGy\|	NYDaOnZERGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
RD	MWPxTHRUKGG\|c3H5				MmTHdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFKGIHPlcIx{	M3K0clxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SK-N-SH	NWTTd2lPeUiWUzDhd5NigQ>?				MXTxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0tvTj3TTEBk\Wyucx?=	MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
BT-12	NFfyPZByUFSVIHHzd4F6				MYLxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhSlRvMUKgZ4VtdHN?	M3z6XFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
MG 63 (6-TG R)	NFfaU3hyUFSVIHHzd4F6				MWDxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVUdiNkOgLFYuXEdiUjmgZ4VtdHN?	M3\qUlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
NB1643	MnjIdWhVWyCjc4PhfS=>				NF7rSpZyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTlKxOlQ{KGOnbHzz	NIDne2I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
OHS-50	MYLxTHRUKGG\|c3H5				MljHdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKE:KUz21NEBk\Wyucx?=	Moq5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
fibroblast cells	NFK2e2hyUFSVIHHzd4F6				MXvxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5Ih[2:wdILvcEBJcCC5aXzkJJR6eGViZnnido9jdGG\|dDDj[Yxtew>?	NVvrU5NYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Rh41	M1mycJFJXFNiYYPzZZk>				MVPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWmh2MTDj[Yxtew>?	MkWzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
Rh30	NGjmRZpyUFSVIHHzd4F6				MYrxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWmh\|MDDj[Yxtew>?	MlnnQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SJ-GBM2	MkHSdWhVWyCjc4PhfS=>				NV\TUmxQeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGPKMWdDVTJiY3XscJM>	M{\RV\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SK-N-MC	MYLxTHRUKGG\|c3H5				NXLzNXZSeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGPLMW4uVUNiY3XscJM>	M2C5eVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
NB-EBc1	MXzxTHRUKGG\|c3H5				MXrxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVkJvRVLjNUBk\Wyucx?=	M4X1flxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
LAN-5	NUPSXW8xeUiWUzDhd5NigQ>?				MnqzdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEyDTj21JINmdGy\|	NIiwXoE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
Rh18	NH3IcZhyUFSVIHHzd4F6				NYHafZRQeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGLoNVgh[2WubIO=	M3KzeVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	α-SMA / Fibronectin / Collagen-1; PubMed: 27732564 Oncotarget Normally cultured NRK-49F cells were treated with I-BET151 (0-5μM) for 36 h. Then, cell lysates were prepared and subjected to immunoblot analysis with antibodies against α-SMA, collagen-1, fibronectin, and GAPDH. FoxM1 / AURKB / Survivin / cyclin B / PLK1; PubMed: 26877780 Theranostics OVTOKO and OVCA420 cells were treated with DMSO, JQ1 (1 μM) or I-BET151 (1 μM). Cell lysates were immunoblotted with indicated antibodies. HP1α / HP1β / HP1γ; PubMed: 30386240 Front Pharmacol Protein expression levels of HP1α, β, and γ in U937, R-U937, HL-60, and R-HL-60 cells after incubation with I-BET151 at indicated dose for 48 h. Typical blots from a representative experiment are shown. The experiments were repeated three times.	27732564 26877780 30386240

In vivo

Administration of I-BET151 at 30 mg/kg/day significantly inhibits tumor growth of murine MLL-AF9 and human MLL-AF4 leukaemia in mice, and provides marked survival benefit. ^[1]

Protocol

Kinase Assay: ^[1]	- Collapse Fluorescence anisotropy (FP) ligand displacement assay: All components are dissolved in buffer of composition 50 mM HEPES pH 7.4, 150 mM NaCl and 0.5 mM CHAPS with final concentrations of BRD 2/3/4 75 nM, fluorescent ligand 5 nM. 10 μL of this reaction mixture is added using a micro multidrop to wells containing 100 nL of various concentrations of I-BET151 or DMSO vehicle (1% final) in Greiner 384 well Black low volume microtitre plate and equilibrated in the dark for 60 minutes at room temperature. Fluorescence anisotropy is read in Envision (lex = 485 nm, lEM = 530 nm; Dichroic = 505 nM).
Cell Research: ^[1]	- Collapse Cell lines: MV4;11, MOLM13, NOMO1, RS4;11, HEL, HL60 and K562 Concentrations: Dissolved in DMSO, final concentrations ~100 μM Incubation Time: 24, or 72 hours Method: Cells are exposed to various concentrations of I-BET151 for 24 or 72 hours in 384-well or 96-well plates. For cell growth inhibition assays, plates are added with CellTiter-Glo reagent using a volume equivalent to the cell culture volume in the wells, shaken for approximately 2 minutes and chemiluminescent signal is read on the Analyst GT or EnVision Plate Reader. For cell proliferation assays, CellTiter-Aqueous One is added to each well and plates are incubated for 4 hours at 37 °C. Absorbance is read at 490 nm on a SpectraMax Gemini reader (Only for Reference)
Animal Research: ^[1]	- Collapse Animal Models: NOD-SCID mice injected intravenously with MV4;11 cells, and C57BL/6 mice injected intravenously with MLL-AF9 cells Dosages: ~30 mg/kg/day Administration: Intraperitoneal injection (Only for Reference)

References

[1] Dawson MA, et al. Nature, 2011, 478(7370), 529-533.

Solubility (25°C)

In vitro	Ethanol	27 mg/mL (64.99 mM)
	DMSO	Insoluble
	Water	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 I-BET151 (GSK1210151A) SDF

Molecular Weight	415.44
Formula	C₂₃H₂₁N₅O₃
CAS No.	1300031-49-5
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	N/A
Smiles	CC1=C(C(=NO1)C)C2=C(C=C3C(=C2)N=CC4=C3N(C(=O)N4)C(C)C5=CC=CC=N5)OC

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)

% DMSO+ % + % Tween 80+ % ddH₂O

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Calculation results:

Working concentration： mg/ml；

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

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

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

Bio Calculators

Molarity Calculator

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

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Dilution Calculator

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

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

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The Serial Dilution Calculator Equation

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Computed Result

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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'.

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

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

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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

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Epigenetic Reader Domain Signaling Pathway Map

Epigenetic Reader Domain Inhibitors with Unique Features

Selective BET Inhibitor

PFI-1 (PF-6405761) : BRD4-selective, IC50=0.22 μM.
Most Potent BET Inhibitor

I-BET-762 : BET proteins, IC50=~35 nM.
BET Inhibitor in Clinical Trial

RVX-208 ^New : Phase II for Dyslipidemia.
Newest BET Inhibitor

Bromosporine : Broad spectrum inhibitor for bromodomains with IC50 of 0.41 μM, 0.29 μM, 0.122 μM and 0.017 μM for BRD2, BRD4, BRD9 and CECR2, respectively.

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I-BET151 (GSK1210151A)