I-BET151 (GSK1210151A)

Name: I-BET151 (GSK1210151A)
Brand: Selleck Chemicals
SKU: S2780
Rating: 5 (33 reviews)

For research use only.

Catalog No.S2780

33 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 33 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 )

Nat Commun, 2021, 12(1):1045

PubMed: 33594072 ( 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	MWTjfZRwfG:6aXPpeJkh[XO\|YYm=	MnTaglExOCEQvF2=		MYrEUXNQ	MoD2TWM2OD1{NjDuUS=>	MonBQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7NkSzOFAoRjJzOU[0N\|QxRC:jPh?=
RS4;11	M2LOPYN6fG:2b4jpZ4l1gSCjc4PhfS=>	M1PGd54yODBizszN		MX7EUXNQ	NEG4NHJKSzVyPUG5NkBvVQ>?	MYC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTl4NEO0NEc,OjF7NkSzOFA9N2F-
MOLM13	NF7HS5VkgXSxdH;4bYNqfHliYYPzZZk>	NWfpXYFzhjFyMDFOwG0>		MXfEUXNQ	MojRTWM2OD1zMkCgcm0>	NWHMSYFURGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG5OlQ{PDBpPkKxPVY1OzRyPD;hQi=>
NOMO1	NX\xVJpx[3m2b4TvfIlkcXS7IHHzd4F6	NFL5TlB,OTByIN88US=>		MVXEUXNQ	MoHCTWM2OD1zNTDuUS=>	NWC5d4U5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG5OlQ{PDBpPkKxPVY1OzRyPD;hQi=>
HEL	NEXxOVFkgXSxdH;4bYNqfHliYYPzZZk>	MnG5glExOCEQvF2=		NGDGd4ZFVVOR	MYTJR\|UxRTFizszN	M1[zblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOU[0N\|QxLz5{MUm2OFM1ODxxYU6=
K562	NELXN4RkgXSxdH;4bYNqfHliYYPzZZk>	NEXHO3Z,OTByIN88US=>		NVzQWms5TE2VTx?=	M363[WlEPTB-MUCwJO69VQ>?	NHT2cnM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUm2OFM1OCd-MkG5OlQ{PDB:L3G+
MEG01	Mk\zZ5l1d3SxeHnjbZR6KGG\|c3H5	MlK1glExOCEQvF2=		MnrGSG1UVw>?	M4KzT2lEPTB;MkWg{txO	NUTI[2k5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG5OlQ{PDBpPkKxPVY1OzRyPD;hQi=>
HL60	NVPVXpNk[3m2b4TvfIlkcXS7IHHzd4F6	NYixcYlEhjFyMDFOwG0>		Ml\3SG1UVw>?	MWPJR\|UxRTh7MDDuUS=>	M1LKRlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOU[0N\|QxLz5{MUm2OFM1ODxxYU6=
MV4;11	MXrBdI9xfG:\|aYOgZZN{[Xl?	NGrvWHZ,OTByIN88US=>		MXvEUXNQ	M1[3R4lv\HWlZYOgZZBweHSxc3nz	MkLpQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7NkSzOFAoRjJzOU[0N\|QxRC:jPh?=
MOLM13	NFrGTYtCeG:ydH;zbZMh[XO\|YYm=	NG\yc45,OTByIN88US=>		NEG1WYhFVVOR	MoLlbY5lfWOnczDhdI9xfG:\|aYO=	NV[xOnhzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG5OlQ{PDBpPkKxPVY1OzRyPD;hQi=>
MV4;11	MnnoSpVv[3Srb36gZZN{[Xl?			M2nCO2ROW09?	Mk\x[IVkemWjc3XzJJRp\SC{ZXPyeYl1dWWwdDDv[kBDWkR\|L{SgZY5lKGmvcHHpdoVlKHKnY4L1bZRu\W62IH;mJGNFUzliYX7kJHBCTjFidH:geIhmKHS{YX7zZ5JqeHSrb37hcEB{fGG{dDDzbZRm	MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTl4NEO0NEc,OjF7NkSzOFA9N2F-
PBMC	NEC2SppHfW6ldHnvckBie3OjeR?=			MkfxSG1UVw>?	MVHpcohq[mm2czDJUE03KHerdHigdGlEPTBib3[gOk44	NF3YbI09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkSzO\|EyPSd-MkK0N\|cyOTV:L3G+
A2	MVnGeY5kfGmxbjDhd5NigQ>?	MYr+NVAh\|ryP		M3uxWWROW09?	Mn7VdoVi[3SrdnH0[ZMhdGG2ZX70JGhKXi1z	MWC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzJ3NUKxPEc,OjN{NUWyNVg9N2F-
A72	MlXVSpVv[3Srb36gZZN{[Xl?	NGjXdnR,OTBizszN		MXLEUXNQ	NFHlVGJz\WGldHn2ZZRmeyCuYYTlcpQhUEmYLUG=	M{fO[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|MkW1NlE5Lz5{M{K1OVIyQDxxYU6=
BC1	MULHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	M3HIR54yKM7:TR?=		MYDEUXNQ	MnO4TWM2OD1{MkCgcm0>	NX;ESIJXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO3PVI1PDhpPkKzO\|kzPDR6PD;hQi=>
BC3	MlnrS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	M{e1Vp4yKM7:TR?=		M2P3dmROW09?	Mn3uTWM2OD12NkCgcm0>	Mn3kQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN5OUK0OFgoRjJ\|N{myOFQ5RC:jPh?=
BCBL1	MoHmS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MonGglEh\|ryP		MYXEUXNQ	MUjJR\|UxRTN\|MDDuUS=>	MnW0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN5OUK0OFgoRjJ\|N{myOFQ5RC:jPh?=
BJAB	M4DlXWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	NYT6ZodVhjFizszN		NH\zbopFVVOR	NGfEd3hKSzVyPUm3NEBvVQ>?	NYLrenRVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO3PVI1PDhpPkKzO\|kzPDR6PD;hQi=>
Namalwa	MUfHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	MXH+NUDPxE1?		MnrWSG1UVw>?	MUjJR\|UxRTl5MDDuUS=>	NF7kbIc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e5NlQ1QCd-MkO3PVI1PDh:L3G+
Jurkat	M17XOGdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MknpglEh\|ryP		NEXlbIVFVVOR	NUTYfXg5UUN3ME2xNlIxKG6P	M2\FXFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|N{myOFQ5Lz5{M{e5NlQ1QDxxYU6=
MM1S	Mk\OS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	M2i1NZ4yKM7:TR?=		NUjk[mlyTE2VTx?=	NGD4bplKSzVyPUe2NEBvVQ>?	MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzd7MkS0PEc,OjN5OUK0OFg9N2F-
U266	MnvYS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	M2rRc54yKM7:TR?=		NVzURW5ITE2VTx?=	NEfhVlFKSzVyPUm1NEBvVQ>?	NGjybmI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e5NlQ1QCd-MkO3PVI1PDh:L3G+
UM-PEL-1	NWqwUnUxT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	M1HCWJ4yKM7:TR?=		NEjKfnVFVVOR	Mn;uTWM2OD1{MUCgcm0>	NWHjRmtxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO3PVI1PDhpPkKzO\|kzPDR6PD;hQi=>
UM-PEL-3	Mn:0S5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	M4D4TZ4yKM7:TR?=		M1fLNmROW09?	NFrtdJpKSzVyPUG4NEBvVQ>?	M2f6T\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|N{myOFQ5Lz5{M{e5NlQ1QDxxYU6=
BC1	MXXGeY5kfGmxbjDhd5NigQ>?	MYe1NFAhdk1?		MoP6SG1UVw>?	NVjTfFZ5cW6mdXPld{Bk\WyuLXP5Z4xmKGG{cnXzeC=>	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzd7MkS0PEc,OjN5OUK0OFg9N2F-
BC3	M2XmVGZ2dmO2aX;uJIF{e2G7	NWjVWXVOPTByIH7N		MVnEUXNQ	NIf1T2RqdmS3Y3XzJINmdGxvY4njcIUh[XK{ZYP0	NYjGTYg6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO3PVI1PDhpPkKzO\|kzPDR6PD;hQi=>
BC1	M{fLfGZ2dmO2aX;uJIF{e2G7	M{HMV\|gxOCCwTR?=		MWLEUXNQ	MlTKdoVlfWOnczDjMW16[yCycn;0[YlvKGyndnXsdy=>	NGXyb3g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e5NlQ1QCd-MkO3PVI1PDh:L3G+
BC3	NHnNTGVHfW6ldHnvckBie3OjeR?=	MlHmPFAxKG6P		NIrIV2JFVVOR	MVfy[YR2[2W\|IHOtUZlkKHC{b4TlbY4hdGW4ZXzz	NVfP[nVVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO3PVI1PDhpPkKzO\|kzPDR6PD;hQi=>
H929	M{CwfGZ2dmO2aX;uJIF{e2G7	NH7M[nR,OSEQvF2=		M1u5fWROW09?	MmO1bY5lfWOnczDj[YxtKGO7Y3zlJIFzemW\|dB?=	MlLPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR\|M{W0PVkoRjJ2M{O1OFk6RC:jPh?=
KMS12PE	M3XXcmZ2dmO2aX;uJIF{e2G7	MoG5glEh\|ryP		NYLPN4c3TE2VTx?=	MYHpcoR2[2W\|IHPlcIwh[3mlbHWgZZJz\XO2	NVTjdFVKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzN\|U1QTlpPkK0N\|M2PDl7PD;hQi=>
KMS12BM	M1LG[WZ2dmO2aX;uJIF{e2G7	NH73blJ,OSEQvF2=		MoG3SG1UVw>?	NFrEU2lqdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0	NWqxTmN4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzN\|U1QTlpPkK0N\|M2PDl7PD;hQi=>
KMS18	NIXR[XBHfW6ldHnvckBie3OjeR?=	M2jhVp4yKM7:TR?=		NFG3ZVNFVVOR	NFm1dHhqdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0	NGLCPHQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEOzOVQ6QSd-MkSzN\|U1QTl:L3G+
KMS11	M1S4d2Z2dmO2aX;uJIF{e2G7	MXf+NUDPxE1?		MV7EUXNQ	M1;icIlv\HWlZYOgZ4VtdCCleXPs[UBienKnc4S=	MW[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN\|NUS5PUc,OjR\|M{W0PVk9N2F-
RPMI8226	NFTtTlZHfW6ldHnvckBie3OjeR?=	NXHUdIVUhjFizszN		NFL3dXpFVVOR	NU\2VVZlcW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeC=>	MWO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN\|NUS5PUc,OjR\|M{W0PVk9N2F-
H929	NETr[pBCeG:ydH;zbZMh[XO\|YYm=	NV3k[3hPhjFizszN		MV;EUXNQ	MVfpcoR2[2W\|IHPlcIwh[XCxcITvd4l{	M3HKcVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{O1OFk6Lz5{NEOzOVQ6QTxxYU6=
KMS12PE	NYHaZllySXCxcITvd4l{KGG\|c3H5	M2L6ep4yKM7:TR?=		NYqyOlU1TE2VTx?=	NYrqZlA4cW6mdXPld{Bk\WyuIHHwc5B1d3Orcx?=	MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN\|NUS5PUc,OjR\|M{W0PVk9N2F-
KMS12BM	MnezRZBweHSxc3nzJIF{e2G7	M4mxW54yKM7:TR?=		NHjW[YRFVVOR	M1jiO4lv\HWlZYOgZ4VtdCCjcH;weI9{cXN?	MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN\|NUS5PUc,OjR\|M{W0PVk9N2F-
KMS18	M{j2TWFxd3C2b4Ppd{Bie3OjeR?=	NXPT[ooxhjFizszN		NUDEUIQzTE2VTx?=	NV;hS4NicW6mdXPld{Bk\WyuIHHwc5B1d3Orcx?=	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN\|NUS5PUc,OjR\|M{W0PVk9N2F-
KMS11	MXLBdI9xfG:\|aYOgZZN{[Xl?	MVn+NUDPxE1?		M2iyPWROW09?	M{D6bIlv\HWlZYOgZ4VtdCCjcH;weI9{cXN?	Mmj2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR\|M{W0PVkoRjJ2M{O1OFk6RC:jPh?=
RPMI8226	M3nPVWFxd3C2b4Ppd{Bie3OjeR?=	NU[wXZRihjFizszN		NIrCVHpFVVOR	MWnpcoR2[2W\|IHPlcIwh[XCxcITvd4l{	MoTyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR\|M{W0PVkoRjJ2M{O1OFk6RC:jPh?=
U87MG	M1;ZWGZ2dmO2aX;uJIF{e2G7	MXv+NVAh\|ryP		NVnrbpdnTE2VTx?=	M3H0XpJm\HWlZYOgWVg4VUdiY3XscJVt[XJiQWTQJJdqfGhiSVO1NEBw\iBzLkC1JO69VQ>?	NEDoV\|I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NES5OlM5OSd-MkS0PVY{QDF:L3G+
A172	MofkSpVv[3Srb36gZZN{[Xl?	NYfUO5dShjFyIN88US=>		M3\Qd2ROW09?	MXny[YR2[2W\|IHPlcIx2dGG{IFHUVEB4cXSqIFnDOVAhd2ZiMT6yPEDPxE1?	NX3SSHNNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS0PVY{QDFpPkK0OFk3OzhzPD;hQi=>
SW1783	M4jEc2Z2dmO2aX;uJIF{e2G7	NHPJd4F,OTBizszN		MXrEUXNQ	MX3y[YR2[2W\|IHPlcIx2dGG{IFHUVEB4cXSqIFnDOVAhd2ZiMj62PEDPxE1?	NX;2Z3lxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS0PVY{QDFpPkK0OFk3OzhzPD;hQi=>
U87MG	NX;6d\|UxTnWwY4Tpc44h[XO\|YYm=	MX3+NVAh\|ryP		MnzGSG1UVw>?	MWHpcoNz\WG\|ZYOgdJJweG:{dHnvckBw\iClZXzsd{BqdiC2aHWgS\|EwWyC2cnHud4l1cW:w	NYTn[\|R[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS0PVY{QDFpPkK0OFk3OzhzPD;hQi=>
RAW267.4	NEXmSpNHfW6ldHnvckBie3OjeR?=	M1noVVEh\|ryP		M{HxfGROW09?	NXfWS2V{emWmdXPld{BKVC14IIDyc4R2[3Srb36gbY5lfWOnZDDifUBNWFN?	M2jFPFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OEW5NFA5Lz5{NEi1PVAxQDxxYU6=
RAW267.4	MkfqSpVv[3Srb36gZZN{[Xl?	NHPC[Y0yKM7:TR?=		Mlv5SG1UVw>?	MWHy[YR2[2W\|IITo[UBie3OxY3nheIlwdiCkZYT3[YVvKEKURESgZY5lKGGlZYT5cIF1\WRicE[1	MlLsQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR6NUmwNFgoRjJ2OEW5NFA5RC:jPh?=
Me007	MlXNS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NXK3[FFYhjFyMDFOwG0>		Mm[0SG1UVw>?	MkPxbY5pcWKrdIOgeIhmKGe{b4f0bC=>	NE\lSGc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
SK-Mel-28	NVfre\|NtT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NYPLdFVlhjFyMDFOwG0>		M3jTd2ROW09?	M4LFPIlvcGmkaYTzJJRp\SCpcn;3eIg>	NVTsO2xXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
Mel-RMU	MYLHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	MnrnglExOCEQvF2=		MUXEUXNQ	MUjpcohq[mm2czD0bIUh\3Kxd4To	MojvQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7ME[xN\|coRjJ2OUC2NVM4RC:jPh?=
Mel-JD	MUHHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NYj1emQ1hjFyMDFOwG0>		NWfCUJNUTE2VTx?=	NVX5ZodMcW6qaXLpeJMhfGinIHfyc5d1cA>?	NFG0VIo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
Mel-RM	M1HBO2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7	NVOwOppPhjFyMDFOwG0>		NVTn[G4zTE2VTx?=	NWrFOohRcW6qaXLpeJMhfGinIHfyc5d1cA>?	NIDCXGo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
Me007	MUDBdI9xfG:\|aYOgZZN{[Xl?	M{KzWZ4yODBizszN		MnTqSG1UVw>?	NILFcpVqdmS3Y3XzJIFxd3C2b4Ppdy=>	MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
SK-Mel-28	NYPnNYxbSXCxcITvd4l{KGG\|c3H5	NGDhN5V,OTByIN88US=>		MkXDSG1UVw>?	MU\pcoR2[2W\|IHHwc5B1d3Orcx?=	M2m5blxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
Mel-RMU	Mn7uRZBweHSxc3nzJIF{e2G7	MXr+NVAxKM7:TR?=		NXz3dWZZTE2VTx?=	NXX0WZlFcW6mdXPld{BieG:ydH;zbZM>	M3zQNVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
Mel-JD	M{nDTWFxd3C2b4Ppd{Bie3OjeR?=	M13sO54yODBizszN		NYC2eXFiTE2VTx?=	M3u0dYlv\HWlZYOgZZBweHSxc3nz	MYi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
Mel-RM	M{naUWFxd3C2b4Ppd{Bie3OjeR?=	NF7OT\|d,OTByIN88US=>		NHHZVJVFVVOR	MXzpcoR2[2W\|IHHwc5B1d3Orcx?=	NUfmSot2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
Me007	MkO2SpVv[3Srb36gZZN{[Xl?	NHLrfmoyOCEQvF2=		NGS0dY5FVVOR	NX72e2ZDcW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeEBjgSC3cILl[5Vt[XSrb36gc4YheDJz	NEP5TWM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
SK-Mel-28	M3zrSmZ2dmO2aX;uJIF{e2G7	M1zkZlExKM7:TR?=		M4HL[2ROW09?	MULpcoR2[2W\|IHPlcIwh[3mlbHWgZZJz\XO2IHL5JJVxemWpdXzheIlwdiCxZjDwNlE>	NHzkcGs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
Mel-RMU	MVTGeY5kfGmxbjDhd5NigQ>?	Mni4NVAh\|ryP		MmjRSG1UVw>?	M3fXTolv\HWlZYOgZ4VtdCCleXPs[UBienKnc4SgZpkhfXC{ZXf1cIF1cW:wIH;mJJAzOQ>?	Mmf2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7ME[xN\|coRjJ2OUC2NVM4RC:jPh?=
Mel-JD	MlLnSpVv[3Srb36gZZN{[Xl?	NWTVUpl{OTBizszN		MVXEUXNQ	M32yb4lv\HWlZYOgZ4VtdCCleXPs[UBienKnc4SgZpkhfXC{ZXf1cIF1cW:wIH;mJJAzOQ>?	MkfEQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7ME[xN\|coRjJ2OUC2NVM4RC:jPh?=
Mel-RM	MoH4SpVv[3Srb36gZZN{[Xl?	MoLjNVAh\|ryP		NYm1T3FbTE2VTx?=	NVO4eVBTcW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeEBjgSC3cILl[5Vt[XSrb36gc4YheDJz	NFzqRWc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
Me007	MWDGeY5kfGmxbjDhd5NigQ>?	MXuxNEDPxE1?		M{PMWmROW09?	NV;PR2RofXC{ZXf1cIF1\XNicILvZZBweHSxdHnjJIFv\CClZXzsJIN6[2ynIHHydoV{fCCpZX7ldy=>	NXnJXmFkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
SK-Mel-28	NX[3WVEzTnWwY4Tpc44h[XO\|YYm=	NYjk[VZoOTBizszN		M13YXmROW09?	NVy2OmdzfXC{ZXf1cIF1\XNicILvZZBweHSxdHnjJIFv\CClZXzsJIN6[2ynIHHydoV{fCCpZX7ldy=>	MXK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
Mel-RMU	NUf5[pVFTnWwY4Tpc44h[XO\|YYm=	NFP0TlUyOCEQvF2=		NXLiVo5TTE2VTx?=	NIrxOZR2eHKnZ4XsZZRmeyCycn;hdI9xfG:2aXOgZY5lKGOnbHygZ5lkdGViYYLy[ZN1KGenbnXz	NGHQVWo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
Mel-JD	MmDPSpVv[3Srb36gZZN{[Xl?	NG\ENpcyOCEQvF2=		NInMcWpFVVOR	NX7DfGJ6fXC{ZXf1cIF1\XNicILvZZBweHSxdHnjJIFv\CClZXzsJIN6[2ynIHHydoV{fCCpZX7ldy=>	M4rRO\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
Mel-RM	M2W0V2Z2dmO2aX;uJIF{e2G7	NEfoWo4yOCEQvF2=		NH\nOmRFVVOR	MkOweZBz\We3bHH0[ZMheHKxYYDvdJRwfGmlIHHu[EBk\WyuIHP5Z4xmKGG{cnXzeEBo\W6ncx?=	MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
HepG2	NUT1W\|B4TnWwY4Tpc44h[XO\|YYm=		MWOxPEBpenN?		MX\VdJJm\3WuYYTpc44hd2ZiQYDvRVEh\XiycnXzd4lwdiCrbjDoeY1idiCKZYDHNkBk\WyuczDhd5Nme3OnZDDhd{Bkd26lZX70doF1cW:wIILldZVqemWmIITvJIlv[3KnYYPlJFcxLSCxZjDseYNq\mW{YYPlJIFkfGm4aYT5JIFnfGW{IEG4JIhzeyCkeTDseYNq\mW{YYPlJJJmeG:{dHXyJIdmdmViYYPzZZktKEWFMUewJF0hOC5yOTFOwG0v	Ml6wQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ\|OE[1NlkoRjJ{M{i2OVI6RC:jPh?=
Raji	MlLqSpVv[3Srb36gZZN{[Xl?		M1PBXFQhcHK\|		M3LZUmlvcGmkaYTpc44hd2ZiQmLEOEBqdiCqdX3hckBT[WqrIHPlcIx{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDv[kBOYUNiZYjwdoV{e2mxbjDh[pRmeiB2IHjyd{whUUN3MDC9JFAvOTNizszNMi=>	M4[1d\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUCwO\|U5Lz5{NEmwNFc2QDxxYU6=
MV4-11	M{nacGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7		MUS3NkBpenN?		MlnES5Jwf3SqIHnubIljcXSrb36gc4YhcHWvYX6gUXY1NTFzIHPlcIx{KGGodHXyJFczKGi{czDifUBUWkJiYYPzZZktKEmFNUCgQUAxNjFzOTFOwG0v	M4PW[\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NUW5OFI5Lz5{NUW1PVQzQDxxYU6=
MM1S	M2i5Umdzd3e2aDDpcohq[mm2aX;uJIF{e2G7		NHGxXok4OiCqcoO=		NWjUfoZ7T3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hVU1zUzDj[YxteyCjZoTldkA4OiCqcoOgZpkhW1KEIHHzd4F6NCCLQ{WwJF0hOC5{OUmg{txONg>?	M{C2UlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NUW5OFI5Lz5{NUW1PVQzQDxxYU6=
HT-29	MWjHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>?		MnrZO\|IhcHK\|		NGj3c\|RIem:5dHigbY5pcWKrdHnvckBw\iCqdX3hckBJXC1{OTDj[YxteyCjZoTldkA4OiCqcoOgZpkhW1KEIHHzd4F6NCCLQ{WwJF0hOC57NEWg{txONg>?	MonLQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV3NUm0NlgoRjJ3NUW5OFI5RC:jPh?=
Rosetta2 DE3	MWTGeY5kfGmxbjDhd5NigQ>?		MljHN\|AhdWmwcx?=		M3nrZWRqe3CuYXPlcYVvfCCxZjDGRW0udGGkZXzl[EBbSkF{NEig[pJwdSCEUlS0JGJFOSBqNESgeI8hOTZ6IHHtbY5wKGGlaXSgdoV{cWS3ZYOpJEh2dmuwb4fuJI9zcWerbjmg[ZhxemW\|c3XkJIlvKFKxc3X0eIEzKESHMzDj[YxteyCjZoTldkA{OCCvaX7zJIJ6KG[udX;y[ZNk\W6lZTDwc4xiemm8YYTpc44h[XO\|YYmsJGlEPTBiPTCwMlA{OTdizszNMi=>	NV;VNo06RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wPFAxPjRpPkK2NFgxODZ2PD;hQi=>
MV4-11	NVvIeWJDS3m2b4TvfIlkcXS7IHHzd4F6		NEfmeFY1KGSjeYO=		MULDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDNWlQuOTFiY3XscJMhcGG{Yn;ybY5oKE2OTEGg[pV{cW:wIHflcoUh[XO\|ZYPz[YQh[XNiZ4Lve5RpKGmwaHnibZRqd25iYX\0[ZIhPCCmYYnzJIJ6KEOnbHzUbZRmei2JbH:gcJVucW6nc3PlcpQh[XO\|YYmsJGlEPTBiPTCwMlE3OiEQvF2u	MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjB6MEC2OEc,OjZyOECwOlQ9N2F-
Rosetta2 DE3	MmXNSpVv[3Srb36gZZN{[Xl?		MoLHN\|AhdWmwcx?=		NGTES3VFcXOybHHj[Y1mdnRib3[gSmFONWyjYnXs[YQhYkKDMkS4JIZzd21iQmLEOEBDTDJiKEOzN{B1dyB2NkCgZY1qdm9iYXPp[EBz\XOrZIXld{khMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHHmeIVzKDNyIH3pcpMh[nliZnz1c5Jme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfUwhUUN3MDC9JFAvOjJ4IN88UU4>	M3;GfVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MEiwNFY1Lz5{NkC4NFA3PDxxYU6=
MOLM13	MW\DfZRwfG:6aXPpeJkh[XO\|YYm=		MlPGOEBl[Xm\|		NEDZXoZEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBOV0yPMUOgZ4VtdHNiaHHyZo9zcW6pIF3MUFEh\nW\|aX;uJIdmdmViYYPz[ZN{\WRiYYOg[5Jwf3SqIHnubIljcXSrb36gZYZ1\XJiNDDkZZl{KGK7IFPlcIxVcXSncj3HcI8hdHWvaX7ld4NmdnRiYYPzZZktKEmFNUCgQUAxNjJ{ODFOwG0v	Mn6xQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyOECwOlQoRjJ4MEiwNFY1RC:jPh?=
Rosetta2 DE3	MkWwSpVv[3Srb36gZZN{[Xl?		NHLU[VA{OCCvaX7z		NUX1SnJKUW6qaXLpeIlwdiCxZjDGRW0udGGkZXzl[EBbSkF{NEigZolv\GmwZzD0c{Bz\WOxbXLpcoFvfCCqdX3hckBPNXSncn3pcoFtKEirc{[teIFo\2WmIFLSSFQh[nKxbX;kc41icW5iMTCoOFQhfG9iMU[4JJJme2mmdXXzLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHHmeIVzKDNyIH3pcpMh[nliRnzveZJme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfUwhUUN3MDC9JFAvODNzNzFOwG0v	NH3BT409[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OES2N\|Q5Pyd-Mki0OlM1QDd:L3G+
MV4-11	NXjBcI45T3Kxd4ToJIlvcGmkaYTpc44h[XO\|YYm=		MknjOEBl[Xm\|		NUTROlhFT3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hVVZ2LUGxJINmdGy\|IHHmeIVzKDRiZHH5d{BjgSCZU2StPEBie3OjeTygTWM2OCB;IECuNVYzKM7:TT6=	Mn20QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh2NkO0PFcoRjJ6NE[zOFg4RC:jPh?=
Rosetta2 DE3	NEXUOpRHfW6ldHnvckBie3OjeR?=		MWOzNEBucW6\|		NFzkOZhKdmirYnn0bY9vKG:oIF\BUU1t[WKnbHXkJHpDSTJ2ODDibY5lcW6pIITvJJJm[2:vYnnuZY51KGi3bXHuJG4ufGW{bXnuZYwhUGm\|Nj30ZYdo\WRiQmLEOEBjem:vb3TvcYFqdiB{IDizN\|MhfG9iNE[wJJJme2mmdXXzLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHHmeIVzKDNyIH3pcpMh[nliRnzveZJme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfUwhUUN3MDC9JFAvOjJ4IN88UU4>	NHPKdWM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OES2N\|Q5Pyd-Mki0OlM1QDd:L3G+
MOLM13	NUWwZm5ZT3Kxd4ToJIlvcGmkaYTpc44h[XO\|YYm=		MnrIOEBl[Xm\|		NVjOcYJST3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hVU:OTUGzJINmdGy\|IHHmeIVzKDRiZHH5d{BjgSCZU2StPEBie3OjeTygTWM2OCB;IECuNlI5KM7:TT6=	NEDXW2Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OES2N\|Q5Pyd-Mki0OlM1QDd:L3G+
Rosetta2 DE3	MYDGeY5kfGmxbjDhd5NigQ>?				NFTKcJpDcW6maX7nJIFn\mmwaYT5JJRwKGKrb4Tpcplt[XSnZDDCVmQ{KEKGMTCoNlQhfG9iMUS0JIFucW6xIHHjbYQhemW\|aXT1[ZMqKCi3bnvuc5dvKG:{aXfpckkh\XiycnXzd4VlKGmwIGLvd4V1fGF{IFTFN{Bk\WyuczDifUBjcW9vbHH5[ZIhcW62ZYLm[ZJwdWW2comgcYV1cG:mLDDL[EA:KDBwMEK5PEDPxE1w	MlnTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyOECwOlQoRjJ4MEiwNFY1RC:jPh?=
Rosetta2 DE3	MYDGeY5kfGmxbjDhd5NigQ>?				NGP2[HRDcW6maX7nJIFn\mmwaYT5JJRwKGKrb4Tpcplt[XSnZDDCVmQ{KEKGMjCoN\|A3KHSxIESxO{BidWmwbzDhZ4llKHKnc3nkeYV{MSBqdX7rco94diCxcnnnbY4qKGW6cILld5Nm\CCrbjDSc5NmfHSjMjDESVMh[2WubIOgZpkh[mmxLXzhfYVzKGmwdHXy[oVzd22ndIL5JI1mfGixZDygT4QhRSByLkC0NFUh\|ryPLh?=	MmnEQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyOECwOlQoRjJ4MEiwNFY1RC:jPh?=
Rosetta2 DE3	NH;U[VNHfW6ldHnvckBie3OjeR?=				NGfXbVFDcW6maX7nJIFn\mmwaYT5JJRwKGKrb4Tpcplt[XSnZDDCVmQ1KEKGMTCoOFQhfG9iMU[4JIFucW6xIHHjbYQhemW\|aXT1[ZMqKCi3bnvuc5dvKG:{aXfpckkh\XiycnXzd4VlKGmwIGLvd4V1fGF{IFTFN{Bk\WyuczDifUBjcW9vbHH5[ZIhcW62ZYLm[ZJwdWW2comgcYV1cG:mLDDL[EA:KDBwMEWyPEDPxE1w	Mon4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyOECwOlQoRjJ4MEiwNFY1RC:jPh?=
Rosetta2 DE3	NXnvN4lVTnWwY4Tpc44h[XO\|YYm=				M{PPXGJqdmSrbnegZYZncW6rdImgeI8h[mmxdHnufYxifGWmIFLSSFIhSkRzIDi3NkB1dyB{MEWgZY1qdm9iYXPp[EBz\XOrZIXld{khMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHL5JIJqdy2uYYnldkBqdnSncn\ldo9u\XS{eTDt[ZRpd2RuIFvkJF0hOC5yNUS4JO69VS5?	M2TOc\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MEiwNFY1Lz5{NkC4NFA3PDxxYU6=
Rosetta2 DE3	MVzGeY5kfGmxbjDhd5NigQ>?				MnXoRolv\GmwZzDh[oZqdmm2eTD0c{BjcW:2aX75cIF1\WRiQmLENkBDTDJiKEO0PUB1dyB2NkCgZY1qdm9iYXPp[EBz\XOrZIXld{khMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHL5JIJqdy2uYYnldkBqdnSncn\ldo9u\XS{eTDt[ZRpd2RuIFvkJF0hOC5yN{CzJO69VS5?	NEPxSXQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkC4NFA3PCd-Mk[wPFAxPjR:L3G+
Rosetta2 DE3	MmP5SpVv[3Srb36gZZN{[Xl?				MonHRolv\GmwZzDh[oZqdmm2eTD0c{BjcW:2aX75cIF1\WRiQmLEOEBDTDJiKEOzN{B1dyB2NkCgZY1qdm9iYXPp[EBz\XOrZIXld{khMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHL5JIJqdy2uYYnldkBqdnSncn\ldo9u\XS{eTDt[ZRpd2RuIFvkJF0hOC5{MUWg{txONg>?	NHvDRWk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkC4NFA3PCd-Mk[wPFAxPjR:L3G+
Rosetta2 DE3	M1jzTmZ2dmO2aX;uJIF{e2G7				M2rlVWJqdmSrbnegZYZncW6rdImgeI8h[mmxdHnufYxifGWmIFPSSWJDWCBqMUC0N{B1dyBzMUW5JIFucW6xIHHjbYQhemW\|aXT1[ZMqKCi3bnvuc5dvKG:{aXfpckkh\XiycnXzd4VlKGmwIGLvd4V1fGF{IFTFN{Bk\WyuczDifUBjcW9vbHH5[ZIhcW62ZYLm[ZJwdWW2comgcYV1cG:mLDDL[EA:KDNwMEi0JO69VS5?	NFLXcmI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkC4NFA3PCd-Mk[wPFAxPjR:L3G+
Rosetta2 DE3	MV7GeY5kfGmxbjDhd5NigQ>?		Mly1N\|AhdWmwcx?=		NUiwdG95TGm\|cHzhZ4Vu\W62IH;mJGZCVS2uYXLlcIVlKFqEQUK0PEBnem:vIFLSSFMhSkRzIDiyOEB1dyBzNESgZY1qdm9iYXPp[EBz\XOrZIXld{khMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHHmeIVzKDNyIH3pcpMh[nliZnz1c5Jme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfUwhU2liPTCwMlAxPzJizszNMi=>	M{P6cFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MEiwNFY1Lz5{NkC4NFA3PDxxYU6=
Rosetta2 DE3	MXHGeY5kfGmxbjDhd5NigQ>?		M3XZRlMxKG2rboO=		MmKxSIl{eGyjY3Xt[Y51KG:oIF\BUU1t[WKnbHXkJHpDSTJ2ODDmdo9uKEKURESgRmQyKCh2NDD0c{AyPjhiYX3pco8h[WOrZDDy[ZNq\HWnczmgLJVvc26xd36gc5Jq\2mwKTDlfJBz\XO\|ZXSgbY4hWm:\|ZYT0ZVIhTEV\|IHPlcIx{KGGodHXyJFMxKG2rboOgZpkh\my3b4Lld4NmdmOnIIDvcIFzcXqjdHnvckBie3OjeTygT4khRSByLkCwPUDPxE1w	MnzSQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyOECwOlQoRjJ4MEiwNFY1RC:jPh?=
Rosetta2 DE3	Mn\xSpVv[3Srb36gZZN{[Xl?		M4f6flMxKG2rboO=		NGLyNlZFcXOybHHj[Y1mdnRib3[gSmFONWyjYnXs[YQhYkKDMkS4JIZzd21iQmLENkBDTDFiKEeyJJRwKDJyNTDhcYlvdyCjY3nkJJJme2mmdXXzLUApfW6tbn;3ckBwemmpaX6pJIV5eHKnc4Pl[EBqdiCUb4PleJRiOiCGRUOgZ4VtdHNiYX\0[ZIhOzBibXnud{BjgSCobIXvdoV{[2WwY3WgdI9t[XKrenH0bY9vKGG\|c3H5MEBMcSB;IECuNFA6KM7:TT6=	M2PsUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MEiwNFY1Lz5{NkC4NFA3PDxxYU6=
Rosetta2 DE3	NW\uNXVuTnWwY4Tpc44h[XO\|YYm=		NYjxc5FtOzBibXnudy=>		NGfifmtFcXOybHHj[Y1mdnRib3[gSmFONWyjYnXs[YQhYkKDMkS4JIZzd21iQmLEN{BDTDJiKEOwOkB1dyB2MUegZY1qdm9iYXPp[EBz\XOrZIXld{khMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHHmeIVzKDNyIH3pcpMh[nliZnz1c5Jme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfUwhU2liPTCwMlAzOjNizszNMi=>	MmPzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyOECwOlQoRjJ4MEiwNFY1RC:jPh?=
Rosetta2 DE3	NHP3PJpHfW6ldHnvckBie3OjeR?=		MlfDN\|AhdWmwcx?=		MVXEbZNxdGGlZX3lcpQhd2ZiRlHNMYxi[mWuZXSgXmJCOjR6IH\yc40hSlKGMjDCSFIhMDN2OTD0c{A1PjBiYX3pco8h[WOrZDDy[ZNq\HWnczmgLJVvc26xd36gc5Jq\2mwKTDlfJBz\XO\|ZXSgbY4hWm:\|ZYT0ZVIhTEV\|IHPlcIx{KGGodHXyJFMxKG2rboOgZpkh\my3b4Lld4NmdmOnIIDvcIFzcXqjdHnvckBie3OjeTygT4khRSByLkC0PVYh\|ryPLh?=	MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjB6MEC2OEc,OjZyOECwOlQ9N2F-
Rosetta2 DE3	MmPoSpVv[3Srb36gZZN{[Xl?		NYn1VW9YOzBibXnudy=>		M4LIVmRqe3CuYXPlcYVvfCCxZjDGRW0udGGkZXzl[EBbSkF{NEig[pJwdSCEUlS0JGJFOiBqM{OzJJRwKDR4MDDhcYlvdyCjY3nkJJJme2mmdXXzLUApfW6tbn;3ckBwemmpaX6pJIV5eHKnc4Pl[EBqdiCUb4PleJRiOiCGRUOgZ4VtdHNiYX\0[ZIhOzBibXnud{BjgSCobIXvdoV{[2WwY3WgdI9t[XKrenH0bY9vKGG\|c3H5MEBMcSB;IECuNFc1QCEQvF2u	M1:5WlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MEiwNFY1Lz5{NkC4NFA3PDxxYU6=
Rosetta2 DE3	MUnGeY5kfGmxbjDhd5NigQ>?		M3n0dFMxKG2rboO=		M3LwN2lvcGmkaYTpc44hd2ZiRlHNMYxi[mWuZXSgXmJCOjR6IHLpcoRqdmdidH:gdoVkd22kaX7hcpQhcHWvYX6gUk11\XKvaX7hcEBJcXN4LYTh[4dm\CCEUlS0JIJzd22xZH;tZYlvKDFiKES0JJRwKDF4ODDy[ZNq\HWnczmg[ZhxemW\|c3XkJIlvKFKxc3X0eIEzKESHMzDj[YxteyCjZoTldkA{OCCvaX7zJIJ6KE[ub4Xy[ZNk\W6lZTDwc4xiemm8YYTpc44h[XO\|YYmsJGtqKD1iMD6wNFkh\|ryPLh?=	MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDR4M{S4O{c,Ojh2NkO0PFc9N2F-
Rosetta2 DE3	M1P4[WZ2dmO2aX;uJIF{e2G7		M4i3eFMxKG2rboO=		NWrWNZdjUW6qaXLpeIlwdiCxZjDGRW0udGGkZXzl[EBbSkF{NEigZolv\GmwZzD0c{Bz\WOxbXLpcoFvfCCqdX3hckBPNXSncn3pcoFtKEirc{[teIFo\2WmIFLSSFQh[nKxbX;kc41icW5iMjCoN\|M{KHSxIES2NEBz\XOrZIXld{kh\XiycnXzd4VlKGmwIGLvd4V1fGF{IFTFN{Bk\WyuczDh[pRmeiB\|MDDtbY5{KGK7IF\sc5Vz\XOlZX7j[UBxd2yjcnn6ZZRqd25iYYPzZZktKEurIE2gNE4xPzR6IN88UU4>	MlPUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh2NkO0PFcoRjJ6NE[zOFg4RC:jPh?=
THP1	NIjnZ5hCdnSraX7mcIFudWG2b4L5JIF{e2G7				MYrBcpRqcW6obHHtcYF1d3K7IHHjeIl3cXS7IHnuJIh2dWGwIGTIVFEh[2WubIO=	MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN6NkWyPUc,OjJ\|OE[1Nlk9N2F-
HT-29	M33sb2Z2dmO2aX;uJIF{e2G7	NHWwbYoxNjNzMkWgeW0hfG9iNTD1US=>	MYqyOEBpenN?		NVrtelVjUW6qaXLpeIlwdiCxZjDCVmQ1KGmwIHj1cYFvKEiWLUK5JINmdGy\|IHHzd4V{e2WmIHHzJJJm\HWldHnvckBqdiClLV35Z{Bxem:2ZXnuJIV5eHKnc4Ppc44h[XRiMD6zNVI2KHWPIITvJFUhfU1idV2gZYZ1\XJiMkSgbJJ{KGK7IGfld5Rmem5iYnzveJRqdmdibXX0bI9l	M3Sy[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NUW5OFI5Lz5{NUW1PVQzQDxxYU6=
MV4-11	NFvmVplHfW6ldHnvckBie3OjeR?=				NUjIXlJHUW6qaXLpeIlwdiCxZjDCVmQ1KGmwIHj1cYFvKE2YND2xNUBk\WyuczDhd5Nme3OnZDDhd{Bld3ewcnXneYxifGmxbjDv[kBDS0x{IGLORUBmgHC{ZYPzbY9vKGK7IGLORU1{\XFiYX7hcJl{cXN?	MmryQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl{NUm3OVEoRjJ7MkW5O\|UyRC:jPh?=
MV4-11	NYnVNI9MTnWwY4Tpc44h[XO\|YYm=				MWHJcohq[mm2aX;uJI9nKEKURESgbY4hcHWvYX6gUXY1NTFzIHPlcIx{KGG\|c3Xzd4VlKGG\|IHTve45z\We3bHH0bY9vKG:oIHPNXWMhWk6DIHX4dJJme3Orb36gZpkhWk6DLYPldUBidmGueYPpdy=>	NWT4NG1RRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkmyOVk4PTFpPkK5NlU6PzVzPD;hQi=>
U-2 OS	Ml3odWhVWyCjc4PhfS=>				NWG0U49peUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGWtNkBQWyClZXzsdy=>	NVXPXWNNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
A673	MYPxTHRUKGG\|c3H5				NFLhT4dyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiQU[3N{Bk\Wyucx?=	NIrBRpA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
DAOY	NUH4RoZVeUiWUzDhd5NigQ>?				MXXxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhTEGRWTDj[Yxtew>?	MWm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
BT-37	NFn5UlVyUFSVIHHzd4F6				MnfVdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEKWLUO3JINmdGy\|	NEHyNmU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
RD	MXfxTHRUKGG\|c3H5				MkfodWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFKGIHPlcIx{	MW[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SK-N-SH	NV7IVm1oeUiWUzDhd5NigQ>?				MVXxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0tvTj3TTEBk\Wyucx?=	NWfkXZdJRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
BT-12	MWfxTHRUKGG\|c3H5				MoXmdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEKWLUGyJINmdGy\|	NW\FbXNnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
MG 63 (6-TG R)	NYrOOWlFeUiWUzDhd5NigQ>?				MlnMdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKE2JIE[zJEg3NVSJIGKpJINmdGy\|	MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
NB1643	Mnz1dWhVWyCjc4PhfS=>				NFHzR5NyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTlKxOlQ{KGOnbHzz	NXnVe5o6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
OHS-50	MlnadWhVWyCjc4PhfS=>				NVTxZ5J5eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF;IV{02OCClZXzsdy=>	NH\1N3U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
fibroblast cells	Mnv1dWhVWyCjc4PhfS=>				M2jDXpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiClb370do9tKEiqIIfpcIQhfHmyZTDmbYJzd2KuYYP0JINmdGy\|	M2rMW\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Rh41	M1\FWpFJXFNiYYPzZZk>				MV;xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWmh2MTDj[Yxtew>?	M4HzPVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Rh30	NFjMOZVyUFSVIHHzd4F6				NIDI[3hyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiUnizNEBk\Wyucx?=	MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SJ-GBM2	NYm5UZhueUiWUzDhd5NigQ>?				NUHXUIl[eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGPKMWdDVTJiY3XscJM>	NGG3TXQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
SK-N-MC	NUXjfpNleUiWUzDhd5NigQ>?				MWXxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0tvTj3NR{Bk\Wyucx?=	M2jqPVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
NB-EBc1	MX7xTHRUKGG\|c3H5				NGXIe4JyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTlKtSWJkOSClZXzsdy=>	NX\0SXI{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
LAN-5	NH;kT5pyUFSVIHHzd4F6				NFfX[5RyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTFHOMVUh[2WubIO=	NHHzVVE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
Rh18	NGe3O21yUFSVIHHzd4F6				M3HNUZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCUaEG4JINmdGy\|	MkTKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=

... 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

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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Dilution Calculator

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 )

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

Serial Dilutions
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Computed Result

C1=C0/X	C1:	LOG(C1):
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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.

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

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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)