I-BET151 (GSK1210151A)

Name: I-BET151 (GSK1210151A)
Brand: Selleck Chemicals
SKU: S2780
Rating: 5 (34 reviews)

For research use only.

Catalog No.S2780

34 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 34 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 )

Acta Neuropathol, 2021, 10.1007/s00401-021-02341-z

PubMed: 34283254 ( 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.e6

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	NHvX[IhkgXSxdH;4bYNqfHliYYPzZZk>	MVr+NVAxKM7:TR?=		MYnEUXNQ	NFPNdWFKSzVyPUK2JI5O	M1TwOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOU[0N\|QxLz5{MUm2OFM1ODxxYU6=
RS4;11	MUfjfZRwfG:6aXPpeJkh[XO\|YYm=	Mk[xglExOCEQvF2=		NWD0WmJNTE2VTx?=	MX3JR\|UxRTF7MjDuUS=>	M2DjSlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOU[0N\|QxLz5{MUm2OFM1ODxxYU6=
MOLM13	M1nONoN6fG:2b4jpZ4l1gSCjc4PhfS=>	M1m0U54yODBizszN		M17CcmROW09?	MnmxTWM2OD1zMkCgcm0>	NF30UW09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUm2OFM1OCd-MkG5OlQ{PDB:L3G+
NOMO1	NH;GO5NkgXSxdH;4bYNqfHliYYPzZZk>	MUD+NVAxKM7:TR?=		NYXvepZ5TE2VTx?=	MYXJR\|UxRTF3IH7N	NHzhW2Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUm2OFM1OCd-MkG5OlQ{PDB:L3G+
HEL	NUfI[WFW[3m2b4TvfIlkcXS7IHHzd4F6	MVX+NVAxKM7:TR?=		NY\4WlZsTE2VTx?=	NWDsdYlbUUN3ME2xJO69VQ>?	M{n3WVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOU[0N\|QxLz5{MUm2OFM1ODxxYU6=
K562	MX7jfZRwfG:6aXPpeJkh[XO\|YYm=	M{\iVZ4yODBizszN		NIiyfmJFVVOR	Ml3mTWM2OD5zMECg{txO	MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTl4NEO0NEc,OjF7NkSzOFA9N2F-
MEG01	M{j0WoN6fG:2b4jpZ4l1gSCjc4PhfS=>	M2K3XZ4yODBizszN		MoPSSG1UVw>?	Ml7mTWM2OD1{NTFOwG0>	NVu0UXVGRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG5OlQ{PDBpPkKxPVY1OzRyPD;hQi=>
HL60	NFnTcmRkgXSxdH;4bYNqfHliYYPzZZk>	MUH+NVAxKM7:TR?=		M336WWROW09?	NXv6c3dpUUN3ME24PVAhdk1?	NVHIdm4yRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG5OlQ{PDBpPkKxPVY1OzRyPD;hQi=>
MV4;11	NHK2bYhCeG:ydH;zbZMh[XO\|YYm=	MofrglExOCEQvF2=		NFT0UWRFVVOR	NEDhbG5qdmS3Y3XzJIFxd3C2b4Ppdy=>	M1rLWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOU[0N\|QxLz5{MUm2OFM1ODxxYU6=
MOLM13	M4e3fGFxd3C2b4Ppd{Bie3OjeR?=	M1XQUZ4yODBizszN		Mk\FSG1UVw>?	NULVW5gycW6mdXPld{BieG:ydH;zbZM>	MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTl4NEO0NEc,OjF7NkSzOFA9N2F-
MV4;11	MnL1SpVv[3Srb36gZZN{[Xl?			MmjISG1UVw>?	NGnPUZVl\WO{ZXHz[ZMhfGinIILlZ5J2cXSvZX70JI9nKEKUREOvOEBidmRiaX3wZYlz\WRicnXjdpVqfG2nboSgc4YhS0SNOTDhcoQhWEGIMTD0c{B1cGVidILhcpNkemmydHnvcoFtKHO2YYL0JJNqfGV?	M4TudFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOU[0N\|QxLz5{MUm2OFM1ODxxYU6=
PBMC	NFfS[IpHfW6ldHnvckBie3OjeR?=			MmPySG1UVw>?	MVnpcohq[mm2czDJUE03KHerdHigdGlEPTBib3[gOk44	M3rHSlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{NEO3NVE2Lz5{MkSzO\|EyPTxxYU6=
A2	NIHVZ5pHfW6ldHnvckBie3OjeR?=	Mn3JglExKM7:TR?=		M4jJ[GROW09?	MV;y[YFkfGm4YYTld{Bt[XSnboSgTGlXNTF?	NGnFU3E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{K1OVIyQCd-MkOyOVUzOTh:L3G+
A72	NIjBZ\|RHfW6ldHnvckBie3OjeR?=	MX;+NVAh\|ryP		NESyfWlFVVOR	MkXOdoVi[3SrdnH0[ZMhdGG2ZX70JGhKXi1z	NIPCVI09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{K1OVIyQCd-MkOyOVUzOTh:L3G+
BC1	M1K1bWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MmD5glEh\|ryP		MmT3SG1UVw>?	MkfTTWM2OD1{MkCgcm0>	M1KzT\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|N{myOFQ5Lz5{M{e5NlQ1QDxxYU6=
BC3	MmPuS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MXT+NUDPxE1?		NXOyb2ZwTE2VTx?=	M4PNcGlEPTB;NE[wJI5O	NI\NcnA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e5NlQ1QCd-MkO3PVI1PDh:L3G+
BCBL1	MYrHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NVnRPZp6hjFizszN		NGLwN\|dFVVOR	NWXwNYJzUUN3ME2zN\|Ahdk1?	MkPKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN5OUK0OFgoRjJ\|N{myOFQ5RC:jPh?=
BJAB	MojmS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	M4fPep4yKM7:TR?=		M3vPbmROW09?	MWTJR\|UxRTl5MDDuUS=>	MmK4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN5OUK0OFgoRjJ\|N{myOFQ5RC:jPh?=
Namalwa	M4C3T2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7	Ml20glEh\|ryP		NYjmN\|FxTE2VTx?=	NWrudItsUUN3ME25O\|Ahdk1?	Mn;BQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN5OUK0OFgoRjJ\|N{myOFQ5RC:jPh?=
Jurkat	M4fsXGdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	NIfvSIN,OSEQvF2=		MULEUXNQ	NHn4V2dKSzVyPUGyNlAhdk1?	Mm\PQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN5OUK0OFgoRjJ\|N{myOFQ5RC:jPh?=
MM1S	NEDmU4dIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	MYf+NUDPxE1?		MnfnSG1UVw>?	MWTJR\|UxRTd4MDDuUS=>	MoDTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN5OUK0OFgoRjJ\|N{myOFQ5RC:jPh?=
U266	M2PjSWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MYH+NUDPxE1?		M1G0ZWROW09?	NEj0OGhKSzVyPUm1NEBvVQ>?	Mlv4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN5OUK0OFgoRjJ\|N{myOFQ5RC:jPh?=
UM-PEL-1	M3XsdGdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MVT+NUDPxE1?		Mk\hSG1UVw>?	M1zKemlEPTB;MkGwJI5O	M{S1TVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|N{myOFQ5Lz5{M{e5NlQ1QDxxYU6=
UM-PEL-3	M1Lkdmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	NVLySHN4hjFizszN		MnnlSG1UVw>?	MWfJR\|UxRTF6MDDuUS=>	MlvQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN5OUK0OFgoRjJ\|N{myOFQ5RC:jPh?=
BC1	NXr4cGFUTnWwY4Tpc44h[XO\|YYm=	NEHENnU2ODBibl2=		M1fL[GROW09?	NFPXdI5qdmS3Y3XzJINmdGxvY4njcIUh[XK{ZYP0	MlmzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN5OUK0OFgoRjJ\|N{myOFQ5RC:jPh?=
BC3	NVvC[XdSTnWwY4Tpc44h[XO\|YYm=	MnjIOVAxKG6P		M3nRRWROW09?	MXPpcoR2[2W\|IHPlcIwu[3mlbHWgZZJz\XO2	MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzd7MkS0PEc,OjN5OUK0OFg9N2F-
BC1	MYTGeY5kfGmxbjDhd5NigQ>?	MlrCPFAxKG6P		MlnGSG1UVw>?	MmLTdoVlfWOnczDjMW16[yCycn;0[YlvKGyndnXsdy=>	MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzd7MkS0PEc,OjN5OUK0OFg9N2F-
BC3	MWnGeY5kfGmxbjDhd5NigQ>?	NVvhPVZtQDByIH7N		MYPEUXNQ	MYny[YR2[2W\|IHOtUZlkKHC{b4TlbY4hdGW4ZXzz	NFzHN489[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e5NlQ1QCd-MkO3PVI1PDh:L3G+
H929	Mn22SpVv[3Srb36gZZN{[Xl?	M{HSRZ4yKM7:TR?=		MXfEUXNQ	MUXpcoR2[2W\|IHPlcIwh[3mlbHWgZZJz\XO2	MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN\|NUS5PUc,OjR\|M{W0PVk9N2F-
KMS12PE	M3HPRmZ2dmO2aX;uJIF{e2G7	NFrZNGt,OSEQvF2=		Mne1SG1UVw>?	MojtbY5lfWOnczDj[YxtKGO7Y3zlJIFzemW\|dB?=	Mm[wQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR\|M{W0PVkoRjJ2M{O1OFk6RC:jPh?=
KMS12BM	MmLmSpVv[3Srb36gZZN{[Xl?	NV\QRnhThjFizszN		MnfqSG1UVw>?	NV3jdnNWcW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeC=>	M3rrWFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{O1OFk6Lz5{NEOzOVQ6QTxxYU6=
KMS18	NUfVRXRFTnWwY4Tpc44h[XO\|YYm=	MlvxglEh\|ryP		MoD4SG1UVw>?	NWLMN3o5cW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeC=>	NIXoNVM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEOzOVQ6QSd-MkSzN\|U1QTl:L3G+
KMS11	MnnaSpVv[3Srb36gZZN{[Xl?	MWL+NUDPxE1?		NEDFOW5FVVOR	Mm[wbY5lfWOnczDj[YxtKGO7Y3zlJIFzemW\|dB?=	NX7BfXJYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzN\|U1QTlpPkK0N\|M2PDl7PD;hQi=>
RPMI8226	NYHjVlBYTnWwY4Tpc44h[XO\|YYm=	MUD+NUDPxE1?		NVS5[WhmTE2VTx?=	MWDpcoR2[2W\|IHPlcIwh[3mlbHWgZZJz\XO2	MkjHQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR\|M{W0PVkoRjJ2M{O1OFk6RC:jPh?=
H929	NGTTfZhCeG:ydH;zbZMh[XO\|YYm=	NXfLcmRHhjFizszN		NGPyOoZFVVOR	MWjpcoR2[2W\|IHPlcIwh[XCxcITvd4l{	NFjjOYU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEOzOVQ6QSd-MkSzN\|U1QTl:L3G+
KMS12PE	NWjsUII6SXCxcITvd4l{KGG\|c3H5	MljOglEh\|ryP		NF[ze3BFVVOR	NY\LSHJQcW6mdXPld{Bk\WyuIHHwc5B1d3Orcx?=	NWnX[HBbRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzN\|U1QTlpPkK0N\|M2PDl7PD;hQi=>
KMS12BM	M3HvXWFxd3C2b4Ppd{Bie3OjeR?=	M2nTcp4yKM7:TR?=		NVuwNlZCTE2VTx?=	MVTpcoR2[2W\|IHPlcIwh[XCxcITvd4l{	NV[xOpBxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzN\|U1QTlpPkK0N\|M2PDl7PD;hQi=>
KMS18	NFPoXZhCeG:ydH;zbZMh[XO\|YYm=	MV\+NUDPxE1?		NYPvSVZOTE2VTx?=	NWDRVG5PcW6mdXPld{Bk\WyuIHHwc5B1d3Orcx?=	NHzSNFM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEOzOVQ6QSd-MkSzN\|U1QTl:L3G+
KMS11	M1rpTmFxd3C2b4Ppd{Bie3OjeR?=	M3zIPZ4yKM7:TR?=		MXvEUXNQ	M3eyN4lv\HWlZYOgZ4VtdCCjcH;weI9{cXN?	M2nKclxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{O1OFk6Lz5{NEOzOVQ6QTxxYU6=
RPMI8226	M3LUWGFxd3C2b4Ppd{Bie3OjeR?=	NF[0[pV,OSEQvF2=		Mmf3SG1UVw>?	NWfZO4wxcW6mdXPld{Bk\WyuIHHwc5B1d3Orcx?=	Ml\mQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR\|M{W0PVkoRjJ2M{O1OFk6RC:jPh?=
U87MG	NV;XPJgxTnWwY4Tpc44h[XO\|YYm=	NXfyWmxshjFyIN88US=>		NYfCeph3TE2VTx?=	MUny[YR2[2W\|IGW4O21IKGOnbHz1cIFzKEGWUDD3bZRpKEmFNUCgc4YhOS5yNTFOwG0>	Mki2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR2OU[zPFEoRjJ2NEm2N\|gyRC:jPh?=
A172	NH3mVWNHfW6ldHnvckBie3OjeR?=	MnG1glExKM7:TR?=		NHHCNnlFVVOR	NEjKUnVz\WS3Y3XzJINmdGy3bHHyJGFVWCC5aYToJGlEPTBib3[gNU4zQCEQvF2=	M4jiZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NEm2N\|gyLz5{NES5OlM5OTxxYU6=
SW1783	NHLvZ2ZHfW6ldHnvckBie3OjeR?=	MlnVglExKM7:TR?=		NXjWc45zTE2VTx?=	M2nIcJJm\HWlZYOgZ4VtdHWuYYKgRXRRKHerdHigTWM2OCCxZjCyMlY5KM7:TR?=	NHnKZWQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NES5OlM5OSd-MkS0PVY{QDF:L3G+
U87MG	NHzBZ3BHfW6ldHnvckBie3OjeR?=	Ml[0glExKM7:TR?=		NIDJSJhFVVOR	NUXCfoxlcW6lcnXhd4V{KHC{b4DvdpRqd25ib3[gZ4VtdHNiaX6geIhmKEdzL2OgeJJidnOrdHnvci=>	NUHrUYRsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS0PVY{QDFpPkK0OFk3OzhzPD;hQi=>
RAW267.4	M13oc2Z2dmO2aX;uJIF{e2G7	NVHmdpoyOSEQvF2=		MlXQSG1UVw>?	M1HxVpJm\HWlZYOgTWwuPiCycn;keYN1cW:wIHnu[JVk\WRiYomgUHBU	NVfTfpR{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS4OVkxODhpPkK0PFU6ODB6PD;hQi=>
RAW267.4	M4HjR2Z2dmO2aX;uJIF{e2G7	MnzKNUDPxE1?		MlXkSG1UVw>?	NU\SOnl{emWmdXPld{B1cGViYYPzc4Nq[XSrb36gZoV1f2WnbjDCVmQ1KGGwZDDhZ4V1gWyjdHXkJJA3PQ>?	NX;xeIhbRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS4OVkxODhpPkK0PFU6ODB6PD;hQi=>
Me007	M{XpZWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	NG\FdoV,OTByIN88US=>		NVO5cGtrTE2VTx?=	MoXJbY5pcWKrdIOgeIhmKGe{b4f0bC=>	NH7D[Yw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
SK-Mel-28	NWjWN5F[T3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	MYT+NVAxKM7:TR?=		MWPEUXNQ	M2jlPIlvcGmkaYTzJJRp\SCpcn;3eIg>	M1LaOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
Mel-RMU	NVj4elduT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	M{\m[Z4yODBizszN		MWrEUXNQ	MYTpcohq[mm2czD0bIUh\3Kxd4To	M1XPbFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
Mel-JD	M{Dacmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	M4jQRp4yODBizszN		M{XPS2ROW09?	M{\IfIlvcGmkaYTzJJRp\SCpcn;3eIg>	NGCySmU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
Mel-RM	MkLMS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MlLJglExOCEQvF2=		M2jsWWROW09?	MWPpcohq[mm2czD0bIUh\3Kxd4To	NF3hPHk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
Me007	NE\iNolCeG:ydH;zbZMh[XO\|YYm=	MoLzglExOCEQvF2=		NIOy[WpFVVOR	NGTCWnBqdmS3Y3XzJIFxd3C2b4Ppdy=>	MmjEQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7ME[xN\|coRjJ2OUC2NVM4RC:jPh?=
SK-Mel-28	MWfBdI9xfG:\|aYOgZZN{[Xl?	NHyycGJ,OTByIN88US=>		NXnjVVF1TE2VTx?=	MkLUbY5lfWOnczDhdI9xfG:\|aYO=	M3zJRlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
Mel-RMU	MmW0RZBweHSxc3nzJIF{e2G7	MkLXglExOCEQvF2=		MVvEUXNQ	M2rmNYlv\HWlZYOgZZBweHSxc3nz	MmnjQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7ME[xN\|coRjJ2OUC2NVM4RC:jPh?=
Mel-JD	M4PaOGFxd3C2b4Ppd{Bie3OjeR?=	MUL+NVAxKM7:TR?=		NWjYO5loTE2VTx?=	MmT4bY5lfWOnczDhdI9xfG:\|aYO=	NX;vXmIzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
Mel-RM	Mnr4RZBweHSxc3nzJIF{e2G7	MlH1glExOCEQvF2=		NXXkd3pDTE2VTx?=	MYjpcoR2[2W\|IHHwc5B1d3Orcx?=	MUK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
Me007	NHnvXHJHfW6ldHnvckBie3OjeR?=	NUPofndoOTBizszN		MkHHSG1UVw>?	M1foNIlv\HWlZYOgZ4VtdCCleXPs[UBienKnc4SgZpkhfXC{ZXf1cIF1cW:wIH;mJJAzOQ>?	NIHYVnU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
SK-Mel-28	MoHOSpVv[3Srb36gZZN{[Xl?	NELFPHIyOCEQvF2=		NU\YOZNqTE2VTx?=	M4DIVIlv\HWlZYOgZ4VtdCCleXPs[UBienKnc4SgZpkhfXC{ZXf1cIF1cW:wIH;mJJAzOQ>?	MnXlQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7ME[xN\|coRjJ2OUC2NVM4RC:jPh?=
Mel-RMU	NXflZZJHTnWwY4Tpc44h[XO\|YYm=	M33WRVExKM7:TR?=		NHWyeVFFVVOR	MYjpcoR2[2W\|IHPlcIwh[3mlbHWgZZJz\XO2IHL5JJVxemWpdXzheIlwdiCxZjDwNlE>	MlntQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7ME[xN\|coRjJ2OUC2NVM4RC:jPh?=
Mel-JD	NFO3c3JHfW6ldHnvckBie3OjeR?=	NVTNfnJjOTBizszN		NU\6Z41MTE2VTx?=	MXTpcoR2[2W\|IHPlcIwh[3mlbHWgZZJz\XO2IHL5JJVxemWpdXzheIlwdiCxZjDwNlE>	MoTYQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7ME[xN\|coRjJ2OUC2NVM4RC:jPh?=
Mel-RM	Mk[ySpVv[3Srb36gZZN{[Xl?	MVKxNEDPxE1?		NEHaSINFVVOR	M{ez[Ylv\HWlZYOgZ4VtdCCleXPs[UBienKnc4SgZpkhfXC{ZXf1cIF1cW:wIH;mJJAzOQ>?	M2X3TFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
Me007	MWfGeY5kfGmxbjDhd5NigQ>?	MWSxNEDPxE1?		MlTISG1UVw>?	NEizdWR2eHKnZ4XsZZRmeyCycn;hdI9xfG:2aXOgZY5lKGOnbHygZ5lkdGViYYLy[ZN1KGenbnXz	NYC3SVdTRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
SK-Mel-28	NIrD[npHfW6ldHnvckBie3OjeR?=	MY[xNEDPxE1?		NFyyeVNFVVOR	M1LVTJVxemWpdXzheIV{KHC{b3Hwc5B1d3SrYzDhcoQh[2WubDDjfYNt\SCjcoLld5Qh\2WwZYO=	M4\HPFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
Mel-RMU	MUXGeY5kfGmxbjDhd5NigQ>?	MXmxNEDPxE1?		MmPOSG1UVw>?	MWr1dJJm\3WuYYTld{Bxem:jcH;weI91cWNiYX7kJINmdGxiY4njcIUh[XK{ZYP0JIdmdmW\|	M1vLcVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
Mel-JD	MkLNSpVv[3Srb36gZZN{[Xl?	MXGxNEDPxE1?		MlvZSG1UVw>?	MYT1dJJm\3WuYYTld{Bxem:jcH;weI91cWNiYX7kJINmdGxiY4njcIUh[XK{ZYP0JIdmdmW\|	M4jiO\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
Mel-RM	MVrGeY5kfGmxbjDhd5NigQ>?	NU\TfVBVOTBizszN		NFTzcVVFVVOR	MVj1dJJm\3WuYYTld{Bxem:jcH;weI91cWNiYX7kJINmdGxiY4njcIUh[XK{ZYP0JIdmdmW\|	NH3HNGI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
HepG2	M17rZWZ2dmO2aX;uJIF{e2G7		MYKxPEBpenN?		NIq2S\|NWeHKnZ4XsZZRqd25ib3[gRZBwSTFiZYjwdoV{e2mxbjDpckBpfW2jbjDI[ZBIOiClZXzsd{Bie3Onc4Pl[EBieyClb37j[Y51emG2aX;uJJJmeXWrcnXkJJRwKGmwY4LlZZNmKDdyJTDv[kBtfWOrZnXyZZNmKGGldHn2bZR6KGGodHXyJFE5KGi{czDifUBtfWOrZnXyZZNmKHKncH;yeIVzKGenbnWgZZN{[XluIFXDNVcxKD1iMD6wPUDPxE1w	NFXVZYc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkO4OlUzQSd-MkKzPFY2Ojl:L3G+
Raji	MmDySpVv[3Srb36gZZN{[Xl?		M4T1d\|QhcHK\|		NHnQcohKdmirYnn0bY9vKG:oIFLSSFQhcW5iaIXtZY4hWmGsaTDj[YxteyCjc4Pld5Nm\CCjczDy[YR2[3Srb36gc4YhVVmFIHX4dJJme3Orb36gZYZ1\XJiNDDodpMtKEmFNUCgQUAxNjF\|IN88UU4>	MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyMEe1PEc,OjR7MEC3OVg9N2F-
MV4-11	M3\Mcmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7		NH3YZ5U4OiCqcoO=		NGPjbYJIem:5dHigbY5pcWKrdHnvckBw\iCqdX3hckBOXjRvMUGgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KFOUQjDhd5NigSxiSVO1NEA:KDBwMUG5JO69VS5?	NV7PTG9IRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW1OVk1OjhpPkK1OVU6PDJ6PD;hQi=>
MM1S	M1\scGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7		MnrMO\|IhcHK\|		NH;ldlRIem:5dHigbY5pcWKrdHnvckBw\iCqdX3hckBOVTGVIHPlcIx{KGGodHXyJFczKGi{czDifUBUWkJiYYPzZZktKEmFNUCgQUAxNjJ7OTFOwG0v	NUfxWng6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW1OVk1OjhpPkK1OVU6PDJ6PD;hQi=>
HT-29	NXrrZYFnT3Kxd4ToJIlvcGmkaYTpc44h[XO\|YYm=		MmfPO\|IhcHK\|		Mn7wS5Jwf3SqIHnubIljcXSrb36gc4YhcHWvYX6gTHQuOjliY3XscJMh[W[2ZYKgO\|IhcHK\|IHL5JHNTSiCjc4PhfUwhUUN3MDC9JFAvQTR3IN88UU4>	M1m3N\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NUW5OFI5Lz5{NUW1PVQzQDxxYU6=
Rosetta2 DE3	M37VbmZ2dmO2aX;uJIF{e2G7		MYezNEBucW6\|		M3jTVWRqe3CuYXPlcYVvfCCxZjDGRW0udGGkZXzl[EBbSkF{NEig[pJwdSCEUlS0JGJFOSBqNESgeI8hOTZ6IHHtbY5wKGGlaXSgdoV{cWS3ZYOpJEh2dmuwb4fuJI9zcWerbjmg[ZhxemW\|c3XkJIlvKFKxc3X0eIEzKESHMzDj[YxteyCjZoTldkA{OCCvaX7zJIJ6KG[udX;y[ZNk\W6lZTDwc4xiemm8YYTpc44h[XO\|YYmsJGlEPTBiPTCwMlA{OTdizszNMi=>	NH;TW3c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkC4NFA3PCd-Mk[wPFAxPjR:L3G+
MV4-11	M2nxfmN6fG:2b4jpZ4l1gSCjc4PhfS=>		NGfJNm81KGSjeYO=		MoXJR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gUXY1NTFzIHPlcIx{KGijcnLvdolv\yCPTFyxJIZ2e2mxbjDn[Y5mKGG\|c3Xzd4VlKGG\|IHfyc5d1cCCrbnjpZol1cW:wIHHmeIVzKDRiZHH5d{BjgSCFZXzsWIl1\XJvR3zvJIx2dWmwZYPj[Y51KGG\|c3H5MEBKSzVyIE2gNE4yPjJizszNMi=>	Ml[zQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyOECwOlQoRjJ4MEiwNFY1RC:jPh?=
Rosetta2 DE3	NFTW[4ZHfW6ldHnvckBie3OjeR?=		NEDCd2o{OCCvaX7z		NEe3PVNFcXOybHHj[Y1mdnRib3[gSmFONWyjYnXs[YQhYkKDMkS4JIZzd21iQmLEOEBDTDJiKEOzN{B1dyB2NkCgZY1qdm9iYXPp[EBz\XOrZIXld{khMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHHmeIVzKDNyIH3pcpMh[nliZnz1c5Jme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfUwhUUN3MDC9JFAvOjJ4IN88UU4>	MlnCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyOECwOlQoRjJ4MEiwNFY1RC:jPh?=
MOLM13	NFrjZpNEgXSxdH;4bYNqfHliYYPzZZk>		NX\sOJlYPCCmYYnz		NVPxfod5S3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hVU:OTUGzJINmdGy\|IHjhdoJwemmwZzDNUGwyKG[3c3nvckBo\W6nIHHzd4V{e2WmIHHzJIdzd3e2aDDpcohq[mm2aX;uJIFnfGW{IESg[IF6eyCkeTDD[YxtXGm2ZYKtS4xwKGy3bXnu[ZNk\W62IHHzd4F6NCCLQ{WwJF0hOC5{Mkig{txONg>?	NUjGTWhpRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wPFAxPjRpPkK2NFgxODZ2PD;hQi=>
Rosetta2 DE3	MX3GeY5kfGmxbjDhd5NigQ>?		NXv0[HBQOzBibXnudy=>		MXrJcohq[mm2aX;uJI9nKE[DTT3sZYJmdGWmIGrCRVI1QCCkaX7kbY5oKHSxIILlZ49u[mmwYX70JIh2dWGwIF6teIVzdWmwYXygTIl{Pi22YXfn[YQhSlKGNDDido9ud2SxbXHpckAyKCh2NDD0c{AyPjhicnXzbYR2\XNrIHX4dJJme3OnZDDpckBTd3OndIThNkBFTTNiY3XscJMh[W[2ZYKgN\|AhdWmwczDifUBHdG:3cnXzZ4Vv[2VicH;sZZJqgmG2aX;uJIF{e2G7LDDJR\|UxKD1iMD6wN\|E4KM7:TT6=	MkG0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh2NkO0PFcoRjJ6NE[zOFg4RC:jPh?=
MV4-11	M4PuWWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7		NIXsZZA1KGSjeYO=		MXrHdo94fGhiaX7obYJqfGmxbjDv[kBpfW2jbjDNWlQuOTFiY3XscJMh[W[2ZYKgOEBl[Xm\|IHL5JHdUXC16IHHzd4F6NCCLQ{WwJF0hOC5zNkKg{txONg>?	M1W2[\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6NE[zOFg4Lz5{OES2N\|Q5PzxxYU6=
Rosetta2 DE3	NVnHc3RYTnWwY4Tpc44h[XO\|YYm=		M{HWW\|MxKG2rboO=		NUC0U4J[UW6qaXLpeIlwdiCxZjDGRW0udGGkZXzl[EBbSkF{NEigZolv\GmwZzD0c{Bz\WOxbXLpcoFvfCCqdX3hckBPNXSncn3pcoFtKEirc{[teIFo\2WmIFLSSFQh[nKxbX;kc41icW5iMjCoN\|M{KHSxIES2NEBz\XOrZIXld{kh\XiycnXzd4VlKGmwIGLvd4V1fGF{IFTFN{Bk\WyuczDh[pRmeiB\|MDDtbY5{KGK7IF\sc5Vz\XOlZX7j[UBxd2yjcnn6ZZRqd25iYYPzZZktKEmFNUCgQUAxNjJ{NjFOwG0v	MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDR4M{S4O{c,Ojh2NkO0PFc9N2F-
MOLM13	M{nZNmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7		NE\tcmE1KGSjeYO=		NV3uZmh3T3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hVU:OTUGzJINmdGy\|IHHmeIVzKDRiZHH5d{BjgSCZU2StPEBie3OjeTygTWM2OCB;IECuNlI5KM7:TT6=	MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDR4M{S4O{c,Ojh2NkO0PFc9N2F-
Rosetta2 DE3	M1PWVWZ2dmO2aX;uJIF{e2G7				NWq0PZlYSmmwZHnu[{Bi\m[rbnn0fUB1dyCkaX;0bY56dGG2ZXSgRnJFOyCEREGgLFI1KHSxIEG0OEBidWmwbzDhZ4llKHKnc3nkeYV{MSBqdX7rco94diCxcnnnbY4qKGW6cILld5Nm\CCrbjDSc5NmfHSjMjDESVMh[2WubIOgZpkh[mmxLXzhfYVzKGmwdHXy[oVzd22ndIL5JI1mfGixZDygT4QhRSByLkCyPVgh\|ryPLh?=	MlnrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyOECwOlQoRjJ4MEiwNFY1RC:jPh?=
Rosetta2 DE3	NWrLPFBlTnWwY4Tpc44h[XO\|YYm=				NHX4cJJDcW6maX7nJIFn\mmwaYT5JJRwKGKrb4Tpcplt[XSnZDDCVmQ{KEKGMjCoN\|A3KHSxIESxO{BidWmwbzDhZ4llKHKnc3nkeYV{MSBqdX7rco94diCxcnnnbY4qKGW6cILld5Nm\CCrbjDSc5NmfHSjMjDESVMh[2WubIOgZpkh[mmxLXzhfYVzKGmwdHXy[oVzd22ndIL5JI1mfGixZDygT4QhRSByLkC0NFUh\|ryPLh?=	MWO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjB6MEC2OEc,OjZyOECwOlQ9N2F-
Rosetta2 DE3	Mo\mSpVv[3Srb36gZZN{[Xl?				MXPCbY5lcW6pIHHm[olvcXS7IITvJIJqd3SrbonsZZRm\CCEUlS0JGJFOSBqNESgeI8hOTZ6IHHtbY5wKGGlaXSgdoV{cWS3ZYOpJEh2dmuwb4fuJI9zcWerbjmg[ZhxemW\|c3XkJIlvKFKxc3X0eIEzKESHMzDj[YxteyCkeTDibY8udGG7ZYKgbY51\XKoZYLvcYV1enlibXX0bI9lNCCNZDC9JFAvODV{ODFOwG0v	M4fZdVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MEiwNFY1Lz5{NkC4NFA3PDxxYU6=
Rosetta2 DE3	MUPGeY5kfGmxbjDhd5NigQ>?				M1voTWJqdmSrbnegZYZncW6rdImgeI8h[mmxdHnufYxifGWmIFLSSFIhSkRzIDi3NkB1dyB{MEWgZY1qdm9iYXPp[EBz\XOrZIXld{khMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHL5JIJqdy2uYYnldkBqdnSncn\ldo9u\XS{eTDt[ZRpd2RuIFvkJF0hOC5yNUS4JO69VS5?	MWq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjB6MEC2OEc,OjZyOECwOlQ9N2F-
Rosetta2 DE3	Mlf3SpVv[3Srb36gZZN{[Xl?				MWXCbY5lcW6pIHHm[olvcXS7IITvJIJqd3SrbonsZZRm\CCEUlSyJGJFOiBqM{S5JJRwKDR4MDDhcYlvdyCjY3nkJJJme2mmdXXzLUApfW6tbn;3ckBwemmpaX6pJIV5eHKnc4Pl[EBqdiCUb4PleJRiOiCGRUOgZ4VtdHNiYomgZolwNWyjeXXyJIlvfGW{ZnXyc41mfHK7IH3leIhw\CxiS3SgQUAxNjB5MEOg{txONg>?	M3OyfVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MEiwNFY1Lz5{NkC4NFA3PDxxYU6=
Rosetta2 DE3	NXLiVYRiTnWwY4Tpc44h[XO\|YYm=				Mn\ORolv\GmwZzDh[oZqdmm2eTD0c{BjcW:2aX75cIF1\WRiQmLEOEBDTDJiKEOzN{B1dyB2NkCgZY1qdm9iYXPp[EBz\XOrZIXld{khMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHL5JIJqdy2uYYnldkBqdnSncn\ldo9u\XS{eTDt[ZRpd2RuIFvkJF0hOC5{MUWg{txONg>?	M2LpcFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MEiwNFY1Lz5{NkC4NFA3PDxxYU6=
Rosetta2 DE3	NInr[Y9HfW6ldHnvckBie3OjeR?=				MUfCbY5lcW6pIHHm[olvcXS7IITvJIJqd3SrbonsZZRm\CCFUlXCRnAhMDFyNEOgeI8hOTF3OTDhcYlvdyCjY3nkJJJme2mmdXXzLUApfW6tbn;3ckBwemmpaX6pJIV5eHKnc4Pl[EBqdiCUb4PleJRiOiCGRUOgZ4VtdHNiYomgZolwNWyjeXXyJIlvfGW{ZnXyc41mfHK7IH3leIhw\CxiS3SgQUA{NjB6NDFOwG0v	MnPEQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyOECwOlQoRjJ4MEiwNFY1RC:jPh?=
Rosetta2 DE3	MknJSpVv[3Srb36gZZN{[Xl?		NH;ub3A{OCCvaX7z		Mn3HSIl{eGyjY3Xt[Y51KG:oIF\BUU1t[WKnbHXkJHpDSTJ2ODDmdo9uKEKUREOgRmQyKCh{NDD0c{AyPDRiYX3pco8h[WOrZDDy[ZNq\HWnczmgLJVvc26xd36gc5Jq\2mwKTDlfJBz\XO\|ZXSgbY4hWm:\|ZYT0ZVIhTEV\|IHPlcIx{KGGodHXyJFMxKG2rboOgZpkh\my3b4Lld4NmdmOnIIDvcIFzcXqjdHnvckBie3OjeTygT4khRSByLkCwO\|Ih\|ryPLh?=	MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjB6MEC2OEc,OjZyOECwOlQ9N2F-
Rosetta2 DE3	NV7VT3lxTnWwY4Tpc44h[XO\|YYm=		MnS2N\|AhdWmwcx?=		MYrEbZNxdGGlZX3lcpQhd2ZiRlHNMYxi[mWuZXSgXmJCOjR6IH\yc40hSlKGNDDCSFEhMDR2IITvJFE3QCCjbXnuc{Bi[2mmIILld4llfWW\|KTCoeY5sdm:5bjDvdolocW5rIHX4dJJme3OnZDDpckBTd3OndIThNkBFTTNiY3XscJMh[W[2ZYKgN\|AhdWmwczDifUBndHWxcnXzZ4Vv[2VicH;sZZJqgmG2aX;uJIF{e2G7LDDLbUA:KDBwMEC5JO69VS5?	NWLQbYVLRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wPFAxPjRpPkK2NFgxODZ2PD;hQi=>
Rosetta2 DE3	NVnuV2ZYTnWwY4Tpc44h[XO\|YYm=		NEW1eoM{OCCvaX7z		MkHrSIl{eGyjY3Xt[Y51KG:oIF\BUU1t[WKnbHXkJHpDSTJ2ODDmdo9uKEKUREKgRmQyKCh5MjD0c{AzODViYX3pco8h[WOrZDDy[ZNq\HWnczmgLJVvc26xd36gc5Jq\2mwKTDlfJBz\XO\|ZXSgbY4hWm:\|ZYT0ZVIhTEV\|IHPlcIx{KGGodHXyJFMxKG2rboOgZpkh\my3b4Lld4NmdmOnIIDvcIFzcXqjdHnvckBie3OjeTygT4khRSByLkCwPUDPxE1w	MkTuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyOECwOlQoRjJ4MEiwNFY1RC:jPh?=
Rosetta2 DE3	NFqyN2tHfW6ldHnvckBie3OjeR?=		MXuzNEBucW6\|		MX7EbZNxdGGlZX3lcpQhd2ZiRlHNMYxi[mWuZXSgXmJCOjR6IH\yc40hSlKGMzDCSFIhMDNyNjD0c{A1OTdiYX3pco8h[WOrZDDy[ZNq\HWnczmgLJVvc26xd36gc5Jq\2mwKTDlfJBz\XO\|ZXSgbY4hWm:\|ZYT0ZVIhTEV\|IHPlcIx{KGGodHXyJFMxKG2rboOgZpkh\my3b4Lld4NmdmOnIIDvcIFzcXqjdHnvckBie3OjeTygT4khRSByLkCyNlMh\|ryPLh?=	NGn4dGQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkC4NFA3PCd-Mk[wPFAxPjR:L3G+
Rosetta2 DE3	NGjIc\|lHfW6ldHnvckBie3OjeR?=		MmfvN\|AhdWmwcx?=		NYL2TmRuTGm\|cHzhZ4Vu\W62IH;mJGZCVS2uYXLlcIVlKFqEQUK0PEBnem:vIFLSSFIhSkR{IDizOFkhfG9iNE[wJIFucW6xIHHjbYQhemW\|aXT1[ZMqKCi3bnvuc5dvKG:{aXfpckkh\XiycnXzd4VlKGmwIGLvd4V1fGF{IFTFN{Bk\WyuczDh[pRmeiB\|MDDtbY5{KGK7IH\seY9z\XOlZX7j[UBxd2yjcnn6ZZRqd25iYYPzZZktKEurIE2gNE4xPDl4IN88UU4>	NWLnc4NwRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wPFAxPjRpPkK2NFgxODZ2PD;hQi=>
Rosetta2 DE3	MW\GeY5kfGmxbjDhd5NigQ>?		MWCzNEBucW6\|		MYrEbZNxdGGlZX3lcpQhd2ZiRlHNMYxi[mWuZXSgXmJCOjR6IH\yc40hSlKGNDDCSFIhMDN\|MzD0c{A1PjBiYX3pco8h[WOrZDDy[ZNq\HWnczmgLJVvc26xd36gc5Jq\2mwKTDlfJBz\XO\|ZXSgbY4hWm:\|ZYT0ZVIhTEV\|IHPlcIx{KGGodHXyJFMxKG2rboOgZpkh\my3b4Lld4NmdmOnIIDvcIFzcXqjdHnvckBie3OjeTygT4khRSByLkC3OFgh\|ryPLh?=	MWO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjB6MEC2OEc,OjZyOECwOlQ9N2F-
Rosetta2 DE3	MlPBSpVv[3Srb36gZZN{[Xl?		M3XQTFMxKG2rboO=		NFK4Xm5KdmirYnn0bY9vKG:oIF\BUU1t[WKnbHXkJHpDSTJ2ODDibY5lcW6pIITvJJJm[2:vYnnuZY51KGi3bXHuJG4ufGW{bXnuZYwhUGm\|Nj30ZYdo\WRiQmLEOEBjem:vb3TvcYFqdiBzIDi0OEB1dyBzNkigdoV{cWS3ZYOpJIV5eHKnc4Pl[EBqdiCUb4PleJRiOiCGRUOgZ4VtdHNiYX\0[ZIhOzBibXnud{BjgSCIbH;1doV{[2WwY3WgdI9t[XKrenH0bY9vKGG\|c3H5MEBMcSB;IECuNFA6KM7:TT6=	NWXVe4VHRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki0OlM1QDdpPkK4OFY{PDh5PD;hQi=>
Rosetta2 DE3	MYLGeY5kfGmxbjDhd5NigQ>?		NWSyNVBOOzBibXnudy=>		M4TweWlvcGmkaYTpc44hd2ZiRlHNMYxi[mWuZXSgXmJCOjR6IHLpcoRqdmdidH:gdoVkd22kaX7hcpQhcHWvYX6gUk11\XKvaX7hcEBJcXN4LYTh[4dm\CCEUlS0JIJzd22xZH;tZYlvKDJiKEOzN{B1dyB2NkCgdoV{cWS3ZYOpJIV5eHKnc4Pl[EBqdiCUb4PleJRiOiCGRUOgZ4VtdHNiYX\0[ZIhOzBibXnud{BjgSCIbH;1doV{[2WwY3WgdI9t[XKrenH0bY9vKGG\|c3H5MEBMcSB;IECuNFc1QCEQvF2u	M4i4XFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6NE[zOFg4Lz5{OES2N\|Q5PzxxYU6=
THP1	M4[5WmFvfGmrbn\sZY1u[XSxcomgZZN{[Xl?				NVXmeJdvSW62aXnu[oxidW2jdH;yfUBi[3Srdnn0fUBqdiCqdX3hckBVUFBzIHPlcIx{	M{PlOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{i2OVI6Lz5{MkO4OlUzQTxxYU6=
HT-29	NHvVcXlHfW6ldHnvckBie3OjeR?=	MoK2NE4{OTJ3IIXNJJRwKDVidV2=	MoO4NlQhcHK\|		MUHJcohq[mm2aX;uJI9nKEKURESgbY4hcHWvYX6gTHQuOjliY3XscJMh[XO\|ZYPz[YQh[XNicnXkeYN1cW:wIHnuJIMuVXmlIIDyc5RmcW5iZYjwdoV{e2mxbjDheEAxNjNzMkWgeW0hfG9iNTD1UUB2VSCjZoTldkAzPCCqcoOgZpkhX2W\|dHXyckBjdG:2dHnu[{Bu\XSqb3S=	MmLMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV3NUm0NlgoRjJ3NUW5OFI5RC:jPh?=
MV4-11	NFrWd\|hHfW6ldHnvckBie3OjeR?=				M2HifGlvcGmkaYTpc44hd2ZiQmLEOEBqdiCqdX3hckBOXjRvMUGgZ4VtdHNiYYPz[ZN{\WRiYYOg[I94dnKnZ4XsZZRqd25ib3[gRmNNOiCUTlGg[ZhxemW\|c3nvckBjgSCUTlGtd4VyKGGwYXz5d4l{	NV;GNWwyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkmyOVk4PTFpPkK5NlU6PzVzPD;hQi=>
MV4-11	MmDVSpVv[3Srb36gZZN{[Xl?				MWDJcohq[mm2aX;uJI9nKEKURESgbY4hcHWvYX6gUXY1NTFzIHPlcIx{KGG\|c3Xzd4VlKGG\|IHTve45z\We3bHH0bY9vKG:oIHPNXWMhWk6DIHX4dJJme3Orb36gZpkhWk6DLYPldUBidmGueYPpdy=>	M{TiNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7MkW5O\|UyLz5{OUK1PVc2OTxxYU6=
U-2 OS	MWPxTHRUKGG\|c3H5				MWLxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhXS1{IF;TJINmdGy\|	NHX5Wok9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
A673	NUjhXWZEeUiWUzDhd5NigQ>?				MWjxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhSTZ5MzDj[Yxtew>?	NX\leIdVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
DAOY	MXvxTHRUKGG\|c3H5				NUTMZW9meUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IFTBU3kh[2WubIO=	NFPSOJM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
BT-37	NIftd4ZyUFSVIHHzd4F6				NF7VOVRyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiQmStN\|ch[2WubIO=	M4PjOFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
RD	NX\1NVRzeUiWUzDhd5NigQ>?				M3KyZZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCURDDj[Yxtew>?	MojPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SK-N-SH	M3zucJFJXFNiYYPzZZk>				MXjxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0tvTj3TTEBk\Wyucx?=	MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
BT-12	NXe5dmt3eUiWUzDhd5NigQ>?				Mom3dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEKWLUGyJINmdGy\|	M3T2VlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
MG 63 (6-TG R)	NYjr[3AzeUiWUzDhd5NigQ>?				MYTxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVUdiNkOgLFYuXEdiUjmgZ4VtdHN?	MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
NB1643	MXLxTHRUKGG\|c3H5				NVH5e\|NYeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF7CNVY1OyClZXzsdy=>	MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
OHS-50	MYfxTHRUKGG\|c3H5				NHzhSJJyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiT1jTMVUxKGOnbHzz	M1jqeVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
fibroblast cells	M3f2NZFJXFNiYYPzZZk>				NGLtVWJyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiY3;ueJJwdCCKaDD3bYxlKHS7cHWg[oljem:kbHHzeEBk\Wyucx?=	NHPDV4Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
Rh41	M1nlXZFJXFNiYYPzZZk>				M4nWeJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCUaESxJINmdGy\|	M{XafVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Rh30	MnnxdWhVWyCjc4PhfS=>				M17aRpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCUaEOwJINmdGy\|	NWD0VpZMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
SJ-GBM2	NUDwNlNveUiWUzDhd5NigQ>?				M3PYdJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSj3HRm0zKGOnbHzz	MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SK-N-MC	M{nlepFJXFNiYYPzZZk>				NXjyVo92eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGPLMW4uVUNiY3XscJM>	NFqyZ2k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
NB-EBc1	NUjvT2N3eUiWUzDhd5NigQ>?				MYjxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVkJvRVLjNUBk\Wyucx?=	M{[4NlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
LAN-5	M4TmeZFJXFNiYYPzZZk>				MlnZdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEyDTj21JINmdGy\|	M3nhOFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Rh18	MUjxTHRUKGG\|c3H5				NInBZnNyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiUnixPEBk\Wyucx?=	MlHIQIEhfGG{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)

Dosage

mg/kg

Average weight of animals

Dosing volume per animal

Number of animals

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO+ % + % Tween 80+ % ddH₂O

Calculate Reset

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)

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and SDS / COA (available on product pages).

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 SDS / COA (available online).

The Serial Dilution Calculator Equation

Serial Dilutions
Concertration (start):
Dilution-folds:

Computed Result

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

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

Instructions to calculate molar mass (molecular weight) of a chemical compound:

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

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

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

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.

Choose Your Country or Region

By Signaling Pathways

By product type

I-BET151 (GSK1210151A)