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Ricolinostat (ACY-1215)

Name: Ricolinostat (ACY-1215)
Brand: Selleck Chemicals
SKU: S8001
Rating: 5 (56 reviews)

Catalog No.S8001 Synonyms: Rocilinostat

For research use only.

Ricolinostat (ACY-1215, Rocilinostat) is a selective HDAC6 inhibitor with IC50 of 5 nM in a cell-free assay. It is >10-fold more selective for HDAC6 than HDAC1/2/3 (class I HDACs) with slight activity against HDAC8, minimal activity against HDAC4/5/7/9/11, Sirtuin1, and Sirtuin2. Ricolinostat (ACY-1215) suppresses cell proliferation and promotes apoptosis. Phase 2.

Ricolinostat (ACY-1215) Chemical Structure

CAS No. 1316214-52-4

Selleck's Ricolinostat (ACY-1215) has been cited by 56 publications

Purity & Quality Control

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HDAC Signaling Pathway Map

Biological Activity

Description

Features

Induced less cytotoxicity in PHA-stimulated PBMCs from 4 healthy donors compared with the pan-HDAC inhibitor SAHA.

Targets

HDAC6 ^[1] (Cell-free assay)	HDAC2 ^[1] (Cell-free assay)	HDAC3 ^[1] (Cell-free assay)	HDAC1 ^[1] (Cell-free assay)	HDAC8 ^[1] (Cell-free assay)
4.7 nM	48 nM	51 nM	58 nM	100 nM

In vitro

ACY-1215 is a hydroxamic acid derivative. ACY-1215 is 12-, 10-, and 11-fold less active against HDAC1, HDAC2, and HDAC3 (class I HDACs), respectively. ACY-1215 has minimal activity (IC50 > 1μM) against HDAC4, HDAC5, HDAC7, HDAC9, HDAC11, Sirtuin1, and Sirtuin2, and has slight activity against HDAC8 (IC50 = 0.1μM). The IC50 values for ACY-1215 for T-cell toxicity is 2.5μM. ACY-1215 overcomes tumor cell growth and survival conferred by BMSCs and cytokines in the BM milieu. ACY-1215 in combination with bortezomib induces synergistic anti-MM activity. ACY-1215 induces potent acetylation of α-tubulin at very low doses and triggers acetylation of lysine on histone H3 and histone H4 only at higher doses, confirming its specific inhibitory effect on HDAC6 activity. ^[1]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID

A-172	NIT5e2RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	M3fFS\|ExyqCwTR?=	NUPme\|JXOjRxNEigbC=>	MV\pcohq[mm2czDj[YxtKGe{b4f0bEB1cW2nIHTldIVv\GWwdHz5	NYDid4xHRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xOVA{PDBpPkK2NVUxOzRyPD;hQi=>
U87MG	MoDaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MWixNOKhdk1?	NUHK[4I3OjRxNEigbC=>	M2nsTYlvcGmkaYTzJINmdGxiZ4Lve5RpKHSrbXWg[IVx\W6mZX70cJk>	M3X6UlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUWwN\|QxLz5{NkG1NFM1ODxxYU6=
Hbl-1	NXHGRlZYT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		MVm0PEBp	MYPJR\|UxRTFwNjFOwG0>	NGnTb5c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkGxOlI4OCd-Mk[xNVYzPzB:L3G+
OCI-Ly10	MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		M3f3OVQ5KGh?	NHXM[WdKSzVyPUCuPUDPxE1?	NUTQO5RqRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xNVYzPzBpPkK2NVE3OjdyPD;hQi=>
Riva	MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		MW[0PEBp	MnewTWM2OD1{LkKg{txO	M2TFOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUG2NlcxLz5{NkGxOlI4ODxxYU6=
Su-DHL2	MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		Mm\iOFghcA>?	MWrJR\|UxRTNwMzFOwG0>	M3XkTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUG2NlcxLz5{NkGxOlI4ODxxYU6=
OCI-Ly1	Mk\iS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		NFfudnE1QCCq	M3jsOGlEPTB;Mj60JO69VQ>?	NWXJZ2lxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xNVYzPzBpPkK2NVE3OjdyPD;hQi=>
OCI-Ly7	MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		MmfxOFghcA>?	NX\ldWxpUUN3ME2xMlIh\|ryP	NYjxZ2trRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xNVYzPzBpPkK2NVE3OjdyPD;hQi=>
Su-DHL4	NEGxWlRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=		NWX1eod2PDhiaB?=	MlHqTWM2OD12Lkeg{txO	NHLkNZo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkGxOlI4OCd-Mk[xNVYzPzB:L3G+
Su-DHL6	M2T2WWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		MorrOFghcA>?	Mlu0TWM2OD1\|LkKg{txO	MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjFzNkK3NEc,OjZzMU[yO\|A9N2F-
Hbl-2	MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		NHz5SII1QCCq	MUHJR\|UxRTFwOTFOwG0>	MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjFzNkK3NEc,OjZzMU[yO\|A9N2F-
Jeko-1	M3HvUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		MUC0PEBp	NVvmdoZ5UUN3ME2xMlUh\|ryP	NWfie2cyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xNVYzPzBpPkK2NVE3OjdyPD;hQi=>
Jvm-2	NVr1bodkT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		MUe0PEBp	MUPJR\|UxRTRwMDFOwG0>	NIDHWlg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkGxOlI4OCd-Mk[xNVYzPzB:L3G+
Rec-1	NEHncndIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=		M2\sNVQ5KGh?	MmDYTWM2OD1{LkOg{txO	NVnRXmx[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xNVYzPzBpPkK2NVE3OjdyPD;hQi=>
CCL-119	NYPvUoF3T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		M3XMeFQ5KGh?	MVnJR\|UxRTFwNzFOwG0>	MoPFQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzMU[yO\|AoRjJ4MUG2NlcxRC:jPh?=
H9	MoTkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		MmLvOFghcA>?	NV;QbIQ1UUN3ME2xMlIh\|ryP	MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjFzNkK3NEc,OjZzMU[yO\|A9N2F-
HH	NV;a[pJoT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		MYi0PEBp	MWfJR\|UxRTJwNTFOwG0>	NXzpOFhIRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xNVYzPzBpPkK2NVE3OjdyPD;hQi=>
Sup-T1	MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		NHz1bWY1QCCq	MU\JR\|UxRTFwNjFOwG0>	MljxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzMU[yO\|AoRjJ4MUG2NlcxRC:jPh?=
MM.1S	MV;GeY5kfGmxbjDBd5NigQ>?	NFq0NpcxNTYQvF2=	NFnRVI43KGh?	NH7vVYpqdmO{ZXHz[ZMh[WOndInsZZRm\CEQsT30eYJ2dGmw	M1\yflxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{Mk[yO\|YxLz5{MkK2Nlc3ODxxYU6=
MM.1S	NVLyPXU3TnWwY4Tpc44hSXO\|YYm=	NEPrdVcxNjJ3L{JOwG0>	MUSxPEBp	NUjhdI43cW6lcnXhd4V{KGGlZYT5cIF1\WRizsGteJVjfWyrbh?=	MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjJ4Mke2NEc,OjJ{NkK3OlA9N2F-
MM.1R	M3HZSmZ2dmO2aX;uJGF{e2G7	NIXNUIIxNjJ3L{JOwG0>	Ml:wNVghcA>?	MYnpcoNz\WG\|ZYOgZYNmfHmuYYTl[EDPuS22dXL1cIlv	NWHGR3ZXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKyOlI4PjBpPkKyNlYzPzZyPD;hQi=>
RPMI8226	NUTWZlZPTnWwY4Tpc44hSXO\|YYm=	MUCwMlI2NzIQvF2=	M1TQeVE5KGh?	MkfpbY5kemWjc3XzJIFk\XS7bHH0[YQh\|rFvdIXieYxqdg>?	NIT6NVY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkK2Nlc3OCd-MkKyOlI4PjB:L3G+
MM.1S	NVjhOWtKS2WubDDWbYFjcWyrdImgRZN{[Xl?	MknJNE05\|ryP	MnXtOFghcA>?	M3[4bIRm[3KnYYPld{BOVS2lZXzsJJZq[WKrbHn0fUBqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=>	MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjJ4Mke2NEc,OjJ{NkK3OlA9N2F-
OPM1	NFfOZXJE\WyuIG\pZYJqdGm2eTDBd5NigQ>?	NYqxWnExOC16zszN	NEnGRWQ1QCCq	MYfk[YNz\WG\|ZYOgUW0u[2WubDD2bYFjcWyrdImgbY4h[SCmb4PlMYRmeGWwZHXueEBu[W6wZYK=	NUDvXpU3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKyOlI4PjBpPkKyNlYzPzZyPD;hQi=>
RPMI	MXrD[YxtKF[rYXLpcIl1gSCDc4PhfS=>	NXiwS\|RwOC16zszN	MY[0PEBp	MkjH[IVkemWjc3XzJG1ONWOnbHygeoli[mmuaYT5JIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy	M1;idFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{Mk[yO\|YxLz5{MkK2Nlc3ODxxYU6=
MM.1R	NXH5WmN6S2WubDDWbYFjcWyrdImgRZN{[Xl?	NX3lTlBrOC16zszN	M334ZVQ5KGh?	M4PabIRm[3KnYYPld{BOVS2lZXzsJJZq[WKrbHn0fUBqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=>	Mk\EQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ{NkK3OlAoRjJ{Mk[yO\|YxRC:jPh?=
LR5	Mk\uR4VtdCCYaXHibYxqfHliQYPzZZk>	M1LFclAuQM7:TR?=	M2\odVQ5KGh?	M4e2dIRm[3KnYYPld{BOVS2lZXzsJJZq[WKrbHn0fUBqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=>	NF;yXFA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkK2Nlc3OCd-MkKyOlI4PjB:L3G+
OPM2	M2LqNmNmdGxiVnnhZoltcXS7IFHzd4F6	M4rFZlAuQM7:TR?=	Mln5OFghcA>?	M{S3OIRm[3KnYYPld{BOVS2lZXzsJJZq[WKrbHn0fUBqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=>	Mmm5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ{NkK3OlAoRjJ{Mk[yO\|YxRC:jPh?=
Sf9	MYrGeY5kfGmxbjDhd5NigQ>?		NUPGWmZ6OTBibXnudy=>	MoDJTY5pcWKrdHnvckBw\iCodXzsJIxmdme2aDDoeY1idiC{ZXPvcYJqdmGwdDDOMZRmem2rbnHsJGdUXC22YXfn[YQhUESDQ{[g[ZhxemW\|c3XkJIlvKFOoOTDj[YxteyC3c3nu[{BHXFNiYYOgd5Vje3S{YYTlJJBz\WmwY4XiZZRm\CCob4KgNVAhdWmwczDmc4xtd3enZDDifUB{fWK\|dILheIUh[WSmaYTpc44hdWWjc4Xy[YQhd3[ncjCzNEBucW6\|LDDJR\|UxKD1iMD6wNFQ4KM7:TT6=	NG\LU3Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OECzPFMzPCd-MkiwN\|g{OjR:L3G+
Sf9	NWTP[phjTnWwY4Tpc44h[XO\|YYm=		MoLLNVUhdWmwcx?=	MoS4TY5pcWKrdHnvckBw\iCodXzsJIxmdme2aDDy[YNwdWKrbnHueEBpfW2jbjDOMZRmem2rbnHsJGdUXC22YXfn[YQhUESDQ{[g[ZhxemW\|c3XkJIlvKGKjY4Xsc5ZqenW\|IHnu[oVkfGWmIIPmPUBk\WyuczD1d4lv\yCEb3OtUJl{NSiDYzmtRW1EKGG\|IIP1ZpN1emG2ZTDwdoVqdmO3YnH0[YQh\m:{IEG1JI1qdnNiZn;scI94\WRiYomgd5Vje3S{YYTlJIFl\Gm2aX;uJI1m[XO3cnXkJIFnfGW{IE[wJI1qdnNiYomg[ox2d3Knc3PlcoNmKGG\|c3H5MEBKSzVyIE2gNE4xODlizszNMi=>	NEfXV4M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUWwNFE{OCd-Mkm1NFAyOzB:L3G+
Sf9	NEPB[nhHfW6ldHnvckBie3OjeR?=		MoX4NVUhdWmwcx?=	NVS4cYRiUW6qaXLpeIlwdiCxZjDmeYxtKGynbnf0bEBz\WOxbXLpcoFvfCCqdX3hckBENXSncn3pcoFtKEircz30ZYdo\WRiSFTBR\|MwVi22ZYLtbY5idCCJU2SteIFo\2WmIF7DU3IzKCh\|OUWgeI8hPDh7IILld4llfWW\|KTDlfJBz\XO\|ZXSgbY4h[mGldXzveolzfXNiaX7m[YN1\WRic3[5JINmdGy\|IIXzbY5oKEKxYz3MfZMuMEGlKT3BUWMh[XNic4Xid5Rz[XSnIIDy[Ylv[3WkYYTl[EBnd3JiMUWgcYlveyCob3zsc5dm\CCkeTDzeYJ{fHKjdHWgZYRlcXSrLDDJR\|UxKD1iMD6wN\|ch\|ryPLh?=	NGnOXYE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUWwNFE{OCd-Mkm1NFAyOzB:L3G+
Sf9	MlKzSpVv[3Srb36gZZN{[Xl?		M4nsRlExKG2rboO=	M13JZWlvcGmkaYTpc44hd2ZiZoXscEBt\W6pdHigbJVu[W5icnXjc41jcW6jboSgR{11\XKvaX7hcEBHVEGJLYTh[4dm\CCKRFHDNkBmgHC{ZYPz[YQhcW5iU3[5JINmdGy\|IIXzbY5oKE[WUzDhd{B{fWK\|dILheIUheHKnaX7jeYJifGWmIH\vdkAyOCCvaX7zJIZwdGyxd3XkJIJ6KHO3YoP0doF1\SCjZHTpeIlwdiCvZXHzeZJm\CCxdnXyJFMxKG2rboOsJGlEPTBiPTCwMlA1QCEQvF2u	M4rUclxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6MEO4N\|I1Lz5{OECzPFMzPDxxYU6=
Sf9	MmTsSpVv[3Srb36gZZN{[Xl?		MV:xNEBucW6\|	MlHTTY5pcWKrdHnvckBw\iCodXzsJIxmdme2aDDoeY1idiC{ZXPvcYJqdmGwdDDDMZRmem2rbnHsJGZNSUdvSHnzMZRi\2enZDDISGFEOSCneIDy[ZN{\WRiaX6gV4Y6KGOnbHzzJJV{cW6pIF\UV{BieyC\|dXLzeJJifGVicILlbY5kfWKjdHXkJIZweiBzMDDtbY5{KG[xbHzve4VlKGK7IIP1ZpN1emG2ZTDh[IRqfGmxbjDt[YF{fXKnZDDveoVzKDNyIH3pcpMtKEmFNUCgQUAxNjB3ODFOwG0v	NETW[W09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OECzPFMzPCd-MkiwN\|g{OjR:L3G+
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BCP-ALL	NITlZnNEgXSxdH;4bYNqfHliYYPzZZk>		M2XnXVczKGi{cx?=	NXn3TINoS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hSkOSLVHMUEBk\WyuczDk[ZJqfmWmIH\yc40heGG2aXXueEAyKGGodHXyJFczKGi{czDifUBE\WyuVHn0[ZIuT2yxIHz1cYlv\XOlZX70JINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwJF0hOC5{OTFOwG0v	MX68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODN4NUi5Nkc,OzB\|NkW4PVI9N2F-
BCP-ALL	NWfGUJVVS3m2b4TvfIlkcXS7IHHzd4F6		NVuxdmE{PzJiaILz	M3;mSWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGJEWC2DTFygZ4VtdHNiZHXybZZm\CCocn;tJJBifGmnboSgOEBi\nSncjC3NkBpenNiYomgR4VtdFSrdHXyMWdtdyCudX3pcoV{[2WwdDDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3MDC9JFAvPTRizszNMi=>	Mo[wQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB\|NkW4PVIoRjNyM{[1PFkzRC:jPh?=
BCP-ALL	MnXqR5l1d3SxeHnjbZR6KGG\|c3H5		MknsO\|IhcHK\|	NY\v[JhmS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hSkOSLVHMUEBk\WyuczDk[ZJqfmWmIH\yc40heGG2aXXueEAzKGGodHXyJFczKGi{czDifUBE\WyuVHn0[ZIuT2yxIHz1cYlv\XOlZX70JINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwJF0hOC53ODFOwG0v	NW\pOmJERGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CzOlU5QTJpPkOwN\|Y2QDl{PD;hQi=>
RPMI8226	NHPZVlhEgXSxdH;4bYNqfHliYYPzZZk>		MWG3NkBpenN?	MUnDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDSVG1KQDJ{NjDj[YxteyCjZoTldkA4OiCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwJF0hOS52Nkig{txONg>?	NVr6VGd[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[0OFMxPzhpPkK2OFQ{ODd6PD;hQi=>
SEM	M4fsZmN6fG:2b4jpZ4l1gSCjc4PhfS=>		M2fBeFczKGi{cx?=	NGr6VJhEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBUTU1iY3XscJMh[W[2ZYKgO\|IhcHK\|IHL5JGNmdGyWaYTldk1IdG9ibIXtbY5me2OnboSgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUCgQUAyNjZzIN88UU4>	M2DmbFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyM{[1PFkzLz5\|MEO2OVg6OjxxYU6=
SUP-B15	Moe3R5l1d3SxeHnjbZR6KGG\|c3H5		M{C4OlczKGi{cx?=	NUKzZXk1S3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hW1WSLVKxOUBk\WyuczDh[pRmeiB5MjDodpMh[nliQ3XscHRqfGW{LVfsc{BtfW2rbnXzZ4VvfCClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OCB;IEGuPVIh\|ryPLh?=	NWTKenZqRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CzOlU5QTJpPkOwN\|Y2QDl{PD;hQi=>
RPMI18226	M4P0SGN6fG:2b4jpZ4l1gSCjc4PhfS=>		NYj4co84PzJiaILz	MY\DfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDSVG1KOTh{Mk[gZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KEOnbHzUbZRmei2JbH:gcJVucW6nc3PlcpQh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVAhRSBzLkm3JO69VS5?	MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODN4NUi5Nkc,OzB\|NkW4PVI9N2F-
HL60	NUjvVlBXS3m2b4TvfIlkcXS7IHHzd4F6		NIDETo84OiCqcoO=	M1vtS2N6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGhNPjBiY3XscJMh[W[2ZYKgO\|IhcHK\|IHL5JGNmdGyWaYTldk1IdG9ibIXtbY5me2OnboSgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUCgQUAzNjN4IN88UU4>	MnHwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB\|NkW4PVIoRjNyM{[1PFkzRC:jPh?=
HL60	M4L6SGFvfGmycn;sbYZmemG2aY\lJIF{e2G7		NGrDXIw1QCCqcoO=	NUP1PW9bSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDIUFYxKGOnbHzzJIFnfGW{IES4JIhzeyCrbjDwdoV{\W6lZTDv[kBLSUt{IHnubIljcXSxcjDDXXQuOzh5IHL5JGNEUy16IHHzd4F6NCCLQ{WwJF0hOi53NDFOwG0v	MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTl2MEGxOUc,Ojl7NECxNVU9N2F-
K562	MVXBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		M3O4NlQ5KGi{cx?=	MnLyRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCNNU[yJINmdGy\|IHHmeIVzKDR6IHjyd{BqdiCycnXz[Y5k\SCxZjDKRWszKGmwaHnibZRweiCFWWStN\|g4KGK7IFPDT{05KGG\|c3H5MEBKSzVyIE2gNk42PCEQvF2u	MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTl2MEGxOUc,Ojl7NECxNVU9N2F-
HEL	MkPzRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		NGXUbWw1QCCqcoO=	NHXLUYVCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFjFUEBk\WyuczDh[pRmeiB2ODDodpMhcW5icILld4Vv[2Vib3[gTmFMOiCrbnjpZol1d3JiQ2nUMVM5PyCkeTDDR2suQCCjc4PhfUwhUUN3MDC9JFIvPTRizszNMi=>	M2myT\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7OUSwNVE2Lz5{OUm0NFEyPTxxYU6=
KCL22	MX7DfZRwfG:6aXPpeJkh[XO\|YYm=		NV\Ic4hRPzJiaILz	NVvhV5RsS3m2b4TvfIlkcXS7IHHnZYlve3RiaX3heIlvcWJvcnXzbZN1[W62IHj1cYFvKEuFTEKyJINmdGy\|IHHmeIVzKDd{IHjyd{BjgSCFZXzsWIl1\XJvR3zvJIx2dWmwZYPj[Y51KGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR\|UxKD1iMz6zPEDPxE1w	NIfjZlU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEO2OVg6Oid-M{CzOlU5QTJ:L3G+
U266	NYLpOZA{S3m2b4TvfIlkcXS7IHHzd4F6		M2K4bFczKGi{cx?=	NXrjd\|doS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hXTJ4NjDj[YxteyCjZoTldkA4OiCqcoOgZpkhS2WubGTpeIVzNUeubzDseY1qdmW\|Y3XueEBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NEA:KDNwNUKg{txONg>?	NEHyU5A9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEO2OVg6Oid-M{CzOlU5QTJ:L3G+
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KCL22	NWHGVI9YS3m2b4TvfIlkcXS7IHHzd4F6		MUi3NkBpenN?	NWTNVGQ3S3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hU0OOMkKgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KEOnbHzUbZRmei2JbH:gcJVucW6nc3PlcpQh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVAhRSB\|Lke1JO69VS5?	NVG3dm05RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CzOlU5QTJpPkOwN\|Y2QDl{PD;hQi=>
HL60	MVPBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		M1y4bFQ5KGi{cx?=	MonURY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCKTE[wJINmdGy\|IHHmeIVzKDR6IHjyd{BjgSCFQ1utPEBie3OjeTygTWM2OCB;IEOuO\|Uh\|ryPLh?=	MWq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTl2MEGxOUc,Ojl7NECxNVU9N2F-
K562	NIPVV21CdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		MoPKOFghcHK\|	NFjxWWdCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFu1OlIh[2WubIOgZYZ1\XJiNEigbJJ{KGK7IFPDT{05KGG\|c3H5MEBKSzVyIE2gN{44PSEQvF2u	NEHvVIk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUm0NFEyPSd-Mkm5OFAyOTV:L3G+
HEL	NYfINplISW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		MVm0PEBpenN?	NEP3dHZCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFjFUEBk\WyuczDh[pRmeiB2ODDodpMh[nliQ1PLMVgh[XO\|YYmsJGlEPTBiPTCzMlc2KM7:TT6=	NIHNNlA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUm0NFEyPSd-Mkm5OFAyOTV:L3G+
BCP-ALL	M4HsSWN6fG:2b4jpZ4l1gSCjc4PhfS=>		M1n6UFczKGi{cx?=	M1v0WGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGJEWC2DTFygZ4VtdHNiZHXybZZm\CCocn;tJJBifGmnboSgN{Bi\nSncjC3NkBpenNiYomgR4VtdFSrdHXyMWdtdyCudX3pcoV{[2WwdDDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3MDC9JFQvPDVizszNMi=>	MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODN4NUi5Nkc,OzB\|NkW4PVI9N2F-
MV4-11	NX7SVVFyTnWwY4Tpc44h[XO\|YYm=	M3XrR\|ExODBibl2=	NHLyOJQ3KGi{cx?=	MV\Jcohq[mm2aX;uJI9nKEiGQVOxM\|IwOyCrbjDoeY1idiCPVkStNVEh[2WubIOgZZN{\XO\|ZXSgZZMhfXC{ZXf1cIF1cW:wIH;mJIhqe3SxbnWgTFMh[WOndInsZZRqd25iYYSgNVAxOCCwTTDh[pRmeiB4IHjyd{BjgSCZZYP0[ZJvKGKub4SgZY5idHm\|aYO=	M4\3b\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NESzNFc5Lz5{NkS0N\|A4QDxxYU6=
TC32	MUHxTHRUKGG\|c3H5			MnnMdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFSFM{KgZ4VtdHN?	NHXLU5A9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
DAOY	MoHrdWhVWyCjc4PhfS=>			NImyW\|RyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiRFHPXUBk\Wyucx?=	M4jLW\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
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A673	M{Py[pFJXFNiYYPzZZk>			MlLtdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEF4N{OgZ4VtdHN?	MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SK-N-MC	Mn3ldWhVWyCjc4PhfS=>			MY\xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0tvTj3NR{Bk\Wyucx?=	MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
BT-37	NH6yPYFyUFSVIHHzd4F6			M13XS5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCEVD2zO{Bk\Wyucx?=	NH\C[VI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
NB-EBc1	MnjydWhVWyCjc4PhfS=>			MVPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVkJvRVLjNUBk\Wyucx?=	NUn3WodkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Saos-2	MU\xTHRUKGG\|c3H5			NEjWUm5yUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU3Hvd{0zKGOnbHzz	NYDHW4c6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
SK-N-SH	NESybFByUFSVIHHzd4F6			NG\MbJNyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU1utUk1UUCClZXzsdy=>	NFPES3Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
NB1643	MonSdWhVWyCjc4PhfS=>			M1vlWZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCQQkG2OFMh[2WubIO=	MmHrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
LAN-5	MVrxTHRUKGG\|c3H5			NV;YfnU3eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IFzBUk02KGOnbHzz	NYTMW2NnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
BT-12	NYHmXI5GeUiWUzDhd5NigQ>?			NGXyTpZyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiQmStNVIh[2WubIO=	MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Rh18	MmfQdWhVWyCjc4PhfS=>			MYrxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWmhzODDj[Yxtew>?	Ml;xQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
OHS-50	NInIO4lyUFSVIHHzd4F6			NYLBTGxkeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF;IV{02OCClZXzsdy=>	Mle5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
RD	NVnCZm5FeUiWUzDhd5NigQ>?			MXrxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWkRiY3XscJM>	NWrscHJuRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
MG 63 (6-TG R)	MYnxTHRUKGG\|c3H5			MWnxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVUdiNkOgLFYuXEdiUjmgZ4VtdHN?	Mm\SQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
Rh30	NUHRT2ZFeUiWUzDhd5NigQ>?			NXT1U5I{eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGLoN\|Ah[2WubIO=	NF3rT5A9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
Rh41	NV;Lco9zeUiWUzDhd5NigQ>?			M{PkW5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCUaESxJINmdGy\|	NV\vOZhZRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
HL60	MkDDSpVv[3Srb36gZZN{[Xl?	MlvKNE4yKHSxIEGwJJVO	M4HhV\|I1KGi{cx?=	Mm\hTY5pcWKrdHnvckBw\iCKRFHDOkBqdiCqdX3hckBJVDZyIHPlcIx{KGG\|c3Xzd4VlKGG\|IHnuZ5Jm[XOnIHnuJIFk\XS7bD3hcJBp[SC2dXL1cIlvKGW6cILld5Nqd25iYYSgNE4yKHSxIEGwJJVOKGGodHXyJFI1KGi{czDifUBqdW23bn;icI91KGG\|c3H5	NUL5NmRSRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CzOlU5QTJpPkOwN\|Y2QDl{PD;hQi=>
SEM	NEK1ZVZHfW6ldHnvckBie3OjeR?=	MXqwMlEhfG9iMUCgeW0>	NInzfJkzPCCqcoO=	NX62S4h5UW6qaXLpeIlwdiCxZjDISGFEPiCrbjDoeY1idiCVRV2gZ4VtdHNiYYPz[ZN{\WRiYYOgbY5kemWjc3WgbY4h[WOndInsMYFteGijIIT1ZpVtcW5iZYjwdoV{e2mxbjDheEAxNjFidH:gNVAhfU1iYX\0[ZIhOjRiaILzJIJ6KGmvbYXuc4Jtd3RiYYPzZZk>	NHTZbJQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEO2OVg6Oid-M{CzOlU5QTJ:L3G+
SUP-B15	NYDPWItVTnWwY4Tpc44h[XO\|YYm=	M4rz[lAvOSC2bzCxNEB2VQ>?	NGDUWGwzPCCqcoO=	M{XLVGlvcGmkaYTpc44hd2ZiSFTBR\|YhcW5iaX3heIlvcWJvcnXzbZN1[W62IHj1cYFvKFOXUD3CNVUh[2WubIOgZZN{\XO\|ZXSgZZMhcW6lcnXhd4UhcW5iYXPleJltNWGucHjhJJR2[nWuaX6g[ZhxemW\|c3nvckBifCByLkGgeI8hOTBidV2gZYZ1\XJiMkSgbJJ{KGK7IHntcZVvd2Kub4SgZZN{[Xl?	MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODN4NUi5Nkc,OzB\|NkW4PVI9N2F-
HL60	M4PKbmZ2dmO2aX;uJIF{e2G7	M13BT\|AvOSC2bzCxNEB2VQ>?	MmnJNlQhcHK\|	M1HDV2lvcGmkaYTpc44hd2ZiSFTBR\|YhcW5iaIXtZY4hUEx4MDDj[YxteyCjc4Pld5Nm\CCjczDpcoNz\WG\|ZTDpckBi[2W2eXytbIl{fG:wZTDIN{BmgHC{ZYPzbY9vKGG2IECuNUB1dyBzMDD1UUBi\nSncjCyOEBpenNiYomgbY1ufW6xYnzveEBie3OjeR?=	MoP0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB\|NkW4PVIoRjNyM{[1PFkzRC:jPh?=
SEM	M1:yZWZ2dmO2aX;uJIF{e2G7	MVuwMlEhfG9iMUCgeW0>	MmDuNlQhcHK\|	MXzJcohq[mm2aX;uJI9nKEiGQVO2JIlvKGi3bXHuJHNGVSClZXzsd{Bie3Onc4Pl[EBieyCrbnPy[YF{\SCrbjDhZ4V1gWxvaHnzeI9v\SCKMzDlfJBz\XO\|aX;uJIF1KDBwMTD0c{AyOCC3TTDh[pRmeiB{NDDodpMh[nliaX3teY5w[myxdDDhd5NigQ>?	M3jt[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyM{[1PFkzLz5\|MEO2OVg6OjxxYU6=
SUP-B15	M{Ps[WZ2dmO2aX;uJIF{e2G7	MmX3NE4yKHSxIEGwJJVO	NEH3XZEzPCCqcoO=	NWrZVJZWUW6qaXLpeIlwdiCxZjDISGFEPiCrbjDpcYF1cW6rYj3y[ZNqe3SjboSgbJVu[W5iU2XQMWIyPSClZXzsd{Bie3Onc4Pl[EBieyCrbnPy[YF{\SCrbjDhZ4V1gWxvaHnzeI9v\SCKMzDlfJBz\XO\|aX;uJIF1KDBwMTD0c{AyOCC3TTDh[pRmeiB{NDDodpMh[nliaX3teY5w[myxdDDhd5NigQ>?	MkjOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB\|NkW4PVIoRjNyM{[1PFkzRC:jPh?=
HL60	M3OzW2Z2dmO2aX;uJIF{e2G7	NITWcYExNjFidH:gNVAhfU1?	NH;QdZozPCCqcoO=	NIHzUmtKdmirYnn0bY9vKG:oIFjERWM3KGmwIHj1cYFvKEiONkCgZ4VtdHNiYYPz[ZN{\WRiYYOgbY5kemWjc3WgbY4h[2ynYY\l[EBRSVKSIHX4dJJme3Orb36gZZQhOC5zIITvJFExKHWPIHHmeIVzKDJ2IHjyd{BjgSCrbX31co9jdG:2IHHzd4F6	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODN4NUi5Nkc,OzB\|NkW4PVI9N2F-
SEM	MXHGeY5kfGmxbjDhd5NigQ>?	MY[wMlEhfG9iMUCgeW0>	M{\2UVI1KGi{cx?=	MWLJcohq[mm2aX;uJI9nKEiGQVO2JIlvKGi3bXHuJHNGVSClZXzsd{Bie3Onc4Pl[EBieyCrbnPy[YF{\SCrbjDjcIVifmWmIGDBVnAh\XiycnXzd4lwdiCjdDCwMlEhfG9iMUCgeW0h[W[2ZYKgNlQhcHK\|IHL5JIludXWwb3Lsc5Qh[XO\|YYm=	NGP5SFQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEO2OVg6Oid-M{CzOlU5QTJ:L3G+
SUP-B15	NELlZ\|lHfW6ldHnvckBie3OjeR?=	MX6wMlEhfG9iMUCgeW0>	M3n6clI1KGi{cx?=	M{jl[WlvcGmkaYTpc44hd2ZiSFTBR\|YhcW5iaX3heIlvcWJvcnXzbZN1[W62IHj1cYFvKFOXUD3CNVUh[2WubIOgZZN{\XO\|ZXSgZZMhcW6lcnXhd4UhcW5iY3zlZZZm\CCSQWLQJIV5eHKnc4Ppc44h[XRiMD6xJJRwKDFyIIXNJIFnfGW{IEK0JIhzeyCkeTDpcY12dm:kbH;0JIF{e2G7	M1W2Z\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyM{[1PFkzLz5\|MEO2OVg6OjxxYU6=
SEM	M1jzc2FvfGmycn;sbYZmemG2aY\lJIF{e2G7		NUXrSGpMOjRidH:gO\|IhcHK\|	Mk\0RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCVRV2gZ4VtdHNiYYSgTWM2OCC2bzCyJJRqdWW\|IFnDOVAh[W[2ZYKgNlQhfG9iN{KgbJJ{KGK7IITyfZBidiCneHPseZNqd25ibXX0bI9l	NHrVNpQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEO2OVg6Oid-M{CzOlU5QTJ:L3G+
HEL	M1ewOWNmdGxiY4njcIUh[XO\|YYm=	NUX0e2I6OSC2bzCxNEB2VQ>?	NIjtUpQ1QCCqcoO=	MUHD[YxtKGO7Y3zlJIFzemW\|dDDpckBpfW2jbjDISWwh[2WubIOgZZN{\XO\|ZXSgZZMh[WOldX31cIF1cW:wIHH0JGcyKHCqYYPlJIF1KDFidH:gNVAhfU1iYX\0[ZIhPDhiaILzJJBzd3CrZHn1cUBqd2SrZHWgd5RicW6rbnegZoF{\WRiZnzve{BkgXSxbXX0dpk>	NW\YRnRlRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm5OFAyOTVpPkK5PVQxOTF3PD;hQi=>
SEM	NU\ndnQ{TnWwY4Tpc44h[XO\|YYm=		MVqxPEBpenN?	M1fXcGlvcGmkaYTpc44hd2ZiSFTBR\|YhcW5iaIXtZY4hW0WPIHPlcIx{KGG\|c3Xzd4VlKGG\|IHTlZ5Jm[XOnIHnuJIFo\3Knc3;t[UBi[2O3bYXsZZRqd25iYYSgTWM2OCCjZoTldkAyQCCqcoOgZpkh\my3b4Lld4NmdmOnIH3pZ5Jwe2OxcHnjJI1mfGixZB?=	MWC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODN4NUi5Nkc,OzB\|NkW4PVI9N2F-
SEM	MlLJSpVv[3Srb36gZZN{[Xl?	MXyxMlYhfU1?	NF;kcWwyQCCqcoO=	M2DvN2lvcGmkaYTpc44hd2ZiSFTBR\|YhcW5iaIXtZY4hW0WPIHPlcIx{KGG\|c3Xzd4VlKGG\|IHTlZ5Jm[XOnIHnuJIFo\3Knc3;t[UBi[2O3bYXsZZRqd25iYYSgNU43KHWPIHHmeIVzKDF6IHjyd{BjgSCIQVPTJIFv[Wy7c3nz	MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODN4NUi5Nkc,OzB\|NkW4PVI9N2F-
SH-SY5Y	MVLGeY5kfGmxbjDhd5NigQ>?	NXjmTWo1OC5zIITvJFEhfU1?	Ml;NNlQhcHK\|	M1jLcGlvcGmkaYTpc44hd2ZiSFTBR\|YhcW5iaIXtZY4hW0hvU2m1XUBk\WyuczDhd5Nme3OnZDDhd{BqdmO{ZXHz[UBqdiCjY3X0fYxifGmxbjDv[kBidHCqYT30eYJ2dGmwIHH0JFAvOSC2bzCxJJVOKGGodHXyJFI1KGi{czDifUBY\XO2ZYLuJIJtd3RiYX7hcJl{cXN?	NFjpeFU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MECyPFYyPid-M{CwNlg3OTZ:L3G+
SH-SY5Y	MYDGeY5kfGmxbjDhd5NigQ>?	M2jqb\|AvOSC2bzCxJJVO	M1v4OFI1KGi{cx?=	NVTjbJNpUW6qaXLpeIlwdiCxZjDjcIF{eyBzIFjERWMhcW5iaIXtZY4hW0hvU2m1XUBk\WyuczDhd5Nme3OnZDDhd{BqdmO{ZXHz[UBqdiCjY3X0fYxifGmxbjDv[kBpcXO2b37lJGg{KGG2IECuNUB1dyBzIIXNJIFnfGW{IEK0JIhzeyCkeTDX[ZN1\XKwIHLsc5Qh[W6jbInzbZM>	M2f3d\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyMEK4OlE3Lz5\|MECyPFYyPjxxYU6=

Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID

Western blot	Ac-α-tubulin / Ac-Histone H4 ; Survivin / P21 / CDC2 / p53 / p-p53(S392) / Cyclin A2 / Cyclin B1 ; Bax / Bim / Bcl2 / Cleaved caspase-3 / Cleaved caspase-9 / Cleaved PARP ; PI3K(p85) / AKT / p-AKT(S473) / PRAS40 / Rag C / mTOR / p-mTOR / ERK / p-ERK ; Ac-β-catenin(K49) / p-β-catenin / β-catenin	31015208 30050135 25546293
Immunofluorescence	β-tubulin / β-catenin	25546293
Growth inhibition assay	Cell viability	31015208

In vivo

ACY-1215 in combination with bortezomib triggered more significant anti-MM activity than either agent alone in suppressing tumor growth and prolonging survival in both plasmacytoma model and disseminated MM model without significant adverse effects. ACY-1215 is readily absorbed by tumor tissue. Moreover, the drug does not accumulate in tumor tissue, as evidenced by the parallel decline of acetylated α-tubulin in blood cells and tumor tissue by 24 hours after dose. ^[1]

Protocol (from reference)

Kinase Assay: ^[1]	HDAC enzymatic assays: ACY-1215 is dissolved and subsequently diluted in assay buffer [50 mM HEPES, pH 7.4, 100 mM KCl, 0.001% Tween-20, 0.05% BSA, and 20 μM tris(2-carboxyethyl)phosphine] to 6-fold the final concentration. HDAC enzymes are diluted to 1.5-fold of the final concentration in assay buffer and pre-incubated with ACY-1215 for 10 minutes before the addition of the substrate. The amount of FTS (HDAC1, HDAC2, HDAC3, and HDAC6) or MAZ-1675 (HDAC4, HDAC5, HDAC7, HDAC8, and HDAC9) used for each enzyme is equal to the Michaelis constant (Km), as determined by a titration curve. FTS or MAZ-1675 is diluted in assay buffer to 6-fold the final concentration with 0.3μM sequencing grade trypsin. The substrate/trypsin mix is added to the enzyme/compound mix and the plate is shaken for 60 seconds and then placed into a SpectraMax M5 microtiter plate reader. The enzymatic reaction is monitored for release of 7-amino-4-methoxy-coumarin over 30 minutes, after deacetylation of the lysine side chain in the peptide substrate, and the linear rate of the reaction is calculated.
Cell Research: [1]	Cell lines: MM cell lines, patient MM cells, and PBMCs Concentrations: ~8 μM Incubation Time: 48 hours Method: PBMCs from healthy donors are isolated and stimulated with 2.5 μg/mL of phytohemagglutinin (PHA) for 48 hours in the presence of increasing concentrations of ACY-1215. DNA synthesis is measured by tritiated thymidine uptake. CD4⁺T cells are purified from human blood with the Rosette Sep negative-selection kit. Cells are stimulated by CD3/CD28 Dynabeads for 7 days in the presence of compounds. Cell viability is assessed using alamarBlue. MM cells (2-3 × 10⁴cells/well) are incubated in 96-well culture plates with medium and different concentrations of ACY-1215, bortezomib, and/or recombinant IL-6 (10 ng/mL) or insulin-like growth factor-1 (IGF-1; 50 ng/mL) for 24 hours at 37°C, and tritiated thymidine incorporation is measured.
Animal Research: ^[1]	Animal Models: MM xenograft SCID mouse model Dosages: 50 mg/kg Administration: ip

References

[1] Santo L, et al. Blood, 2012, 119(11), 2579-2589.

Solubility (25°C)

In vitro	DMSO	86 mg/mL (198.38 mM)
	Water	Insoluble
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order (Data is from Selleck tests instead of citations): 5% DMSO+ 40% PEG 300+ 5% Tween 80+ 50% ddH2O For best results, use promptly after mixing. Click to purchase: PEG300 Tween 80	0.62mg/mL

Chemical Information

Molecular Weight	433.5
Formula	C₂₄H₂₇N₅O₃
CAS No.	1316214-52-4
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
Smiles	C1=CC=C(C=C1)N(C2=CC=CC=C2)C3=NC=C(C=N3)C(=O)NCCCCCCC(=O)NO

Download Ricolinostat (ACY-1215) SDF

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: g Dosing volume per animal:μL 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

%DMSO+ %

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.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, 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.

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
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Dilution Calculator Molecular Weight Calculator

Clinical Trial Information

NCT Number	Recruitment	Interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT02632071	Completed	Drug: ACY-1215\|Drug: Nab-paclitaxel	Metastatic Breast Cancer\|Breast Carcinoma	Columbia University\|Acetylon Pharmaceuticals Incorporated\|National Cancer Institute (NCI)	March 1 2016	Phase 1
NCT01583283	Active not recruiting	Drug: ACY-1215\|Drug: lenalidomide\|Drug: Dexamethasone	Multiple Myeloma	Celgene	July 12 2012	Phase 1\|Phase 2
NCT01323751	Completed	Drug: ACY-1215	Multiple Myeloma	Celgene\|The Leukemia and Lymphoma Society	July 2011	Phase 1\|Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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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Frequently Asked Questions

Question 1:
What would you suggest to obtain a clear solution?

Answer:
S8001 ACY-1215 can be dissolved in 2% DMSO/30% PEG 300/ddH2O at 5 mg/ml clearly while it in 1% DMSO/30% polyethylene glycol/1% Tween 80 at 30 mg/ml is a suspension for oral administration. Please note that the precipitation will go out from the clear solution after stayed for about half an hour, So it is recommended to prepare the solution just before use.

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