Ricolinostat (ACY-1215)

Name: Ricolinostat (ACY-1215)
Brand: Selleck Chemicals
SKU: S8001
Rating: 5 (54 reviews)

For research use only.

Catalog No.S8001 Synonyms: Rocilinostat

54 publications

Ricolinostat (ACY-1215) Chemical Structure

CAS No. 1316214-52-4

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.

Selleck's Ricolinostat (ACY-1215) has been cited by 54 publications

Science, 2020, 369(6510)eaas8995

PubMed: 32943500 ( click the link to review the publication )

Cancer Res, 2021, 81(20):5325-5335

PubMed: 34548333 ( click the link to review the publication )

Elife, 2021, 10e63810

PubMed: 33835029 ( click the link to review the publication )

J Inflamm Res, 2021, 14:1473-1485

PubMed: 33883923 ( click the link to review the publication )

J Cell Mol Med, 2021, 10.1111/jcmm.16751

PubMed: 34180140 ( click the link to review the publication )

Int J Mol Sci, 2021, 22(3)1341

PubMed: 33572814 ( click the link to review the publication )

Breast Cancer Res Treat, 2021, 186(1):37-51

PubMed: 33452951 ( click the link to review the publication )

Oncol Lett, 2021, 22(3):680

PubMed: 34345305 ( click the link to review the publication )

Cancers (Basel), 2020, 12(12)E3734

PubMed: 33322608 ( click the link to review the publication )

Front Cell Dev Biol, 2020, 8:689

PubMed: 32984302 ( click the link to review the publication )

Cancer Immunol Immunother, 2020, 20

PubMed: 32435850 ( click the link to review the publication )

Int J Biol Sci, 2020, 16(14):2595-2611

PubMed: 32792859 ( click the link to review the publication )

Am J Physiol Renal Physiol, 2020, 319(6):F1003-F1014

PubMed: 33103445 ( click the link to review the publication )

Oncol Lett, 2020, 20(1):533-540

PubMed: 32565979 ( click the link to review the publication )

BMC Pharmacol Toxicol, 2020, 21(1):21

PubMed: 32178737 ( click the link to review the publication )

Histol Histopathol, 2020, 18237

PubMed: 32572875 ( click the link to review the publication )

Front Cell Dev Biol, 2020, 8:610

PubMed: 32754596 ( click the link to review the publication )

bioRxiv, 2020, 10.1101/2020.12.20.423672

PubMed: None ( click the link to review the publication )

J Immunother Cancer, 2019, 7(1):33

PubMed: 30728070 ( click the link to review the publication )

Cancer Res, 2019, 79(21):5482-5489

PubMed: 31311810 ( click the link to review the publication )

J Neurochem, 2019, 10.1111/jnc.14849

PubMed: 31390677 ( click the link to review the publication )

Front Pharmacol, 2019, 10:653

PubMed: 31244662 ( click the link to review the publication )

Biomed Pharmacother, 2019, 117:109166

PubMed: 31255993 ( click the link to review the publication )

Ann Transl Med, 2019, 7(1):2

PubMed: 30788349 ( click the link to review the publication )
Int J Oncol, 2019, 55(2):499-512

PubMed: 31268156 ( click the link to review the publication )

Life Sci, 2019, 238:116976

PubMed: 31634464 ( click the link to review the publication )

Neurochem Res, 2019, 44(11):2460-2469

PubMed: 31571096 ( click the link to review the publication )

ACS Omega, 2019, 4(22):19895-19904

PubMed: 31788622 ( click the link to review the publication )

Nucl Med Biol, 2019, 74-75:1-11

PubMed: 31421440 ( click the link to review the publication )

Anticancer Res, 2019, 39(12):6731-6741

PubMed: 31810938 ( click the link to review the publication )

Cancer Res, 2018, 78(20):5731-5740

PubMed: 30135193 ( click the link to review the publication )

J Pathol, 2018, 246(2):141-153

PubMed: 29876933 ( click the link to review the publication )

Cell Death Dis, 2018,

PubMed: 30050135 ( click the link to review the publication )

Int J Mol Sci, 2018, 19(8)

PubMed: 30081552 ( click the link to review the publication )

J Biol Chem, 2018, 293(6):1976-1993

PubMed: 29259132 ( click the link to review the publication )

Int J Oncol, 2018, 53(2):844-854

PubMed: 29749542 ( click the link to review the publication )

Br J Cancer, 2018, 119(10):1278-1287

PubMed: 30318510 ( click the link to review the publication )

Mol Cancer Ther, 2018, 17(6):1280-1290

PubMed: 29483217 ( click the link to review the publication )

Biochem Pharmacol, 2018, 155:316-325

PubMed: 30028995 ( click the link to review the publication )

Biomed Pharmacother, 2018, 97:818-824

PubMed: 29112935 ( click the link to review the publication )

Nat Cell Biol, 2017, 19(8):962-973

PubMed: 28737768 ( click the link to review the publication )

Oncogene, 2017, 10.1038/onc.2016.495

PubMed: 28114281 ( click the link to review the publication )

ACS Chem Biol, 2017, 12(8):2139-2148

PubMed: 28628306 ( click the link to review the publication )

Dis Model Mech, 2017, 10(10):1245-1252

PubMed: 28819043 ( click the link to review the publication )

Int J Parasitol Drugs Drug Resist, 2017, 7(1):51-60

PubMed: 28110187 ( click the link to review the publication )

J Periodontol, 2017, 88(1):e12-e23

PubMed: 27562218 ( click the link to review the publication )

Clin Cancer Res, 2017, 23(15):4280-4289

PubMed: 28270494 ( click the link to review the publication )

Drug Des Devel Ther, 2017, 11:1369-1382

PubMed: 28496307 ( click the link to review the publication )
Oncotarget, 2017, 8(61):103797-103814

PubMed: 29262601 ( click the link to review the publication )

Oncotarget, 2016, 7(7):7715-31

PubMed: 26735339 ( click the link to review the publication )

Nat Commun, 2015, 3;6:10091

PubMed: 26631872 ( click the link to review the publication )

Cancer Immunol Res, 2015, 3(12):1375-85

PubMed: 26297712 ( click the link to review the publication )

Tumour Biol, 2015, 36(12):9661-5

PubMed: 26150340 ( click the link to review the publication )

Mol Cancer Ther, 2014, 10.1158/1535-7163.MCT-14-0481

PubMed: 25552369 ( click the link to review the publication )

Purity & Quality Control

Choose Selective HDAC Inhibitors

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	Activity Description	PMID
A-172	NIP6eXdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MXSxNOKhdk1?	M3;DeVI1NzR6IHi=	MVzpcohq[mm2czDj[YxtKGe{b4f0bEB1cW2nIHTldIVv\GWwdHz5	Mn;QQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzNUCzOFAoRjJ4MUWwN\|QxRC:jPh?=
U87MG	Mk\tS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MkPlNVDDqG6P	MlXCNlQwPDhiaB?=	M37KPYlvcGmkaYTzJINmdGxiZ4Lve5RpKHSrbXWg[IVx\W6mZX70cJk>	NGjVcJQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkG1NFM1OCd-Mk[xOVA{PDB:L3G+
Hbl-1	MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		M{TVO\|Q5KGh?	NVTRbGV7UUN3ME2xMlYh\|ryP	NYrYd4N{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xNVYzPzBpPkK2NVE3OjdyPD;hQi=>
OCI-Ly10	NHzXVlZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=		Mlz3OFghcA>?	MmHQTWM2OD1yLkmg{txO	M2HxVVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUG2NlcxLz5{NkGxOlI4ODxxYU6=
Riva	MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		MoTMOFghcA>?	MX;JR\|UxRTJwMjFOwG0>	MmTHQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzMU[yO\|AoRjJ4MUG2NlcxRC:jPh?=
Su-DHL2	NHjlbGxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=		Mn\QOFghcA>?	NVPlVVhWUUN3ME2zMlMh\|ryP	M3rtblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUG2NlcxLz5{NkGxOlI4ODxxYU6=
OCI-Ly1	NX\tZ4VST3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		NVHZSmRKPDhiaB?=	M1TSVmlEPTB;Mj60JO69VQ>?	MWm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjFzNkK3NEc,OjZzMU[yO\|A9N2F-
OCI-Ly7	MlXhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		MWC0PEBp	NX:5SnViUUN3ME2xMlIh\|ryP	M2XBbFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUG2NlcxLz5{NkGxOlI4ODxxYU6=
Su-DHL4	MmT6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		MXG0PEBp	MYLJR\|UxRTRwNzFOwG0>	MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjFzNkK3NEc,OjZzMU[yO\|A9N2F-
Su-DHL6	NYrLeGRyT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		NEHEOnQ1QCCq	MnvGTWM2OD1\|LkKg{txO	MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjFzNkK3NEc,OjZzMU[yO\|A9N2F-
Hbl-2	M1j5e2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7		NV\5[\|l5PDhiaB?=	M4PYcmlEPTB;MT65JO69VQ>?	MX68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjFzNkK3NEc,OjZzMU[yO\|A9N2F-
Jeko-1	MlrRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		MYC0PEBp	NYTiNnJuUUN3ME2xMlUh\|ryP	MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjFzNkK3NEc,OjZzMU[yO\|A9N2F-
Jvm-2	MmPwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		M4nnWVQ5KGh?	NWjPUXU6UUN3ME20MlAh\|ryP	MnzTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzMU[yO\|AoRjJ4MUG2NlcxRC:jPh?=
Rec-1	NGXJfnVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=		Moq4OFghcA>?	NEjxS\|RKSzVyPUKuN{DPxE1?	MmHMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzMU[yO\|AoRjJ4MUG2NlcxRC:jPh?=
CCL-119	MoLYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		NVewc5U6PDhiaB?=	M4j2NGlEPTB;MT63JO69VQ>?	NVH3OXlZRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xNVYzPzBpPkK2NVE3OjdyPD;hQi=>
H9	NGjob3VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=		M{HNZVQ5KGh?	M1vhXmlEPTB;MT6yJO69VQ>?	NFizXI09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkGxOlI4OCd-Mk[xNVYzPzB:L3G+
HH	MleyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		NYjlOm1RPDhiaB?=	MoHQTWM2OD1{LkWg{txO	NFTRbFM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkGxOlI4OCd-Mk[xNVYzPzB:L3G+
Sup-T1	NV;KNGtUT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		M4HrcFQ5KGh?	Ml7kTWM2OD1zLk[g{txO	MofwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzMU[yO\|AoRjJ4MUG2NlcxRC:jPh?=
MM.1S	MV3GeY5kfGmxbjDBd5NigQ>?	MnPtNE02\|ryP	NXXqNXp1PiCq	NHraNmxqdmO{ZXHz[ZMh[WOndInsZZRm\CEQsT30eYJ2dGmw	M1TUcVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{Mk[yO\|YxLz5{MkK2Nlc3ODxxYU6=
MM.1S	NUPYd3B[TnWwY4Tpc44hSXO\|YYm=	MmDDNE4zPS9zzszN	MojxNVghcA>?	MUPpcoNz\WG\|ZYOgZYNmfHmuYYTl[EDPuS22dXL1cIlv	M{e1eFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{Mk[yO\|YxLz5{MkK2Nlc3ODxxYU6=
MM.1R	NULlVHJCTnWwY4Tpc44hSXO\|YYm=	NV;UVmlLOC5{NT:x{txO	M33xZlE5KGh?	NVnyTZBFcW6lcnXhd4V{KGGlZYT5cIF1\WRizsGteJVjfWyrbh?=	Moq5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ{NkK3OlAoRjJ{Mk[yO\|YxRC:jPh?=
RPMI8226	NIr5UIRHfW6ldHnvckBCe3OjeR?=	NIizS4YxNjJ3L{JOwG0>	MmK5NVghcA>?	M2\qNYlv[3KnYYPld{Bi[2W2eXzheIVlKM7zLYT1ZpVtcW5?	MX68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjJ4Mke2NEc,OjJ{NkK3OlA9N2F-
MM.1S	NHrOdW1E\WyuIG\pZYJqdGm2eTDBd5NigQ>?	MVOwMVjPxE1?	NYrOZ3pUPDhiaB?=	MkfI[IVkemWjc3XzJG1ONWOnbHygeoli[mmuaYT5JIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy	MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjJ4Mke2NEc,OjJ{NkK3OlA9N2F-
OPM1	M{DmfWNmdGxiVnnhZoltcXS7IFHzd4F6	MkDnNE05\|ryP	MkfsOFghcA>?	NEPTcFZl\WO{ZXHz[ZMhVU1vY3XscEB3cWGkaXzpeJkhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI>	M1\wXFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{Mk[yO\|YxLz5{MkK2Nlc3ODxxYU6=
RPMI	NIDEcXFE\WyuIG\pZYJqdGm2eTDBd5NigQ>?	MWCwMVjPxE1?	MkTaOFghcA>?	NXLoR2xH\GWlcnXhd4V{KE2PLXPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz	NIrvb2g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkK2Nlc3OCd-MkKyOlI4PjB:L3G+
MM.1R	MUXD[YxtKF[rYXLpcIl1gSCDc4PhfS=>	M1PqUlAuQM7:TR?=	MYS0PEBp	MlzF[IVkemWjc3XzJG1ONWOnbHygeoli[mmuaYT5JIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy	M{nMRlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{Mk[yO\|YxLz5{MkK2Nlc3ODxxYU6=
LR5	NGW3[5VE\WyuIG\pZYJqdGm2eTDBd5NigQ>?	MmHlNE05\|ryP	NFvMWW01QCCq	NYjDOFJy\GWlcnXhd4V{KE2PLXPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz	NVfQW2t6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKyOlI4PjBpPkKyNlYzPzZyPD;hQi=>
OPM2	MlX1R4VtdCCYaXHibYxqfHliQYPzZZk>	MVOwMVjPxE1?	MYG0PEBp	NUfSZpNR\GWlcnXhd4V{KE2PLXPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz	NW[3[YNjRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKyOlI4PjBpPkKyNlYzPzZyPD;hQi=>
Sf9	NHnwWlFHfW6ldHnvckBie3OjeR?=		M1\pZVExKG2rboO=	NUSyfYxvUW6qaXLpeIlwdiCxZjDmeYxtKGynbnf0bEBpfW2jbjDy[YNwdWKrbnHueEBPNXSncn3pcoFtKEeVVD30ZYdo\WRiSFTBR\|Yh\XiycnXzd4VlKGmwIGPmPUBk\WyuczD1d4lv\yCIVGOgZZMhe3Wkc4TyZZRmKHC{ZXnuZ5Vj[XSnZDDmc5IhOTBibXnud{Bnd2yub4fl[EBjgSC\|dXLzeJJifGViYXTkbZRqd25ibXXhd5Vz\WRib4\ldkA{OCCvaX7zMEBKSzVyIE2gNE4xODR5IN88UU4>	MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDB\|OEOyOEc,OjhyM{izNlQ9N2F-
Sf9	MXLGeY5kfGmxbjDhd5NigQ>?		M4LVRlE2KG2rboO=	NVXpZ5d[UW6qaXLpeIlwdiCxZjDmeYxtKGynbnf0bEBz\WOxbXLpcoFvfCCqdX3hckBPNXSncn3pcoFtKEeVVD30ZYdo\WRiSFTBR\|Yh\XiycnXzd4VlKGmwIHLhZ5Vtd3[rcoXzJIlv\mWldHXkJJNnQSClZXzsd{B2e2mwZzDCc4MuVHm\|LTjBZ{kuSU2FIHHzJJN2[nO2cnH0[UBxemWrbnP1ZoF1\WRiZn;yJFE2KG2rboOg[o9tdG:5ZXSgZpkhe3Wkc4TyZZRmKGGmZHn0bY9vKG2nYYP1doVlKGGodHXyJFYxKG2rboOgZpkh\my3b4Lld4NmdmOnIHHzd4F6NCCLQ{WwJF0hOC5yMEmg{txONg>?	M4PwN\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NUCwNVMxLz5{OUWwNFE{ODxxYU6=
Sf9	MkC5SpVv[3Srb36gZZN{[Xl?		NWHwbY4{OTVibXnudy=>	NYL1b5ZxUW6qaXLpeIlwdiCxZjDmeYxtKGynbnf0bEBz\WOxbXLpcoFvfCCqdX3hckBENXSncn3pcoFtKEircz30ZYdo\WRiSFTBR\|MwVi22ZYLtbY5idCCJU2SteIFo\2WmIF7DU3IzKCh\|OUWgeI8hPDh7IILld4llfWW\|KTDlfJBz\XO\|ZXSgbY4h[mGldXzveolzfXNiaX7m[YN1\WRic3[5JINmdGy\|IIXzbY5oKEKxYz3MfZMuMEGlKT3BUWMh[XNic4Xid5Rz[XSnIIDy[Ylv[3WkYYTl[EBnd3JiMUWgcYlveyCob3zsc5dm\CCkeTDzeYJ{fHKjdHWgZYRlcXSrLDDJR\|UxKD1iMD6wN\|ch\|ryPLh?=	M2ryPFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NUCwNVMxLz5{OUWwNFE{ODxxYU6=
Sf9	MmLqSpVv[3Srb36gZZN{[Xl?		NFuxO4MyOCCvaX7z	NYHue5lNUW6qaXLpeIlwdiCxZjDmeYxtKGynbnf0bEBpfW2jbjDy[YNwdWKrbnHueEBENXSncn3pcoFtKE[OQVeteIFo\2WmIFjERWMzKGW6cILld5Nm\CCrbjDT[lkh[2WubIOgeZNqdmdiRmTTJIF{KHO3YoP0doF1\SCycnXpcoN2[mG2ZXSg[o9zKDFyIH3pcpMh\m:ubH;3[YQh[nlic4Xid5Rz[XSnIHHk[Il1cW:wIH3lZZN2emWmIH;2[ZIhOzBibXnud{whUUN3MDC9JFAvODR6IN88UU4>	M1HmUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6MEO4N\|I1Lz5{OECzPFMzPDxxYU6=
Sf9	NWnNcnRZTnWwY4Tpc44h[XO\|YYm=		NEnkXG8yOCCvaX7z	NX\k[JFrUW6qaXLpeIlwdiCxZjDmeYxtKGynbnf0bEBpfW2jbjDy[YNwdWKrbnHueEBENXSncn3pcoFtKE[OQVetTIl{NXSjZ3fl[EBJTEGFMTDlfJBz\XO\|ZXSgbY4hW2Z7IHPlcIx{KHW\|aX7nJGZVWyCjczDzeYJ{fHKjdHWgdJJmcW6ldXLheIVlKG[xcjCxNEBucW6\|IH\vcIxwf2WmIHL5JJN2[nO2cnH0[UBi\GSrdHnvckBu\WG\|dYLl[EBwfmW{IEOwJI1qdnNuIFnDOVAhRSByLkC1PEDPxE1w	M{Hz[\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6MEO4N\|I1Lz5{OECzPFMzPDxxYU6=
Sf9	M2ntOGZ2dmO2aX;uJIF{e2G7		MlrRNVUhdWmwcx?=	M3i5c2lvcGmkaYTpc44hd2ZiZoXscEBt\W6pdHigdoVkd22kaX7hcpQhcHWvYX6gR{11\XKvaX7hcEBJcXNvdHHn[4VlKEiGQVOyJIV5eHKnc4Pl[EBqdiCkYXP1cI93cXK3czDpcoZm[3SnZDDz[lkh[2WubIOgeZNqdmdiQn;jMWx6ey1qQXOpMWFOSyCjczDzeYJ{fHKjdHWgdJJmcW6ldXLheIVlKG[xcjCxOUBucW6\|IH\vcIxwf2WmIHL5JJN2[nO2cnH0[UBi\GSrdHnvckBu\WG\|dYLl[EBi\nSncjC2NEBucW6\|IHL5JIZtfW:{ZYPj[Y5k\SCjc4PhfUwhUUN3MDC9JFAvODZ4IN88UU4>	MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTVyMEGzNEc,Ojl3MECxN\|A9N2F-
Sf9	MYTGeY5kfGmxbjDhd5NigQ>?		NILEXYEyPSCvaX7z	NV\JeHVWUW6qaXLpeIlwdiCxZjDmeYxtKGynbnf0bEBz\WOxbXLpcoFvfCCqdX3hckBENXSncn3pcoFtKE[OQVevTIl{NXSjZ3fl[EBJTEGFMTDlfJBz\XO\|ZXSgbY4h[mGldXzveolzfXNiaX7m[YN1\WRic3[5JINmdGy\|IIXzbY5oKEKxYz3MfZMuMEGlKT3BUWMh[XNic4Xid5Rz[XSnIIDy[Ylv[3WkYYTl[EBnd3JiMUWgcYlveyCob3zsc5dm\CCkeTDzeYJ{fHKjdHWgZYRlcXSrb36gcYVie3W{ZXSgZYZ1\XJiNkCgcYlveyCkeTDmcJVwemW\|Y3XuZ4Uh[XO\|LDDJR\|UxKD1iMD6xJO69VS5?	NHjNXWU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUWwNFE{OCd-Mkm1NFAyOzB:L3G+
BCP-ALL	M1W3emN6fG:2b4jpZ4l1gSCjc4PhfS=>		MXu3NkBpenN?	MlLqR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gRmNRNUGOTDDj[YxteyCmZYLpeoVlKG[{b32gdIF1cWWwdDCxJIFnfGW{IEeyJIhzeyCkeTDD[YxtXGm2ZYKtS4xwKGy3bXnu[ZNk\W62IHPlcIwhfmmjYnnsbZR6KGG\|c3H5MEBKSzVyIE2gNE4zQSEQvF2u	MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODN4NUi5Nkc,OzB\|NkW4PVI9N2F-
BCP-ALL	NHzFVlREgXSxdH;4bYNqfHliYYPzZZk>		MmfDO\|IhcHK\|	M3nLWGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGJEWC2DTFygZ4VtdHNiZHXybZZm\CCocn;tJJBifGmnboSgOEBi\nSncjC3NkBpenNiYomgR4VtdFSrdHXyMWdtdyCudX3pcoV{[2WwdDDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3MDC9JFAvPTRizszNMi=>	NWm4fVRORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CzOlU5QTJpPkOwN\|Y2QDl{PD;hQi=>
BCP-ALL	M1;icWN6fG:2b4jpZ4l1gSCjc4PhfS=>		MWW3NkBpenN?	M1\uTWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGJEWC2DTFygZ4VtdHNiZHXybZZm\CCocn;tJJBifGmnboSgNkBi\nSncjC3NkBpenNiYomgR4VtdFSrdHXyMWdtdyCudX3pcoV{[2WwdDDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3MDC9JFAvPThizszNMi=>	NYr1SWJ5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CzOlU5QTJpPkOwN\|Y2QDl{PD;hQi=>
RPMI8226	MmrWR5l1d3SxeHnjbZR6KGG\|c3H5		NInDfnI4OiCqcoO=	MmSwR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gVnBOUTh{Mk[gZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigSxiSVO1NEA:KDFwNE[4JO69VS5?	M4jCdVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NESzNFc5Lz5{NkS0N\|A4QDxxYU6=
SEM	MVrDfZRwfG:6aXPpeJkh[XO\|YYm=		MXS3NkBpenN?	M3HRNWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJHNGVSClZXzsd{Bi\nSncjC3NkBpenNiYomgR4VtdFSrdHXyMWdtdyCudX3pcoV{[2WwdDDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3MDC9JFEvPjFizszNMi=>	NXv4S\|FNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CzOlU5QTJpPkOwN\|Y2QDl{PD;hQi=>
SUP-B15	M2rmOWN6fG:2b4jpZ4l1gSCjc4PhfS=>		M1HsT\|czKGi{cx?=	NYDGV\|lPS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hW1WSLVKxOUBk\WyuczDh[pRmeiB5MjDodpMh[nliQ3XscHRqfGW{LVfsc{BtfW2rbnXzZ4VvfCClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OCB;IEGuPVIh\|ryPLh?=	Mmm4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB\|NkW4PVIoRjNyM{[1PFkzRC:jPh?=
RPMI18226	NIDhPIhEgXSxdH;4bYNqfHliYYPzZZk>		NF\aUlY4OiCqcoO=	NIjxW2hEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBTWE2LMUiyNlYh[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IFPlcIxVcXSncj3HcI8hdHWvaX7ld4NmdnRiY3XscEB3cWGkaXzpeJkh[XO\|YYmsJGlEPTBiPTCxMlk4KM7:TT6=	MmjjQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB\|NkW4PVIoRjNyM{[1PFkzRC:jPh?=
HL60	MYnDfZRwfG:6aXPpeJkh[XO\|YYm=		NEnERmU4OiCqcoO=	NF:xWZFEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBJVDZyIHPlcIx{KGGodHXyJFczKGi{czDifUBE\WyuVHn0[ZIuT2yxIHz1cYlv\XOlZX70JINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwJF0hOi5\|NjFOwG0v	NFf2OFA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEO2OVg6Oid-M{CzOlU5QTJ:L3G+
HL60	NH7uV2FCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		NYGwNHI3PDhiaILz	NHL6Xo5CdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFjMOlAh[2WubIOgZYZ1\XJiNEigbJJ{KGmwIIDy[ZNmdmOnIH;mJGpCUzJiaX7obYJqfG:{IFPZWE0{QDdiYomgR2NMNThiYYPzZZktKEmFNUCgQUAzNjV2IN88UU4>	MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTl2MEGxOUc,Ojl7NECxNVU9N2F-
K562	MV7BcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		MX[0PEBpenN?	MnWyRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCNNU[yJINmdGy\|IHHmeIVzKDR6IHjyd{BqdiCycnXz[Y5k\SCxZjDKRWszKGmwaHnibZRweiCFWWStN\|g4KGK7IFPDT{05KGG\|c3H5MEBKSzVyIE2gNk42PCEQvF2u	NIrPWlE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUm0NFEyPSd-Mkm5OFAyOTV:L3G+
HEL	Mm\TRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		NVXGV\|I4PDhiaILz	Ml;ORY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCKRVygZ4VtdHNiYX\0[ZIhPDhiaILzJIlvKHC{ZYPlcoNmKG:oIFrBT\|IhcW6qaXLpeI9zKEO\VD2zPFch[nliQ1PLMVgh[XO\|YYmsJGlEPTBiPTCyMlU1KM7:TT6=	MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTl2MEGxOUc,Ojl7NECxNVU9N2F-
KCL22	MXnDfZRwfG:6aXPpeJkh[XO\|YYm=		MkjYO\|IhcHK\|	NELPTplEgXSxdH;4bYNqfHliYXfhbY5{fCCrbXH0bY5q[i2{ZYPpd5RidnRiaIXtZY4hU0OOMkKgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KEOnbHzUbZRmei2JbH:gcJVucW6nc3PlcpQh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVAhRSB\|LkO4JO69VS5?	MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODN4NUi5Nkc,OzB\|NkW4PVI9N2F-
U266	NXy0PZB6S3m2b4TvfIlkcXS7IHHzd4F6		MXK3NkBpenN?	NVfG[ppbS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hXTJ4NjDj[YxteyCjZoTldkA4OiCqcoOgZpkhS2WubGTpeIVzNUeubzDseY1qdmW\|Y3XueEBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NEA:KDNwNUKg{txONg>?	NE[0eZU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEO2OVg6Oid-M{CzOlU5QTJ:L3G+
SUP-B15	Mkj5R5l1d3SxeHnjbZR6KGG\|c3H5		M1u2WVczKGi{cx?=	M4XVNmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGmvYYTpcoljNXKnc3nzeIFvfCCqdX3hckBUXVBvQkG1JINmdGy\|IHHmeIVzKDd{IHjyd{BjgSCFZXzsWIl1\XJvR3zvJIx2dWmwZYPj[Y51KGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR\|UxKD1iMz61OEDPxE1w	M37KcFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyM{[1PFkzLz5\|MEO2OVg6OjxxYU6=
KCL22	MUPDfZRwfG:6aXPpeJkh[XO\|YYm=		NFy1W2o4OiCqcoO=	MXPDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDLR2wzOiClZXzsd{Bi\nSncjC3NkBpenNiYomgR4VtdFSrdHXyMWdtdyCudX3pcoV{[2WwdDDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3MDC9JFMvPzVizszNMi=>	NFqzb3U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEO2OVg6Oid-M{CzOlU5QTJ:L3G+
HL60	M1TyXGFvfGmycn;sbYZmemG2aY\lJIF{e2G7		Mm\6OFghcHK\|	NGTnO3lCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFjMOlAh[2WubIOgZYZ1\XJiNEigbJJ{KGK7IFPDT{05KGG\|c3H5MEBKSzVyIE2gN{44PSEQvF2u	M3zCe\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7OUSwNVE2Lz5{OUm0NFEyPTxxYU6=
K562	NHvXNZdCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		NUe3TWRjPDhiaILz	M3PkbGFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iS{W2NkBk\WyuczDh[pRmeiB2ODDodpMh[nliQ1PLMVgh[XO\|YYmsJGlEPTBiPTCzMlc2KM7:TT6=	M4XR[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7OUSwNVE2Lz5{OUm0NFEyPTxxYU6=
HEL	NGLv[XJCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		NV\zelF{PDhiaILz	MlzURY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCKRVygZ4VtdHNiYX\0[ZIhPDhiaILzJIJ6KEOFSz24JIF{e2G7LDDJR\|UxKD1iMz63OUDPxE1w	NInWcXo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUm0NFEyPSd-Mkm5OFAyOTV:L3G+
BCP-ALL	MmjMR5l1d3SxeHnjbZR6KGG\|c3H5		NIfSe204OiCqcoO=	NVrlXYVRS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hSkOSLVHMUEBk\WyuczDk[ZJqfmWmIH\yc40heGG2aXXueEA{KGGodHXyJFczKGi{czDifUBE\WyuVHn0[ZIuT2yxIHz1cYlv\XOlZX70JINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwJF0hPC52NTFOwG0v	NXfaemt1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CzOlU5QTJpPkOwN\|Y2QDl{PD;hQi=>
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TC32	NUTIcXQyeUiWUzDhd5NigQ>?			M17xSZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCWQ{OyJINmdGy\|	MorUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
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HEL	MmnSR4VtdCCleXPs[UBie3OjeR?=	MmTKNUB1dyBzMDD1US=>	NVe1Z49EPDhiaILz	M3\iT2NmdGxiY4njcIUh[XK{ZYP0JIlvKGi3bXHuJGhGVCClZXzsd{Bie3Onc4Pl[EBieyCjY3P1cZVt[XSrb36gZZQhTzFicHjhd4Uh[XRiMTD0c{AyOCC3TTDh[pRmeiB2ODDodpMheHKxcHnkbZVuKGmxZHnk[UB{fGGrbnnu[{Bj[XOnZDDmcI94KGO7dH;t[ZRzgQ>?	M17YfVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7OUSwNVE2Lz5{OUm0NFEyPTxxYU6=
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SEM	MonHSpVv[3Srb36gZZN{[Xl?	NX;t[4R6OS54IIXN	NFTXbHUyQCCqcoO=	Ml3uTY5pcWKrdHnvckBw\iCKRFHDOkBqdiCqdX3hckBUTU1iY3XscJMh[XO\|ZYPz[YQh[XNiZHXjdoVie2ViaX6gZYdoemW\|b33lJIFk[3WvdXzheIlwdiCjdDCxMlYhfU1iYX\0[ZIhOThiaILzJIJ6KE[DQ2OgZY5idHm\|aYO=	Mk[wQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB\|NkW4PVIoRjNyM{[1PFkzRC:jPh?=
SH-SY5Y	NYLx[IN[TnWwY4Tpc44h[XO\|YYm=	M1fmZlAvOSC2bzCxJJVO	MlzCNlQhcHK\|	MljKTY5pcWKrdHnvckBw\iCKRFHDOkBqdiCqdX3hckBUUC2VWUXZJINmdGy\|IHHzd4V{e2WmIHHzJIlv[3KnYYPlJIlvKGGlZYT5cIF1cW:wIH;mJIFteGijLYT1ZpVtcW5iYYSgNE4yKHSxIEGgeW0h[W[2ZYKgNlQhcHK\|IHL5JHdme3Sncn6gZoxwfCCjbnHsfZNqew>?	MlfMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzByMki2NVYoRjNyMEK4OlE3RC:jPh?=
SH-SY5Y	NVrwNWpWTnWwY4Tpc44h[XO\|YYm=	M2LncFAvOSC2bzCxJJVO	MmC3NlQhcHK\|	MVXJcohq[mm2aX;uJI9nKGOuYYPzJFEhUESDQzDpckBpfW2jbjDTTE1UYTW\IHPlcIx{KGG\|c3Xzd4VlKGG\|IHnuZ5Jm[XOnIHnuJIFk\XS7bHH0bY9vKG:oIHjpd5RwdmViSEOgZZQhOC5zIITvJFEhfU1iYX\0[ZIhOjRiaILzJIJ6KFenc4Tldo4h[myxdDDhcoFtgXOrcx?=	Ml\EQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzByMki2NVYoRjNyMEK4OlE3RC:jPh?=

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	Ac-α-tubulin / Ac-Histone H4 ; PubMed: 31015208 Blood Adv Ricolinostat promotes the accumulation of acetylated (Ac) α-tubulin. MM cells were treated with the indicated concentrations of ricolinostat for 24 hours. Protein expression was measured by immunoblotting. Survivin / P21 / CDC2 / p53 / p-p53(S392) / Cyclin A2 / Cyclin B1; PubMed: 30050135 Cell Death Dis Western blot analysis of G2/M phase cell cycle regulatory-proteins for 48 h Bax / Bim / Bcl2 / Cleaved caspase-3 / Cleaved caspase-9 / Cleaved PARP; PubMed: 30050135 Cell Death Dis Western blot analysis of apoptosis regulatory-proteins for 48 h PI3K(p85) / AKT / p-AKT(S473) / PRAS40 / Rag C / mTOR / p-mTOR / ERK / p-ERK; PubMed: 30050135 Cell Death Dis ACY-1215 treatment inhibited PI3K/AKT/mTOR and ERK signaling protein levels in ESCC EC109 and TE-1 cell lines for 48 h. Ac-β-catenin(K49) / p-β-catenin / β-catenin; PubMed: 25546293 ACS Chem Biol Time-course immunoblot analysis of human NPCs treated with an HDAC6 inhibitor. Human NPCs were treated with HDAC6 inhibitor ACY-1215 at 5 μM for the times points indicated and the lysates immunoblotted with antibodies against β-catenin, Ac-Lys49-β-catenin, phos-Ser45 and phos-Ser33, Ser37, and Thr41. β-actin is using shown as loading control.	31015208 30050135 25546293
Immunofluorescence	β-tubulin / β-catenin; PubMed: 25546293 ACS Chem Biol Immunofluorescence staining for β-catenin treated with HDAC6 inhibitor in human NPCs. Cells were treated with 5 μM ACY-1215 or DMSO for 18 h and imaged with anti-β-catenin antibody (green), anti-β-tubulin antibody (red), and Hoechst 33342 (blue). Scale bar, 20 μm. Quantification of β-catenin levels at the membrane represent two independent experiments with three fields of view each at 20× magnification. Error bars indicate standard deviation. and ** denote significance at p < 0.01 and p < 0.0001, respectively (unpaired t test).	25546293
Growth inhibition assay	Cell viability; PubMed: 31015208 Blood Adv Ricolinostat decreases MM cell viability. A panel of MM cell lines was treated with the indicated concentrations of ricolinostat for 72 hours. Cell viability was measured by MTT assay.	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

Kinase Assay: ^[1]	- Collapse 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]	- Collapse 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. (Only for Reference)
Animal Research: ^[1]	- Collapse Animal Models: MM xenograft SCID mouse model Dosages: 50 mg/kg Administration: ip (Only for Reference)

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.	0.62mg/mL

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

Chemical Information Download Ricolinostat (ACY-1215) SDF

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

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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.
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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2021-09-06)

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

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.

HDAC Signaling Pathway Map

HDAC Inhibitors with Unique Features

Pan HDAC Inhibitor

Panobinostat (LBH589) : Pan-HDAC inhibitor, IC50=5 nM.
Most Potent HDAC Inhibitor

Quisinostat (JNJ-26481585) : HDAC1, IC50=0.11 nM; HDAC2, IC50=0.33 nM.
FDA-approved HDAC Inhibitor

Vorinostat (SAHA, MK0683) : Approved by FDA against cutaneous T cell lymphoma.
Newest HDAC Inhibitor

RG2833 (RGFP109) ^New : Brain-penetrant HDAC inhibitor with IC50 of 60 nM and 50 nM for HDAC1 and HDAC3, respectively.

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Panobinostat (LBH589)

Panobinostat (LBH589, NVP-LBH589) is a novel broad-spectrum HDAC inhibitor with IC50 of 5 nM in a cell-free assay. Panobinostat (LBH589) induces autophagy and apoptosis. Panobinostat effectively disrupts HIV latency in vivo. Phase 3.
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Vorinostat (suberoylanilide hydroxamic acid, SAHA, MK0683, Zolinza) is an HDAC inhibitor with IC50 of ~10 nM in a cell-free assay. Vorinostat abrogates productive HPV-18 DNA amplification.
Entinostat (MS-275)

Entinostat (MS-275, SNDX-275) strongly inhibits HDAC1 and HDAC3 with IC50 of 0.51 μM and 1.7 μM in cell-free assays, compared with HDACs 4, 6, 8, and 10. Entinostat induces autophagy and apoptosis. Phase 3.
Trichostatin A (TSA)

Trichostatin A (TSA) is an HDAC inhibitor with IC50 of ~1.8 nM in cell-free assays.
Romidepsin (FK228, Depsipeptide)

Romidepsin (FK228, Depsipeptide, FR 901228, NSC 630176) is a potent HDAC1 and HDAC2 inhibitor with IC50 of 36 nM and 47 nM in cell-free assays, respectively. Romidepsin (FK228/depsipeptide) controls growth and induces apoptosis in neuroblastoma tumor cells.

Features:More effective than other classical HDAC inhibitors such as TSA, TPX, and butyrate.
Tubastatin A

Tubastatin A is a potent and selective HDAC6 inhibitor with IC50 of 15 nM in a cell-free assay. It is selective against all the other isozymes (1000-fold) except HDAC8 (57-fold). Tubastatin A promotes autophagy and increases apoptosis.
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Ricolinostat (ACY-1215)