Ricolinostat (ACY-1215)

Name: Ricolinostat (ACY-1215)
Brand: Selleck Chemicals
SKU: S8001
Rating: 5 (52 reviews)

For research use only.

Catalog No.S8001 Synonyms: Rocilinostat

52 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 52 publications

Science, 2020, 369(6510)eaas8995

PubMed: 32943500 ( 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 )

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	NXrs[G5VT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MmfQNVDDqG6P	M1;nU\|I1NzR6IHi=	NHq2dHlqdmirYnn0d{Bk\WyuIHfyc5d1cCC2aX3lJIRmeGWwZHXueIx6	M2Czc\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUWwN\|QxLz5{NkG1NFM1ODxxYU6=
U87MG	M3;RT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MWqxNOKhdk1?	NInDUpkzPC92ODDo	NHz3WlFqdmirYnn0d{Bk\WyuIHfyc5d1cCC2aX3lJIRmeGWwZHXueIx6	M1TpTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUWwN\|QxLz5{NkG1NFM1ODxxYU6=
Hbl-1	NWLwVINPT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		NHvjT2o1QCCq	MX;JR\|UxRTFwNjFOwG0>	NYe4e2FZRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xNVYzPzBpPkK2NVE3OjdyPD;hQi=>
OCI-Ly10	M4G2VGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		NFLHT4Y1QCCq	MXHJR\|UxRTBwOTFOwG0>	MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjFzNkK3NEc,OjZzMU[yO\|A9N2F-
Riva	Mmf2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		MUe0PEBp	NEm2NpBKSzVyPUKuNkDPxE1?	MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjFzNkK3NEc,OjZzMU[yO\|A9N2F-
Su-DHL2	M2fndmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		NEjM[Yw1QCCq	MnnITWM2OD1\|LkOg{txO	Moq2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzMU[yO\|AoRjJ4MUG2NlcxRC:jPh?=
OCI-Ly1	M1vRW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7		NG[zflU1QCCq	M2DaeWlEPTB;Mj60JO69VQ>?	MW[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjFzNkK3NEc,OjZzMU[yO\|A9N2F-
OCI-Ly7	M4r5Nmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		NH7KOIg1QCCq	NX3tfW1jUUN3ME2xMlIh\|ryP	MnS0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzMU[yO\|AoRjJ4MUG2NlcxRC:jPh?=
Su-DHL4	NIi2TWxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=		NIDPNYQ1QCCq	MVXJR\|UxRTRwNzFOwG0>	M4LNS\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUG2NlcxLz5{NkGxOlI4ODxxYU6=
Su-DHL6	MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		NIjncpE1QCCq	NFPrellKSzVyPUOuNkDPxE1?	MnXFQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzMU[yO\|AoRjJ4MUG2NlcxRC:jPh?=
Hbl-2	MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		MXq0PEBp	MXfJR\|UxRTFwOTFOwG0>	M3H3ZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUG2NlcxLz5{NkGxOlI4ODxxYU6=
Jeko-1	NUntRmxkT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		NFLzc3o1QCCq	NHfEW3dKSzVyPUGuOUDPxE1?	MnLiQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzMU[yO\|AoRjJ4MUG2NlcxRC:jPh?=
Jvm-2	NWfQTIxPT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		M{fKOlQ5KGh?	M{fBPWlEPTB;ND6wJO69VQ>?	NWnWdJpERGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xNVYzPzBpPkK2NVE3OjdyPD;hQi=>
Rec-1	MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		MXi0PEBp	Mon0TWM2OD1{LkOg{txO	NYLCUnljRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xNVYzPzBpPkK2NVE3OjdyPD;hQi=>
CCL-119	NILjZ29Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=		NFjqZY81QCCq	NHWzTZRKSzVyPUGuO{DPxE1?	NHvjdZk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkGxOlI4OCd-Mk[xNVYzPzB:L3G+
H9	M172Tmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		NGHy[nc1QCCq	M2ewemlEPTB;MT6yJO69VQ>?	NXK4O2RURGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xNVYzPzBpPkK2NVE3OjdyPD;hQi=>
HH	MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		NIXtSpM1QCCq	M364TGlEPTB;Mj61JO69VQ>?	MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjFzNkK3NEc,OjZzMU[yO\|A9N2F-
Sup-T1	NWnGZldUT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		M33CU\|Q5KGh?	M4W0fGlEPTB;MT62JO69VQ>?	M4XzWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUG2NlcxLz5{NkGxOlI4ODxxYU6=
MM.1S	M17ZemZ2dmO2aX;uJGF{e2G7	NWDuemJmOC13zszN	NYH4[2kyPiCq	M{PNUYlv[3KnYYPld{Bi[2W2eXzheIVlKM7zLYT1ZpVtcW5?	NGmyUlQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkK2Nlc3OCd-MkKyOlI4PjB:L3G+
MM.1S	NFTaSWxHfW6ldHnvckBCe3OjeR?=	M4myN\|AvOjVxMd88US=>	MVKxPEBp	MUXpcoNz\WG\|ZYOgZYNmfHmuYYTl[EDPuS22dXL1cIlv	MoDUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ{NkK3OlAoRjJ{Mk[yO\|YxRC:jPh?=
MM.1R	M4LTSGZ2dmO2aX;uJGF{e2G7	M1Hwb\|AvOjVxMd88US=>	MoGzNVghcA>?	NVKwVIFscW6lcnXhd4V{KGGlZYT5cIF1\WRizsGteJVjfWyrbh?=	M2\vbFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{Mk[yO\|YxLz5{MkK2Nlc3ODxxYU6=
RPMI8226	MXLGeY5kfGmxbjDBd5NigQ>?	MoTsNE4zPS9zzszN	MVWxPEBp	NY\YNWpGcW6lcnXhd4V{KGGlZYT5cIF1\WRizsGteJVjfWyrbh?=	Mk\4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ{NkK3OlAoRjJ{Mk[yO\|YxRC:jPh?=
MM.1S	MVjD[YxtKF[rYXLpcIl1gSCDc4PhfS=>	MVmwMVjPxE1?	NFn6e5A1QCCq	MofG[IVkemWjc3XzJG1ONWOnbHygeoli[mmuaYT5JIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy	M1LZOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{Mk[yO\|YxLz5{MkK2Nlc3ODxxYU6=
OPM1	MlTIR4VtdCCYaXHibYxqfHliQYPzZZk>	NV22WVJqOC16zszN	M4jtcFQ5KGh?	MnTV[IVkemWjc3XzJG1ONWOnbHygeoli[mmuaYT5JIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy	MoPBQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ{NkK3OlAoRjJ{Mk[yO\|YxRC:jPh?=
RPMI	MX7D[YxtKF[rYXLpcIl1gSCDc4PhfS=>	NHXHe\|IxNTkQvF2=	M4rKXlQ5KGh?	NX;WWmxl\GWlcnXhd4V{KE2PLXPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz	NVTDTXB[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKyOlI4PjBpPkKyNlYzPzZyPD;hQi=>
MM.1R	M3;wT2NmdGxiVnnhZoltcXS7IFHzd4F6	MYWwMVjPxE1?	NYnjWXA3PDhiaB?=	NH;KRVZl\WO{ZXHz[ZMhVU1vY3XscEB3cWGkaXzpeJkhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI>	NVjBdopFRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKyOlI4PjBpPkKyNlYzPzZyPD;hQi=>
LR5	NUX5SlhRS2WubDDWbYFjcWyrdImgRZN{[Xl?	M2PBSVAuQM7:TR?=	MoK5OFghcA>?	Mm\P[IVkemWjc3XzJG1ONWOnbHygeoli[mmuaYT5JIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy	NVHlU3VNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKyOlI4PjBpPkKyNlYzPzZyPD;hQi=>
OPM2	NFn3UXZE\WyuIG\pZYJqdGm2eTDBd5NigQ>?	MWiwMVjPxE1?	NFvIOYg1QCCq	NYqzUJh7\GWlcnXhd4V{KE2PLXPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz	MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjJ4Mke2NEc,OjJ{NkK3OlA9N2F-
Sf9	NIH3WWVHfW6ldHnvckBie3OjeR?=		M2DYe\|ExKG2rboO=	NXzmXXk6UW6qaXLpeIlwdiCxZjDmeYxtKGynbnf0bEBpfW2jbjDy[YNwdWKrbnHueEBPNXSncn3pcoFtKEeVVD30ZYdo\WRiSFTBR\|Yh\XiycnXzd4VlKGmwIGPmPUBk\WyuczD1d4lv\yCIVGOgZZMhe3Wkc4TyZZRmKHC{ZXnuZ5Vj[XSnZDDmc5IhOTBibXnud{Bnd2yub4fl[EBjgSC\|dXLzeJJifGViYXTkbZRqd25ibXXhd5Vz\WRib4\ldkA{OCCvaX7zMEBKSzVyIE2gNE4xODR5IN88UU4>	NVyxOmJFRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkiwN\|g{OjRpPkK4NFM5OzJ2PD;hQi=>
Sf9	NHSwXI9HfW6ldHnvckBie3OjeR?=		MnrWNVUhdWmwcx?=	M2Wye2lvcGmkaYTpc44hd2ZiZoXscEBt\W6pdHigdoVkd22kaX7hcpQhcHWvYX6gUk11\XKvaX7hcEBIW1RvdHHn[4VlKEiGQVO2JIV5eHKnc4Pl[EBqdiCkYXP1cI93cXK3czDpcoZm[3SnZDDz[lkh[2WubIOgeZNqdmdiQn;jMWx6ey1qQXOpMWFOSyCjczDzeYJ{fHKjdHWgdJJmcW6ldXLheIVlKG[xcjCxOUBucW6\|IH\vcIxwf2WmIHL5JJN2[nO2cnH0[UBi\GSrdHnvckBu\WG\|dYLl[EBi\nSncjC2NEBucW6\|IHL5JIZtfW:{ZYPj[Y5k\SCjc4PhfUwhUUN3MDC9JFAvODB7IN88UU4>	MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTVyMEGzNEc,Ojl3MECxN\|A9N2F-
Sf9	NXTJems2TnWwY4Tpc44h[XO\|YYm=		MmCxNVUhdWmwcx?=	NI\VSnFKdmirYnn0bY9vKG:oIH\1cIwhdGWwZ4ToJJJm[2:vYnnuZY51KGi3bXHuJGMufGW{bXnuZYwhUGm\|LYTh[4dm\CCKRFHDN{9PNXSncn3pcoFtKEeVVD30ZYdo\WRiTlPPVlIhMDN7NTD0c{A1QDlicnXzbYR2\XNrIHX4dJJme3OnZDDpckBj[WO3bH;2bZJ2eyCrbn\lZ5Rm\CC\|ZkmgZ4VtdHNidYPpcochSm:lLVz5d{0pSWNrLVHNR{BieyC\|dXLzeJJifGVicILlbY5kfWKjdHXkJIZweiBzNTDtbY5{KG[xbHzve4VlKGK7IIP1ZpN1emG2ZTDh[IRqfGluIFnDOVAhRSByLkCzO{DPxE1w	MknHQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl3MECxN\|AoRjJ7NUCwNVMxRC:jPh?=
Sf9	M4i0dWZ2dmO2aX;uJIF{e2G7		M3LzfFExKG2rboO=	MWrJcohq[mm2aX;uJI9nKG[3bHygcIVv\3SqIHj1cYFvKHKnY3;tZolv[W62IFOteIVzdWmwYXygSmxCTy22YXfn[YQhUESDQ{Kg[ZhxemW\|c3XkJIlvKFOoOTDj[YxteyC3c3nu[{BHXFNiYYOgd5Vje3S{YYTlJJBz\WmwY4XiZZRm\CCob4KgNVAhdWmwczDmc4xtd3enZDDifUB{fWK\|dILheIUh[WSmaYTpc44hdWWjc4Xy[YQhd3[ncjCzNEBucW6\|LDDJR\|UxKD1iMD6wOFgh\|ryPLh?=	NX3lbYpORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkiwN\|g{OjRpPkK4NFM5OzJ2PD;hQi=>
Sf9	MUDGeY5kfGmxbjDhd5NigQ>?		NGj0c44yOCCvaX7z	MkDyTY5pcWKrdHnvckBw\iCodXzsJIxmdme2aDDoeY1idiC{ZXPvcYJqdmGwdDDDMZRmem2rbnHsJGZNSUdvSHnzMZRi\2enZDDISGFEOSCneIDy[ZN{\WRiaX6gV4Y6KGOnbHzzJJV{cW6pIF\UV{BieyC\|dXLzeJJifGVicILlbY5kfWKjdHXkJIZweiBzMDDtbY5{KG[xbHzve4VlKGK7IIP1ZpN1emG2ZTDh[IRqfGmxbjDt[YF{fXKnZDDveoVzKDNyIH3pcpMtKEmFNUCgQUAxNjB3ODFOwG0v	MorrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjhyM{izNlQoRjJ6MEO4N\|I1RC:jPh?=
Sf9	NIfucXJHfW6ldHnvckBie3OjeR?=		NYK4WJJlOTVibXnudy=>	NWCzNZc1UW6qaXLpeIlwdiCxZjDmeYxtKGynbnf0bEBz\WOxbXLpcoFvfCCqdX3hckBENXSncn3pcoFtKEircz30ZYdo\WRiSFTBR\|Ih\XiycnXzd4VlKGmwIHLhZ5Vtd3[rcoXzJIlv\mWldHXkJJNnQSClZXzsd{B2e2mwZzDCc4MuVHm\|LTjBZ{kuSU2FIHHzJJN2[nO2cnH0[UBxemWrbnP1ZoF1\WRiZn;yJFE2KG2rboOg[o9tdG:5ZXSgZpkhe3Wkc4TyZZRmKGGmZHn0bY9vKG2nYYP1doVlKGGodHXyJFYxKG2rboOgZpkh\my3b4Lld4NmdmOnIHHzd4F6NCCLQ{WwJF0hOC5yNk[g{txONg>?	M2n6S\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NUCwNVMxLz5{OUWwNFE{ODxxYU6=
Sf9	M{DVd2Z2dmO2aX;uJIF{e2G7		MlfFNVUhdWmwcx?=	MkjITY5pcWKrdHnvckBw\iCodXzsJIxmdme2aDDy[YNwdWKrbnHueEBpfW2jbjDDMZRmem2rbnHsJGZNSUdxSHnzMZRi\2enZDDISGFEOSCneIDy[ZN{\WRiaX6gZoFkfWyxdnnyeZMhcW6oZXP0[YQhe2Z7IHPlcIx{KHW\|aX7nJGJw[y2OeYOtLGFkMS2DTVOgZZMhe3Wkc4TyZZRmKHC{ZXnuZ5Vj[XSnZDDmc5IhOTVibXnud{Bnd2yub4fl[EBjgSC\|dXLzeJJifGViYXTkbZRqd25ibXXhd5Vz\WRiYX\0[ZIhPjBibXnud{BjgSCobIXvdoV{[2WwY3WgZZN{NCCLQ{WwJF0hOC5zIN88UU4>	NETR[4Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUWwNFE{OCd-Mkm1NFAyOzB:L3G+
BCP-ALL	Mo\yR5l1d3SxeHnjbZR6KGG\|c3H5		NX7Xdo1rPzJiaILz	Mkm2R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gRmNRNUGOTDDj[YxteyCmZYLpeoVlKG[{b32gdIF1cWWwdDCxJIFnfGW{IEeyJIhzeyCkeTDD[YxtXGm2ZYKtS4xwKGy3bXnu[ZNk\W62IHPlcIwhfmmjYnnsbZR6KGG\|c3H5MEBKSzVyIE2gNE4zQSEQvF2u	NVj0WFNtRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CzOlU5QTJpPkOwN\|Y2QDl{PD;hQi=>
BCP-ALL	MYjDfZRwfG:6aXPpeJkh[XO\|YYm=		MlfaO\|IhcHK\|	Ml\BR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gRmNRNUGOTDDj[YxteyCmZYLpeoVlKG[{b32gdIF1cWWwdDC0JIFnfGW{IEeyJIhzeyCkeTDD[YxtXGm2ZYKtS4xwKGy3bXnu[ZNk\W62IHPlcIwhfmmjYnnsbZR6KGG\|c3H5MEBKSzVyIE2gNE42PCEQvF2u	NFnDbJA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEO2OVg6Oid-M{CzOlU5QTJ:L3G+
BCP-ALL	Mo\OR5l1d3SxeHnjbZR6KGG\|c3H5		NF;BW3c4OiCqcoO=	M2XTZ2N6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGJEWC2DTFygZ4VtdHNiZHXybZZm\CCocn;tJJBifGmnboSgNkBi\nSncjC3NkBpenNiYomgR4VtdFSrdHXyMWdtdyCudX3pcoV{[2WwdDDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3MDC9JFAvPThizszNMi=>	MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODN4NUi5Nkc,OzB\|NkW4PVI9N2F-
RPMI8226	NULabo9NS3m2b4TvfIlkcXS7IHHzd4F6		M3vGb\|czKGi{cx?=	MmrTR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gVnBOUTh{Mk[gZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigSxiSVO1NEA:KDFwNE[4JO69VS5?	MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjR2M{C3PEc,OjZ2NEOwO\|g9N2F-
SEM	M1O5bWN6fG:2b4jpZ4l1gSCjc4PhfS=>		MY[3NkBpenN?	NWnRPIxpS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hW0WPIHPlcIx{KGGodHXyJFczKGi{czDifUBE\WyuVHn0[ZIuT2yxIHz1cYlv\XOlZX70JINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwJF0hOS54MTFOwG0v	MnvwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB\|NkW4PVIoRjNyM{[1PFkzRC:jPh?=
SUP-B15	M{H5XGN6fG:2b4jpZ4l1gSCjc4PhfS=>		NHHu[mY4OiCqcoO=	MmntR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gV3VRNUJzNTDj[YxteyCjZoTldkA4OiCqcoOgZpkhS2WubGTpeIVzNUeubzDseY1qdmW\|Y3XueEBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NEA:KDFwOUKg{txONg>?	NUnvN3VVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CzOlU5QTJpPkOwN\|Y2QDl{PD;hQi=>
RPMI18226	MWPDfZRwfG:6aXPpeJkh[XO\|YYm=		MoC5O\|IhcHK\|	MmXLR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gVnBOUTF6MkK2JINmdGy\|IHHmeIVzKDd{IHjyd{BjgSCFZXzsWIl1\XJvR3zvJIx2dWmwZYPj[Y51KGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR\|UxKD1iMT65O{DPxE1w	NFHMOVg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEO2OVg6Oid-M{CzOlU5QTJ:L3G+
HL60	NYPzdWlGS3m2b4TvfIlkcXS7IHHzd4F6		M1izU\|czKGi{cx?=	MlS5R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gTGw3OCClZXzsd{Bi\nSncjC3NkBpenNiYomgR4VtdFSrdHXyMWdtdyCudX3pcoV{[2WwdDDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3MDC9JFIvOzZizszNMi=>	M4HLUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyM{[1PFkzLz5\|MEO2OVg6OjxxYU6=
HL60	MVrBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		MWC0PEBpenN?	NEHQWFZCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFjMOlAh[2WubIOgZYZ1\XJiNEigbJJ{KGmwIIDy[ZNmdmOnIH;mJGpCUzJiaX7obYJqfG:{IFPZWE0{QDdiYomgR2NMNThiYYPzZZktKEmFNUCgQUAzNjV2IN88UU4>	M1;uZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7OUSwNVE2Lz5{OUm0NFEyPTxxYU6=
K562	NYjxOoV4SW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		MoLSOFghcHK\|	NImyOJlCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFu1OlIh[2WubIOgZYZ1\XJiNEigbJJ{KGmwIIDy[ZNmdmOnIH;mJGpCUzJiaX7obYJqfG:{IFPZWE0{QDdiYomgR2NMNThiYYPzZZktKEmFNUCgQUAzNjV2IN88UU4>	NYizPXl3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm5OFAyOTVpPkK5PVQxOTF3PD;hQi=>
HEL	MXLBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		MUS0PEBpenN?	NGm1Z4JCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFjFUEBk\WyuczDh[pRmeiB2ODDodpMhcW5icILld4Vv[2Vib3[gTmFMOiCrbnjpZol1d3JiQ2nUMVM5PyCkeTDDR2suQCCjc4PhfUwhUUN3MDC9JFIvPTRizszNMi=>	NVrle2o3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm5OFAyOTVpPkK5PVQxOTF3PD;hQi=>
KCL22	M{PXVmN6fG:2b4jpZ4l1gSCjc4PhfS=>		MkLuO\|IhcHK\|	MX;DfZRwfG:6aXPpeJkh[WejaX7zeEBqdWG2aX7pZk1z\XOrc4ThcpQhcHWvYX6gT2NNOjJiY3XscJMh[W[2ZYKgO\|IhcHK\|IHL5JGNmdGyWaYTldk1IdG9ibIXtbY5me2OnboSgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUCgQUA{NjN6IN88UU4>	M1T1eVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyM{[1PFkzLz5\|MEO2OVg6OjxxYU6=
U266	MYXDfZRwfG:6aXPpeJkh[XO\|YYm=		MoTIO\|IhcHK\|	MmLRR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gWVI3PiClZXzsd{Bi\nSncjC3NkBpenNiYomgR4VtdFSrdHXyMWdtdyCudX3pcoV{[2WwdDDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3MDC9JFMvPTJizszNMi=>	MofOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB\|NkW4PVIoRjNyM{[1PFkzRC:jPh?=
SUP-B15	MYrDfZRwfG:6aXPpeJkh[XO\|YYm=		NI\sfWE4OiCqcoO=	MVrDfZRwfG:6aXPpeJkh[WejaX7zeEBqdWG2aX7pZk1z\XOrc4ThcpQhcHWvYX6gV3VRNUJzNTDj[YxteyCjZoTldkA4OiCqcoOgZpkhS2WubGTpeIVzNUeubzDseY1qdmW\|Y3XueEBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NEA:KDNwNUSg{txONg>?	MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODN4NUi5Nkc,OzB\|NkW4PVI9N2F-
KCL22	MX;DfZRwfG:6aXPpeJkh[XO\|YYm=		NVrHXGtlPzJiaILz	M4nHWWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGtEVDJ{IHPlcIx{KGGodHXyJFczKGi{czDifUBE\WyuVHn0[ZIuT2yxIHz1cYlv\XOlZX70JINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwJF0hOy55NTFOwG0v	M1\FcFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyM{[1PFkzLz5\|MEO2OVg6OjxxYU6=
HL60	NHLC[WlCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		NUXsNnpwPDhiaILz	Mli4RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCKTE[wJINmdGy\|IHHmeIVzKDR6IHjyd{BjgSCFQ1utPEBie3OjeTygTWM2OCB;IEOuO\|Uh\|ryPLh?=	NEHhb4o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUm0NFEyPSd-Mkm5OFAyOTV:L3G+
K562	NGG0NJlCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		NH[5R4o1QCCqcoO=	MVHBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEt3NkKgZ4VtdHNiYX\0[ZIhPDhiaILzJIJ6KEOFSz24JIF{e2G7LDDJR\|UxKD1iMz63OUDPxE1w	MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTl2MEGxOUc,Ojl7NECxNVU9N2F-
HEL	MnThRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		M1v0OFQ5KGi{cx?=	NVvlPFR{SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDISWwh[2WubIOgZYZ1\XJiNEigbJJ{KGK7IFPDT{05KGG\|c3H5MEBKSzVyIE2gN{44PSEQvF2u	NHXSWG49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUm0NFEyPSd-Mkm5OFAyOTV:L3G+
BCP-ALL	NV7FO\|dDS3m2b4TvfIlkcXS7IHHzd4F6		NIPvPJI4OiCqcoO=	MmHsR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gRmNRNUGOTDDj[YxteyCmZYLpeoVlKG[{b32gdIF1cWWwdDCzJIFnfGW{IEeyJIhzeyCkeTDD[YxtXGm2ZYKtS4xwKGy3bXnu[ZNk\W62IHPlcIwhfmmjYnnsbZR6KGG\|c3H5MEBKSzVyIE2gOE41PSEQvF2u	MoDVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB\|NkW4PVIoRjNyM{[1PFkzRC:jPh?=
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TC32	NI\IVFhyUFSVIHHzd4F6			M4LQeZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCWQ{OyJINmdGy\|	NHTZUYo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
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SEM	NYDJUXp4TnWwY4Tpc44h[XO\|YYm=	MVGxMlYhfU1?	M1P2[\|E5KGi{cx?=	M{LTOGlvcGmkaYTpc44hd2ZiSFTBR\|YhcW5iaIXtZY4hW0WPIHPlcIx{KGG\|c3Xzd4VlKGG\|IHTlZ5Jm[XOnIHnuJIFo\3Knc3;t[UBi[2O3bYXsZZRqd25iYYSgNU43KHWPIHHmeIVzKDF6IHjyd{BjgSCIQVPTJIFv[Wy7c3nz	MkjsQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB\|NkW4PVIoRjNyM{[1PFkzRC:jPh?=
SH-SY5Y	M2jqZmZ2dmO2aX;uJIF{e2G7	M2fkSlAvOSC2bzCxJJVO	NVPoN3kzOjRiaILz	NX3DWo1QUW6qaXLpeIlwdiCxZjDISGFEPiCrbjDoeY1idiCVSD3TXVV[KGOnbHzzJIF{e2W\|c3XkJIF{KGmwY4LlZZNmKGmwIHHj[ZR6dGG2aX;uJI9nKGGucHjhMZR2[nWuaX6gZZQhOC5zIITvJFEhfU1iYX\0[ZIhOjRiaILzJIJ6KFenc4Tldo4h[myxdDDhcoFtgXOrcx?=	M{LEWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyMEK4OlE3Lz5\|MECyPFYyPjxxYU6=
SH-SY5Y	M3vNc2Z2dmO2aX;uJIF{e2G7	NFzLNngxNjFidH:gNUB2VQ>?	MlnuNlQhcHK\|	NWjrc\|ZiUW6qaXLpeIlwdiCxZjDjcIF{eyBzIFjERWMhcW5iaIXtZY4hW0hvU2m1XUBk\WyuczDhd5Nme3OnZDDhd{BqdmO{ZXHz[UBqdiCjY3X0fYxifGmxbjDv[kBpcXO2b37lJGg{KGG2IECuNUB1dyBzIIXNJIFnfGW{IEK0JIhzeyCkeTDX[ZN1\XKwIHLsc5Qh[W6jbInzbZM>	MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODB{OE[xOkc,OzByMki2NVY9N2F-

... 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.

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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, 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) 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)

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Tubastatin A

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Ricolinostat (ACY-1215)