Ricolinostat (ACY-1215)

別名:Rocilinostat

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) 化学構造

CAS No. 1316214-52-4

サイズ 価格(税別) 在庫状況
10mM (1mL in DMSO) JPY 28500 国内在庫あり
JPY 22000 国内在庫あり
JPY 85500 国内在庫あり
JPY 448500 国内在庫なし(納期7~10日)

代表番号: 045-509-1970|電子メール:[email protected]
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製品安全説明書

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Ricolinostat (ACY-1215) と併用されることが多い化合物

(+)-JQ1


Ricolinostat and JQ1 increase apoptosis, diminish the expression of c-MYC and BCL-2, and lower multiple myeloma cells proliferation.

Carew JS, et al. Blood Adv. 2019 Apr 23;3(8):1318-1329.

Ricolinostat (ACY-1215) 関連製品

シグナル伝達経路

HDAC阻害剤の選択性比較

Cell Data

Cell Lines Assay Type Concentration Incubation Time 活性情報 PMID
SUP-B15 Function assay 0.1 to 10 uM 24 hrs Inhibition of HDAC6 in imatinib-resistant human SUP-B15 cells assessed as increase in cleaved PARP expression at 0.1 to 10 uM after 24 hrs by immunoblot assay 30365892
SEM Function assay 0.1 to 10 uM 24 hrs Inhibition of HDAC6 in human SEM cells assessed as increase in cleaved PARP expression at 0.1 to 10 uM after 24 hrs by immunoblot assay 30365892
HL60 Function assay 0.1 to 10 uM 24 hrs Inhibition of HDAC6 in human HL60 cells assessed as increase in cleaved PARP expression at 0.1 to 10 uM after 24 hrs by immunoblot assay 30365892
SUP-B15 Function assay 0.1 to 10 uM 24 hrs Inhibition of HDAC6 in imatinib-resistant human SUP-B15 cells assessed as increase in acetyl-histone H3 expression at 0.1 to 10 uM after 24 hrs by immunoblot assay 30365892
SEM Function assay 0.1 to 10 uM 24 hrs Inhibition of HDAC6 in human SEM cells assessed as increase in acetyl-histone H3 expression at 0.1 to 10 uM after 24 hrs by immunoblot assay 30365892
HL60 Function assay 0.1 to 10 uM 24 hrs Inhibition of HDAC6 in human HL60 cells assessed as increase in acetyl-histone H3 expression at 0.1 to 10 uM after 24 hrs by immunoblot assay 30365892
SUP-B15 Function assay 0.1 to 10 uM 24 hrs Inhibition of HDAC6 in imatinib-resistant human SUP-B15 cells assessed as increase in acetyl-alpha tubulin expression at 0.1 to 10 uM after 24 hrs by immunoblot assay 30365892
SEM Function assay 0.1 to 10 uM 24 hrs Inhibition of HDAC6 in human SEM cells assessed as increase in acetyl-alpha tubulin expression at 0.1 to 10 uM after 24 hrs by immunoblot assay 30365892
HL60 Function assay 0.1 to 10 uM 24 hrs Inhibition of HDAC6 in human HL60 cells assessed as increase in acetyl-alpha tubulin expression at 0.1 to 10 uM after 24 hrs by immunoblot assay 30365892
MV4-11 Function assay 1000 nM 6 hrs Inhibition of HDAC1/2/3 in human MV4-11 cells assessed as upregulation of histone H3 acetylation at 1000 nM after 6 hrs by Western blot analysis 26443078
OPM2 Cell Viability Assay 0-8μM 48 h decreases MM-cell viability in a dose-dependent manner 22262760
MM.1R Cell Viability Assay 0-8μM 48 h decreases MM-cell viability in a dose-dependent manner 22262760
LR5 Cell Viability Assay 0-8μM 48 h decreases MM-cell viability in a dose-dependent manner 22262760
RPMI Cell Viability Assay 0-8μM 48 h decreases MM-cell viability in a dose-dependent manner 22262760
OPM1 Cell Viability Assay 0-8μM 48 h decreases MM-cell viability in a dose-dependent manner 22262760
MM.1S Cell Viability Assay 0-8μM 48 h decreases MM-cell viability in a dose-dependent manner 22262760
RPMI8226  Function Assay 0.25/1μM 18 h increases acetylated α-tubulin 22262760
MM.1S Function Assay 0.25/1μM 18 h increases acetylated α-tubulin 22262760
MM.1R Function Assay 0.25/1μM 18 h increases acetylated α-tubulin 22262760
MM.1S Function Assay 0-5μM 6 h increases acetylated α-tubulin 22262760
A-172 Growth Inhibition Assay 10 nM 24/48 h inhibits cell growth time dependently 26150340
U87MG Growth Inhibition Assay 10 nM 24/48 h inhibits cell growth time dependently 26150340
HEL Cell cycle assay 1 to 10 uM 48 hrs Cell cycle arrest in human HEL cells assessed as accumulation at G1 phase at 1 to 10 uM after 48 hrs propidium iodide staining based flow cytometry 29940115
SEM Function assay 1.6 uM 18 hrs Inhibition of HDAC6 in human SEM cells assessed as decrease in aggresome accumulation at 1.6 uM after 18 hrs by FACS analysis 30365892
SH-SY5Y Function assay 0.1 to 1 uM 24 hrs Inhibition of HDAC6 in human SH-SY5Y cells assessed as increase in acetylation of alpha-tubulin at 0.1 to 1 uM after 24 hrs by Western blot analysis 30028616
SH-SY5Y Function assay 0.1 to 1 uM 24 hrs Inhibition of class 1 HDAC in human SH-SY5Y cells assessed as increase in acetylation of histone H3 at 0.1 to 1 uM after 24 hrs by Western blot analysis 30028616
BCP-ALL Cytotoxicity assay 72 hrs Cytotoxicity against human BCP-ALL cells derived from patient 3 after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 4.45 μM. 30365892
HEL Antiproliferative assay 48 hrs Antiproliferative activity against human HEL cells after 48 hrs by CCK-8 assay, IC50 = 3.75 μM. 29940115
K562 Antiproliferative assay 48 hrs Antiproliferative activity against human K562 cells after 48 hrs by CCK-8 assay, IC50 = 3.75 μM. 29940115
HL60 Antiproliferative assay 48 hrs Antiproliferative activity against human HL60 cells after 48 hrs by CCK-8 assay, IC50 = 3.75 μM. 29940115
KCL22 Cytotoxicity assay 72 hrs Cytotoxicity against human KCL22 cells after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 3.75 μM. 30365892
SUP-B15 Cytotoxicity assay 72 hrs Cytotoxicity against imatinib-resistant human SUP-B15 cells after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 3.54 μM. 30365892
U266 Cytotoxicity assay 72 hrs Cytotoxicity against human U266 cells after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 3.52 μM. 30365892
KCL22 Cytotoxicity assay 72 hrs Cytotoxicity against imatinib-resistant human KCL22 cells after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 3.38 μM. 30365892
HEL Antiproliferative assay 48 hrs Antiproliferative activity against human HEL cells after 48 hrs in presence of JAK2 inhibitor CYT-387 by CCK-8 assay, IC50 = 2.54 μM. 29940115
K562 Antiproliferative assay 48 hrs Antiproliferative activity against human K562 cells after 48 hrs in presence of JAK2 inhibitor CYT-387 by CCK-8 assay, IC50 = 2.54 μM. 29940115
HL60 Antiproliferative assay 48 hrs Antiproliferative activity against human HL60 cells after 48 hrs in presence of JAK2 inhibitor CYT-387 by CCK-8 assay, IC50 = 2.54 μM. 29940115
HL60 Cytotoxicity assay 72 hrs Cytotoxicity against human HL60 cells after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 2.36 μM. 30365892
RPMI18226 Cytotoxicity assay 72 hrs Cytotoxicity against human RPMI18226 cells after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 1.97 μM. 30365892
SUP-B15 Cytotoxicity assay 72 hrs Cytotoxicity against human SUP-B15 cells after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 1.92 μM. 30365892
SEM Cytotoxicity assay 72 hrs Cytotoxicity against human SEM cells after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 1.61 μM. 30365892
RPMI8226 Cytotoxicity assay 72 hrs Cytotoxicity against human RPMI8226 cells after 72 hrs by MTT assay, IC50 = 1.468 μM. 26443078
BCP-ALL Cytotoxicity assay 72 hrs Cytotoxicity against human BCP-ALL cells derived from patient 2 after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 0.58 μM. 30365892
BCP-ALL Cytotoxicity assay 72 hrs Cytotoxicity against human BCP-ALL cells derived from patient 4 after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 0.54 μM. 30365892
BCP-ALL Cytotoxicity assay 72 hrs Cytotoxicity against human BCP-ALL cells derived from patient 1 after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 0.29 μM. 30365892
Sf9 Function assay 15 mins Inhibition of full length recombinant human C-terminal FLAG/His-tagged HDAC1 expressed in baculovirus infected sf9 cells using Boc-Lys-(Ac)-AMC as substrate preincubated for 15 mins followed by substrate addition measured after 60 mins by fluorescence ass, IC50 = 0.1 μM. 29500130
Sf9 Function assay 15 mins Inhibition of full length recombinant human C-terminal His-tagged HDAC2 expressed in baculovirus infected sf9 cells using Boc-Lys-(Ac)-AMC as substrate preincubated for 15 mins followed by substrate addition measured after 60 mins by fluorescence assay, IC50 = 0.066 μM. 29500130
Sf9 Function assay 10 mins Inhibition of full length human recombinant C-terminal FLAG-His-tagged HDAC1 expressed in Sf9 cells using FTS as substrate preincubated for 10 mins followed by substrate addition measured over 30 mins, IC50 = 0.058 μM. 28038324
Sf9 Function assay 10 mins Inhibition of full length human recombinant C-terminal FLAG-tagged HDAC2 expressed in Sf9 cells using FTS as substrate preincubated for 10 mins followed by substrate addition measured over 30 mins, IC50 = 0.048 μM. 28038324
Sf9 Function assay 15 mins Inhibition of full length recombinant human C-terminal His-tagged HDAC3/N-terminal GST-tagged NCOR2 (395 to 489 residues) expressed in baculovirus infected sf9 cells using Boc-Lys-(Ac)-AMC as substrate preincubated for 15 mins followed by substrate additi, IC50 = 0.037 μM. 29500130
Sf9 Function assay 15 mins Inhibition of full length recombinant human N-terminal GST-tagged HDAC6 expressed in baculovirus infected sf9 cells using Boc-Lys-(Ac)-AMC as substrate preincubated for 15 mins followed by substrate addition measured after 60 mins by fluorescence assay, IC50 = 0.009 μM. 29500130
Sf9 Function assay 10 mins Inhibition of full length human recombinant N-terminal GST-tagged HDAC6 expressed in Sf9 cells using FTS as substrate preincubated for 10 mins followed by substrate addition measured over 30 mins, IC50 = 0.0047 μM. 28038324
HH Growth Inhibition Assay 48 h IC50=2.5 μM 26116270
Sup-T1 Growth Inhibition Assay 48 h IC50=1.6 μM 26116270
CCL-119 Growth Inhibition Assay 48 h IC50=1.7 μM 26116270
H9 Growth Inhibition Assay 48 h IC50=1.2 μM 26116270
Rec-1  Growth Inhibition Assay 48 h IC50=2.3 μM 26116270
Jeko-1 Growth Inhibition Assay 48 h IC50=1.5 μM 26116270
Jvm-2 Growth Inhibition Assay 48 h IC50=4.0 μM 26116270
Su-DHL6 Growth Inhibition Assay 48 h IC50=3.2 μM 26116270
Hbl-2 Growth Inhibition Assay 48 h IC50=1.9 μM 26116270
Su-DHL4 Growth Inhibition Assay 48 h IC50=4.7 μM 26116270
OCI-Ly1 Growth Inhibition Assay 48 h IC50=2.4 μM 26116270
OCI-Ly7 Growth Inhibition Assay 48 h IC50=1.2 μM 26116270
Su-DHL2 Growth Inhibition Assay 48 h IC50=3.3 μM 26116270
OCI-Ly10 Growth Inhibition Assay 48 h IC50=0.9 μM 26116270
Riva Growth Inhibition Assay 48 h IC50=2.2 μM 26116270
Hbl-1 Growth Inhibition Assay 48 h IC50=1.6 μM 26116270
SEM Antiproliferative assay 24 to 72 hrs Antiproliferative activity against human SEM cells at IC50 to 2 times IC50 after 24 to 72 hrs by trypan exclusion method 30365892
SEM Function assay 18 hrs Inhibition of HDAC6 in human SEM cells assessed as decrease in aggresome accumulation at IC50 after 18 hrs by fluorescence microscopic method 30365892
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
Rh30 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
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生物活性

製品説明 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.
特性 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
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.

Kinase Assay 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.
細胞実験 細胞株 MM cell lines, patient MM cells, and PBMCs
濃度 ~8 μM
反応時間 48 hours
実験の流れ

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. 

実験結果図 Methods Biomarkers 結果図 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
Immunofluorescence β-tubulin / β-catenin 25546293
Growth inhibition assay Cell viability 31015208
In Vivo
In Vivo

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]

動物実験 動物モデル MM xenograft SCID mouse model
投与量 50 mg/kg
投与経路 ip
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02632071 Completed
Metastatic Breast Cancer|Breast Carcinoma
Columbia University|Acetylon Pharmaceuticals Incorporated|National Cancer Institute (NCI)
March 1 2016 Phase 1
NCT01583283 Completed
Multiple Myeloma
Celgene
July 12 2012 Phase 1
NCT01323751 Completed
Multiple Myeloma
Celgene|The Leukemia and Lymphoma Society
July 2011 Phase 1|Phase 2

化学情報

分子量 433.5 化学式

C24H27N5O3

CAS No. 1316214-52-4 SDF Download Ricolinostat (ACY-1215) SDFをダウンロードする
Smiles C1=CC=C(C=C1)N(C2=CC=CC=C2)C3=NC=C(C=N3)C(=O)NCCCCCCC(=O)NO
保管

In vitro
Batch:

DMSO : 42 mg/mL ( (96.88 mM); 吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量 濃度 体積 分子量

投与溶液組成計算機(クリア溶液)

ステップ1:実験データを入力してください。(実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します)

mg/kg g μL

ステップ2:投与溶媒の組成を入力してください。(ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください)

% DMSO % % Tween 80 % ddH2O
%DMSO %

計算結果:

投与溶媒濃度: mg/ml;

DMSOストック溶液調製方法: mg 試薬を μL DMSOに溶解する(濃度 mg/mL, 注:濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法:Take μL DMSOストック溶液に μL PEG300,を加え、完全溶解後μL Tween 80,を加えて完全溶解させた後 μL ddH2O,を加え完全に溶解させます。

投与溶媒調製方法:μL DMSOストック溶液に μL Corn oil,を加え、完全溶解。

注意:1.ストック溶液に沈殿、混濁などがないことをご確認ください;
2.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

技術サポート

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Handling Instructions

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よくある質問(FAQ)

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

回答
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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