Home Epigenetics HDAC Inhibitor Ricolinostat (ACY-1215)

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Ricolinostat (ACY-1215) HDAC Inhibitor

Kat.-Nr.: S8001

Ricolinostat (ACY-1215, Rocilinostat) ist ein selektiver HDAC6-Inhibitor mit einer IC50 von 5 nM in einem zellfreien Assay. Er ist >10-fach selektiver für HDAC6 als für HDAC1/2/3 (Klasse-I-HDACs) mit leichter Aktivität gegen HDAC8, minimaler Aktivität gegen HDAC4/5/7/9/11, Sirtuin1 und Sirtuin2. Ricolinostat (ACY-1215) unterdrückt die Zellproliferation und fördert die Apoptose. Phase 2.
Ricolinostat (ACY-1215) HDAC Inhibitor Chemical Structure

Chemische Struktur

Molekulargewicht: 433.5

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Qualitätskontrolle (Quality Control)

Charge: Reinheit: 99.96%
99.96

Produkte, die oft zusammen verwendet werden mit Ricolinostat (ACY-1215)

(+)-JQ1

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

Zellkultur, Behandlung & Arbeitskonzentration
(Cell Culture, Treatment & Working Concentration)

Zelllinien Assay-Typ Konzentration Inkubationszeit Formulierung Aktivitätsbeschreibung PMID
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
Hbl-1 Growth Inhibition Assay 48 h IC50=1.6 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
Su-DHL2 Growth Inhibition Assay 48 h IC50=3.3 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-DHL4 Growth Inhibition Assay 48 h IC50=4.7 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
Jeko-1 Growth Inhibition Assay 48 h IC50=1.5 μM 26116270
Jvm-2 Growth Inhibition Assay 48 h IC50=4.0 μM 26116270
Rec-1  Growth Inhibition Assay 48 h IC50=2.3 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
HH Growth Inhibition Assay 48 h IC50=2.5 μM 26116270
Sup-T1 Growth Inhibition Assay 48 h IC50=1.6 μM 26116270
MM.1S Function Assay 0-5μM 6 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
RPMI8226  Function Assay 0.25/1μM 18 h increases acetylated α-tubulin 22262760
MM.1S 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
RPMI 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
OPM2 Cell Viability Assay 0-8μM 48 h decreases MM-cell viability in a dose-dependent manner 22262760
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
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 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 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 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 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 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
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
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 2 after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 0.58 μM. 30365892
RPMI8226 Cytotoxicity assay 72 hrs Cytotoxicity against human RPMI8226 cells after 72 hrs by MTT assay, IC50 = 1.468 μM. 26443078
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
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
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
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
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
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
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
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
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
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
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
HL60 Antiproliferative assay 48 hrs Antiproliferative activity against human HL60 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
HEL Antiproliferative assay 48 hrs Antiproliferative activity against human HEL cells after 48 hrs by CCK-8 assay, IC50 = 3.75 μM. 29940115
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
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
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 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
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 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
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
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 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
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 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
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 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
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD 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
Rh30 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
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
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
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
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
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
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
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
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
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 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
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 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
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
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Chemische Informationen, Lagerung & Stabilität (Chemical Information, Storage & Stability)

Molekulargewicht 433.5 Formel

C24H27N5O3

 Lagerung (Ab Erhaltdatum)
CAS-Nr. 1316214-52-4 SDF herunterladen Lagerung von Stammlösungen

Synonyme Rocilinostat Smiles C1=CC=C(C=C1)N(C2=CC=CC=C2)C3=NC=C(C=N3)C(=O)NCCCCCCC(=O)NO

Löslichkeit (Solubility)

In vitro
Charge:

DMSO : 42 mg/mL (96.88 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molaritätsrechner

Masse Konzentration Volumen Molekulargewicht
Verdünnungsrechner Molekulargewicht-Rechner

In vivo
Charge:

In-vivo-Formulierungsrechner (Klare Lösung)

Schritt 1: Geben Sie unten die Informationen ein (Empfohlen: Ein zusätzliches Tier einplanen, um Verluste während des Experiments auszugleichen)

mg/kg g μL

Schritt 2: Geben Sie die In-vivo-Formulierung ein (Dies ist nur der Rechner, nicht die Formulierung. Bitte kontaktieren Sie uns zuerst, wenn im Abschnitt Löslichkeit keine In-vivo-Formulierung angegeben ist.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Berechnungsergebnisse:

Arbeitskonzentration: mg/ml;

Methode zur Herstellung der DMSO-Stammflüssigkeit: mg Wirkstoff voraufgelöst in μL DMSO ( Konzentration der Stammflüssigkeit mg/mL, Bitte kontaktieren Sie uns zuerst, wenn die Konzentration die DMSO-Löslichkeit der jeweiligen Wirkstoffcharge überschreitet. )

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammflüssigkeit, fügen Sie als Nächstes hinzuμL PEG300, mischen und aufklären, fügen Sie als Nächstes hinzuμL Tween 80, mischen und aufklären, fügen Sie als Nächstes hinzu μL ddH2O, mischen und aufklären.

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammflüssigkeit, fügen Sie als Nächstes hinzu μL Maisöl, mischen und aufklären.

Hinweis: 1. Bitte stellen Sie sicher, dass die Flüssigkeit klar ist, bevor Sie das nächste Lösungsmittel hinzufügen.
2. Achten Sie darauf, die Lösungsmittel in der richtigen Reihenfolge hinzuzufügen. Sie müssen sicherstellen, dass die im vorherigen Schritt erhaltene Lösung klar ist, bevor Sie das nächste Lösungsmittel hinzufügen. Physikalische Methoden wie Vortexen, Ultraschall oder ein warmes Wasserbad können zur Unterstützung des Lösungsvorgangs verwendet werden.

Wirkungsmechanismus (Mechanism of Action)

Eigenschaften
Induced less cytotoxicity in PHA-stimulated PBMCs from 4 healthy donors compared with the pan-HDAC inhibitor SAHA.
Targets/IC50/Ki
HDAC6
(Cell-free assay)
4.7 nM
HDAC2
(Cell-free assay)
48 nM
HDAC3
(Cell-free assay)
51 nM
HDAC1
(Cell-free assay)
58 nM
HDAC8
(Cell-free assay)
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.
Kinase-Assay
HDAC enzymatische Assays
ACY-1215 wird in Assay-Puffer [50 mM HEPES, pH 7,4, 100 mM KCl, 0,001 % Tween-20, 0,05 % BSA und 20 μM Tris(2-carboxyethyl)phosphin] gelöst und anschließend auf das 6-fache der Endkonzentration verdünnt. HDAC-Enzyme werden auf das 1,5-fache der Endkonzentration in Assay-Puffer verdünnt und 10 Minuten lang mit ACY-1215 vorinkubiert, bevor das Substrat hinzugefügt wird. Die Menge an FTS (HDAC1, HDAC2, HDAC3 und HDAC6) oder MAZ-1675 (HDAC4, HDAC5, HDAC7, HDAC8 und HDAC9), die für jedes Enzym verwendet wird, entspricht der Michaelis-Konstante (Km), wie durch eine Titrationskurve bestimmt. FTS oder MAZ-1675 wird in Assay-Puffer auf das 6-fache der Endkonzentration mit 0,3μM Trypsin in Sequenzierqualität verdünnt. Die Substrat-/Trypsinmischung wird zur Enzym-/Verbindungsmischung gegeben, die Platte wird 60 Sekunden lang geschüttelt und dann in einen SpectraMax M5 Mikrotiterplattenleser gelegt. Die enzymatische Reaktion wird 30 Minuten lang auf die Freisetzung von 7-Amino-4-methoxy-cumarin nach Deacetylierung der Lysin-Seitenkette im Peptidsubstrat überwacht, und die lineare Rate der Reaktion wird berechnet.
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.

Referenzen

Anwendungen (Applications)

Methoden Biomarker Bilder 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
S8001-WB1
31015208
Immunofluorescence β-tubulin / β-catenin
S8001-IF1
25546293
Growth inhibition assay Cell viability
S8001-viability1
31015208

Informationen zu klinischen Studien (Clinical Trial Information)

(Daten von https://clinicaltrials.gov, aktualisiert am 2024-05-22)

NCT-Nummer Rekrutierung Bedingungen Sponsor/Kollaboratoren Startdatum 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

Häufig gestellte Fragen (FAQ) (Frequently Asked Questions)

Frage 1:
What would you suggest to obtain a clear solution of it?

Antwort:
It can be dissolved in 2% DMSO/30% PEG 300/ddH2O at 5 mg/ml clearly, while in 1% DMSO/30% polyethylene glycol/1% Tween 80 at 30 mg/ml it 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.