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Ricolinostat (ACY-1215) HDAC Inhibitor

Name: Ricolinostat (ACY-1215)
Brand: Selleck Chemicals
SKU: S8001
Rating: 5 (71 reviews)

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

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.

Verwandte Ziele	JAK BET Histone Methyltransferase PKC PARP HIF PRMT EZH2 AMPK Histone Acetyltransferase
Weitere HDAC Inhibitoren	ITF-2357 (Givinostat) Hydrochloride Monohydrate Fimepinostat (CUDC-907) Trichostatin A (TSA) Entinostat (MS-275) RGFP966 Quisinostat (JNJ-26481585) Dihydrochloride Tubastatin A HCl Tubastatin A Mocetinostat (MGCD0103) PCI-34051

Zellkultur, Behandlung & Arbeitskonzentration

Zelllinien	Assay-Typ	Konzentration	Inkubationszeit	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
Klicken Sie hier, um weitere experimentelle Daten zu Zelllinien anzuzeigen

Chemische Informationen, Lagerung & Stabilität

Molekulargewicht	433.5	Formel	C₂₄H₂₇N₅O₃	Lagerung (Ab dem Eingangsdatum)	3 Jahre-20°CPulver
CAS-Nr.	1316214-52-4	SDF herunterladen		Lagerung von Stammlösungen	1 Jahr-80°Cin Lösungsmittel 1 Monat-20°Cin Lösungsmittel
Synonyme	Rocilinostat			Smiles	C1=CC=C(C=C1)N(C2=CC=CC=C2)C3=NC=C(C=N3)C(=O)NCCCCCCC(=O)NO

Löslichkeit

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

DMSO : 86 mg/mL (198.38 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 217 mg/mL (500.57 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 87 mg/mL (200.69 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 87 mg/mL (200.69 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molaritätsrechner

Masse	Konzentration	Volumen	Molekulargewicht
=	×	×

Verdünnungsrechner Molekulargewichtsrechner

In vivo Charge:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 Corn oil Von Selleck Labs validiert. Sollten Sie Anpassungen an dieser Formulierung benötigen, kontaktieren Sie unser Verkaufsteam für kundenspezifische Tests.	4.000mg/ml (9.23mM)	Taking the 1 mL working solution as an example, add 50 μL of 80 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Von Selleck Labs validiert. Sollten Sie Anpassungen an dieser Formulierung benötigen, kontaktieren Sie unser Verkaufsteam für kundenspezifische Tests.	5.000mg/ml (11.53mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Von Selleck Labs validiert. Sollten Sie Anpassungen an dieser Formulierung benötigen, kontaktieren Sie unser Verkaufsteam für kundenspezifische Tests.	4.000mg/ml (9.23mM)	Taking the 1 mL working solution as an example, add 50 μL of 80 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In-vivo-Formulierungsrechner (Klare Lösung)

Schritt 1: Geben Sie die untenstehenden Informationen ein (Empfohlen: Ein zusätzliches Tier zur Berücksichtigung von Verlusten während des Experiments)

Dosierung: mg/kg Durchschnittsgewicht der Tiere: g Dosiervolumen pro Tier:μL Anzahl der Tiere:

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

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berechnungsergebnisse:

Arbeitskonzentration: mg/ml;

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

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammlösung, dann hinzufügenμL PEG300, mischen und klären, dann hinzufügenμL Tween 80, mischen und klären, dann hinzufügen μL ddH₂O, mischen und klären.

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammlösung, dann hinzufügen μL Maisöl, mischen und klären.

Hinweis: 1. Bitte stellen Sie sicher, dass die Flüssigkeit klar ist, bevor Sie das nächste Lösungsmittel hinzufügen.
2. Achten Sie darauf, das/die Lösungsmittel der Reihe nach hinzuzufügen. Sie müssen sicherstellen, dass die bei der vorherigen Zugabe erhaltene Lösung eine klare Lösung ist, bevor Sie mit der Zugabe des nächsten Lösungsmittels fortfahren. Physikalische Methoden wie Vortex, Ultraschall oder ein heißes Wasserbad können zur Unterstützung des Lösens verwendet werden.

Wirkmechanismus

Merkmale	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 ist ein Hydroxamsäurederivat. ACY-1215 ist 12-, 10- und 11-fach weniger aktiv gegen HDAC1, HDAC2 bzw. HDAC3 (Klasse-I-HDACs). ACY-1215 hat eine minimale Aktivität (IC50 > 1μM) gegen HDAC4, HDAC5, HDAC7, HDAC9, HDAC11, Sirtuin1 und Sirtuin2 und eine leichte Aktivität gegen HDAC8 (IC50 = 0.1μM). Die IC50-Werte für ACY-1215 für die T-Zell-Toxizität betragen 2,5μM. ACY-1215 überwindet das durch BMSCs und Zytokine im BM-Milieu verliehene Tumorwachstum und -überleben.
Kinase-Assay	HDAC enzymatische Assays
Kinase-Assay	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 wird leicht von Tumorgewebe aufgenommen. Darüber hinaus reichert sich das Medikament nicht im Tumorgewebe an, wie der parallele Rückgang von acetyliertem α-Tubulin in Blutzellen und Tumorgewebe 24 Stunden nach der Dosis zeigt.
Literatur	[1] https://pubmed.ncbi.nlm.nih.gov/22262760/

Anwendungen

Methoden	Biomarker	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

Klinische Studieninformationen

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

NCT-Nummer	Rekrutierung	Erkrankungen	Sponsor/Kooperationspartner	Startdatum	Phasen
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

Technischer Support

Handhabungshinweise

Tel: +1-832-582-8158 Ext:3

Wenn Sie weitere Fragen haben, hinterlassen Sie bitte eine Nachricht.

Häufig gestellte Fragen

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.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):