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Dacinostat (LAQ824) HDAC Inhibitor

Name: Dacinostat (LAQ824)
Brand: Selleck Chemicals
SKU: S1095
Rating: 5 (22 reviews)

Kat.-Nr.: S1095

Dacinostat (LAQ824, NVP-LAQ824) ist ein neuartiger HDAC-Inhibitor mit einer IC50 von 32 nM und ist dafür bekannt, den p21-Promotor zu aktivieren.

Dacinostat (LAQ824) HDAC Inhibitor Chemical Structure

Chemische Struktur

Molekulargewicht: 379.459

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Qualitätskontrolle (Quality Control)

Charge: Reinheit: 99.17%

99.17

Verwandte Targets	JAK BET Histone Methyltransferase PKC PARP HIF PRMT EZH2 AMPK Histone Acetyltransferase
Andere HDAC Inhibitors	ITF-2357 (Givinostat) Hydrochloride Monohydrate Fimepinostat (CUDC-907) Trichostatin A (TSA) Entinostat (MS-275) RGFP966 Quisinostat (JNJ-26481585) Dihydrochloride Tubastatin A Hydrochloride Tubastatin A Mocetinostat (MGCD0103) Ricolinostat (ACY-1215)

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

Zelllinien	Assay-Typ	Konzentration	Inkubationszeit	Aktivitätsbeschreibung
H1299	Growth inhibition assay			Inhibitory activity against H1299 human lung carcinoma cell growth, IC50=0.15 μM
HCT116	Growth inhibition assay			Inhibitory activity against HCT116 human colon cell growth, IC50=0.01 μM
HCT116	Cytotoxicity assay			Cytotoxicity against human HCT116 cells by MTT assay, IC50=0.05 μM
human mammary epithelial cells	Cytotoxicity assay			Cytotoxicity against human mammary epithelial cells by MTT assay, IC50=1 μM
HEK293 cells	Function assay			Inhibition of HDAC1 in HEK293 cells, IC50=0.0026 μM
HeLa cells	Function assay	0.3 μM	16 h	Inhibition of HDAC4-mediated repression of MEF2-dependent transcription in HeLa cells at 0.3 uM after 16 hrs by luciferase reporter gene assay
HCT116 cells	Proliferation assay			Antiproliferative activity against human HCT116 cells by MTS assay, IC50=0.013 μM
H1299 cells	Proliferation assay			Antiproliferative activity against human H1299 cells by MTS assay, IC50=0.161 μM
H460 cells	Growth inhibition assay		48 h	Growth inhibition of human H460 cells after 48 hrs by SRB assay, IC50=0.07 μM
HCT116 cells	Growth inhibition assay		48 h	Growth inhibition of human HCT116 cells after 48 hrs by SRB assay, IC50=0.018 μM
CCRF-CEM cells	Proliferation assay			Antiproliferative activity against human CCRF-CEM cells by SRB assay, GI50=0.251 μM
K562 cells	Proliferation assay			Antiproliferative activity against human K562 cells by SRB assay, GI50=0.55 μM
MOLT4 cells	Proliferation assay			Antiproliferative activity against human MOLT4 cells by SRB assay, GI50=0.311 μM
SR cells	Proliferation assay			Antiproliferative activity against human SR cells by SRB assay, GI50=2.99 μM
A549 cells	Proliferation assay			Antiproliferative activity against human A549 cells by SRB assay, GI50=1.09 μM
EKVX cells	Proliferation assay			Antiproliferative activity against human EKVX cells by SRB assay, GI50=1.75 μM
HOP62 cells	Proliferation assay			Antiproliferative activity against human HOP62 cells by SRB assay, GI50=0.502 μM
HOP92 cells	Proliferation assay			Antiproliferative activity against human HOP92 cells by SRB assay, GI50=0.199 μM
NCI-H226 cells	Proliferation assay			Antiproliferative activity against human NCI-H226 cells by SRB assay, GI50=1.41 μM
NCI-H23 cells	Proliferation assay			Antiproliferative activity against human NCI-H23 cells by SRB assay, GI50=1.5 μM
NCI-H322M cells	Proliferation assay			Antiproliferative activity against human NCI-H322M cells by SRB assay, GI50=2.26 μM
NCI-H460 cells	Proliferation assay			Antiproliferative activity against human NCI-H460 cells by SRB assay, GI50=0.7 μM
COLO205 cells	Proliferation assay			Antiproliferative activity against human COLO205 cells by SRB assay, GI50=1.08 μM
HCT116 cells	Proliferation assay			Antiproliferative activity against human HCT116 cells by SRB assay, GI50=0.347 μM
HCT15 cells	Proliferation assay			Antiproliferative activity against human HCT15 cells by SRB assay, GI50=2.07 μM
HT-29 cells	Proliferation assay			Antiproliferative activity against human HT-29 cells by SRB assay, GI50=0.566 μM
KM12 cells	Proliferation assay			Antiproliferative activity against human KM12 cells by SRB assay, GI50=1.04 μM
SW620 cells	Proliferation assay			Antiproliferative activity against human SW620 cells by SRB assay, GI50=0.478 μM
SF268 cells	Proliferation assay			Antiproliferative activity against human SF268 cells by SRB assay, GI50=1.53 μM
SF295 cells	Proliferation assay			Antiproliferative activity against human SF295 cells by SRB assay, GI50=0.743 μM
SF539 cells	Proliferation assay			Antiproliferative activity against human SF539 cells by SRB assay, GI50=0.965 μM
SNB19 cells	Proliferation assay			Antiproliferative activity against human SNB19 cells by SRB assay, GI50=1.53 μM
SNB75 cells	Proliferation assay			Antiproliferative activity against human SNB75 cells by SRB assay, GI50=0.318 μM
U251 cells	Proliferation assay			Antiproliferative activity against human U251 cells by SRB assay, GI50=0.773 μM
LOXIMVI cells	Proliferation assay			Antiproliferative activity against human LOXIMVI cells by SRB assay, GI50=1.08 μM
MALME-3M cells	Proliferation assay			Antiproliferative activity against human MALME-3M cells by SRB assay, GI50=0.461 μM
M14 cells	Proliferation assay			Antiproliferative activity against human M14 cells by SRB assay, GI50=0.849 μM
MDA-MB-435 cells	Proliferation assay			Antiproliferative activity against human MDA-MB-435 cells by SRB assay, GI50=0.537 μM
SK-MEL-28 cells	Proliferation assay			Antiproliferative activity against human SK-MEL-28 cells by SRB assay, GI50=0.993 μM
SK-MEL-5 cells	Proliferation assay			Antiproliferative activity against human SK-MEL-5 cells by SRB assay, GI50=0.271 μM
UACC257 cells	Proliferation assay			Antiproliferative activity against human UACC257 cells by SRB assay, GI50=0.393 μM
UACC62 cells	Proliferation assay			Antiproliferative activity against human UACC62 cells by SRB assay, GI50=0.379 μM
IGROV1 cells	Proliferation assay			Antiproliferative activity against human IGROV1 cells by SRB assay, GI50=0.187 μM
OVCAR3 cells	Proliferation assay			Antiproliferative activity against human OVCAR3 cells by SRB assay, GI50=1.11 μM
OVCAR4 cells	Proliferation assay			Antiproliferative activity against human OVCAR4 cells by SRB assay, GI50=3.21 μM
OVCAR5 cells	Proliferation assay			Antiproliferative activity against human OVCAR5 cells by SRB assay, GI50=0.26 μM
OVCAR8 cells	Proliferation assay			Antiproliferative activity against human OVCAR8 cells by SRB assay, GI50=0.45 μM
NCI/ADR-RES cells	Proliferation assay			Antiproliferative activity against human NCI/ADR-RES cells by SRB assay, GI50=0.18 μM
SKOV3 cells	Proliferation assay			Antiproliferative activity against human SKOV3 cells by SRB assay, GI50=0.524 μM
786-0 cells	Proliferation assay			Antiproliferative activity against human 786-0 cells by SRB assay, GI50=2.38 μM
A498 cells	Proliferation assay			Antiproliferative activity against human A498 cells by SRB assay, GI50=1.11 μM
ACHN cells	Proliferation assay			Antiproliferative activity against human ACHN cells by SRB assay, GI50=1.1 μM
Caki1 cells	Proliferation assay			Antiproliferative activity against human Caki1 cells by SRB assay, GI50=0.619 μM
SN12C cells	Proliferation assay			Antiproliferative activity against human SN12C cells by SRB assay, GI50=3.92 μM
TK10 cells	Proliferation assay			Antiproliferative activity against human TK10 cells by SRB assay, GI50=0.444 μM
UO31 cells	Proliferation assay			Antiproliferative activity against human UO31 cells by SRB assay, GI50=0.452 μM
PC3 cells	Proliferation assay			Antiproliferative activity against human PC3 cells by SRB assay, GI50=20 μM
DU145 cells	Proliferation assay			Antiproliferative activity against human DU145 cells by SRB assay, GI50=29.9 μM
MCF7 cells	Proliferation assay			Antiproliferative activity against human MCF7 cells by SRB assay, GI50=6.91 μM
MDA-MB-231 cells	Proliferation assay			Antiproliferative activity against human MDA-MB-231 cells by SRB assay, GI50=31.7 μM
Hs 578T cells	Proliferation assay			Antiproliferative activity against human Hs 578T cells by SRB assay, GI50=5.82 μM
BT549 cells	Proliferation assay			Antiproliferative activity against human BT549 cells by SRB assay, GI50=6.04 μM
T47D cells	Proliferation assay			Antiproliferative activity against human T47D cells by SRB assay, GI50=28.8 μM
MDA-MB-468 cells	Proliferation assay			Antiproliferative activity against human MDA-MB-468 cells by SRB assay, GI50=5.88 μM
NCI-H226 cells	Cytotoxicity assay			Cytotoxicity against human NCI-H226 cells, LC50=20 μM
KM12 cells	Cytotoxicity assay			Cytotoxicity against human KM12 cells, LC50=29.9 μM
SF295 cells	Cytotoxicity assay			Cytotoxicity against human SF295 cells, LC50=6.91 μM
SNB19 cells	Cytotoxicity assay			Cytotoxicity against human SNB19 cells, LC50=31.7 μM
U251 cells	Cytotoxicity assay			Cytotoxicity against human U251 cells, LC50=5.82 μM
LOXIMVI cells	Cytotoxicity assay			Cytotoxicity against human LOXIMVI cells, LC50=6.04 μM
MDA-MB-435 cells	Cytotoxicity assay			Cytotoxicity against human MDA-MB-435 cells, LC50=28.8 μM
SK-MEL-28 cells	Cytotoxicity assay			Cytotoxicity against human SK-MEL-28 cells, LC50=31.9 μM
SK-MEL-5 cells	Cytotoxicity assay			Cytotoxicity against human SK-MEL-5 cells, LC50=4.02 μM
UACC257 cells	Cytotoxicity assay			Cytotoxicity against human UACC257 cells, LC50=44.8 μM
UACC62 cells	Cytotoxicity assay			Cytotoxicity against human UACC62 cells, LC50=6.39 μM
IGROV1 cells	Cytotoxicity assay			Cytotoxicity against human IGROV1 cells, LC50=48.9 μM
OVCAR5 cells	Cytotoxicity assay			Cytotoxicity against human OVCAR5 cells, LC50=38.9 μM
SKOV3 cells	Cytotoxicity assay			Cytotoxicity against human SKOV3 cells, LC50=28.5 μM
A498 cells	Cytotoxicity assay			Cytotoxicity against human A498 cells, LC50=5.88 μM
Caki1 cells	Cytotoxicity assay			Cytotoxicity against human Caki1 cells, LC50=5.79 μM
HCT116 cells	Proliferation assay			Antiproliferative activity against human HCT116 cells, IC50=0.019 μM
HCT116 cells	Proliferation assay			Antiproliferative activity against human HCT116 cells assessed as growth inhibition, IC50=0.019 μM
H1299 cells	Proliferation assay			Antiproliferative activity against human H1299 cells, IC50=0.1 μM
HCT116 cells	Proliferation assay			Inhibitory concentration against HCT116 cells proliferation, IC50=0.01 μM
RPMI8226 cells	Proliferation assay			Antiproliferative activity against human RPMI8226 cells by SRB assay, GI50=0.523 μM
CHO cells	Function assay			Inhibition of human ERG expressed in CHO cells by automated patch clamp electrophysiology assay, IC50=12.2 μM
HL-60(TB) cells	Proliferation assay			Antiproliferative activity against human HL-60(TB) cells by SRB assay, GI50=0.249 μM
RXF393 cells	Proliferation assay			Antiproliferative activity against human RXF393 cells by SRB assay, GI50=0.01 μM
RXF393 cells	Cytotoxicity assay			Cytotoxicity against human RXF393 cells, LC50=15.3 μM
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Chemische Informationen, Lagerung & Stabilität (Chemical Information, Storage & Stability)

Molekulargewicht	379.459	Formel	C₂₂H₂₅N₃O₃	Lagerung (Ab Erhaltdatum)	3 Jahre-20°CPulver
CAS-Nr.	404951-53-7	SDF herunterladen		Lagerung von Stammlösungen	1 Jahr-80°Cin Lösungsmittel 1 Monat-20°Cin Lösungsmittel
Synonyme	NVP-LAQ824			Smiles	C1=CC=C2C(=C1)C(=CN2)CCN(CCO)CC3=CC=C(C=C3)C=CC(=O)NO

Löslichkeit (Solubility)

In vitro
Charge:

DMSO : 76 mg/mL (200.28 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 76 mg/mL (200.28 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:
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	4% DMSO 1 40% PEG300 2 56%saline Von Selleck-Laboren validiert. Sollten Sie Anpassungen an dieser Formulierung benötigen, wenden Sie sich für kundenspezifische Tests an unser Vertriebsteam.	3.760mg/ml (9.91mM)	Taking the 1 mL working solution as an example, add 40 μL of 94 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; then continue to add 560 μL of saline 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 unten die Informationen ein (Empfohlen: Ein zusätzliches Tier einplanen, um Verluste während des Experiments auszugleichen)

Dosierung: mg/kg Durchschnittliches Gewicht der Tiere: g Dosierungsvolumen pro Tier:μL Anzahl der Tiere:

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)

Targets/IC₅₀/Ki	p21 HDAC (Cell-free assay) 32 nM
In vitro	Dacinostat (LAQ824) activates the expression of the gene encoding the p21 cell cycle inhibitor by activating the p21 promoter with 50% of the maximal promoter activation (AC50) of 0.30 μM. It inhibits the cell growth of both H1299, a non-small cell lung carcinoma line, and HCT116, a colon cancer cell line with IC50 of 0.15 μM and 0.01 μM, respectively, and the antiproliferative effect of this compound is selective toward the tumor cell lines while inducing only growth arrest in normal fibroblasts. Furthermore, it induces a dose-dependent increase of p21 protein in A549 cells and an increase in the hypophosphorylated state of the Rb tumor suppressor. A recent study shows that LAQ824 induces chromatin changes at the level of the IL-10 gene promoter that lead to enhanced recruitment of the transcriptional repressors HDAC11 and PU.1 and inhibits IL-10 production in BALB/c murine macrophages.
Kinase-Assay	In-vitro-Histondeacetylase-Assay
Kinase-Assay	HDAC-Enzyme werden teilweise aus H1299-Zelllysaten durch Ionenaustauschchromatographie unter Verwendung der Q Sepharose Fast Flow-Säule gereinigt. Enzymkomplexe werden aus 500 mg Gesamtzelllysat durch Immunpräzipitation mit cdk2-polyklonalem Antikörper oder cdk1/cdc2-monoklonalem Antikörper gewonnen. Immunpräzipitate werden in Kinasepuffer (50 mM Hepes, pH 8, 10 mM MgCl₂, 2,5 mM EDTA, 1 mM Dithiothreitol, 20 mM ATP, 10 mM β-Glycerophosphat, 0,1 mM NaVO₄, 1 mM Natriumfluorid, 50 mM ATP, 10 μCi [γ-³²P]ATP) zusammen mit 1 μg pRb-rekombinantem Proteinsubstrat (cdk2) oder 10 ml H1-Histongemisch, das 20 μg Substrat (cdc2) enthält, resuspendiert. Phosphorylierte Rb- und H1-Histone werden durch Elektrophorese getrennt und mit einem PhosphorImager quantifiziert. Diese Verbindung, Dacinostat (LAQ824), wird im Assay verwendet.
In vivo	Dacinostat (LAQ824) produces inhibitory effects on tumor growth in a dose-dependent mode without general cytotoxicity in HCT116 and human colon tumor xenografts in nude mice when administered at 100 mg/kg.
Referenzen	[1] https://pubmed.ncbi.nlm.nih.gov/14744786/ [2] https://pubmed.ncbi.nlm.nih.gov/21368229/

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