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Dacinostat (LAQ824) HDAC inhibiteur

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

Réf. CatalogueS1095

Dacinostat (LAQ824, NVP-LAQ824) est un nouvel inhibiteur de la HDAC avec une IC50 de 32 nM et est connu pour activer le promoteur p21.

Dacinostat (LAQ824) HDAC inhibiteur Chemical Structure

Structure chimique

Poids moléculaire: 379.459

Aller à

Contrôle Qualité

Lot : Pureté : 99.17%

99.17

Cibles apparentées	JAK BET Histone Methyltransferase PKC PARP HIF PRMT EZH2 AMPK Histone Acetyltransferase
Autre HDAC Inhibiteurs	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) Ricolinostat (ACY-1215)

Culture cellulaire, traitement et concentration de travail

Lignées cellulaires	Type dessai	Concentration	Temps dincubation	Description de lactivité
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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Informations chimiques, stockage et stabilité

Poids moléculaire	379.459	Formule	C₂₂H₂₅N₃O₃	Stockage (À compter de la date de réception)	3 ans-20°Cpoudre
N° CAS	404951-53-7	Télécharger le SDF		Stockage des solutions mères	1 an-80°Cen solvant 1 mois-20°Cen solvant
Synonymes	NVP-LAQ824			Smiles	C1=CC=C2C(=C1)C(=CN2)CCN(CCO)CC3=CC=C(C=C3)C=CC(=O)NO

Solubilité

In vitro
Lot:

DMSO : 76 mg/mL (200.28 mM)
(Le DMSO contaminé par lhumidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Water : Insoluble

Ethanol : Insoluble

Calculateur de molarité

Masse	Concentration	Volume	Poids moléculaire
=	×	×

Calculateur de dilution Calculateur de poids moléculaire

In vivo Lot:
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 Validé par les laboratoires Selleck. Si vous avez besoin dajustements à cette formulation, contactez notre équipe commerciale pour des tests personnalisés.	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.

Calculateur de formulation in vivo (Solution claire)

Étape 1 : Saisir les informations ci-dessous (Recommandé : Un animal supplémentaire pour tenir compte des pertes pendant lexpérience)

Dosage : mg/kg Poids moyen des animaux : g Volume de dosage par animal :μL Nombre danimaux :

Étape 2 : Saisir la formulation in vivo (Ceci est seulement le calculateur, pas la formulation. Veuillez nous contacter dabord sil ny a pas de formulation in vivo dans la section Solubilité.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Résultats du calcul :

Concentration de travail : mg/ml;

Méthode de préparation du liquide maître DMSO : mg médicament prédissous dans μL DMSO ( Concentration du liquide maître mg/mL, Veuillez nous contacter dabord si la concentration dépasse la solubilité du DMSO du lot de médicament. )

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouterμL PEG300, mélanger et clarifier, puis ajouterμL Tween 80, mélanger et clarifier, puis ajouter μL ddH₂O, mélanger et clarifier.

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouter μL Huile de maïs, mélanger et clarifier.

Note : 1. Veuillez vous assurer que le liquide est clair avant dajouter le solvant suivant.
2. Assurez-vous dajouter le(s) solvant(s) dans lordre. Vous devez vous assurer que la solution obtenue, lors de lajout précédent, est une solution claire avant de procéder à lajout du solvant suivant. Des méthodes physiques telles que le vortex, les ultrasons ou le bain-marie chaud peuvent être utilisées pour faciliter la dissolution.

Mécanisme daction

Targets/IC₅₀/Ki	p21 HDAC (Cell-free assay) 32 nM
In vitro	Dacinostat (LAQ824) active l'expression du gène codant pour l'inhibiteur du cycle cellulaire p21 en activant le promoteur p21 avec 50 % de l'activation maximale du promoteur (AC50) de 0,30 μM. Il inhibe la croissance cellulaire des lignées de carcinome pulmonaire non à petites cellules H1299 et de cellules de cancer du côlon HCT116 avec des IC50 respectives de 0,15 μM et 0,01 μM. L'effet antiprolifératif de ce composé est sélectif envers les lignées de cellules tumorales, n'induisant qu'un arrêt de croissance dans les fibroblastes normaux. De plus, il induit une augmentation dose-dépendante de la protéine p21 dans les cellules A549 et une augmentation de l'état hypophosphorylé du suppresseur de tumeurs Rb. Une étude récente montre que LAQ824 induit des changements de chromatine au niveau du promoteur du gène IL-10 qui conduisent à un recrutement accru des répresseurs transcriptionnels HDAC11 et PU.1 et inhibe la production d'IL-10 dans les macrophages murins BALB/c.
Essai kinase	Essai d'histone désacétylase in vitro
Essai kinase	Les enzymes HDAC sont partiellement purifiées à partir de lysat cellulaire H1299 par chromatographie d'échange d'ions en utilisant la colonne Q Sepharose Fast Flow. Les complexes enzymatiques sont collectés à partir de 500 mg de lysat cellulaire total par immunoprécipitation avec un anticorps polyclonal cdk2 ou un anticorps monoclonal cdk1/cdc2. Les immunoprécipités sont remis en suspension dans un tampon kinase (50 mM Hepes, pH 8, 10 mM MgCl₂, 2,5 mM EDTA, 1 mM dithiothréitol, 20 mM ATP, 10 mM β-glycérophosphate, 0,1 mM NaVO₄, 1 mM fluorure de sodium, 50 mM ATP, 10 μCi de [γ-³²P]ATP) avec 1 μg de substrat protéique recombinant pRb (cdk2) ou 10 ml de mélange d'histones H1 contenant 20 μg de substrat (cdc2). Les histones Rb et H1 phosphorylées sont résolues par électrophorèse et quantifiées à l'aide d'un PhosphorImager. Ce composé, Dacinostat (LAQ824), est utilisé dans l'essai.
In vivo	Dacinostat (LAQ824) produit des effets inhibiteurs sur la croissance tumorale de manière dose-dépendante sans cytotoxicité générale dans les xénogreffes de tumeurs du côlon humain et HCT116 chez la souris nude lorsqu'il est administré à 100 mg/kg.
Références	[1] https://pubmed.ncbi.nlm.nih.gov/14744786/ [2] https://pubmed.ncbi.nlm.nih.gov/21368229/

Support technique

Instructions de manipulation

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

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