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Serdemetan (JNJ-26854165) p53 activateur

Name: Serdemetan (JNJ-26854165)
Brand: Selleck Chemicals
SKU: S1172
Rating: 5 (15 reviews)

N° Cat.S1172

Serdemetan (JNJ-26854165) agit comme un antagoniste de l'E3 Ligase HDM2 et induit également une Apoptosis précoce dans les cellules p53 de type sauvage, inhibe la prolifération cellulaire suivie d'une Apoptosis retardée en l'absence de p53 fonctionnelle. Phase 1.

Serdemetan (JNJ-26854165) p53 activateur Chemical Structure

Structure chimique

Poids moléculaire: 328.41

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Contrôle qualité

Lot : Pureté : 99.62%

99.62

Cibles apparentées	Bcl-2 Caspase PD-1/PD-L1 Ferroptosis Apoptosis related Synthetic Lethality STAT TNF-alpha Ras KRas
Autre p53 Inhibiteurs	Eprenetapopt (APR-246) CBL0137 Hydrochloride Pifithrin-α (PFTα) Hhydrobromide Pifithrin-μ RITA PRIMA-1 NSC 319726 (ZMC1) NSC348884 Tenovin-6 Tenovin-1

Culture cellulaire, traitement et concentration de travail

Lignées cellulaires	Type dessai	Description de lactivité
KU-19-19 cell	Growth inhibition assay	Inhibition of human KU-19-19 cell growth in a cell viability assay, IC50=0.93236 μM
H4 cell	Growth inhibition assay	Inhibition of human H4 cell growth in a cell viability assay, IC50=1.06707 μM
KGN cell	Growth inhibition assay	Inhibition of human KGN cell growth in a cell viability assay, IC50=1.6205 μM
786-0 cell	Growth inhibition assay	Inhibition of human 786-0 cell growth in a cell viability assay, IC50=1.72989 μM
769-P cell	Growth inhibition assay	Inhibition of human 769-P cell growth in a cell viability assay, IC50=1.82224 μM
K5 cell	Growth inhibition assay	Inhibition of human K5 cell growth in a cell viability assay, IC50=2.01624 μM
MLMA cell	Growth inhibition assay	Inhibition of human KOSC-2 cell growth in a cell viability assay, IC50=2.03217 μM
MLMA cell	Growth inhibition assay	Inhibition of human MLMA cell growth in a cell viability assay, IC50=2.28703 μM
EW-7 cell	Growth inhibition assay	Inhibition of human EW-7 cell growth in a cell viability assay, IC50=2.32695 μM
SW1088 cell	Growth inhibition assay	Inhibition of human SW1088 cell growth in a cell viability assay, IC50=2.80651 μM
MC-IXC cell	Growth inhibition assay	Inhibition of human MC-IXC cell growth in a cell viability assay, IC50=2.87792 μM
NCI-H2052 cell	Growth inhibition assay	Inhibition of human NCI-H2052 cell growth in a cell viability assay, IC50=3.08157 μM
IGR-1 cell	Growth inhibition assay	Inhibition of human IGR-1 cell growth in a cell viability assay, IC50=3.12028 μM
DSH1 cell	Growth inhibition assay	Inhibition of human DSH1 cell growth in a cell viability assay, IC50=3.24296 μM
PA-1 cell	Growth inhibition assay	Inhibition of human PA-1 cell growth in a cell viability assay, IC50=3.30059μM
SK-MEL-3 cell	Growth inhibition assay	Inhibition of human SK-MEL-3 cell growth in a cell viability assay, IC50=3.31207 μM
SW900 cell	Growth inhibition assay	Inhibition of human SW900 cell growth in a cell viability assay, IC50=3.48255 μM
CAKI-1 cell	Growth inhibition assay	Inhibition of human CAKI-1 cell growth in a cell viability assay, IC50=3.52738 μM
ES1 cell	Growth inhibition assay	Inhibition of human ES1 cell growth in a cell viability assay, IC50=3.52897 μM
SK-N-DZ cell	Growth inhibition assay	Inhibition of human SK-N-DZ cell growth in a cell viability assay, IC50=3.62595 μM
RH-1 cell	Growth inhibition assay	Inhibition of human RH-1 cell growth in a cell viability assay, IC50=3.68463 μM
ES8 cell	Growth inhibition assay	Inhibition of human ES8 cell growth in a cell viability assay, IC50=3.69702 μM
NEC8 cell	Growth inhibition assay	Inhibition of human NEC8 cell growth in a cell viability assay, IC50=3.76982 μM
LNCaP-Clone-FGC cell	Growth inhibition assay	Inhibition of human LNCaP-Clone-FGC cell growth in a cell viability assay, IC50=3.83536 μM
HCE-4 cell	Growth inhibition assay	Inhibition of human HCE-4 cell growth in a cell viability assay, IC50=3.9807 μM
U-118-MG cell	Growth inhibition assay	Inhibition of human U-118-MG cell growth in a cell viability assay, IC50=4.01066 μM
GI-ME-N cell	Growth inhibition assay	Inhibition of human GI-ME-N cell growth in a cell viability assay, IC50=4.08796 μM
LB1047-RCC cell	Growth inhibition assay	Inhibition of human LB1047-RCC cell growth in a cell viability assay, IC50=4.16143 μM
HT-1080 cell	Growth inhibition assay	Inhibition of human HT-1080 cell growth in a cell viability assay, IC50=4.19921 μM
NB69 cell	Growth inhibition assay	Inhibition of human NB69 cell growth in a cell viability assay, IC50=4.35047 μM
NCI-H1693 cell	Growth inhibition assay	Inhibition of human NCI-H1693 cell growth in a cell viability assay, IC50=4.44895 μM
HSC-3 cell	Growth inhibition assay	Inhibition of human HSC-3 cell growth in a cell viability assay, IC50=4.49933 μM
MDA-MB-231 cell	Growth inhibition assay	Inhibition of human MDA-MB-231 cell growth in a cell viability assay, IC50=4.55899 μM
HOS cell	Growth inhibition assay	Inhibition of human HOS cell growth in a cell viability assay, IC50=4.7863 μM
BT-549 cell	Growth inhibition assay	Inhibition of human BT-549 cell growth in a cell viability assay, IC50=4.7887 μM
NB17 cell	Growth inhibition assay	Inhibition of human NB17 cell growth in a cell viability assay, IC50=4.78976 μM
5637 cell	Growth inhibition assay	Inhibition of human 5637 cell growth in a cell viability assay, IC50=4.79652 μM
OVCAR-8 cell	Growth inhibition assay	Inhibition of human OVCAR-8 cell growth in a cell viability assay, IC50=4.92436 μM
G-402 cell	Growth inhibition assay	Inhibition of human G-402 cell growth in a cell viability assay, IC50=4.93035 μM
BB30-HNC cell	Growth inhibition assay	Inhibition of human BB30-HNC cell growth in a cell viability assay, IC50=5.07218 μM
HCC1806 cell	Growth inhibition assay	Inhibition of human HCC1806 cell growth in a cell viability assay, IC50=5.08339 μM
COLO-800 cell	Growth inhibition assay	Inhibition of human COLO-800 cell growth in a cell viability assay, IC50=5.1264 μM
FADU cell	Growth inhibition assay	Inhibition of human FADU cell growth in a cell viability assay, IC50=5.36557 μM
NCI-H1651 cell	Growth inhibition assay	Inhibition of human NCI-H1651 cell growth in a cell viability assay, IC50=5.39409 μM
AGS cell	Growth inhibition assay	Inhibition of human AGS cell growth in a cell viability assay, IC50=5.47711 μM
CHP-212 cell	Growth inhibition assay	Inhibition of human CHP-212 cell growth in a cell viability assay, IC50=5.39409 μM
YAPC cell	Growth inhibition assay	Inhibition of human YAPC cell growth in a cell viability assay, IC50=5.47711 μM
GOTO cell	Growth inhibition assay	Inhibition of human GOTO cell growth in a cell viability assay, IC50=5.49576 μM
KYSE-510 cell	Growth inhibition assay	Inhibition of human KYSE-510 cell growth in a cell viability assay, IC50=5.511 μM
NCI-H2342 cell	Growth inhibition assay	Inhibition of human NCI-H2342 cell growth in a cell viability assay, IC50=5.53278 μM
BFTC-905 cell	Growth inhibition assay	Inhibition of human BFTC-905 cell growth in a cell viability assay, IC50=5.62835 μM
EW-16 cell	Growth inhibition assay	Inhibition of human EW-16 cell growth in a cell viability assay, IC50=5.72093 μM
SK-MEL-30 cell	Growth inhibition assay	Inhibition of human SK-MEL-30 cell growth in a cell viability assay, IC50=5.74543 μM
HLE cell	Growth inhibition assay	Inhibition of human HLE cell growth in a cell viability assay, IC50=5.77489 μM
T98G cell	Growth inhibition assay	Inhibition of human T98G cell growth in a cell viability assay, IC50=5.79635 μM
HUTU-80 cell	Growth inhibition assay	Inhibition of human HUTU-80 cell growth in a cell viability assay, IC50=5.84228 μM
NOS-1 cell	Growth inhibition assay	Inhibition of human NOS-1 cell growth in a cell viability assay, IC50=5.94766 μM
SW780 cell	Growth inhibition assay	Inhibition of human SW780 cell growth in a cell viability assay, IC50=5.96949 μM
KYSE-180 cell	Growth inhibition assay	Inhibition of human KYSE-180 cell growth in a cell viability assay, IC50=5.97654 μM
MDA-MB-361 cell	Growth inhibition assay	Inhibition of human MDA-MB-361 cell growth in a cell viability assay, IC50=5.98647 μM
SNU-C2B cell	Growth inhibition assay	Inhibition of human SNU-C2B cell growth in a cell viability assay, IC50=6.01138 μM
NCI-H661 cell	Growth inhibition assay	Inhibition of human NCI-H661 cell growth in a cell viability assay, IC50=6.0694 μM
OE33 cell	Growth inhibition assay	Inhibition of human OE33 cell growth in a cell viability assay, IC50=6.14389 μM
TYK-nu cell	Growth inhibition assay	Inhibition of human TYK-nu cell growth in a cell viability assay, IC50=6.21863 μM
COLO-792 cell	Growth inhibition assay	Inhibition of human COLO-792 cell growth in a cell viability assay, IC50=6.25219 μM
HEL cell	Growth inhibition assay	Inhibition of human HEL cell growth in a cell viability assay, IC50=6.2676 μM
D-566MG cell	Growth inhibition assay	Inhibition of human D-566MG cell growth in a cell viability assay, IC50=6.33491 μM
U031 cell	Growth inhibition assay	Inhibition of human U031 cell growth in a cell viability assay, IC50=6.41816 μM
COR-L23 cell	Growth inhibition assay	Inhibition of human COR-L23 cell growth in a cell viability assay, IC50=6.43346 μM
NCI-H2452 cell	Growth inhibition assay	Inhibition of human NCI-H2452 cell growth in a cell viability assay, IC50=6.52281 μM
BB65-RCC cell	Growth inhibition assay	Inhibition of human BB65-RCC cell growth in a cell viability assay, IC50=6.6459 μM
CAL-33 cell	Growth inhibition assay	Inhibition of human CAL-33 cell growth in a cell viability assay, IC50=6.65665 μM
Cliquez pour voir plus de données expérimentales sur les lignées cellulaires

Informations chimiques, stockage et stabilité

Poids moléculaire	328.41	Formule	C₂₁H₂₀N₄	Stockage (À partir de la date de réception)	3 ans-20°Cpoudre
N° CAS	881202-45-5	Télécharger le SDF		Stockage des solutions mères	1 an-80°Cen solvant 1 mois-20°Cen solvant
Synonymes	N/A			Smiles	C1=CC=C2C(=C1)C(=CN2)CCNC3=CC=C(C=C3)NC4=CC=NC=C4

Solubilité

In vitro
Lot:

DMSO : 66 mg/mL (200.96 mM)
(Le DMSO contaminé par lhumidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Ethanol : 2 mg/mL

Water : 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.
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 Validé par les laboratoires Selleck. Si vous avez besoin dajustements à cette formulation, contactez notre équipe de vente pour des tests personnalisés.	3.300mg/ml (10.05mM)	Taking the 1 mL working solution as an example, add 50 μL of 66 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.
Clear solution	5% DMSO 1 95% Corn oil Validé par les laboratoires Selleck. Si vous avez besoin dajustements à cette formulation, contactez notre équipe de vente pour des tests personnalisés.	0.400mg/ml (1.22mM)	Taking the 1 mL working solution as an example, add 50 μL of 8 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.

Calculateur de formulation in vivo (Solution claire)

Étape 1 : Entrez 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 : Entrez la formulation in vivo (Ceci nest que 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, ajouter ensuiteμL PEG300, mélanger et clarifier, ajouter ensuiteμL Tween 80, mélanger et clarifier, ajouter ensuite μL ddH₂O, mélanger et clarifier.

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

Remarque : 1. Assurez-vous 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 peuvent être utilisées pour faciliter la dissolution.

Mécanisme daction

Targets/IC₅₀/Ki	p53 (Cell-free assay) HDM2 (Cell-free assay) Mdm2 (Cell-free assay)
In vitro	JNJ 26854165 est un nouveau dérivé de la tryptamine qui active p53 et agit comme un antagoniste de l'E3 Ligase HDM2. JNJ 26854165 inhibe la croissance cellulaire et induit l'Apoptosis dans les lignées cellulaires de leucémie avec des valeurs d'IC50 de 0,24, 0,33, 0,32 et 0,44 μM à 72 heures pour les cellules OCI-AML-3, MOLM-13, NALM-6 et REH, respectivement. De plus, JNJ 26854165 accélère la dégradation de p21 médiée par le protéasome et antagonise l'induction transcriptionnelle de p21 par p53. Il induit également un retard de la phase S et régule positivement l'expression de E2F1 dans les cellules mutantes p53, entraînant une Apoptosis préférentielle des cellules en phase S. JNJ 26854165 est un inhibiteur oral de Mdm2 qui peut inhiber l'interaction du complexe Mdm2-p53 avec le protéasome et augmenter les niveaux de p53 en se liant au domaine RING de Mdm2. Une étude récente montre que JNJ 26854165 inhibe la survie clonogénique dans quatre lignées cellulaires cancéreuses humaines: H460, A549, p53-WT-HCT116 et p53-null-HCT116.
In vivo	JNJ 26854165 entraîne des différences significatives dans la distribution de l'EFS chez 17 des 36 (47%) xénogreffes de tumeurs solides évaluables et chez 5 des 7 (71%) xénogreffes d'ALL évaluables en utilisant une dose de 20 mg/kg administrée par gavage oral quotidiennement pendant 5 jours, répétée pendant 6 semaines.
Références	[1] https://pubmed.ncbi.nlm.nih.gov/20406950/ [2] https://pubmed.ncbi.nlm.nih.gov/21937165/ [3] https://pubmed.ncbi.nlm.nih.gov/21922647/ [4] http://0-www.ncbi.nlm.nih.gov.elis.tmu.edu.tw/pubmed/21922647

Applications

Méthodes	Biomarqueurs	PMID
Western blot	p53 / HDM2 / HDMX / p21 / Noxa / Puma ABCA1 / ABCG1 / NPC1 / NPC2 / HMGcoR MDM2 / p-MDM2 / p53 Bcr-abl / p-Bcr-abl / p-CrkL / STAT5 / p-STAT5 / STAT3 / p-STAT3	20736344
Growth inhibition assay	Cell viability	23820125
Immunofluorescence	p53	27999193

Informations sur lessai clinique

(données de https://clinicaltrials.gov, mis à jour le 2024-05-22)

Numéro NCT	Recrutement	Conditions	Sponsor/Collaborateurs	Date de début	Phases
NCT00676910	Completed	Neoplasms	Johnson & Johnson Pharmaceutical Research & Development L.L.C.	November 2006	Phase 1

Support technique

Instructions de manipulation

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

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