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Silmitasertib (CX-4945) Casein Kinase 2 Inhibitor

Name: Silmitasertib (CX-4945)
Brand: Selleck Chemicals
SKU: S2248
Rating: 5 (144 reviews)

Réf. CatalogueS2248

Silmitasertib (CX-4945) est un inhibiteur puissant et sélectif de la CK2 (casein kinase 2) avec un IC50 de 1 nM dans un essai sans cellules, bien qu'il soit moins puissant contre Flt3, Pim1 et CDK1 (inactif dans un essai basé sur des cellules). Ce composé induit l'Autophagy et favorise l'apoptosis. Phase 1/2.

Silmitasertib (CX-4945) Casein Kinase Inhibiteur Chemical Structure

Structure chimique

Poids moléculaire: 349.77

Aller à

Contrôle Qualité

Lot : Pureté : 99.96%

99.96

Cibles apparentées	Dehydrogenase HSP Transferase P450 (e.g. CYP17) PDE phosphatase PPAR Vitamin Carbohydrate Metabolism Mitochondrial Metabolism
Autre Casein Kinase Inhibiteurs	Silmitasertib (CX-4945) sodium salt D 4476 TBB IC261 PF-670462 Ellagic Acid hydrate TTP 22 Longdaysin PF 4800567 (E/Z)-GO289

Culture cellulaire, traitement et concentration de travail

Lignées cellulaires	Type dessai	Concentration	Temps dincubation	Formulation	Description de lactivité	PMID
UM-SCC-1	Clonogenic Assay	0.5-5 μM	14 d	DMSO	inhibits clonogenic survival and sphere formation	25379016
U87-MG	Growth Inhibition Assay	1/5/10 μM	24/48/72 h	DMSO	inhibits cell growth both concentration and time dependently	25241897
MDA-MB-231	Function Assay	2/5/10 μM	4 h		inhibits serine 529 phosphorylation and the expression of IL-6, IL-8	25153725
MDA-MB-231	Function Assay	2/5/10 μM	4 h		decreases the constitutive phosphorylation of both p-S529-p65 and p-S129-Akt	25153725
HCT116	Apoptosis Assay	10 μM	24/48 h	DMSO	induces apoptosis	24686080
HCT116	Function Assay	10 μM	4 h	DMSO	causes ER-stress response over the p-eIF2α branch, but does not induce CHOP	24686080
ARPE-19	Function Assay	10 μM	4 h	DMSO	causes ER-stress response over the p-eIF2α branch, but does not induce CHOP	24686080
HCT116	Growth Inhibition Assay	10 μM	24-96 h	DMSO	inhibits cell growth time dependently	24686080
ARPE-19	Growth Inhibition Assay	10 μM	24-96 h	DMSO	inhibits cell growth time dependently	24686080
ARPE-19	Kinase Assay	5/10/20 μM	24/48 h		inhibits CK2 kinase activity at a concentration of 5 μM	24686080
SUP-B15	Apoptosis Assay	6/10 μM	48 h		induces apoptosis	24561792
Nalm6	Apoptosis Assay	6/10 μM	48 h		induces apoptosis	24561792
SUP-B15	Function Assay	10/20 μM	24 h		results in decreased PTEN phosphorylation at the CK2 target residue S380 and concomitant downregulation of PTEN protein expression	24561792
Nalm6	Function Assay	10/20 μM	24 h		results in decreased PTEN phosphorylation at the CK2 target residue S380 and concomitant downregulation of PTEN protein expression	24561792
C2C12	Function Assay	3 μM	12/24/48 h		inhibits the expression of osteoclast differentiation markers and Akt phosphorylation	24293011
MOLT-4	Apoptosis Assay	5 μM	24/48 h		induces apoptosis	24253024
DND-41	Apoptosis Assay	5 μM	24/48 h		induces apoptosis	24253024
ALL-SIL	Apoptosis Assay	5 μM	24/48 h		induces apoptosis	24253024
DND-41	Growth Inhibition Assay	1-10 μM	48 h		IC50=9 μM	24253024
HPB-ALL	Growth Inhibition Assay	1-10 μM	48 h		IC50=6.1 μM	24253024
ALL-SIL	Growth Inhibition Assay	1-10 μM	48 h		IC50=5.7 μM	24253024
PF-382	Growth Inhibition Assay	1-10 μM	48 h		IC50=4.5 μM	24253024
MOLT-4	Growth Inhibition Assay	1-10 μM	48 h		IC50=5.7 μM	24253024
CEM-S	Growth Inhibition Assay	1-10 μM	48 h		IC50=4.6 μM	24253024
CEM-R	Growth Inhibition Assay	1-10 μM	48 h		IC50=4 μM	24253024
Jurkat	Growth Inhibition Assay	1-10 μM	48 h		IC50=4.9 μM	24253024
Rec-1	Growth Inhibition Assay	0-40 μM	48 h		IC50=1.46 µM	24086494
Jeko-1	Growth Inhibition Assay	0-40 μM	48 h		IC50=2.4 µM	24086494
INA-6	Growth Inhibition Assay	0-40 μM	48 h		IC50=2.42 µM	24086494
U-266	Growth Inhibition Assay	0-40 μM	48 h		IC50=19.8 µM	24086494
A549	Function Assay	3 μM	48 h		inhibits TGF-β1-induced activation of Smad and expression of Snail and Twist	24023938
A549	Function Assay	10 μM	12/24/48 h		inhibits TGF-β1-induced migration and invasion	24023938
R-LAMA84	Growth Inhibition Assay	2.5-10 μM	48 h	DMSO	inhibits cell growth concentration dependently	24012109
S-LAMA84	Growth Inhibition Assay	2.5-10 μM	48 h	DMSO	inhibits cell growth concentration dependently	24012109
R-LAMA84	Function Assay	3 μM	24 h	DMSO	reduces CK2 activity	24012109
S-LAMA84	Function Assay	3 μM	24 h	DMSO	reduces CK2 activity	24012109
A549	Function Assay	1/10 μM	48 h	DMSO	leads to a dose-dependent decrease in Notch reporter activity	23651443
H1299	Growth Inhibition Assay	0-30 μM	72 h	DMSO	IC50=1.80 μM, inhibits cell growth concentration dependently	23651443
A549	Growth Inhibition Assay	0-30 μM	72 h	DMSO	IC50=4.15 μM, inhibits cell growth concentration dependently	23651443
LNCap	Growth Inhibition Assay	0-30 μM	4 d		IC50=4.59 μM	22832316
H2170	Function Assay	10 μM	4-24 h		enhances apoptosis with	22387988
A431	Function Assay	10 μM	4-24 h		enhances apoptosis with	22387988
H2170	Function Assay	10 μM	30 min		attenuates PI3K-Akt-mTOR signaling	22387988
A431	Function Assay	10 μM	30 min		attenuates PI3K-Akt-mTOR signaling	22387988
UM-SCC-46	Clonogenic Assay	0.5-5 μM	14 d	DMSO	inhibits clonogenic survival and sphere formation	25379016
H28	Growth Inhibition Assay	0.01-30 μM	72 h	DMSO	IC50=7.2 μM	25422081
H2052	Growth Inhibition Assay	0.01-30 μM	72 h	DMSO	IC50=2.0 μM	25422081
PC9/GR	Function Assay	5 µM	48 h		induces autophagy	25486409
PC9/ER	Function Assay	5 µM	48 h		induces autophagy	25486409
H1299	Growth Inhibition Assay	1/5/10 μM	72 h		inhibits cell growth concentration dependently	25750308
Calu-1	Growth Inhibition Assay	1/5/10 μM	72 h		inhibits cell growth concentration dependently	25750308
H358	Growth Inhibition Assay	1/5/10 μM	72 h		inhibits cell growth concentration dependently	25750308
H1299	Apoptosis Assay	10 μM	72 h		induces apoptosis	25750308
Calu-1	Apoptosis Assay	10 μM	72 h		induces apoptosis	25750308
H358	Apoptosis Assay	10 μM	72 h		induces apoptosis	25750308
NU-DUL	Growth Inhibition Assay	5-25 μM	48 h		inhibits cell growth concentration dependently	25788269
Oci Ly 3	Growth Inhibition Assay	5-25 μM	48 h		inhibits cell growth concentration dependently	25788269
Oci Ly 10	Growth Inhibition Assay	5-25 μM	48 h		inhibits cell growth concentration dependently	25788269
Oci Ly 1	Growth Inhibition Assay	5-25 μM	48 h		inhibits cell growth concentration dependently	25788269
Oci Ly 18	Growth Inhibition Assay	5-25 μM	48 h		inhibits cell growth concentration dependently	25788269
Oci Ly 19	Growth Inhibition Assay	5-25 μM	48 h		inhibits cell growth concentration dependently	25788269
Raji	Growth Inhibition Assay	5-25 μM	48 h		inhibits cell growth concentration dependently	25788269
UM-SCC1	Growth Inhibition Assay	0.1-30 μM	1-5 d		IC50=4.1 μM	25798061
UM-SCC46	Growth Inhibition Assay	0.1-30 μM	1-5 d		IC50=3.4 μM	25798061
UM-SCC1	Function Assay	0.5/4/10 μM	72 h		down-regulates the expression of NF-ĸB, Bcl-XL and up-regulates the expression of p53, p21, AP-1 and IL-8 concentration dependently	25798061
UM-SCC46	Function Assay	0.5/4/10 μM	72 h		down-regulates the expression of NF-ĸB, Bcl-XL, p53, p21, AP-1 and up-regulates the expression IL-8 concentration dependently	25798061
HEK293	Kinase Assay	0.5 μM	15 min	DMSO	reduces CK2 kinase activity	25887626
Hela	Kinase Assay	0.5 μM	15 min	DMSO	reduces CK2 kinase activity	25887626
LAMA84	Kinase Assay	0.5 μM	15 min	DMSO	reduces CK2 kinase activity	25887626
HEK293	Function Assay	3 μM	5 h	DMSO	CK2 phosphorylates eIF3j at Ser127	25887626
HDMEC	Kinase Assay	1-50 μM	5 h	DMSO	decreases CK2 kinase activity without affecting cell viability	26189586
HDMEC	Function Assay	50 μM	1/5 h	DMSO	decreases the nuclear signal of phosphorylated p65 in TNF-α-stimulated HDMEC	26189586
A549	Function Assay	3/10 μM	48 h		suppresses the micropillar-induced expression of p-FAK	26318800
platelets	Kinase Assay	1/5/10 μM	0.5 h	DMSO	reduces CK2 kinase activity and platelet aggregation	26381437
HDMEC	Kinase Assay	0.25/0.5/1 μM	24 h	DMSO	reduces CK2 kinase activity, vWF expression and secretion	26381437
HDMEC	Function Assay	0.25/0.5/1 μM	24 h	DMSO	reduces expression of VCAM-1 but not ICAM-1	26381437
HDMEC	Function Assay	1 μM	24 h	DMSO	affects subcellular localization of NFATc1 and phospho-p65	26381437
Jurkat	Function assay				Inhibition of CK2 in human Jurkat cells assessed as inhibition of [gamma33P]ATP incorporation into substrate by luminescence assay, IC50 = 0.1 μM.	21174434
MIAPaCa2	Antiproliferative assay		4 days		Antiproliferative activity against human MIAPaCa2 cells after 4 days by alamar blue assay, IC50 = 1.1 μM.	21174434
PC3	Antiproliferative assay		4 days		Antiproliferative activity against human PC3 cells after 4 days by alamar blue assay, IC50 = 2.1 μM.	21174434
HCT116	Antiproliferative assay		4 days		Antiproliferative activity against human HCT116 cells after 4 days by alamar blue assay, IC50 = 2.2 μM.	21174434
H1299	Antiproliferative assay		4 days		Antiproliferative activity against human H1299 cells after 4 days by alamar blue assay, IC50 = 2.4 μM.	21174434
Jurkat	Antiproliferative assay		4 days		Antiproliferative activity against human Jurkat cells after 4 days by alamar blue assay, IC50 = 2.5 μM.	21174434
A549	Antiproliferative assay		4 days		Antiproliferative activity against human A549 cells after 4 days by alamar blue assay, IC50 = 3 μM.	21174434
A375	Antiproliferative assay		4 days		Antiproliferative activity against human A375 cells after 4 days by alamar blue assay, IC50 = 3.9 μM.	21174434
BxPC3	Antiproliferative assay		4 days		Antiproliferative activity against human BxPC3 cells after 4 days by alamar blue assay, IC50 = 4.4 μM.	21174434
LNCAP	Antiproliferative assay		4 days		Antiproliferative activity against human LNCAP cells after 4 days by alamar blue assay, IC50 = 4.7 μM.	21174434
K562	Antiproliferative assay		4 days		Antiproliferative activity against human K562 cells after 4 days by alamar blue assay, IC50 = 5.3 μM.	21174434
MDA-MB-231	Antiproliferative assay		4 days		Antiproliferative activity against human MDA-MB-231 cells after 4 days by alamar blue assay, IC50 = 6.4 μM.	21174434
MCF7	Antiproliferative assay		4 days		Antiproliferative activity against human MCF7 cells after 4 days by alamar blue assay, IC50 = 8.9 μM.	21174434
Hs 578T	Antiproliferative assay		4 days		Antiproliferative activity against human Hs 578T cells after 4 days by alamar blue assay, IC50 = 13.1 μM.	21174434
HCT116	Antiproliferative assay		72 hrs		Antiproliferative activity against human HCT116 cells after 72 hrs by MTS assay, IC50 = 5.2 μM.	22339433
MCF7	Antiproliferative assay		72 hrs		Antiproliferative activity against human MCF7 cells after 72 hrs by MTS assay, IC50 = 6.5 μM.	22339433
A549	Antiproliferative assay		72 hrs		Antiproliferative activity against human A549 cells after 72 hrs by MTS assay, IC50 = 8.2 μM.	22339433
MV4-11	Antiproliferative assay		1 to 3 days		Antiproliferative activity against human MV4-11 cells after 1 to 3 days by MTS assay, CC50 = 3 μM.	23711832
U937	Antiproliferative assay		1 to 3 days		Antiproliferative activity against human U937 cells after 1 to 3 days by MTS assay, CC50 = 4.2 μM.	23711832
Jurkat	Antiproliferative assay		1 to 3 days		Antiproliferative activity against human Jurkat cells after 1 to 3 days by MTS assay, CC50 = 4.5 μM.	23711832
K562	Antiproliferative assay		1 to 3 days		Antiproliferative activity against human K562 cells after 1 to 3 days by MTS assay, CC50 = 7 μM.	23711832
Sf9	Function assay				Inhibition of CDK2/cyclin E (unknown origin) expressed in Sf9 cells using histone H1 as substrate in presence of [gamma33P]ATP, IC50 = 1.8 μM.	24681986
A549	Cytotoxicity assay		72 hrs		Cytotoxicity against human A549 cells after 72 hrs by MTS assay, CC50 = 9.9 μM.	26850376
Sf21	Function assay		90 mins		Inhibition of recombinant human full length N-terminal His6-tagged CK2alpha expressed in Sf21 insect cells using CK2tide as substrate treated for 20 mins measured after 90 mins in presence of MgCl2 by caliper mobility shift assay, IC50 = 0.003 μM.	29559278
Vero E6	Antiviral assay		48 h		IC50 for antiviral activity against SARS-CoV-2 in the Vero E6 cell line at 48 h by immunofluorescence-based assay (detecting the viral NP protein in the nucleus of the Vero E6 cells)., IC50 = 3.89045 μM.	32353859
A549	Function assay	30 uM	48 hrs		Inhibition of CK2-mediated MMP2 activation in human A549 cells at 30 uM after 48 hrs by gelatin-zymography	24012124
A549	Function assay	10 uM	15 to 30 mins		Inhibition of CK2-mediated ERK phosphorylation in human A549 cells at 10 uM after 15 to 30 mins by Western blot method	24012124
A549	Function assay	1 to 10 uM	24 hrs		Inhibition of CK2-mediated MT1-MMP expression in human A549 cells at 1 to 10 uM after 24 hrs by Western blot method	24012124
A549	Function assay	10 uM			Inhibition of CK2-mediated ERK phosphorylation in human A549 cells at 10 uM by Western blot method	24012124
A549	Function assay	10 uM	24 hrs		Inhibition of CK2-mediated AKT phosphorylation in human A549 cells at 10 uM after 24 hrs by Western blot method	24012124
A549	Function assay	10 uM	4 to 24 hrs		Inhibition of CK2-mediated AKT phosphorylation in human A549 cells at 10 uM after 4 to 24 hrs by Western blot method	24012124
U-2 OS	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells	29435139
A673	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
DAOY	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY 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
BT-37	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
RD	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD 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
BT-12	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 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
NB1643	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 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
Rh41	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 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
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
NB-EBc1	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 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
Rh18	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
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Informations chimiques, stockage et stabilité

Poids moléculaire	349.77	Formule	C₁₉H₁₂ClN₃O₂	Stockage (À compter de la date de réception)	3 ans-20°Cpoudre
N° CAS	1009820-21-6	Télécharger le SDF		Stockage des solutions mères	1 an-80°Cen solvant 1 mois-20°Cen solvant
Synonymes	N/A			Smiles	C1=CC(=CC(=C1)Cl)NC2=NC3=C(C=CC(=C3)C(=O)O)C4=C2C=CN=C4

Solubilité

In vitro
Lot:

DMSO : 70 mg/mL (200.13 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	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 commerciale pour des tests personnalisés.	1.750mg/ml (5.00mM)	Taking the 1 mL working solution as an example, add 50 μL of 35 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.
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.
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

Caractéristiques	First clinical inhibitor of CK2.
Targets/IC₅₀/Ki	CK2 (Cell-free assay) 1 nM
In vitro	Le Silmitasertib (CX-4945) est sélectif pour la CK2, car il n'inhibe que 7 des 238 kinases de plus de 90 % à une concentration de 0,5 μM, ce qui est 500 fois supérieur à l'IC50 de la CK2. Bien que dans les systèmes acellulaires, ce composé inhibe FLT3, PIM1 et CDK1 avec des IC50 de 35 nM, 46 nM et 56 nM respectivement, le traitement à 10 μM est inactif contre FLT3, PIM1 et CDK1 dans les essais fonctionnels basés sur des cellules. Il présente un large spectre d'activité antiproliférative, et les lignées cellulaires de cancer du sein affichent la plus large gamme de sensibilité avec un EC50 de 1,71 à 20,01 μM. L'activité antiproliférative du CX-4945 est corrélée aux niveaux d'ARNm et de protéines de CK2α, mais pas à la sous-unité catalytique CK2α', à la sous-unité régulatrice CK2β et au statut mutationnel PI3K/Akt ou PTEN. Il inhibe la signalisation PI3K/Akt en bloquant directement la phosphorylation d'Akt à la sérine 129 par CK2 plutôt que par l'activation de PTEN. Le traitement avec ce composé entraîne une phosphorylation réduite de p21 (T145), des niveaux accrus de p21 total et de p27, et l'induction de l'activité de la caspase 3/7. Il induit un arrêt du cycle cellulaire en phase G2/M dans les cellules BT-474 et un arrêt en phase G1 dans les cellules BxPC-3. Ce composé inhibe la prolifération, la migration et la formation de tubes de HUVEC avec un IC50 de 5,5 μM, 2 μM et 4 μM, respectivement. Dans des conditions hypoxiques dans les cellules BT-474 et BxPC-3, il empêche la régulation négative de p53 et pVHL et réduit l'activation de la transcription de HIF-1α. Il inhibe puissamment l'activité endogène intracellulaire de CK2 avec un IC50 de 0,1 μM dans les cellules Jurkat.
Essai kinase	CK2 Kinase Assay
Essai kinase	Le Silmitasertib (CX-4945) est ajouté à un volume de 10 μL à un mélange réactionnel comprenant 10 μL de tampon de dilution d'essai (ADB ; 20 mM MOPS, pH 7,2, 25 mM β-glycérophosphate, 5 mM EGTA, 1 mM orthovanadate de sodium et 1 mM dithiothréitol), 10 μL de peptide substrat (RRRDDDSDDD, dissous dans l'ADB à une concentration de 1 mM), 10 μL de CK2 humaine recombinante (ααββ-holoenzyme, 25 ng dissous dans l'ADB). Les réactions sont initiées par l'ajout de 10 μL de solution d'ATP (90 % de 75 mM MgCl₂, 75 μM ATP (concentration finale d'ATP=15 μM) dissous dans l'ADB ; 10 % de [γ-³³P]ATP (stock 1 mCi/100 μL ; 3000 Ci/mM) et maintenues pendant 10 minutes à 30 °C. Les réactions sont stoppées avec 100 μL d'acide phosphorique à 0,75 %, puis transférées et filtrées à travers une plaque de filtration sur phosphocellulose. Après avoir lavé chaque puits cinq fois avec de l'acide phosphorique à 0,75 %, la plaque est séchée sous vide pendant 5 minutes et, après l'ajout de 15 μL de liquide de scintillation à chaque puits, la radioactivité résiduelle est mesurée à l'aide d'un compteur de luminescence Wallac. Les valeurs IC50 pour ce composé sont dérivées de huit concentrations allant de 0,0001 μM à 1 μM.
In vivo	L'administration orale de Silmitasertib (CX-4945) à 25 mg/kg ou 75 mg/kg deux fois par jour montre une puissante activité antitumorale dans le modèle BT-474, avec un TGI de 88 % et 97 % respectivement, et 2 des 9 animaux de chaque groupe présentant une réduction de plus de 50 % de la taille de la tumeur par rapport au volume tumoral initial. Dans le modèle BxPC-3, le traitement avec ce composé à 75 mg/kg deux fois par jour montre un TGI de 93 % avec 3 animaux n'ayant aucune preuve de tumeur restante à la fin de la période de traitement. Dans le modèle de xénogreffe PC3, l'administration de celui-ci à 25 mg/kg, 50 mg/kg ou 75 mg/kg provoque une inhibition de la croissance tumorale avec un TGI de 19 %, 40 % et 86 % respectivement.
Références	[1] https://pubmed.ncbi.nlm.nih.gov/21159648/ [2] https://pubmed.ncbi.nlm.nih.gov/21174434/ [3] https://pubmed.ncbi.nlm.nih.gov/22267551/ [4] https://pubmed.ncbi.nlm.nih.gov/22387988/

Applications

Méthodes	Biomarqueurs	PMID
Western blot	p-S6K1(T389) / S6K1 / p-S6(S235/236) / S6 p-AKT(S129) / p-AKT(T308) / p-AKT(S473) / AKT / p-ERK / ERK / TP53 / p-p21(Th145) / p21 / Bcl-xl p-Smad2 (Cytosol) / Smad2/3 (Cytosol) / Smad2/3 (Nucleus) / Twist / Snail	30683840
Immunofluorescence	β-catenin E-cadherin / Vimentin	24023938
Growth inhibition assay	Cell viability	30316146

Informations sur lessai clinique

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

Numéro NCT	Recrutement	Conditions	Promoteur/Collaborateurs	Date de début	Phases
NCT05817708	Completed	COVID-19	Senhwa Biosciences Inc.	November 7 2022	Phase 1
NCT04668209	Terminated	Coronavirus	University of Arizona\|Senhwa Biosciences Inc.	January 21 2021	Phase 2
NCT04663737	Completed	Covid19	Chris Recknor MD\|Senhwa Biosciences Inc.	December 3 2020	Phase 2
NCT03904862	Suspended	Medulloblastoma Childhood	Pediatric Brain Tumor Consortium\|National Cancer Institute (NCI)\|American Lebanese Syrian Associated Charities (ALSAC)	July 25 2019	Phase 1\|Phase 2
NCT02128282	Completed	Cholangiocarcinoma	Senhwa Biosciences Inc.	June 2014	Phase 1\|Phase 2

Support technique

Instructions de manipulation

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

Si vous avez dautres questions, veuillez laisser un message.

Foire aux questions

Question 1:
How to reconstitute it (S2248) for in vivo uses?

Réponse :
For injection, it can be dissolved in 2% DMSO+30% PEG 300+2% Tween 80+ddH2O at 5mg/ml clearly. When making the solution, please dissolve this compound in DMSO clearly first. If it dissolves not readily, please sonicate and warm the solution in water bath at about 45-50℃. Then add PEG and Tween. After they mixed well, dilute with water. For oral gavage, it can be dissolved in 1% CMC Na at 30mg/ml as a homogeneous suspension. This is a common formulation for oral gavage, and is convenience to prepare.

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