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Silmitasertib (CX-4945) Casein Kinase 2 Inhibitor

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

Cat. No.S2248

Silmitasertib (CX-4945) es un inhibidor potente y selectivo de CK2 (casein kinase 2) con una IC50 de 1 nM en un ensayo sin células, aunque es menos potente contra Flt3, Pim1 y CDK1 (inactivo en ensayo basado en células). Este compuesto induce Autophagy y promueve la apoptosis. Fase 1/2.

Silmitasertib (CX-4945) Casein Kinase Inhibidor Chemical Structure

Estructura química

Peso molecular: 349.77

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Control de calidad

Lote: Pureza: 99.96%

99.96

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

Cultivo celular, tratamiento y concentración de trabajo

Líneas celulares	Tipo de ensayo	Concentración	Tiempo de incubación	Formulación	Descripción de la actividad	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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Información química, almacenamiento y estabilidad

Peso molecular	349.77	Fórmula	C₁₉H₁₂ClN₃O₂	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	1009820-21-6	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	N/A			Smiles	C1=CC(=CC(=C1)Cl)NC2=NC3=C(C=CC(=C3)C(=O)O)C4=C2C=CN=C4

Solubilidad

In vitro
Lote:

DMSO : 70 mg/mL (200.13 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Water : Insoluble

Ethanol : Insoluble

Calculadora de Molaridad

Masa	Concentración	Volumen	Peso molecular
=	×	×

Calculadora de Dilución Calculadora de Peso Molecular

In vivo Lote:
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 Validado por los laboratorios Selleck. Si necesita ajustes en esta formulación, contacte con nuestro equipo de ventas para pruebas personalizadas.	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.

Calculadora de formulación in vivo (Solución clara)

Paso 1: Introduzca la información a continuación (Recomendado: Un animal adicional para tener en cuenta la pérdida durante el experimento)

Dosis: mg/kg Peso promedio de los animales: g Volumen de dosificación por animal:μL Número de animales:

Paso 2: Introduzca la formulación in vivo (Esto es solo la calculadora, no la formulación. Por favor, contáctenos primero si no hay una formulación in vivo en la sección de Solubilidad.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Resultados del cálculo:

Concentración de trabajo: mg/ml;

Método para preparar el líquido maestro de DMSO: mg fármaco predissuelto en μL DMSO ( Concentración del líquido maestro mg/mL, Por favor, contáctenos primero si la concentración excede la solubilidad del DMSO del lote del fármaco. )

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadirμL PEG300, mezclar y clarificar, luego añadirμL Tween 80, mezclar y clarificar, luego añadir μL ddH₂O, mezclar y clarificar.

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadir μL Aceite de maíz, mezclar y clarificar.

Nota: 1. Por favor, asegúrese de que el líquido esté claro antes de añadir el siguiente disolvente.
2. Asegúrese de añadir el (los) disolvente(s) en orden. Debe asegurarse de que la solución obtenida, en la adición anterior, sea una solución clara antes de proceder a añadir el siguiente disolvente. Se pueden utilizar métodos físicos como el vórtice, el ultrasonido o el baño de agua caliente para ayudar a la disolución.

Mecanismo de acción

Características	First clinical inhibitor of CK2.
Targets/IC₅₀/Ki	CK2 (Cell-free assay) 1 nM
In vitro	Silmitasertib (CX-4945) es selectivo para CK2, ya que solo inhibe 7 de las 238 quinasas en más del 90% a una concentración de 0,5 μM, que es 500 veces mayor que el IC50 de CK2. Aunque en sistemas libres de células este compuesto inhibe FLT3, PIM1 y CDK1 con IC50 de 35 nM, 46 nM y 56 nM, respectivamente, el tratamiento a 10 μM es inactivo contra FLT3, PIM1 y CDK1 en ensayos funcionales basados en células. Exhibe un amplio espectro de actividad antiproliferativa, y las líneas celulares de cáncer de mama muestran el rango más amplio de sensibilidad a este con un EC50 de 1,71-20,01 μM. La actividad antiproliferativa de CX-4945 se correlaciona con los niveles de ARNm y proteínas de CK2α, pero no con la subunidad catalítica CK2α', la subunidad reguladora CK2β y el estado mutacional de PI3K/Akt o PTEN. Inhibe la señalización de PI3K/Akt bloqueando directamente la fosforilación de Akt en Serina 129 por CK2 en lugar de mediante la activación de PTEN. El tratamiento con este compuesto provoca una fosforilación reducida de p21 (T145), un aumento de los niveles totales de p21 y p27, y la inducción de la actividad de la caspasa 3/7. Induce una detención del ciclo celular G2/M en células BT-474 y una detención G1 en células BxPC-3. Este compuesto inhibe la proliferación, migración y formación de tubos de HUVEC con un IC50 de 5,5 μM, 2 μM y 4 μM, respectivamente. En condiciones hipóxicas en células BT-474 y BxPC-3, previene la regulación a la baja de p53 y pVHL y reduce la activación de la transcripción de HIF-1α. Inhibe potentemente la actividad intracelular endógena de CK2 con un IC50 de 0,1 μM en células Jurkat.
Ensayo de quinasa	Ensayo de CK2 Kinase
Ensayo de quinasa	Silmitasertib (CX-4945) se añade en un volumen de 10 μL a una mezcla de reacción que comprende 10 μL de tampón de dilución de ensayo (ADB; 20 mM MOPS, pH 7,2, 25 mM β-glicerofosfato, 5 mM EGTA, 1 mM ortovanadato de sodio y 1 mM ditiotreitol), 10 μL de péptido sustrato (RRRDDDSDDD, disuelto en ADB a una concentración de 1 mM), 10 μL de CK2 humana recombinante (ααββ-holoenzima, 25 ng disuelto en ADB). Las reacciones se inician con la adición de 10 μL de solución de ATP (90% 75 mM MgCl₂, 75 μM ATP (concentración final de ATP=15 μM) disuelto en ADB; 10% [γ-³³P]ATP (stock 1 mCi/100 μL; 3000 Ci/mM) y se mantienen durante 10 minutos a 30 °C. Las reacciones se detienen con 100 μL de ácido fosfórico al 0,75% y luego se transfieren y filtran a través de una placa de filtro de fosfocelulosa. Después de lavar cada pozo cinco veces con ácido fosfórico al 0,75%, la placa se seca al vacío durante 5 minutos y, después de la adición de 15 μL de líquido de centelleo a cada pozo, la radiactividad residual se mide utilizando un contador de luminiscencia Wallac. Los valores de IC50 para este compuesto se derivan de ocho concentraciones en un rango de 0,0001 μM a 1 μM.
In vivo	La administración oral de Silmitasertib (CX-4945) a 25 mg/kg o 75 mg/kg dos veces al día muestra una potente actividad antitumoral en el modelo BT-474, con un TGI del 88 % y 97 %, respectivamente, y 2 de 9 animales en cada grupo mostrando una reducción de más del 50 % en el tamaño del tumor en comparación con el volumen tumoral inicial. En el modelo BxPC-3, el tratamiento con este compuesto a 75 mg/kg dos veces al día muestra un TGI del 93 % con 3 animales sin evidencia de tumor restante al final del período de tratamiento. En el modelo de xenoinjerto PC3, la administración del mismo a 25 mg/kg, 50 mg/kg o 75 mg/kg causa una inhibición del crecimiento tumoral con un TGI del 19 %, 40 % y 86 %, respectivamente.
Referencias	[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/

Aplicaciones

Métodos	Biomarcadores	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

Información del ensayo clínico

(datos de https://clinicaltrials.gov, actualizado el 2024-05-22)

Número NCT	Reclutamiento	Condiciones	Patrocinador/Colaboradores	Fecha de inicio	Fases
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

Soporte técnico

Instrucciones de manipulación

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Preguntas frecuentes

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

Respuesta:
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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