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Silmitasertib (CX-4945) Casein Kinase 2 Inhibitor

N. Cat.: S2248

Silmitasertib (CX-4945) is a potent and selective inhibitor of CK2 (casein kinase 2) with IC50 of 1 nM in a cell-free assay, although it is less potent against Flt3, Pim1 and CDK1 (inactive in cell-based assay). This compound induces autophagy and promotes apoptosis. Phase 1/2.
Silmitasertib (CX-4945) Casein Kinase inhibitor Chemical Structure

Struttura chimica

Peso molecolare: 349.77

Vai a

Controllo Qualità (Quality Control)

Lotto: Purezza: 99.96%
99.96

Coltura cellulare, trattamento e concentrazione di lavoro
(Cell Culture, Treatment & Working Concentration)

Linee cellulari Tipo di saggio Concentrazione Tempo di incubazione Formulazione Descrizione dell'attività 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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Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Peso molecolare 349.77 Formula

C19H12ClN3O2

 Conservazione (Dalla data di ricezione)
N. CAS 1009820-21-6 Scarica SDF Conservazione delle soluzioni stock

Sinonimi N/A Smiles C1=CC(=CC(=C1)Cl)NC2=NC3=C(C=CC(=C3)C(=O)O)C4=C2C=CN=C4

Solubilità (Solubility)

In vitro
Lotto:

DMSO : 70 mg/mL (200.13 mM)
(Il DMSO contaminato da umidità può ridurre la solubilità. Utilizzare DMSO fresco e anidro.)

Water : Insoluble

Ethanol : Insoluble

Calcolatore di Molarità

Massa Concentrazione Volume Peso molecolare
Calcolatore di Diluizione Calcolatore del Peso Molecolare

In vivo
Lotto:

Calcolatore di formulazione in vivo (Soluzione chiara)

Passo 1: Inserire le informazioni di seguito (Consigliato: Un animale aggiuntivo per tenere conto della perdita durante l'esperimento)

mg/kg g μL

Passo 2: Inserire la formulazione in vivo (Questo è solo il calcolatore, non la formulazione. Contattateci prima se non c'è una formulazione in vivo nella sezione Solubilità.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Risultati del calcolo:

Concentrazione di lavoro: mg/ml;

Metodo per preparare il liquido master di DMSO: mg farmaco predissolto in μL DMSO ( Concentrazione del liquido master mg/mL, Vi preghiamo di contattarci prima se la concentrazione supera la solubilità del DMSO del lotto del farmaco. )

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungereμL PEG300, mescolare e chiarire, quindi aggiungereμL Tween 80, mescolare e chiarire, quindi aggiungere μL ddH2O, mescolare e chiarire.

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungere μL Olio di mais, mescolare e chiarire.

Nota: 1. Si prega di assicurarsi che il liquido sia limpido prima di aggiungere il solvente successivo.
2. Assicurarsi di aggiungere il/i solvente/i in ordine. È necessario assicurarsi che la soluzione ottenuta, nell'aggiunta precedente, sia una soluzione limpida prima di procedere all'aggiunta del solvente successivo. Metodi fisici come il vortex, gli ultrasuoni o il bagno d'acqua calda possono essere utilizzati per facilitare la dissoluzione.

Meccanismo d'azione (Mechanism of Action)

Caratteristiche
First clinical inhibitor of CK2.
Targets/IC50/Ki
CK2
(Cell-free assay)
1 nM
In vitro

Silmitasertib (CX-4945) è selettivo per CK2, in quanto inibisce solo 7 delle 238 chinasi di oltre il 90% a una concentrazione di 0,5 μM, che è 500 volte maggiore dell'IC50 di CK2. Sebbene in sistemi privi di cellule questo composto inibisca FLT3, PIM1 e CDK1 con IC50 di 35 nM, 46 nM e 56 nM, rispettivamente, il trattamento a 10 μM è inattivo contro FLT3, PIM1 e CDK1 in saggi funzionali basati su cellule. Esibisce un ampio spettro di attività antiproliferativa e le linee cellulari di cancro al seno mostrano la più ampia gamma di sensibilità ad esso con un EC50 di 1,71-20,01 μM. L'attività antiproliferativa di CX-4945 correla con i livelli di mRNA e proteine di CK2α ma non con la subunità catalitica CK2α', la subunità regolatoria CK2β e lo stato mutazionale di PI3K/Akt o PTEN. Inibisce la segnalazione PI3K/Akt bloccando direttamente la fosforilazione di Akt a Serina 129 da parte di CK2 piuttosto che attraverso l'attivazione di PTEN. Il trattamento con questo composto provoca una ridotta fosforilazione di p21 (T145), livelli aumentati di p21 totale e p27 e induzione dell'attività della caspasi 3/7. Induce un arresto del ciclo cellulare G2/M nelle cellule BT-474 e un arresto G1 nelle cellule BxPC-3. Questo composto inibisce la proliferazione, la migrazione e la formazione di tubi di HUVEC con IC50 di 5,5 μM, 2 μM e 4 μM, rispettivamente. In condizioni ipossiche nelle cellule BT-474 e BxPC-3, previene la downregulation di p53 e pVHL e riduce l'attivazione della trascrizione di HIF-1α. Inibisce potentemente l'attività intracellulare endogena di CK2 con IC50 di 0,1 μM nelle cellule Jurkat.

Saggio chinasico
Saggio della CK2 Kinase
Silmitasertib (CX-4945) viene aggiunto in un volume di 10 μL a una miscela di reazione comprendente 10 μL di tampone di diluizione del saggio (ADB; 20 mM MOPS, pH 7,2, 25 mM β-glicerolfosfato, 5 mM EGTA, 1 mM ortovanadato di sodio e 1 mM ditiotreitolo), 10 μL di peptide substrato (RRRDDDSDDD, disciolto in ADB a una concentrazione di 1 mM), 10 μL di CK2 umana ricombinante (ααββ-oloenzima, 25 ng disciolto in ADB). Le reazioni vengono avviate con l'aggiunta di 10 μL di soluzione di ATP (90% 75 mM MgCl2, 75 μM ATP (concentrazione finale di ATP=15 μM) disciolto in ADB; 10% [γ-33P]ATP (stock 1 mCi/100 μL; 3000 Ci/mM) e mantenute per 10 minuti a 30 °C. Le reazioni vengono bloccate con 100 μL di acido fosforico allo 0,75% e quindi trasferite e filtrate attraverso una piastra filtrante di fosfocellulosa. Dopo aver lavato ogni pozzetto cinque volte con acido fosforico allo 0,75%, la piastra viene asciugata sotto vuoto per 5 minuti e, dopo l'aggiunta di 15 μL di liquido di scintillazione a ogni pozzetto, la radioattività residua viene misurata utilizzando un contatore di luminescenza Wallac. I valori di IC50 per questo composto sono derivati da otto concentrazioni in un intervallo da 0,0001 μM a 1 μM.
In vivo

La somministrazione orale di Silmitasertib (CX-4945) a 25 mg/kg o 75 mg/kg due volte al giorno mostra una potente attività antitumorale nel modello BT-474, con un TGI dell'88% e 97%, rispettivamente, e 2 dei 9 animali in ciascun gruppo che mostrano una riduzione di oltre il 50% della dimensione del tumore rispetto al volume tumorale iniziale. Nel modello BxPC-3, il trattamento con questo composto a 75 mg/kg due volte al giorno mostra un TGI del 93% con 3 animali che non presentano evidenza di tumore residuo alla fine del periodo di trattamento. Nel modello di xenotrapianto PC3, la somministrazione di esso a 25 mg/kg, 50 mg/kg o 75 mg/kg causa l'inibizione della crescita tumorale con un TGI del 19%, 40% e 86%, rispettivamente.

Riferimenti
  • [4] https://pubmed.ncbi.nlm.nih.gov/22387988/

Applicazioni (Applications)

Metodi Biomarcatori Immagini 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
S2248-WB1
30683840
Immunofluorescence β-catenin E-cadherin / Vimentin
S2248-IF1
24023938
Growth inhibition assay Cell viability
S2248-viability1
30316146

Informazioni sullo studio clinico (Clinical Trial Information)

(dati da https://clinicaltrials.gov, aggiornato il 2024-05-22)

Numero NCT Reclutamento Condizioni Sponsor/Collaboratori Data di inizio Fasi
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

Domande Frequenti (Frequently Asked Questions)

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

Risposta:
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.