Home PI3K/Akt/mTOR GSK-3 Inhibitor SB216763

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SB216763 GSK-3 Inhibitor

Kat.-Nr.: S1075

SB216763 ist ein potenter und selektiver GSK-3-Inhibitor mit einer IC50 von 34,3 nM für GSK-3α und ist gleichermaßen wirksam bei der Hemmung von humanem GSK-3β. Diese Verbindung aktiviert die Autophagie.
SB216763 GSK-3 Inhibitor Chemical Structure

Chemische Struktur

Molekulargewicht: 371.22

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Qualitätskontrolle (Quality Control)

Charge: Reinheit: 99.98%
99.98

Zellkultur, Behandlung & Arbeitskonzentration
(Cell Culture, Treatment & Working Concentration)

Zelllinien Assay-Typ Konzentration Inkubationszeit Formulierung Aktivitätsbeschreibung PMID
HEK293 Function assay Glycogen synthase activity of HEK293 cells, inhibition of GSK3-beta, EC50=0.2μM 12941331
HEK293 Function assay Effective concentration of compound against glycogen synthase kinase-3 in HEK293 cells, EC50=0.2μM 15149684
MIAPaCa2 Growth inhibition assay 72 hrs Growth inhibition of human MIAPaCa2 cells after 72 hrs by MTS assay, IC50=25μM 19338355
ST14A Function assay 6 hrs Inhibition of GSK-3-beta-mediated Wnt signaling in human ST14A cells assessed as increase in accumulation of beta-casein around nucleus after 6 hrs by microscopic analysis 20708937
neural precursor cells Function assay Inhibition of neurosphere proliferation of mouse neural precursor cells by MTT assay 17417631
ReNcell VM Antiproliferative assay 3 uM 72 hrs Antiproliferative activity against human ReNcell VM cells assessed as reduction of cell proliferation at 3 uM after 72 hrs 20708937
HepG2 Function assay 34 uM 12 hrs Increase in glucose incorporation in human HepG2 cells at 34 uM after 12 hrs by glucose assay 25467150
3T3L1 Function assay 34 uM 12 hrs Increase in glucose incorporation in mouse 3T3L1 cells at 34 uM after 12 hrs by glucose assay 25467150
HepG2 Function assay 34 uM 12 hrs Inhibition of GSK3beta in human HepG2 cells assessed as decrease in ratio of phosphorylated GS/GS at 34 uM after 12 hrs by Western blot analysis 25467150
Sf9 Function assay 30 min Inhibition of GSK3beta (unknown origin) expressed in Sf9 cells using GS1 as substrate and [gamma32]ATP after 30 min by scinitllation counting, IC50=0.03388μM SANGER
human HDLM-2 cell Growth inhibition assay Inhibition of human HDLM-2 cell growth in a cell viability assay, IC50=0.20984 μM SANGER
human NCI-H1770 cell Growth inhibition assay Inhibition of human NCI-H1770 cell growth in a cell viability assay. IC50=0.29392 μM SANGER
human HOP-62 cell Growth inhibition assay Inhibition of human HOP-62 cell growth in a cell viability assay, IC50=0.85256 μM SANGER
human JAR cell Growth inhibition assay Inhibition of human JAR cell growth in a cell viability assay, IC50=1.21044 μM SANGER
human K5 cell Growth inhibition assay Inhibition of human K5 cell growth in a cell viability, IC50=1.53698 μM SANGER
human MV-4-11 cell Growth inhibition assay Inhibition of human MV-4-11 cell growth in a cell viability assay, IC50=2.69685 μM SANGER
human BT-549 cell Growth inhibition assay Inhibition of human BT-549 cell growth in a cell viability assay, IC50=5.29376 μM SANGER
human LB2241-RCC cell Growth inhibition assay Inhibition of human LB2241-RCC cell growth in a cell viability assay, IC50=6.42874 μM SANGER
human GAMG cell Growth inhibition assay Inhibition of human GAMG cell growth in a cell viability assay, IC50=6.65409 μM SANGER
human HMV-II cell Growth inhibition assay Inhibition of human HMV-II cell growth in a cell viability assay, IC50=7.67607 μM SANGER
human RS4-11 cell Growth inhibition assay Inhibition of human RS4-11 cell growth in a cell viability assay, IC50=8.24141 μM SANGER
human NCI-H1993 cell Growth inhibition assay Inhibition of human NCI-H1993 cell growth in a cell viability assay, IC50=8.36534 μM SANGER
human IST-SL1 cell Growth inhibition assay Inhibition of human IST-SL1 cell growth in a cell viability assay, IC50=9.0204 μM SANGER
human SK-OV-3 cell Growth inhibition assay Inhibition of human SK-OV-3 cell growth in a cell viability assay, IC50=9.1002 μM SANGER
human ESS-1 cell Growth inhibition assay Inhibition of human ESS-1 cell growth in a cell viability assay, IC50=9.59872 μM SANGER
human G-361 cell Growth inhibition assay Inhibition of human G-361 cell growth in a cell viability assay, IC50=10.1798 μM SANGER
human ALL-PO cell Growth inhibition assay Inhibition of human ALL-PO cell growth in a cell viability assay, IC50=10.3477 μM SANGER
human NB5 cell Growth inhibition assay Inhibition of human NB5 cell growth in a cell viability assay, IC50=11.2157 μM SANGER
human DU-145 cell Growth inhibition assay Inhibition of human DU-145 cell growth in a cell viability assay, IC50=11.6535 μM SANGER
human NMC-G1 cell Growth inhibition assay Inhibition of human NMC-G1 cell growth in a cell viability assay, IC50=11.7264 μM SANGER
human RPMI-7951 cell Growth inhibition assay Inhibition of human RPMI-7951 cell growth in a cell viability assay. IC50=11.7864 μM SANGER
human NCI-H2009 cell Growth inhibition assay Inhibition of human NCI-H2009 cell growth in a cell viability assay, IC50=13.2427 μM SANGER
human LoVo cell Growth inhibition assay Inhibition of human LoVo cell growth in a cell viability assay, IC50=13.3771 μM SANGER
human A2058 cell Growth inhibition assay Inhibition of human A2058 cell growth in a cell viability assay, IC50=13.469 μM SANGER
human D-566MG cell Growth inhibition assay Inhibition of human D-566MG cell growth in a cell viability assay, IC50=13.9481 μM SANGER
human QIMR-WIL cell Growth inhibition assay Inhibition of human QIMR-WIL cell growth in a cell viability assay, IC50=15.6394 μM SANGER
human S-117 cell Growth inhibition assay Inhibition of human S-117 cell growth in a cell viability assay, IC50=16.4022 μM SANGER
human YH-13 cell Growth inhibition assay Inhibition of human YH-13 cell growth in a cell viability assay, IC50=16.6865 μM SANGER
human IGROV-1 cell Growth inhibition assay Inhibition of human IGROV-1 cell growth in a cell viability assay, IC50=17.2001 μM SANGER
human BHT-101 cell Growth inhibition assay Inhibition of human BHT-101 cell growth in a cell viability assay, IC50=17.6099 μM SANGER
human MKN45 cell Growth inhibition assay Inhibition of human MKN45 cell growth in a cell viability assay, IC50=18.4128 μM SANGER
human A498 cell Growth inhibition assay Inhibition of human A498 cell growth in a cell viability assay, IC50=19.4549 μM SANGER
human U-266 cell Growth inhibition assay Inhibition of human U-266 cell growth in a cell viability assay, IC50=20.8797 μM SANGER
human BFTC-905 cell Growth inhibition assay Inhibition of human BFTC-905 cell growth in a cell viability assay, IC50=21.1879 μM SANGER
human BxPC-3 cell Growth inhibition assay Inhibition of human BxPC-3 cell growth in a cell viability assay, IC50=21.3554 μM SANGER
human NCI-SNU-1 cell Growth inhibition assay Inhibition of human NCI-SNU-1 cell growth in a cell viability assay, IC50=21.5558 μM SANGER
human SF539 cell Growth inhibition assay Inhibition of human SF539 cell growth in a cell viability assay, IC50=22.0198 μM SANGER
human VA-ES-BJ cell Growth inhibition assay Inhibition of human VA-ES-BJ cell growth in a cell viability assay, IC50=22.5763 μM SANGER
human HuO-3N1 cell Growth inhibition assay Inhibition of human HuO-3N1 cell growth in a cell viability assay, IC50=22.6151 μM SANGER
human EM-2 cell Growth inhibition assay Inhibition of human EM-2 cell growth in a cell viability assay, IC50=22.6689 μM SANGER
human T98G cell Growth inhibition assay Inhibition of human T98G cell growth in a cell viability assay, IC50=23.3009 μM SANGER
human SW1783 cell Growth inhibition assay Inhibition of human SW1783 cell growth in a cell viability assay, IC50=23.5243 μM SANGER
human NKM-1 cell Growth inhibition assay Inhibition of human NKM-1 cell growth in a cell viability assay, IC50=23.8512 μM SANGER
human KOSC-2 cell Growth inhibition assay Inhibition of human KOSC-2 cell growth in a cell viability assay, IC50=24.1292 μM SANGER
human SW48 cell Growth inhibition assay Inhibition of human SW48 cell growth in a cell viability assay, IC50=24.6067 μM SANGER
human NCI-H28 cell Growth inhibition assay Inhibition of human NCI-H28 cell growth in a cell viability assay, IC50=25.2104 μM SANGER
human 5637 cell Growth inhibition assay Inhibition of human 5637 cell growth in a cell viability assay, IC50=25.8111 μM SANGER
human NB69 cell Growth inhibition assay Inhibition of human NB69 cell growth in a cell viability assay, IC50=26.1764 μM SANGER
human HT-29 cell Growth inhibition assay Inhibition of human HT-29 cell growth in a cell viability assay, IC50=27.1752 μM SANGER
human PFSK-1 cell Growth inhibition assay Inhibition of human PFSK-1 cell growth in a cell viability assay, IC50=27.593 μM SANGER
human UACC-257 cell Growth inhibition assay Inhibition of human UACC-257 cell growth in a cell viability assay, IC50=27.743 μM SANGER
human D-423MG cell Growth inhibition assay Inhibition of human D-423MG cell growth in a cell viability assay, IC50=27.9106 μM SANGER
human NH-12 cell Growth inhibition assay Inhibition of human NH-12 cell growth in a cell viability assay, IC50=28.4059 μM SANGER
human DEL cell Growth inhibition assay Inhibition of human DEL cell growth in a cell viability assay, IC50=29.0474 μM SANGER
human LS-513 cell Growth inhibition assay Inhibition of human LS-513 cell growth in a cell viability assay, IC50=30.1334 μM SANGER
human NBsusSR cell Growth inhibition assay Inhibition of human NBsusSR cell growth in a cell viability assay, IC50=30.5678 μM SANGER
human BV-173 cell Growth inhibition assay Inhibition of human BV-173 cell growth in a cell viability assay, IC50=30.7649 μM SANGER
human A101D cell Growth inhibition assay Inhibition of human A101D cell growth in a cell viability assay, IC50=30.9784 μM SANGER
human LU-134-A cell Growth inhibition assay Inhibition of human LU-134-A cell growth in a cell viability assay, IC50=31.0238 μM SANGER
human ES3 cell Growth inhibition assay Inhibition of human ES3 cell growth in a cell viability assay, IC50=31.3376 μM SANGER
human NY cell Growth inhibition assay Inhibition of human NY cell growth in a cell viability assay, IC50=32.2965 μM SANGER
human NCI-H1975 cell Growth inhibition assay Inhibition of human NCI-H1975 cell growth in a cell viability assay, IC50=32.3582 μM SANGER
human A704 cell Growth inhibition assay Inhibition of human A704 cell growth in a cell viability assay, IC50=34.2059 μM SANGER
human SK-MEL-24 cell Growth inhibition assay Inhibition of human SK-MEL-24 cell growth in a cell viability assay, IC50=34.2523 μM SANGER
human SW1088 cell Growth inhibition assay Inhibition of human SW1088 cell growth in a cell viability assay, IC50=34.3452 μM SANGER
human SK-MEL-1 cell Growth inhibition assay Inhibition of human SK-MEL-1 cell growth in a cell viability, IC50=34.714 μM SANGER
human MOLT-4 cell Growth inhibition assay Inhibition of human MOLT-4 cell growth in a cell viability assay, IC50=36.1467 μM SANGER
human T47D cell Growth inhibition assay Inhibition of human T47D cell growth in a cell viability assay, IC50=37.1647 μM SANGER
human SW1710 cell Growth inhibition assay Inhibition of human SW1710 cell growth in a cell viability assay, IC50=37.3608 μM SANGER
human MKN7 cell Growth inhibition assay Inhibition of human MKN7 cell growth in a cell viability assay, IC50=38.0909 μM SANGER
human CAL-72 cell Growth inhibition assay Inhibition of human CAL-72 cell growth in a cell viability assay, IC50=38.1178 μM SANGER
human AGS cell Growth inhibition assay Inhibition of human AGS cell growth in a cell viability assay, IC50=38.2039 μM SANGER
human BE-13 cell Growth inhibition assay Inhibition of human BE-13 cell growth in a cell viability assay, IC50=38.7783 μM SANGER
human Calu-6 cell Growth inhibition assay Inhibition of human Calu-6 cell growth in a cell viability assay, IC50=39.6964 μM SANGER
human CAL-27 cell Growth inhibition assay Inhibition of human CAL-27 cell growth in a cell viability assay, IC50=44.0054 μM SANGER
human BB49-HNC cell Growth inhibition assay Inhibition of human BB49-HNC cell growth in a cell viability assay, IC50=44.0278 μM SANGER
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Chemische Informationen, Lagerung & Stabilität (Chemical Information, Storage & Stability)

Molekulargewicht 371.22 Formel

C19H12N2O2Cl2

 Lagerung (Ab Erhaltdatum)
CAS-Nr. 280744-09-4 SDF herunterladen Lagerung von Stammlösungen

Synonyme N/A Smiles CN1C=C(C2=CC=CC=C21)C3=C(C(=O)NC3=O)C4=C(C=C(C=C4)Cl)Cl

Löslichkeit (Solubility)

In vitro
Charge:

DMSO : 23 mg/mL (61.95 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molaritätsrechner

Masse Konzentration Volumen Molekulargewicht
Verdünnungsrechner Molekulargewicht-Rechner

In vivo
Charge:

In-vivo-Formulierungsrechner (Klare Lösung)

Schritt 1: Geben Sie unten die Informationen ein (Empfohlen: Ein zusätzliches Tier einplanen, um Verluste während des Experiments auszugleichen)

mg/kg g μL

Schritt 2: Geben Sie die In-vivo-Formulierung ein (Dies ist nur der Rechner, nicht die Formulierung. Bitte kontaktieren Sie uns zuerst, wenn im Abschnitt Löslichkeit keine In-vivo-Formulierung angegeben ist.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Berechnungsergebnisse:

Arbeitskonzentration: mg/ml;

Methode zur Herstellung der DMSO-Stammflüssigkeit: mg Wirkstoff voraufgelöst in μL DMSO ( Konzentration der Stammflüssigkeit mg/mL, Bitte kontaktieren Sie uns zuerst, wenn die Konzentration die DMSO-Löslichkeit der jeweiligen Wirkstoffcharge überschreitet. )

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammflüssigkeit, fügen Sie als Nächstes hinzuμL PEG300, mischen und aufklären, fügen Sie als Nächstes hinzuμL Tween 80, mischen und aufklären, fügen Sie als Nächstes hinzu μL ddH2O, mischen und aufklären.

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammflüssigkeit, fügen Sie als Nächstes hinzu μL Maisöl, mischen und aufklären.

Hinweis: 1. Bitte stellen Sie sicher, dass die Flüssigkeit klar ist, bevor Sie das nächste Lösungsmittel hinzufügen.
2. Achten Sie darauf, die Lösungsmittel in der richtigen Reihenfolge hinzuzufügen. Sie müssen sicherstellen, dass die im vorherigen Schritt erhaltene Lösung klar ist, bevor Sie das nächste Lösungsmittel hinzufügen. Physikalische Methoden wie Vortexen, Ultraschall oder ein warmes Wasserbad können zur Unterstützung des Lösungsvorgangs verwendet werden.

Wirkungsmechanismus (Mechanism of Action)

Targets/IC50/Ki
GSK-3α
(Cell-free assay)
34.3 nM
GSK-3β
(Cell-free assay)
~34.3 nM
In vitro
SB 216763 displays similar potency for GSK-3β with 96% inhibition at 10 μM while exhibiting minimal activity against 24 other protein kinases including PKBα and PDK1 with IC50 of >10 μM. This compound stimulates glycogen synthesis in human liver cells with EC50 of 3.6 μM, and induces dose-dependent transcription of a β-catenin-LEF/TCF regulated reporter gene in HEK293 cells with a maximum 2.5-fold induction at 5 μM. It protects the cerebellar granule neurones from apoptotic cell death induced by LY-294002 or potassium-deprivation in a concentration-dependent manner, with a maximal neuroprotection at 3 μM in contrast with the effect of lithium chloride at which 10 mM is required. This chemical at 3 μM also completely prevents death of chicken dorsal root ganglion sensory neurones induced by LY-294002 regardless of NGF. It treatment at 5 μM markedly inhibits the GSK-3-dependent phosphorylation of neuronal-specific microtubule-associated protein tau in cerebellar granule neurones or recombinant tau in HEK293 cells, and induces increased levels of cytoplasmic β-catenin in both cells mimicking the effect of Wnt-mediated inhibition of GSK-3. In pancreatic cancer cell lines including BXPC-3, MIA-PaCa2, PANC1, ASPC1, and CFPAC, this compound treatment at 25-50 μM reduces cell viability in a dose-dependent manner, and leads to significant increase in apoptosis by 50% at 72 hours due to the specific down regulation of GSK-3β, while has no effect in HMEC or WI38 cell lines.
Kinase-Assay
GSK-3-Aktivitätsassay
Die GSK-3-Kinaseaktivität wird in Gegenwart verschiedener Konzentrationen von SB 216763 in einem Reaktionsgemisch gemessen, das Endkonzentrationen von 1 nM humanem GSK-3α, 50 mM MOPS pH 7,0, 0,2 mM EDTA, 10 mM Mg-Acetat, 7,5 mM β-Mercaptoethanol, 5% (w/v) Glycerin, 0,01% (w/v) Tween-20, 10% (v/v) DMSO und 28 μM GS-2-Peptidsubstrat enthält. Die GS-2-Peptidsequenz entspricht einer Region der Glykogensynthase, die durch GSK-3 phosphoryliert wird. Der Assay wird durch die Zugabe von 0,34 μCi [33P]γ-ATP initiiert. Die Gesamt-ATP-Konzentration beträgt 10 μM. Nach 30 Minuten Inkubation bei Raumtemperatur wird der Assay durch die Zugabe eines Drittels des Assayvolumens von 2,5% (v/v) H3PO4, das 21 mM ATP enthält, gestoppt. Proben werden auf P30-Phosphozellulosematten aufgetragen und sechsmal in 0,5% (v/v) H3PO4 gewaschen. Die Filtermatten werden in Probenbeutel mit Wallac-Betaplate-Szintillationsflüssigkeit eingeschweißt. Der 33P-Einbau in das Substratpeptid wird durch Zählen der Matten in einem Wallac-Microbeta-Szintillationszähler bestimmt.
In vivo
Administration of SB 216763 at 20 mg/kg significantly prevents lung inflammation and the subsequent fibrosis in bleomycin (BLM)-induced pulmonary inflammation and fibrosis model in mice by significantly blocking the production of inflammatory cytokines MCP-1 and TNF-α by macrophages, and significantly improves the survival of BLM-treated mice. This compound treatment causes a significant reduction in BLM-induced alveolitis by inhibiting alveolar epithelial cell damage.
Referenzen
  • [4] https://pubmed.ncbi.nlm.nih.gov/19959748/

Anwendungen (Applications)

Methoden Biomarker Bilder PMID
Western blot c-Myb pGSK-3β / GSK-3β / E2F1 / β-catenin
S1075-WB2
21795403
Growth inhibition assay Cell viability
S1075-viability1
24779365