solo per uso di ricerca

SB216763 GSK-3 Inibitore

Name: SB216763
Brand: Selleck Chemicals
SKU: S1075
Rating: 5 (93 reviews)

N. Cat.: S1075

SB216763 è un inibitore potente e selettivo della GSK-3 con una IC50 di 34,3 nM per GSK-3α ed è ugualmente efficace nell'inibire la GSK-3β umana. Questo composto attiva l'autophagy.

SB216763 GSK-3 Inibitore Chemical Structure

Struttura chimica

Peso molecolare: 371.22

Vai a

Controllo Qualità (Quality Control)

Lotto: Purezza: 99.98%

99.98

Target correlati	PI3K Akt mTOR ATM/ATR DNA-PK AMPK PDPK1 PTEN PP2A PDK
Altro GSK-3 Inibitori	CHIR-99021 (Laduviglusib) Laduviglusib (CHIR-99021) Hydrochloride TWS119 CHIR-98014 GSK-3 Inhibitor IX (BIO) LY2090314 Tideglusib SB415286 AR-A014418 1-Azakenpaullone

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

Linee cellulari	Tipo di saggio	Concentrazione	Tempo di incubazione	Descrizione dell'attività	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
Clicca per visualizzare più dati sperimentali sulle linee cellulari

Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Peso molecolare	371.22	Formula	C₁₉H₁₂N₂O₂Cl₂	Conservazione (Dalla data di ricezione)	3 anni-20°Cpolvere
N. CAS	280744-09-4	Scarica SDF		Conservazione delle soluzioni stock	1 anno-80°Cin solvente 1 mese-20°Cin solvente
Sinonimi	N/A			Smiles	CN1C=C(C2=CC=CC=C21)C3=C(C(=O)NC3=O)C4=C(C=C(C=C4)Cl)Cl

Solubilità (Solubility)

In vitro
Lotto:

DMSO : 23 mg/mL (61.95 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:
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 Corn oil Validato dai laboratori Selleck. Se necessiti di modifiche a questa formulazione, contatta il nostro team di vendita per test personalizzati.	4.000mg/ml (10.78mM)	Taking the 1 mL working solution as an example, add 50 μL of 80 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
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.

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)

Dosaggio: mg/kg Peso medio degli animali: g Volume di dosaggio per animale:μL Numero di animali:

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)

Targets/IC₅₀/Ki	GSK-3α (Cell-free assay) 34.3 nM GSK-3β (Cell-free assay) ~34.3 nM
In vitro	SB 216763 mostra una potenza simile per GSK-3β con un'inibizione del 96% a 10 μM, mentre esibisce un'attività minima contro altre 24 protein chinasi, incluse PKBα e PDK1, con IC50 >10 μM. Questo composto stimola la sintesi del glicogeno nelle cellule epatiche umane con una EC50 di 3,6 μM e induce una trascrizione dose-dipendente di un gene reporter regolato da β-catenina-LEF/TCF nelle cellule HEK293 con un'induzione massima di 2,5 volte a 5 μM. Protegge i neuroni granulari cerebellari dalla morte cellulare apoptotica indotta da LY-294002 o dalla deprivazione di potassio in modo concentrazione-dipendente, con una neuroprotezione massima a 3 μM in contrasto con l'effetto del cloruro di litio, per il quale sono richiesti 10 mM. Questa sostanza chimica a 3 μM previene anche completamente la morte dei neuroni sensoriali del ganglio della radice dorsale di pollo indotta da LY-294002, indipendentemente dal NGF. Il trattamento a 5 μM inibisce marcatamente la fosforilazione GSK-3-dipendente della proteina tau associata ai microtubuli specifica dei neuroni nei neuroni granulari cerebellari o della tau ricombinante nelle cellule HEK293, e induce livelli aumentati di β-catenina citoplasmatica in entrambe le cellule, mimando l'effetto dell'inibizione di GSK-3 mediata da Wnt. Nelle linee cellulari di cancro al pancreas, incluse BXPC-3, MIA-PaCa2, PANC1, ASPC1 e CFPAC, il trattamento con questo composto a 25-50 μM riduce la vitalità cellulare in modo dose-dipendente e porta a un aumento significativo dell'apoptosi del 50% a 72 ore a causa della specifica regolazione negativa di GSK-3β, mentre non ha alcun effetto nelle linee cellulari HMEC o WI38.
Saggio chinasico	test di attività GSK-3
Saggio chinasico	L'attività della chinasi GSK-3 viene misurata, in presenza di varie concentrazioni di SB 216763, in una miscela di reazione contenente concentrazioni finali di 1 nM di GSK-3α umana, 50 mM MOPS pH 7,0, 0,2 mM EDTA, 10 mM acetato di Mg, 7,5 mM β-mercaptoetanolo, 5% (p/v) glicerolo, 0,01% (p/v) Tween-20, 10% (v/v) DMSO e 28 μM di substrato peptidico GS-2. La sequenza peptidica GS-2 corrisponde a una regione della glicogeno sintasi che viene fosforilata dalla GSK-3. Il test viene avviato con l'aggiunta di 0,34 μCi di [³³P]γ-ATP. La concentrazione totale di ATP è di 10 μM. Dopo 30 minuti di incubazione a temperatura ambiente, il test viene interrotto con l'aggiunta di un terzo del volume del test di 2,5% (v/v) H₃PO₄ contenente 21 mM ATP. I campioni vengono deposti su tappetini di fosfocellulosa P30 e lavati sei volte in 0,5% (v/v) H₃PO₄. I tappetini filtranti vengono sigillati in sacchetti campione contenenti liquido di scintillazione Wallac betaplate. L'incorporazione di ³³P nel peptide substrato viene determinata contando i tappetini in un contatore a scintillazione Wallac microbeta.
In vivo	La somministrazione di SB 216763 a 20 mg/kg previene significativamente l'infiammazione polmonare e la successiva fibrosi in un modello murino di infiammazione e fibrosi polmonare indotta da bleomicina (BLM) bloccando significativamente la produzione di citochine infiammatorie MCP-1 e TNF-α da parte dei macrofagi e migliora significativamente la sopravvivenza dei topi trattati con BLM. Questo trattamento composto provoca una significativa riduzione dell'alveolite indotta da BLM inibendo il danno alle cellule epiteliali alveolari.
Riferimenti	[1] https://pubmed.ncbi.nlm.nih.gov/11033082/ [2] https://pubmed.ncbi.nlm.nih.gov/11279265/ [3] https://pubmed.ncbi.nlm.nih.gov/15781615/ [4] https://pubmed.ncbi.nlm.nih.gov/19959748/

Applicazioni (Applications)

Metodi	Biomarcatori	Immagini	PMID
Western blot	c-Myb pGSK-3β / GSK-3β / E2F1 / β-catenin		21795403
Growth inhibition assay	Cell viability		24779365

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):