Name: GSK-3 Inhibitor IX (BIO)
Brand: Selleck Chemicals
SKU: S7198
Rating: 5 (40 reviews)

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Batch: Zuiverheid: 99.93%

99.93

Gerelateerde doelwitten	PI3K Akt mTOR ATM/ATR DNA-PK AMPK PDPK1 PTEN PP2A PDK
Overige GSK-3 Inhibitoren	CHIR-99021 (Laduviglusib) Laduviglusib (CHIR-99021) Hydrochloride SB216763 CHIR-98014 TWS119 LY2090314 Tideglusib SB415286 AR-A014418 IM-12

Celkweek, behandeling & werkconcentratie

Cellijnen	Assaytype	Concentratie	Incubatietijd	Activiteitsbeschrijving	PMID
HEI-OC1	Function assay			Protection against cisplatin-induced cell death in neonatal mouse HEI-OC1 cells assessed as reduction in caspase-3/7 activity, EC50 = 0.192 μM.	30091915
SH-SY5Y	Function assay			Inhibition of GSK3-mediated beta-casein phosphorylation in human SH-SY5Y cells in presence of MG132 by Western blot analysis, IC50 = 0.29 μM.	18816110
K562	Antiproliferative assay		72 hrs	Antiproliferative activity against human K562 cells after 72 hrs by MTT assay, IC50 = 1.3 μM.	19783149
IMR90	Antiproliferative assay		72 hrs	Antiproliferative activity against human IMR90 cells after 72 hrs by MTT assay, IC50 = 1.9 μM.	19783149
HCT116	Antiproliferative assay		72 hrs	Antiproliferative activity against human HCT116 cells after 72 hrs by MTT assay, IC50 = 5.2 μM.	19783149
HepG2	Cytotoxicity assay		24 hrs	Cytotoxicity against human HepG2 cells assessed as cell growth inhibition after 24 hrs by alamar blue assay, IC50 = 5.3 μM.	28743492
HL60	Antiproliferative assay		5 days	Antiproliferative activity against human HL60 cells after 5 days by MTT assay, IC50 = 5.4 μM.	19783149
HuH7	Antiproliferative assay		72 hrs	Antiproliferative activity against human HuH7 cells after 72 hrs by MTT assay, IC50 = 6.2 μM.	19783149
SH-SY5Y	Cytotoxicity assay		48 hrs	Cytotoxicity against human SH-SY5Y cells after 48 hrs by MTS reduction assay, IC50 = 9 μM.	18816110
SH-SY5Y	Function assay		48 hrs	Survival of human SH-SY5Y cells after 48 hrs by MTS reduction assay, IC50 = 9.5 μM.	16854069
SH-SY5Y	Function assay			Death of human SH-SY5Y cells in absence of 20 uM Q-VD-OPh by MTS reduction assay, IC50 = 10 μM.	16854069
SH-SY5Y	Function assay			Death of human SH-SY5Y cells in presence of 20 uM Q-VD-OPh by MTS reduction assay, IC50 = 13 μM.	16854069
SH-SY5Y	Function assay		24 hrs	Survival of human SH-SY5Y cells after 24 hrs by MTS reduction assay, IC50 = 18 μM.	16854069
IMR32	Cytotoxicity assay		48 hrs	Cytotoxicity against human IMR32 cells assessed as cell viability after 48 hrs by MTT assay	21802947
SK-N-SH	Cytotoxicity assay		48 hrs	Cytotoxicity against human SK-N-SH cells assessed as cell viability after 48 hrs by MTT assay	21802947
NB39	Cytotoxicity assay		48 hrs	Cytotoxicity against human NB39 cells assessed as cell viability after 48 hrs by MTT assay	21802947
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
Rh30	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 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
A549	Function assay	10 uM	15 mins	Inhibition of human mPGES1 from human A549 cells assessed as PGE2 at 10 uM after 15 mins by HPLC	24697244
HEK293	Function assay	0.5 to 1 uM		Inhibition of human GSK3 activity in HEK293 cells containing the Wnt/beta-catenin activated reporter pSuperTOPFLASH (STF293 cells) at 0.5 to 1 uM by Wnt reporter gene assay	24697244
sf9	Function assay	1 uM		Inhibition of recombinant human N-terminal GST-tagged CDK4 (S4 to E303 residues)/Cyclin D1 (Q4 to I295 residues) expressed in sf9 cells at 1 uM using RB-CTF as substrate by filter binding assay	28557430
sf9	Function assay	1 uM		Inhibition of human N-terminal GST/His6-tagged GSK3beta (M1 to T420 residues) expressed in baculovirus infected sf9 cells at 1 uM using RBER-IRStide as substrate by filter binding assay	28557430
sf9	Function assay	1 uM		Inhibition of recombinant human N-terminal GST-tagged CDK2 (M1 to L298 residues)/Cyclin A2 (M1 to L432 residues) expressed in baculovirus infected sf9 cells at 1 uM using Histone H1 as substrate by filter binding assay	28557430
sf9	Function assay	1 uM		Inhibition of recombinant human N-terminal GST-tagged CDK5 (M1 to P292 residues)/p35NCK (M1 to R307 residues) expressed in baculovirus infected sf9 cells at 1 uM using RB-CTF as substrate by filter binding assay	28557430
sf9	Function assay	1 uM		Inhibition of human N-terminal GST/His6-tagged Aurora B (A2 to A344 residues) expressed in sf9 cells at 1 uM using tetra(LRRLSLG) as substrate by filter binding assay	28557430
sf9	Function assay	1 uM		Inhibition of human N-terminal GST/His6-tagged FGFR1 (G400 to R820 residues) expressed in baculovirus infected sf9 cells at 1 uM using Poly(Glu,Tyr)4:1 as substrate by filter binding assay	28557430
sf9	Function assay	1 uM		Inhibition of recombinant human N-terminal GST/His6-tagged CDK1 (M1 to M297 residues)/Cyclin B1 (M1 to V433 residues) expressed in sf9 cells at 1 uM using RB-CTF as substrate by filter binding assay	28557430
sf9	Function assay	1 uM		Inhibition of recombinant human N-terminal GST-tagged CDK2 (M1 to L298 residues)/Cyclin E1 (M1 to A395 residues) expressed in sf9 cells at 1 uM using RB-CTF as substrate by filter binding assay	28557430
sf9	Function assay	1 uM		Inhibition of human N-terminal GST/His6-tagged Aurora A (M1 to S403 residues) expressed in baculovirus infected sf9 cells at 1 uM using tetra(LRRLSLG) as substrate by filter binding assay	28557430
sf9	Function assay	1 uM		Inhibition of human N-terminal GST-tagged Aurora B (M1 to S27 residues) expressed in sf9 cells at 1 uM using CDC25C-derived peptide as substrate by filter binding assay	28557430
HT22	Function assay	10 uM	24 hrs	Inhibition of GSK3-mediated beta casein phosphorylation in mouse HT22 cells at 10 uM after 24 hrs by Western blot analysis in presence of MG132	22998443
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Chemische informatie, Opslag en Stabiliteit

Moleculair gewicht	356.17	Formule	C₁₆H₁₀BrN₃O₂	Opslag (Vanaf de ontvangstdatum)	3 jaar-20°Cpoeder
CAS-nr.	667463-62-9	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	GSK-3 Inhibitor IX, 6-bromoindirubin-3-oxime, 6-Bromoindirubin-3'-oxime, MLS 2052			Smiles	C1=CC=C2C(=C1)C(=C(N2)C3=C(NC4=C3C=CC(=C4)Br)O)N=O

Oplosbaarheid

In vitro
Batch:

DMSO : 71 mg/mL (199.34 mM)
(Met vocht verontreinigde DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Ethanol : 7 mg/mL

Water : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Moleculair gewicht
=	×	×

Verdunningscalculator Moleculair gewicht calculator

In vivo Batch:
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.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	3.000mg/ml (8.42mM)	Taking the 1 mL working solution as an example, add 50 μL 60 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

In vivo Formuleringscalculator (Heldere oplossing)

Stap 1: Voer de onderstaande informatie in (Aanbevolen: Een extra dier voor het geval van verlies tijdens het experiment)

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in het gedeelte Oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-mastervloeistof: mg geneesmiddel vooraf opgelost in μL DMSO ( Concentratie mastervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de partij geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toeμL PEG300, mengen en helder maken, voeg vervolgens toeμL Tween 80, mengen en helder maken, voeg vervolgens toe μL ddH₂O, mengen en helder maken.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toe μL Maïsolie, mengen en helder maken.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysische methoden zoals vortexen, echografie of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme

Kenmerken	The first pharmacological agent shown to maintain self-renewal in human and mouse embryonic stem cells.
Targets/IC₅₀/Ki	GSK-3 (Cell-free assay) 5 nM TYK2 (Cell-free assay) 30 nM CDK5/p35 (Cell-free assay) 0.08 μM CDK2/CyclinA (Cell-free assay) 0.30 μM CDK1/CyclinB (Cell-free assay) 0.32 μM JAK3 (Cell-free assay) 0.5 μM
In vitro	BIO (6-bromoindirubin-3'-oxime) is een specifieke remmer van glycogeen synthase kinase-3 (GSK-3), met een IC50 van 5 nM voor GSK-3α/β, vertoont een >16-voudige selectiviteit ten opzichte van CDK5. Deze verbinding interageert in de ATP-bindingspocket van deze kinasen, vermindert β-cateninefosforylering op een GSK-3-specifieke plaats in cellulaire modellen, en bootst Wnt-signalering in Xenopus-embryo's nauwkeurig na. In menselijke en muizen embryonale stamcellen handhaaft deze chemische stof het ongedifferentieerde fenotype en ondersteunt het de expressie van de pluripotente staat-specifieke transcriptiefactoren Oct-3/4, Rex-1 en Nanog. Deze door verbindingen gemedieerde Wnt-activering is functioneel reversibel, aangezien het stopzetten van de verbinding leidt tot normale multidifferentiatieprogramma's in zowel menselijke als muizen embryonale stamcellen. Het bevordert proliferatie in zoogdiercardiomyocyten. 6BIO is ook een pan-JAK remmer, met IC50-waarden van 0,03, 1,5, 8,0, 0,5 μM voor TYK2, JAK1, JAK2 en JAK3. Deze verbinding remt selectief de fosforylering van STAT3 en induceert apoptose van menselijke melanoomcellen.
Kinase Assay	Kinasetest
Kinase Assay	Kinase-activiteiten worden getest in Buffer A of C bij 30°C, bij een finale ATP-concentratie van 15 μM. Blanke waarden worden afgetrokken en activiteiten berekend als pmoles fosfaat ingebouwd tijdens een incubatie van 10 min. Controles worden uitgevoerd met geschikte verdunningen van dimethylsulfoxide. In enkele gevallen wordt fosforylering van het substraat beoordeeld door autoradiografie na SDS-PAGE. GSK-3α/β wordt gezuiverd uit varkenshersenen door affiniteitschromatografie op geïmmobiliseerd axine. Het wordt getest, na een 1/100 verdunning in 1 mg BSA/ml 10 mM DTT, met 5 μl 40 μM GS-1 peptide, een specifiek GSK-3 substraat, (YRRAAVPPSPSLSRHSSPHQSpEDEEE), in buffer A, in aanwezigheid van 15 μM [γ-³²P] ATP (3.000 Ci/mmol; 1 mCi/ml) in een finaal volume van 30 μl. Na 30 min incubatie bij 30°C worden aliquots van 25 μl van het supernatant gespot op stukjes Whatman P81 fosfocellulosepapier van 2,5 × 3 cm, en 20 seconden later worden de filters vijf keer gewassen (gedurende ten minste 5 min elke keer) in een oplossing van 10 ml fosforzuur/liter water. De natte filters worden geteld in aanwezigheid van 1 ml ACS-scintillatievloeistof.
In vivo	BIO onderdrukt de groei van melanoomtumoren in een muis xenograftmodel.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/14700633/ [2] https://pubmed.ncbi.nlm.nih.gov/14702635/ [3] https://pubmed.ncbi.nlm.nih.gov/16984885/ [4] https://pubmed.ncbi.nlm.nih.gov/21610112/

Toepassingen

Methoden	Biomarkers	PMID
Western blot	p-AKT / AKT / p21 / p27 p-β-catenin / β-catenin FoxO3a / FoxO1 / p-FoxO3a / p-FoxO1	27510556
Immunofluorescence	pAKT / p21 / p27 TNF-α E-cadherin / Nanog Oct3/4	27510556
Growth inhibition assay	Cell proliferation	27510556

Informatie klinische proef

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2024-05-22)

NCT-nummer	Rekrutering	Aandoeningen	Sponsor/Medewerkers	Startdatum	Fasen
NCT06337422	Not yet recruiting	Healthy Volunteer	International Bio service	September 23 2024	Phase 1
NCT04276857	Not yet recruiting	Locally Advanced Pancreatic Cancer\|Irreversible Electroporation	University of Saskatchewan	September 1 2024	Not Applicable
NCT06359041	Not yet recruiting	Generalized Myasthenia Gravis (gMG)	Cabaletta Bio	August 2024	Phase 1\|Phase 2

Technische ondersteuning

Gebruiksaanwijzing

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

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C5=C4/X	C5:	LOG(C5):
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GSK-3 Inhibitor IX (BIO) GSK-3 remmer

Chemische structuur

Moleculair gewicht: 356.17