Name: SB-525334
Brand: Selleck Chemicals
SKU: S1476
Rating: 5 (117 reviews)

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Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.99%

99.99

Gerelateerde doelwitten	PKC ROCK Bcr-Abl
Overige TGF-beta/Smad Inhibitoren	SB431542 RepSox (E-616452) Vactosertib (TEW-7197) LDN-193189 A-83-01 LDN-193189 Dihydrochloride Galunisertib (LY2157299) SRI-011381 (C381) LY2109761 SIS3 Hydrochloride

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)

Cellijnen	Assaytype	Concentratie	Incubatietijd	Formulering	Activiteitsbeschrijving	PMID
MiaPaCa2	Cell Viability Assay	0-10 μM	72 h		efficiently reduces the viability with	22399597
HUVECs	Function Assay	10 μM	72 h		reduces the phosphorylation of smad2	23968981
HUVECs	Function Assay	10 μM	72 h		blocks signaling	23968981
HUVECs	Function Assay	10 μM	24/48/72 h		leads to a disruption of the HUVEC monolayer after 72 hr	23968981
rhPOSTN	Apoptosis Assay	0.5 μM	48 h		significantly decreases the number of apoptotic cells	24129188
AsPC1	Cell Viability Assay	0-10 μM	72 h		efficiently reduces the viability with	22399597
PASMCs	Function Assay	1 μM	15 min		inhibits TGF-β1-mediated proliferation of familial iPAH PASMCs at an IC50 of 295 nmol/L	19116361
ELT-3	Function Assay	0.5/1.0/2.0 μM	1 h	DMSO	inhibits TGF-β signaling in leiomyomas	17505012
Sf9	Function assay				Inhibition of human recombinant GST-fused ALK5 expressed in Sf9 cells, IC50 = 0.162 μM.	20472445
TC32	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
A673	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 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
BT-12	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 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
Klik om meer experimentele gegevens over de cellijn te bekijken

Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Moleculair gewicht	343.42	Formule	C₂₁H₂₁N₅	Opslag (Vanaf de ontvangstdatum)	3 jaar-20°Cpoeder
CAS-nr.	356559-20-1	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	N/A			Smiles	CC1=NC(=CC=C1)C2=C(N=C(N2)C(C)(C)C)C3=CC4=NC=CN=C4C=C3

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 69 mg/mL (200.92 mM)
(Met vocht verontreinigde DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Ethanol : 69 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.
Clear solution	5%DMSO 1 Corn oil Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	3.450mg/ml (10.05mM)	Taking the 1 mL working solution as an example, add 50 μL of 69 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.
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.

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 (Mechanism of Action)

Targets/IC₅₀/Ki	TGFβR1(ALK5) (Cell-free assay) 14.3 nM
In vitro	SB 525334 shows no inhibition in the enzymes ALK2, 3, and 6, with IC50 values > 10 μM. SB 525334 blocks phosphorylation induced by TGF-β1 and nuclear translocation of Smad2/3 in renal proximal tubule cells. SB 525334 also inhibits the increased mRNA expression levels of plasminogen activator inhibitor-1 (PAI-1) and procollagen α1(I) induced by TGF-β1 in A498 renal epithelial carcinoma cells at 1 μM). SB 525334 (1 μM) attenuates the heightened sensitivity to TGF-β1 exhibited by pulmonary artery smooth muscle cells (PASMCs) from patients with familial forms of idiopathic pulmonary arterial hypertension (PAH).
Kinase Assay	Kinase-assay om de potentie en selectiviteit van SB 525334 te bepalen
Kinase Assay	Om de potentie van SB 525334 te bepalen, wordt gezuiverd GST-getagd kinase domein van ALK5 geïncubeerd met gezuiverd GST-getagd volledig Smad3 in aanwezigheid van ³³P-γATP en verschillende concentraties van SB 525334. De aflezing is radioactief gelabeld Smad3.Om de selectiviteit van SB 525334 te bepalen, worden gezuiverd GST-getagd kinase domein van ALK2 en ALK4 geïncubeerd met respectievelijk GST-getagd volledig Smad1 en Smad3, in aanwezigheid van verschillende concentraties van SB 525334. IC50-waarden worden berekend.
In vivo	SB 525334 (10 mg/kg/day) decreases the renal mRNA levels of PAI-1, procollagen α1(I), and procollagen α1(III) in a nephritis-induced renal fibrosis rat model. Furthermore, PAN-induced proteinuria is significantly inhibited by SB 525334 (10 mg/kg/day). SB 525334 may also be efficacious in mesenchymal tumors. SB 525334 (10 mg/kg/day) significantly decreases uterine mesenchymal tumor incidence, multiplicity, and size in Eker rats. SB 525334 significantly reverses pulmonary arterial pressure and inhibits right ventricular hypertrophy in a rat model of PAH. This is revealed by a significant reduction in pulmonary arteriole muscularization induced by monocrotaline (used to induce PAH) after treatment with SB 525334 (3 or 30 mg/kg). In a induced pulmonary fibrosis mice model, SB 525334 (10 mg/kg or 30 mg/kg) attenuates the histopathological alterations in the lung, and significantly decreased mRNA expression of Type I and III procollagen and fibronectin. SB 525334 also attenuates Smad2/3 nuclear translocation, myofibroblast proliferation, deposition of Type I collagen, and decreases CTGF-expressing cells.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/15769863/ [2] https://pubmed.ncbi.nlm.nih.gov/19116361/ [3] https://pubmed.ncbi.nlm.nih.gov/17505012/ [4] https://pubmed.ncbi.nlm.nih.gov/17274978/

Toepassingen (Applications)

Methoden	Biomarkers	Afbeeldingen	PMID
Western blot	Fibronectin / E-cadherin / Hif-1α		29127306
Immunofluorescence	E-cadherin / Vimentin		27471572

Veelgestelde vragen (Frequently Asked Questions)

Vraag 1:
I want to know the feasibility of using it via oral gavage in rodents (dosing, frequency, formulation…)?

Antwoord:
It can be used for oral gavage in rodents, and the vehicle we suggest is: 30% Propylene glycol, 5% Tween 80, 65% D5W (dextrose(5%)in water) at 20mg/ml maximum. Based on the following reference they administrated this compound at an estimated dose of 10 mg/kg/day in rat for 2 months: http://clincancerres.aacrjournals.org/content/13/10/3087.long

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SB-525334 ALK5-remmer

Moleculair gewicht: 343.42

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)

Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo Formuleringscalculator (Heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

Veelgestelde vragen (Frequently Asked Questions)

SB-525334 ALK5-remmer

Moleculair gewicht: 343.42

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkconcentratie (Cell Culture, Treatment & Working Concentration)

Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo Formuleringscalculator (Heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

Veelgestelde vragen (Frequently Asked Questions)

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)