Name: BMS-536924
Brand: Selleck Chemicals
SKU: S1012
Rating: 5 (26 reviews)

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Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.98%

99.98

Gerelateerde doelwitten	EGFR VEGFR FGFR PDGFR c-Met Src MEK CSF-1R HER2 FLT3
Overige IGF-1R Inhibitoren	Linsitinib (OSI-906) NVP-AEW541 BMS-754807 Picropodophyllin (AXL1717) AG-1024 GSK1904529A NVP-ADW742 NT157 PQ 401 MSDC-0160

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

Moleculair gewicht	479.96	Formule	C₂₅H₂₆ClN₅O₃	Opslag (Vanaf de ontvangstdatum)	3 jaar-20°Cpoeder
CAS-nr.	468740-43-4	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	CS-0117			Smiles	CC1=CC(=CC2=C1N=C(N2)C3=C(C=CNC3=O)NCC(C4=CC(=CC=C4)Cl)O)N5CCOCC5

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 96 mg/mL (200.01 mM)
(Met vocht verontreinigde DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : 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	30%PEG400 1 0.5%Tween80 2 5%propylene glycol Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	30.000mg/ml (62.51mM)	Taking the 1 mL working solution as an example, add 300 μL of 100 mg/ml clarified PEG400 stock solution to 5 μL of Tween80, mix evenly to clarify it; add 50 μL Propylene glycol to the above system, mix evenly to clarify it; then continue to add 645 μL ddH2O to adjust the volume. to 1 mL. 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.

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	Insulin Receptor 73 nM IGF-1R 100 nM FAK 150 nM MEK 182 nM LCK 341 nM VEGFR2 1.4 μM EGF 1.6 μM Met 4.87 μM
In vitro	BMS-536924 also inhibits FAK and Lck with IC50 of 150 nM and 341 nM, respectively. This compound inhibits cellular proliferation and disrupts Akt and MAPK phosphorylation. It inhibits IGF-I-stimulated IGF-1R signaling in MCF10A cells and blocks constitutive IGF-1R activity in CD8-IGF-1R-MCF10A. Preincubation of MCF10A cells with 1 μM of this chemical completely blocks the ability of IGF-I to stimulate IGF-1R phosphorylation. IGF-I stimulation results in increased phosphorylation of ERK1/2, GSK3β, and Akt. This compound inhibits this ligand-induced phosphorylation. Treatment of the CD8-IGF-1R-MCF10A cells with this inhibitor results in a dose-dependent inhibition of phosphorylation with partial inhibition at 0.01 μM and 0.1 μM, but complete receptor inhibition at a concentration of 1 μM. Maximal inhibition of phosphorylated IGF-1R is observed as early as 10 minutes following incubation. It retains its ability to inhibit IGF-1R phosphorylation for up to 48 hours. Addition of this agent time-dependently inhibits Akt phosphorylation starting at 1 hour. By 48 hours, Akt activation is completely blocked. Treatment with this compound shows antiproliferation activity in a panel of cancer cell lines including TC32, HT1080/S, SK-LMS-1, H513 and CTR cells. pIGF-1R/pIR is activated upon IGF-I/insulin stimulation and the activation is inhibited by this chemical at similar potencies in Rh41 and Rh36 cell lines. The expression of programmed cell death 4 (PDCD4), cleavage of poly(ADP-ribose) polymerase (PARP) and caspase-3 are up-regulated in Rh41 cells treated with this inhibitor.
Kinase Assay	IGF-I-Pathactiviteit
Kinase Assay	1 × 10⁶ pBabe-MCF10A-cellen worden gezaaid op schaaltjes van 60 mm. Na 24 uur wordt het medium vervangen door serumvrij medium en 's nachts geïncubeerd bij 37 °C gedurende 24 uur. Cellen worden vervolgens gedurende 1 uur voor-geïncubeerd met of zonder 1 uM BMS-536924 in serumvrij medium, gevolgd door stimulatie met IGF-I (50 ng/mL) gedurende 10 minuten. Celmonolagen worden tweemaal gewassen met PBS en geoogst voor immunoblotanalyse
In vivo	Oral administration of BMS-536924 at 100-300 mpk strongly inhibits IGR-1R Sal tumor model. Efficacy is also observed in the nonengineered Colo205 human colon carcinoma mode. Oral administration of this compound on a once a day schedule (100-300 mpk) or a twice a day schedule (50, 100 mpk) demonstrates antitumor activity in this tumor model. Oral glucose tolerance test (OGTT) shows 100 mpk (b.i.d.) causes a significant elevation in glucose levels after glucose challenge. The pharmacokinetic parameters of this chemical, administered orally in poly(ethylene glycol) 400 and water (80:20 v/v), are determined in mouse, rat, dog, and monkey. Good bioavailability is evident in all species. Significant nonlinear pharmacokinetics is observed in rodents at increasing p.o. dose. This compound reduces the tumor xenografts volume of CD8-IGF-1R-MCF10A cells after two weeks' treatment (100mg/kg) to 76%. Oral administration of 70 mg/kg this chemical significantly inhibits tumor growth (TGBC-1TKB cells) inoculated in nude mice. It up regulates apoptosis in xenografts tumors. The treatment doesn't have adverse effects on the body weight of mice or the glucose levels at the time of death, suggesting tolerable toxicity.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/16134929/ [2] https://pubmed.ncbi.nlm.nih.gov/19118050/ [3] https://pubmed.ncbi.nlm.nih.gov/19117999/ [4] https://pubmed.ncbi.nlm.nih.gov/22044563/ [5] https://pubmed.ncbi.nlm.nih.gov/18765832/ [6] https://pubmed.ncbi.nlm.nih.gov/19117999/

Veelgestelde vragen (Frequently Asked Questions)

Vraag 1:
What are the differences between it and S1034?

Antwoord:
The most remarkable difference between these two IGF-IR inhibitors is that S1012 is an ATP-competitive inhibitor. You will get more information about the differences between IR inhibitors in this reference: http://www.sciencedirect.com/science/article/pii/S1359644605035129.

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BMS-536924 IGF-1R Remmer

Moleculair gewicht: 479.96