Name: Avagacestat (BMS-708163)
Brand: Selleck Chemicals
SKU: S1262
Rating: 5 (22 reviews)

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Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.63%

99.63

Gerelateerde doelwitten	HDAC Caspase Proteasome MMP HCV Protease Cysteine Protease Tyrosinase HIV Protease DPP Serine Protease
Overig Secretase Inhibitoren	DAPT RO4929097 (RG-4733) LY411575 Nirogacestat (PF-03084014) Dibenzazepine (YO-01027) MK-0752 Semagacestat (LY450139) MDL-28170 L-685,458 NGP 555

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)

Cellijnen	Assaytype	Incubatietijd	Activiteitsbeschrijving
human IMR32 cell	Function assay	2 h	Inhibition of gamma-secretase in human IMR32 cell membrane using APP as substrate after 2 hrs by ELISA, IC50=0.13 nM
human H4 cells	Function assay		Inhibition of gamma secretase-mediated amyloid beta42 production in human H4 cells expressing human APP swedish mutant, IC50=0.225 μM
HEK293 cells	Function assay		Inhibition of gamma-secretase in HEK293 cells after overnight incubation by Western blotting analysis, IC50=1.2 nM
CHO cells	Function assay		Inhibition of gamma-secretase in CHO cells assessed expressing APPSw assessed as inhibition of amyloid beta(1 to x) secretion after overnight incubation by ELISA, ED50=1.2 nM
human IMR32 cell	Function assay	2 h	Inhibition of gamma-secretase in human IMR32 cell membrane using Notch as substrate after 2 hrs by ELISA, IC50=1.5 nM
human 786-0 cell	Growth inhibition assay		Inhibition of human 786-0 cell growth in a cell viability assay, IC50=0.32173 μM
human NCI-H810 cell	Growth inhibition assay		Inhibition of human NCI-H810 cell growth in a cell viability assay, IC50=0.42598 μM
human IGR-1 cell	Growth inhibition assay		Inhibition of human IGR-1 cell growth in a cell viability assay, IC50=1.04778 μM
human SK-MEL-3 cell	Growth inhibition assay		Inhibition of human SK-MEL-3 cell growth in a cell viability assay, IC50=1.49922 μM
human HT-1080 cell	Growth inhibition assay		Inhibition of human HT-1080 cell growth in a cell viability assay, IC50=2.48764 μM
human NCI-H23 cell	Growth inhibition assay		Inhibition of human NCI-H23 cell growth in a cell viability assay, IC50=3.9322 μM
human Calu-6 cell	Growth inhibition assay		Inhibition of human Calu-6 cell growth in a cell viability assay, IC50=4.96014 μM
human CAPAN-1 cell	Growth inhibition assay		Inhibition of human CAPAN-1 cell growth in a cell viability assay, IC50=5.17886 μM
human COLO-668 cell	Growth inhibition assay		Inhibition of human COLO-668 cell growth in a cell viability assay, IC50=5.40221 μM
human TE-6 cell	Growth inhibition assay		Inhibition of human TE-6 cell growth in a cell viability assay, IC50=6.19082 μM
human LCLC-97TM1 cell	Growth inhibition assay		Inhibition of human LCLC-97TM1 cell growth in a cell viability assay, IC50=10.0886 μM
human CAS-1 cell	Growth inhibition assay		Inhibition of human CAS-1 cell growth in a cell viability assay, IC50=13.671 μM
human RPMI-2650 cell	Growth inhibition assay		Inhibition of human RPMI-2650 cell growth in a cell viability assay, IC50=13.8124 μM
human MDA-MB-157 cell	Growth inhibition assay		Inhibition of human MDA-MB-157 cell growth in a cell viability assay, IC50=14.2431 μM
human KINGS-1 cell	Growth inhibition assay		Inhibition of human KINGS-1 cell growth in a cell viability assay, IC50=14.3762 μM
human BB49-HNC cell	Growth inhibition assay		Inhibition of human BB49-HNC cell growth in a cell viability assay, IC50=14.4138 μM
human SK-UT-1 cell	Growth inhibition assay		Inhibition of human SK-UT-1 cell growth in a cell viability assay, IC50=14.6882 μM
human EW-11 cell	Growth inhibition assay		Inhibition of human EW-11 cell growth in a cell viability assay, IC50=14.8832 μM
human D-502MG cell	Growth inhibition assay		Inhibition of human D-502MG cell growth in a cell viability assay, IC50=14.9034 μM
human MMAC-SF cell	Growth inhibition assay		Inhibition of human MMAC-SF cell growth in a cell viability assay, IC50=15.0833 μM
human NCI-H1648 cell	Growth inhibition assay		Inhibition of human NCI-H1648 cell growth in a cell viability assay, IC50=15.778 μM
human NCI-H292 cell	Growth inhibition assay		Inhibition of human NCI-H292 cell growth in a cell viability assay, IC50=15.8806 μM
human NMC-G1 cell	Growth inhibition assay		Inhibition of human NMC-G1 cell growth in a cell viability assay, IC50=16.6293 μM
human SAS cell	Growth inhibition assay		Inhibition of human SAS cell growth in a cell viability assay, IC50=17.7812 μM
human HCT-116 cell	Growth inhibition assay		Inhibition of human HCT-116 cell growth in a cell viability assay, IC50=18.7965 μM
human SBC-5 cell	Growth inhibition assay		Inhibition of human SBC-5 cell growth in a cell viability assay, IC50=19.03 μM
Klik om meer experimentele gegevens over cellijnen te bekijken

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Molecuulgewicht	520.88	Formule	C₂₀H₁₇ClF₄N₄O₄S	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	1146699-66-2	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	N/A			Smiles	C1=CC(=CC=C1S(=O)(=O)N(CC2=C(C=C(C=C2)C3=NOC=N3)F)C(CCC(F)(F)F)C(=O)N)Cl

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 104 mg/mL (199.66 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Molecuulgewicht
=	×	×

Verdunningscalculator Molecuulgewichtcalculator

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 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.	5.000mg/ml (9.60mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	1.650mg/ml (3.17mM)	Taking the 1 mL working solution as an example, add 50 μL of 33 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.

In vivo formulatiecalculator (heldere oplossing)

Stap 1: Voer onderstaande informatie in (Aanbevolen: een extra dier om rekening te houden met 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 de sectie oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

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

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toeμL PEG300, mengen en verhelderen, daarna toevoegenμL Tween 80, mengen en verhelderen, daarna toevoegen μL ddH₂O, mengen en verhelderen.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toe μL Maïsolie, mengen en verhelderen.

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. Fysieke methoden zoals vortexen, ultrasoon of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme (Mechanism of Action)

Kenmerken	Appears to be more “notch sparing” than semagacestat (LY450139).
Targets/IC₅₀/Ki	Aβ42 (in H4-8Sw cells) 0.27 nM Aβ40 (in H4-8Sw cells) 0.3 nM
In vitro	Avagacestat (BMS-708163) exhibits weaker selectivity for inhibition of Notch processing with 193-fold IC50 value.
In vivo	Avagacestat (BMS-708163) significantly reduces Aβ40 levels for sustained periods in brain, plasma, and cerebrospinal fluid in rats and dogs following oral administration. It has no dose-limiting effects in dogs (3 mg/kg during 6 months), with a high brain to plasma ratio (2.4).
Referenties	[1] http://pubs.acs.org/doi/abs/10.1021/ml1000239

Informatie over klinische proeven (Clinical Trial Information)

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

NCT-nummer	Werving	Aandoeningen	Sponsor/medewerkers	Startdatum	Fasen
NCT01002079	Completed	Alzheimer Disease	Bristol-Myers Squibb\|PRA Health Sciences	August 2010	Phase 1
NCT01057030	Completed	Alzheimer Disease	Bristol-Myers Squibb	March 2010	Phase 1
NCT01042314	Completed	Alzheimer Disease	Bristol-Myers Squibb	January 2010	Phase 1
NCT01039194	Completed	Alzheimer Disease	Bristol-Myers Squibb	January 2010	Phase 1
NCT00979316	Completed	Alzheimer Disease	Bristol-Myers Squibb	September 2009	Phase 1
NCT00890890	Terminated	Alzheimer''s Disease	Bristol-Myers Squibb	May 2009	Phase 2

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C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Avagacestat (BMS-708163) Secretase Remmer

Molecuulgewicht: 520.88

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo formulatiecalculator (heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Informatie over klinische proeven (Clinical Trial Information)

Avagacestat (BMS-708163) Secretase Remmer

Molecuulgewicht: 520.88

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkzame concentratie (Cell Culture, Treatment & Working Concentration)

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo formulatiecalculator (heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Informatie over klinische proeven (Clinical Trial Information)

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)