Size | Price | |
---|---|---|
25mg | ||
50mg | ||
100mg | ||
250mg |
Purity: ≥98%
BMS 433796 is a novel and potent γ-secretase inhibitor with Aβ lowering activity in a transgenic mouse model of Alzheimer's disease. BMS-433796 exhibited favorable pharmacodynamic and pharmacokinetic profiles. Chronic dosing of BMS-433796 in Tg2576 mice suggested a narrow therapeutic window and Notch-mediated toxicity at higher doses. Reduction of brain beta-amyloid peptide (Abeta) synthesis by gamma-secretase inhibitors is a promising approach for the treatment of Alzheimer's disease.
ln Vitro |
At 1.2 nM, BMS-433796 reduced [3H]IN973 binding in a concentration-dependent manner. This value was comparable to the 0.8 nM inhibitory IC50 value of Aβ40 and the 0.8 nM inhibition of Aβ42 in human embryonic kidney cells overexpressing the Swedish mutant APP. 0.4 nanometers[2].
|
---|---|
ln Vivo |
In a pharmacokinetic investigation using male Sprague-Dawley rats, BMS 433796 was described. The total clearance of 40 was 5.2 ± 0.82 mL/min/kg (mean ± SEM; n = 3), showing decreased clearance, after a 10-minute intravenous infusion of PEG-400 at 2.3 μmol/kg. It appears that the half-life of terminal elimination is 4.6±0.48 hours. With a lengthy absorption period, the oral bioavailability of the 35 μmol/kg PEG-400 solution is 31%. BMS 433796 is not an inhibitor of human CYP (IC50>100 μM) and exhibits acceptable metabolic stability in human liver microsomal preparations [1]. Following administration of BMS-433796, there was a dose-dependent reduction in brain Aβ40, with an ED50 of 2.4 mg/kg [2].
|
References |
[1]. Prasad CV, et al. Discovery of (S)-2-((S)-2-(3,5-difluorophenyl)-2-hydroxyacetamido)-N-((S,Z)-3-methyl-4-oxo-4,5-dihydro-3H-benzo[d][1,2]diazepin-5-yl)propanamide (BMS-433796): a gamma-secretase inhibitor with Abeta lowering activity in a transgenic mouse
[2]. Goldstein ME, et al. Ex vivo occupancy of gamma-secretase inhibitors correlates with brain beta-amyloid peptide reduction in Tg2576 mice. J Pharmacol Exp Ther. 2007 Oct;323(1):102-8 |
Molecular Formula |
C19H16N4O4F2
|
---|---|
Molecular Weight |
402.35154
|
CAS # |
935525-13-6
|
SMILES |
C[C@H](NC([C@H](C1=CC(F)=CC(F)=C1)O)=O)C(N[C@H]2C3=CC=CC=C3C=NN(C)C2=O)=O
|
InChi Key |
HXEHCCYOTHDPPI-NBHSMZAVSA-N
|
InChi Code |
InChI=1S/C21H20F2N4O4/c1-11(25-20(30)18(28)13-7-14(22)9-15(23)8-13)19(29)26-17-16-6-4-3-5-12(16)10-24-27(2)21(17)31/h3-11,17-18,28H,1-2H3,(H,25,30)(H,26,29)/t11-,17-,18-/m0/s1
|
Chemical Name |
(S)-2-((S)-2-(3,5-difluorophenyl)-2-hydroxyacetamido)-N-((S)-3-methyl-4-oxo-4,5-dihydro-3H-benzo[d][1,2]diazepin-5-yl)propanamide
|
Synonyms |
BMS433796; BMS-433796; BMS 433796.
|
Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400  (Please use freshly prepared in vivo formulations for optimal results.) |
---|
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.4854 mL | 12.4270 mL | 24.8540 mL | |
5 mM | 0.4971 mL | 2.4854 mL | 4.9708 mL | |
10 mM | 0.2485 mL | 1.2427 mL | 2.4854 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.