| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Beta-secretase 1 (BACE1) is the primary molecular target. BACE1 is an aspartic protease that cleaves amyloid precursor protein (APP) at the beta-secretase site, initiating the production of amyloid-beta peptides. Lanabecestat acts as a potent inhibitor with unique slow off-rate kinetics, blocking Aβ production.
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|---|---|
| ln Vitro |
Lanabecestat inhibits BACE1 with a Ki of 0.4 nM and IC50 values of 2.2 nM in TR-FRET assays and 0.28 nM in sAPPβ release assays. It demonstrates high permeability and blood-brain barrier penetration. The compound shows approximately equipotent inhibition of BACE1 and BACE2.
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| ln Vivo |
In vivo, Lanabecestat (5-25 mg/kg p.o.) displays significant dose- and time-dependent reductions in plasma, cerebrospinal fluid, and brain concentrations of Aβ40, Aβ42, and sAβPPβ in mice, guinea pigs, and dogs. It reduces Aβ neuritic plaque burden without demonstrating clinical benefits in Alzheimer's disease trials.
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| Enzyme Assay |
BACE1 enzyme activity is measured using recombinant enzyme and a fluorescent peptide substrate. The assay utilizes a FRET-based detection system. Test compounds are pre-incubated with enzyme before substrate addition. Fluorescence is monitored continuously. IC50 values are calculated from dose-response curves.
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| Cell Assay |
Aβ production is measured in cell lines expressing APP. Cells are treated with test compound, and Aβ40 and Aβ42 levels in culture supernatants are quantified by ELISA or mass spectrometry.
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| Animal Protocol |
In vivo studies utilize mice, guinea pigs, and dogs. Compounds are administered by oral gavage at doses of 5-25 mg/kg. Plasma, cerebrospinal fluid, and brain tissue are collected for Aβ measurement by ELISA. Pharmacokinetic samples are collected for exposure-response analysis.
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| References |
| Exact Mass |
448.203
|
|---|---|
| CAS # |
1383986-31-9
|
| Related CAS # |
1383986-31-9 (HCl);1383982-64-6;1628076-74-3 (deleted);1522418-41-2 (camsylate);
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| PubChem CID |
154701347
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| Appearance |
Typically exists as solid at room temperature
|
| Hydrogen Bond Donor Count |
2
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
32
|
| Complexity |
827
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC#CC1=CC(=CN=C1)C2=CC3=C(CC4(C35N=C(C(=N5)N)C)CCC(CC4)OC)C=C2.Cl
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| InChi Key |
DMIXDSROGYHPOP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H28N4O.ClH/c1-4-5-18-12-21(16-28-15-18)19-6-7-20-14-25(10-8-22(31-3)9-11-25)26(23(20)13-19)29-17(2)24(27)30-26;/h6-7,12-13,15-16,22H,8-11,14H2,1-3H3,(H2,27,30);1H
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| 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.) |
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.
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