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| 5mg |
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| 10mg |
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| 25mg |
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| 100mg |
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Purity: ≥98%
Lanabecestat (formerly AZD-3293; LY-3314814; AZD3293; LY3314814) is a novel potent, orally bioactive, highly permeable, brain-penetreable inhibitor of beta-secretase 1 cleaving enzyme (BACE) with a Ki of 0.4 nM. AZD3293 displayed significant dose- and time-dependent reductions in plasma, cerebrospinal fluid, and brain concentrations of Aβ40, Aβ42, and sAβPPβ. The in vitro potency of AZD3293 was demonstrated in several cellular models, including primary cortical neurons. In vivo in mice, guinea pigs, and dogs, AZD3293 displayed significant dose- and time-dependent reductions in plasma, cerebrospinal fluid, and brain concentrations of Aβ40, Aβ42, and sAβPPβ. The in vitro potency of AZD3293 in mouse and guinea pig primary cortical neuronal cells was correlated to the in vivo potency expressed as free AZD3293 concentrations in mouse and guinea pig brains. In mice and dogs, the slow off-rate from BACE1 may have translated into a prolongation of the observed effect beyond the turnover rate of Aβ. The preclinical data strongly support the clinical development of AZD3293, and patients with AD are currently being recruited into a combined Phase 2/3 study to test the disease-modifying properties of AZD3293.
| ln Vitro |
With a competitive and reversible mode of action towards the hBACE1 active site, lanabecestat functions as a complete inhibitor of BACE1 in vitro. Lanabecestat exhibits a notably slow target off-rate along with a very high target affinity. The estimated t1/2 of lanabecestat's off-rate is roughly 9 hours. In primary neuron cultures from mice and guinea pigs as well as in SH-SY5Y cells that overexpress AβPP, lanabecestat exhibits pM potency (IC50=610 pM, 310 pM, and 80 pM, respectively). Using mouse, rat, guinea pig, dog, and human plasma, equilibrium dialysis is used to determine the in vitro plasma protein binding of lanabecestat. For the length of the in vitro incubation period, at least, the compound remains stable in the plasma of these species. For mice, the unbound fractions are 1.3% to 1.8%, for rats, 4.2% to 5.9%, for guinea pigs, 8.3% to 10.3%, for dogs, 9.4% to 10.3%, and for human plasma, 7.7% to 9.4%. Human blood's mean blood:plasma ratio of 0.7 shows no discernible relationship to red blood cells. In the brain tissue binding assay, the free fraction is 4.5%[1].
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| ln Vivo |
Lanabecestat shows notable dose- and time-dependent decreases in the concentrations of Aβ40, Aβ42, and sAβPPβ in the brain, cerebrospinal fluid, and plasma in mice, guinea pigs, and dogs[1].
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| Animal Protocol |
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| References |
[1]. Eketjäll S, et al. AZD3293: A Novel, Orally Active BACE1 Inhibitor with High Potency and Permeability and Markedly Slow Off-Rate Kinetics. J Alzheimers Dis. 2016;50(4):1109-2
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| Molecular Formula |
C26H28N4O
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| Molecular Weight |
412.53
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| CAS # |
1383982-64-6
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| Related CAS # |
(1α,1'S,4β)-Lanabecestat;1384082-96-5
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| SMILES |
CC#CC1=CC(C2=CC([C@@]34N=C(C)C(N)=N4)=C(C[C@@]53CC[C@@H](OC)CC5)C=C2)=CN=C1
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.06 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.06 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.06 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 2.5 mg/mL (6.06 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 5: ≥ 2.5 mg/mL (6.06 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 6: 0.5 mg/mL (1.21 mM) in 1% DMSO 99% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4241 mL | 12.1203 mL | 24.2407 mL | |
| 5 mM | 0.4848 mL | 2.4241 mL | 4.8481 mL | |
| 10 mM | 0.2424 mL | 1.2120 mL | 2.4241 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.
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