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| 25mg |
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Purity: ≥98%
LY2811376 (LY-2811376; LY 2811376) is a novel, potent, selective and the first orally bioavailable non-peptidic β-secretase (BACE1) inhibitor with the potential for the treatment of Alzheimer's Disease (AD). It inhibits BACE1 with an IC50 of 239 nM, and is able to decrease Aβ secretion with EC50 of 300 nM. LY2811376 was identified by fragment-based screening, and was able to lower Aβ levels in a mouse model of Alzheimer's disease as well as in normal dogs.
| ln Vitro |
Treatment with LY2811376 causes a concentration-dependent reduction in Aβ release in a human embryonic kidney cell line that overexpresses APP; the half-maximal effective concentration (EC50) is around 300 nM. When LY2811376 is administered to PDAPP transgenic mouse primary neuronal cells, Aβ production decreases in a concentration-dependent manner, with an approximate EC50 of 100 nM[1]. Good ADME characteristics and selectivity are exhibited by LY2811376 (BACE1 IC50=240 nM, cellular potency IC50=300 nM, and cathepsin D selectivity: around 10- and 65-fold, respectively)[3]. In a dose-dependent way, LY2811376 lowers the Aβ40 levels in cortex and plasma without affecting weight or health[4].
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| ln Vivo |
As the proximal cleavage products of APP proteolysis by BACE1, LY2811376 (10, 30, and 100 mg/kg, po) causes dose-dependent, substantial decreases in Aβ as well as sAPPβ and C99. In PDAPP mice, LY2811376 causes dose-dependent reductions in all APP-related PD indicators of BACE1 inhibition. The CSF sampling study's investigation of low (30 mg) and high (90 mg) dosages of LY2811376 is based on the PK and plasma Aβ1-40 PD found in the SAD study[1]. In mouse cortex, LY2811376 (30 mg/kg, po) can cause a 60% reduction in soluble Aβs[2]. In mice, LY2811376 (100 mg/kg, po) reduces the development and density of spines. The frequency of sEPSC and mEPSC are decreased by LY2811376 (100 mg/kg every 12 hours for 16 days), while the effects of LY2811376 on the amplitude of sEPSC are not significant[4].
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| References |
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| Additional Infomation |
LY2811376 has been used in trials studying the basic science of Alzheimer's Disease.
(S)-4-(2,4-Difluoro-5-(pyrimidin-5-yl)phenyl)-4-methyl-5,6-dihydro-4H-1,3-thiazin-2-amine has been reported in Aspergillus terreus with data available. |
| Molecular Formula |
C15H14F2N4S
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| Molecular Weight |
320.36
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| Exact Mass |
320.09
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| CAS # |
1194044-20-6
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| Related CAS # |
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| PubChem CID |
44251605
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| Appearance |
White to khaki solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
486.5±55.0 °C at 760 mmHg
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| Flash Point |
248.0±31.5 °C
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| Vapour Pressure |
0.0±1.2 mmHg at 25°C
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| Index of Refraction |
1.662
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| LogP |
1.45
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
22
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| Complexity |
430
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@]1(CCSC(=N1)N)C2=C(C=C(C(=C2)C3=CN=CN=C3)F)F
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| InChi Key |
MJQMRGWYPNIERM-HNNXBMFYSA-N
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| InChi Code |
InChI=1S/C15H14F2N4S/c1-15(2-3-22-14(18)21-15)11-4-10(12(16)5-13(11)17)9-6-19-8-20-7-9/h4-8H,2-3H2,1H3,(H2,18,21)/t15-/m0/s1
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| Chemical Name |
(4S)-4-(2,4-difluoro-5-pyrimidin-5-ylphenyl)-4-methyl-5,6-dihydro-1,3-thiazin-2-amine
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| Synonyms |
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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 |
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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 (7.80 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 (7.80 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 (7.80 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: 30% PEG400+0.5% Tween80+5% propylene glycol: 30 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1215 mL | 15.6074 mL | 31.2149 mL | |
| 5 mM | 0.6243 mL | 3.1215 mL | 6.2430 mL | |
| 10 mM | 0.3121 mL | 1.5607 mL | 3.1215 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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