LY2886721 HCl is a specific, orally bioactive beta-amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor (antagonist) with IC50 of 20.3 nM against recombinant human BACE1. LY2886721 HCl is more selective for BACE1 than cathepsin D, pepsin and renin, but lacks selectivity for BACE2 (IC50 of 10.2 nM). LY2886721 HCl crosses the BBB (blood-brain barrier) and may be used in AD/Alzheimer's disease study.

Physicochemical Properties

Molecular Formula	C18H17CLF2N4O2S
Molecular Weight	426.87
Exact Mass	426.073
CAS #	1262036-49-6
Related CAS #	LY2886721;1262036-50-9
PubChem CID	50902942
Appearance	Typically exists as solid at room temperature
LogP	4.028
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	3
Heavy Atom Count	28
Complexity	610
Defined Atom Stereocenter Count	2
SMILES	Cl.FC1C=CC(C(NC2C=CC(F)=C([C@]34COC[C@H]3CSC(=N4)N)C=2)=O)=NC=1
InChi Key	JHHMCINLHBUFHB-GHDSXOKHSA-N
InChi Code	InChI=1S/C18H16F2N4O2S.ClH/c19-11-1-4-15(22-6-11)16(25)23-12-2-3-14(20)13(5-12)18-9-26-7-10(18)8-27-17(21)24-18;/h1-6,10H,7-9H2,(H2,21,24)(H,23,25);1H/t10-,18-;/m0./s1
Chemical Name	N-[3-[(4aS,7aS)-2-amino-4,4a,5,7-tetrahydrofuro[3,4-d][1,3]thiazin-7a-yl]-4-fluorophenyl]-5-fluoropyridine-2-carboxamide;hydrochloride
HS Tariff Code	2934.99.9001
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)

Biological Activity

Targets	IC50: 20.3 nM (Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1)); 10.2 nM (BACE2)[1]
ln Vitro	When HEK293Swe cells are exposed to LY2886721 hydrochloride at increasing concentrations over night, the amount of Aβ released into the condition medium decreases in a concentration-dependent manner. The EC50s for the suppression of Aβ1-40 and Aβ1-42 are roughly 18.5 and 19.7 nM, respectively, which is consistent with a mechanism of BACE inhibition[1]. The synthesis of Aβ decreases concentration-dependently when PDAPP neuronal cells are exposed to increasing concentrations of LY2886721 hydrochloride over night. The EC50s for Aβ1-40 inhibition and identical Aβ1-42 inhibition in PDAPP neuronal cultures are similar at approximately 10 nM, as found in HEK293Swe cells[1].
ln Vivo	Treatment with LY2886721 hydrochloride (3-30 mg/kg; oral dose; PDAPP mice) dramatically lowers Aβ1-x levels in the cortical and hippocampus regions. C99 and sAPPβ levels in brain parenchymal tissue are significantly reduced after treatment with LY2886721 hydrochloride[1].
References	[1]. The potent BACE1 inhibitor LY2886721 elicits robust central Aβ pharmacodynamic responses in mice, dogs, and humans. J Neurosci. 2015 Jan 21;35(3):1199-210.

Solubility Data

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

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.3426 mL	11.7132 mL	23.4263 mL
	5 mM	0.4685 mL	2.3426 mL	4.6853 mL
	10 mM	0.2343 mL	1.1713 mL	2.3426 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.