δ-Secretase inhibitor 11 (compound 11) is an orally bioavailable, BBB (blood-brain barrier) permeable/penetrable, non-toxic, selective and specific δ-secretase inhibitor (antagonist) with IC50 of 0.7 μM. δ-Secretase inhibitor 11 interacts with the active site and allosteric site of δ-Secretase. δ-Secretase inhibitor 11 attenuates tau and APP (amyloid precursor protein) cleavage. δ-Secretase inhibitor 11 can improve synaptic dysfunction and cognitive dysfunction in tau P301S and 5XFAD transgenic mouse models. δ-Secretase inhibitor 11 may be utilized in Alzheimer's disease (AD) research.

Physicochemical Properties

Molecular Formula	C10H12N4O2
Molecular Weight	220.22788
Exact Mass	220.096
Elemental Analysis	C, 54.54; H, 5.49; N, 25.44; O, 14.53
CAS #	842964-18-5
PubChem CID	1095027
Appearance	Brown to dark brown solid powder
LogP	1.287
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	1
Heavy Atom Count	16
Complexity	247
Defined Atom Stereocenter Count	0
SMILES	N1=C2C(=CC=C(C2=NO1)N1CCOCC1)N
InChi Key	LWCSTSZSZFUHAT-UHFFFAOYSA-N
InChi Code	InChI=1S/C10H12N4O2/c11-7-1-2-8(10-9(7)12-16-13-10)14-3-5-15-6-4-14/h1-2H,3-6,11H2
Chemical Name	4-morpholin-4-yl-2,1,3-benzoxadiazol-7-amine
Synonyms	5LUB; 5 LUB; 5-LUB;
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 Note: This product requires protection from light (avoid light exposure) during transportation and storage.
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

ln Vitro	Delta-secretase inhibitor 11 (Compound 11) inhibits delta-secretase inhibitor in a concentration- and time-dependent way (0–1 μM, 10 minutes) [1]. Tau and APP (amyloid precursor protein) fragments are selectively distributed through delta-secretase by Delta-Secretase Inhibitor 11 (0-1 μM) [1].
ln Vivo	Delta-secretase inhibitor 11 (Compound 11) (10 mg/kg, lateral, once daily for 3 months) exhibits neuroprotective properties while attenuating OGD (oxygen glucose augmentation)-induced neuronal damage [1]. In the 5XFAD model, Secretase Inhibitor 11 (0-10 mg/kg, sidewall, once daily for 1.5 and 3 months) reduces Aβ accumulation and cognitive impairments while inhibiting delta-responsive kinase activity [1].
Animal Protocol	Animal/Disease Models: Tau P301S transgenic mice (n=4 mice per group) [1] Doses: 10 mg/kg Route of Administration: Orally, one time/day for 3 months Experimental Results: Significant inhibition of wild-type and tau P301S δ-secretase activity in mouse brains increases PP2A activity and attenuates tau truncation and phosphorylation in tau P301S mice. Ameliorates synaptic loss and restores synaptic dysfunction in tau P301S mice. Animal/Disease Models: 5XFAD mice [1] Doses: 2, 5 or 10 mg kg Route of Administration: Orally, one time/day for 1.5 and 3 months Experimental Results: Attenuated β-secretase-mediated APP processing, Dramatically Reduces Aβ concentrations 1-40 and Aβ 1-42 in brain lysates and attenuates Aβ deposition in a time- and dose-dependent manner.
References	[1]. Inhibition of delta-secretase improves cognitive functions in mouse models of Alzheimer's disease. Nat Commun. 2017 Mar 27;8:14740.

Solubility Data

Solubility (In Vitro)

DMSO : ~125 mg/mL (~567.59 mM)

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	4.5407 mL	22.7035 mL	45.4071 mL
	5 mM	0.9081 mL	4.5407 mL	9.0814 mL
	10 mM	0.4541 mL	2.2704 mL	4.5407 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.