Lesogaberan (AZD-3355) napadisylate is a potent and specific GABAB receptor agonist/activator with EC50 of 8.6 nM for human recombinant GABAB receptor. Affinity (Kis) of Lesogaberan napadisylate for rat GABAB and GABAA receptors, measured by [3H]GABA binding displacement in meninges: 5.1 nM and 1.4 μM, respectively. Lesogaberan napadisylate inhibits transient lower esophageal sphincter relaxation via a peripheral mode of action.

Physicochemical Properties

Molecular Formula	C13H17FNO5PS
Molecular Weight	349.31
Exact Mass	348.047
CAS #	477956-38-0
Related CAS #	Lesogaberan hydrochloride;2925644-17-1;Lesogaberan;344413-67-8
PubChem CID	9950225
Appearance	Typically exists as solid at room temperature
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	4
Heavy Atom Count	22
Complexity	380
Defined Atom Stereocenter Count	1
SMILES	C1=CC=C2C=C(C=CC2=C1)S(=O)(=O)O.C([C@H](C[P+](=O)O)F)N
InChi Key	QERQFECXORQRHA-ZYRQIYSTSA-O
InChi Code	InChI=1S/C10H8O3S.C3H7FNO2P/c11-14(12,13)10-6-5-8-3-1-2-4-9(8)7-10;4-3(1-5)2-8(6)7/h1-7H,(H,11,12,13);3H,1-2,5H2/p+1/t;3-/m.1/s1
Chemical Name	[(2R)-3-amino-2-fluoropropyl]-hydroxy-oxophosphanium;naphthalene-2-sulfonic acid
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	Ki: 5.1±1.2 nM (rat GABAB), 1.4±0.3 μM (rat GABAA)[1] EC50: 8.6±0.77 nM (human GABAB receptor)[1]
ln Vitro	In vitro proliferation of human islet cells is increased by lesogaberan (3–30 nM)[2].
ln Vivo	Lesogaberan (AZD3355) has a biphasic dose-response curve and potently stimulates recombinant human GABAB receptors while inhibiting transient lower esophageal sphincter relaxation (TLESR) in dogs[1]. In mice with islet grafts, oral Lesogaberan (0.08 mg/mL; 48 hours) prevents human islet β-cells from apoptosis[2]. In female Sprague-Dawley rats, lesogaberan (7 μmol/kg) exhibits relatively low systemic clearance and high oral availability (88% in the dog and 100% in the rat)[1].
Cell Assay	Cell Proliferation Assay[2] Cell Types: Human islet cells Tested Concentrations: 3, 10, and 30 nM Incubation Duration: 4 days Experimental Results: Had a small but nonsignificant promitotic effect at 3 nM, while treatment at higher dosages (10 and 30 nM) led to a 2-3-fold increase in proliferation relative to that of islets cultured in medium alone.
Animal Protocol	Animal/Disease Models: Diabetic NOD/SCID (severe combined immunodeficient) mouse were implanted with human islets[2] Doses: 0.08 mg/mL Route of Administration: Oral feeding; 48 hrs (hours) Experimental Results: Dramatically decreased the percentages of apoptotic islet cells and increased the frequency of insulin+ β-cells in human islet grafts. Animal/Disease Models: Female Sprague Dawley rats[1] Doses: 7 μmol/kg (pharmacokinetic/PK Analysis) Route of Administration: Oral Experimental Results: High oral availability (88% in the dog and 100% in the rat) and relatively low systemic clearance. Plasma protein binding was 1% in rat and human plasma.
References	[1]. (R)-(3-amino-2-fluoropropyl) phosphinic acid (AZD3355), a novel GABAB receptor agonist, inhibits transient lower esophageal sphincter relaxation through a peripheral mode of action. J Pharmacol Exp Ther. 2009 Nov;331(2):504-12. [2]. Repurposing Lesogaberan to Promote Human Islet Cell Survival and β-Cell Replication. J Diabetes Res. 2017;2017:6403539.

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	2.8628 mL	14.3139 mL	28.6279 mL
	5 mM	0.5726 mL	2.8628 mL	5.7256 mL
	10 mM	0.2863 mL	1.4314 mL	2.8628 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.