Ladostigil (TV-3326) is an orally bioavailable dual (bifunctional) inhibitor of cholinesterase (cholinesterase) and brain-selective monoamine oxidase (MAO). The IC50s for inhibiting MAO-B and AChE are 37.1 and 31.8 μM, respectively. Ladostigil has neuro-protection, antioxidant and anti-inflammatory effects and may be used in research on depression and AD/Alzheimer's disease. Ladostigil is a click chemical agent. It contains Alkyne groups and could undergo CuAAc (copper-catalyzed azide-alkyne cycloaddition reaction) with compounds bearing an Azide group.

Physicochemical Properties

Molecular Formula	C16H20N2O2
Molecular Weight	272.34
Exact Mass	272.152
CAS #	209394-27-4
Related CAS #	Ladostigil hydrochloride;209394-18-3;Ladostigil hemitartrate;209394-46-7
PubChem CID	208907
Appearance	Typically exists as solid at room temperature
Vapour Pressure	5.19E-07mmHg at 25°C
LogP	2.738
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	5
Heavy Atom Count	20
Complexity	387
Defined Atom Stereocenter Count	1
SMILES	C#CCN[C@@H]1CCC2=C1C=C(C=C2)OC(=O)N(C)CC
InChi Key	LHXOCOHMBFOVJS-OAHLLOKOSA-N
InChi Code	InChI=1S/C16H20N2O2/c1-4-10-17-15-9-7-12-6-8-13(11-14(12)15)20-16(19)18(3)5-2/h1,6,8,11,15,17H,5,7,9-10H2,2-3H3/t15-/m1/s1
Chemical Name	[(3R)-3-(prop-2-ynylamino)-2,3-dihydro-1H-inden-5-yl] N-ethyl-N-methylcarbamate
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	MAO-B 37.1 μM (IC50) AChE 31.8 μM (IC50)
ln Vitro	Neuroprotective effects of ladostigil (1–10 µM) include halting the decline of the mitochondrial membrane potential (ψ), reducing the intensity of apoptotic cascades, and preventing the generation of reactive oxygen species (ROS) brought on by OS insults[2]. Significant neuroprotective effects of lastigil (1–10 µM) on human neuroblastoma SK-N-SH cells include reduction of Bad and Bax gene and protein expression, increase of Bcl-2, and inhibition of caspase-3 activation[2].
ln Vivo	In the forced swim tests (FST) and elevated plus maze (EPM) tests, ladostigil (17 mg/kg; po daily for 6 weeks) completely eliminates their depressive-like behavior and hyperanxiety in adulthood, from puberty to prenatally stressed rats[4]. In the object recognition test, rats given 50 μmol/kg of latstigil as a single dose recover their lost episodic memory[3].
Animal Protocol	Animal/Disease Models: Pathogen-free (SPF) SD (Sprague-Dawley) rats[4] Doses: 17 mg/kg Route of Administration: Po (added to the drinking water) daily for 6 weeks Experimental Results: Inhibited brain MAO-A and B by more than 60%. decreased hyperanxiety of male and female prenatally stressed (PS) rats in the EPM and depressive-like behavior in the FST.
References	[1]. Design, synthesis and evaluation of indole derivatives as multifunctional agents against Alzheimer's disease. Medchemcomm. 2018 Jan 16; 9(2):357-370. [2]. Ladostigil: a novel multimodal neuroprotective drug with cholinesterase and brain-selective monoamine oxidase inhibitory activities for Alzheimer's disease treatment. Curr Drug Targets. 2012 Apr; 13(4): 483-94. [3]. Ladostigil, a novel multifunctional drug for the treatment of dementia co-morbid with depression. J Neural Transm Suppl. 2006; (70):443-6. [4]. Effect of chronic treatment with ladostigil (TV-3326) on anxiogenic and depressive-like behaviour and on activity of the hypothalamic-pituitary-adrenal axis in male and female prenatally stressed rats. Psychopharmacology (Berl). 2005 Aug;181(1): 118-25.
Additional Infomation	Ladostigil is a member of indanes. Ladostigil is under investigation in clinical trial NCT01429623 (A 3 Year Study to Evaluate the Safety and Efficacy of Low Dose Ladostigil in Patients With Mild Cognitive Impairment).

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	3.6719 mL	18.3594 mL	36.7188 mL
	5 mM	0.7344 mL	3.6719 mL	7.3438 mL
	10 mM	0.3672 mL	1.8359 mL	3.6719 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.