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

Physicochemical Properties

Molecular Formula	C16H20N2O2.1/2C4H6O6
Molecular Weight	694.77
Exact Mass	694.321
CAS #	209394-46-7
Related CAS #	Ladostigil hydrochloride;209394-18-3;Ladostigil;209394-27-4
PubChem CID	11607225
Appearance	White to off-white solid powder
Boiling Point	412.4ºC at 760 mmHg
Flash Point	203.2ºC
Vapour Pressure	5.19E-07mmHg at 25°C
LogP	3.353
Hydrogen Bond Donor Count	6
Hydrogen Bond Acceptor Count	12
Rotatable Bond Count	13
Heavy Atom Count	50
Complexity	521
Defined Atom Stereocenter Count	4
SMILES	CCN(C)C(=O)OC1=CC2=C(CC[C@H]2NCC#C)C=C1.CCN(C)C(=O)OC1=CC2=C(CC[C@H]2NCC#C)C=C1.[C@@H]([C@H](C(=O)O)O)(C(=O)O)O
InChi Key	PRLVBVAJMQZMJN-OGOSNNLPSA-N
InChi Code	InChI=1S/2C16H20N2O2.C4H6O6/c2*1-4-10-17-15-9-7-12-6-8-13(11-14(12)15)20-16(19)18(3)5-2;5-1(3(7)8)2(6)4(9)10/h2*1,6,8,11,15,17H,5,7,9-10H2,2-3H3;1-2,5-6H,(H,7,8)(H,9,10)/t2*15-;1-,2-/m111/s1
Chemical Name	(2R,3R)-2,3-dihydroxybutanedioic acid;[(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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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 nM (IC50) AChE 31.8 nM (IC50)
ln Vitro	Neuroprotective effects of levofil (1–10 µM) hemitartrate include halting the decline of the mitochondrial membrane potential (ψ), reducing the intensity of apoptotic cascades, and reducing the generation of ROS brought on by OS insults[2]. In human neuroblastoma SK-N-SH cells, lentistigil (1–10 µM) hemitartrate has strong neuroprotective effects, such as reducing Bad and Bax gene and protein expression, inducing Bcl-2, and inhibiting 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) hemitartrate eliminates the rats' depressive-like behavior and hyperanxiety in adulthood, from puberty to prenatally stressed rats[4]. Rats' episodic memory loss is restored in the object recognition test by ladostigil (50 μmol/kg; single po) hemitartrate[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.

Solubility Data

Solubility (In Vitro)

H2O: 100 mg/mL (143.93 mM) DMSO: 50 mg/mL (71.97 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.25 mg/mL (1.80 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 12.5 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: ≥ 1.25 mg/mL (1.80 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 12.5 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. Solubility in Formulation 3: ≥ 1.25 mg/mL (1.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.4393 mL	7.1966 mL	14.3933 mL
	5 mM	0.2879 mL	1.4393 mL	2.8787 mL
	10 mM	0.1439 mL	0.7197 mL	1.4393 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.