Lu AE58054 (also known as Idalopirdine) is potent and selective antagonist of the 5-HT(6) receptor with Ki value of 0.83 nM. Lu AE58054, in a 5-HT(6) GTPgammaS efficacy assay, exhibited strong inhibition of 5-HT-mediated activation but no agonist activity. Not only did Lu AE58054 exhibit medium affinity for adrenergic alpha(1A)- and alpha(1B)-adrenoreceptors, but it also showed >50-fold selectivity for over 70 targets that were studied. Phase III clinical trials are being conducted on Lu AE58054 as an augmentation therapy to treat cognitive deficits linked to schizophrenia and Alzheimer's disease.

Physicochemical Properties

Molecular Formula	C₂₀H₁₉F₅N₂O
Molecular Weight	398.37
Exact Mass	398.141
Elemental Analysis	C, 60.30; H, 4.81; F, 23.84; N, 7.03; O, 4.02
CAS #	467459-31-0
Related CAS #	Idalopirdine Hydrochloride; 467458-02-2
PubChem CID	21071390
Appearance	Solid powder
Density	1.3±0.1 g/cm3
Boiling Point	500.9±50.0 °C at 760 mmHg
Flash Point	256.7±30.1 °C
Vapour Pressure	0.0±1.3 mmHg at 25°C
Index of Refraction	1.553
LogP	4.38
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	9
Heavy Atom Count	28
Complexity	482
Defined Atom Stereocenter Count	0
SMILES	FC1=CC(NC=C2CCNCC3=CC(OCC(F)(C(F)F)F)=CC=C3)=C2C=C1
InChi Key	YBAWYTYNMZWMMJ-UHFFFAOYSA-N
InChi Code	InChI=1S/C20H19F5N2O/c21-15-4-5-17-14(11-27-18(17)9-15)6-7-26-10-13-2-1-3-16(8-13)28-12-20(24,25)19(22)23/h1-5,8-9,11,19,26-27H,6-7,10,12H2
Chemical Name	2-(6-fluoro-1H-indol-3-yl)-N-[[3-(2,2,3,3-tetrafluoropropoxy)phenyl]methyl]ethanamine
Synonyms	LUAE58054; LU-AE58054; Lu AE58054; Idalopirdine
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	5-HT6 Receptor ( Ki = 0.83 nM )
ln Vitro	In vitro activity: In vivo binding of the 5-HT(6) antagonist radioligand [(3)H]Lu AE60157 was potently inhibited by oral administration of Lu AE58054, with an ED(50) of 2.7 mg/kg. The plasma EC(50) value of 20 ng/ml was found through steady-state modeling of an acute pharmacokinetic/5-HT(6)R occupancy time-course experiment.
ln Vivo	Idalopirdine (intraperitoneal injection, 5 mg/kg, daily, 28 days) can lower body weight and food intake in rat models of overeating[1]. Idalopirdine (1 or 2 mg/kg, i.v) can improve donepezil's effect on cortical gamma oscillations and dose-dependently raise the gamma power during nPO electrical stimulation[2]. However, it has no effect on the rats' sleep-wake cycles.
Animal Protocol	Male Wistar rats 5 mg/kg intraperitoneal injection, daily, 28 days
References	[1]. Idalopirdine, a selective 5-HT6 receptor antagonist, reduces food intake and body weight in a model of excessive eating. Metab Brain Dis. 2018 Jun;33(3):733-740. [2]. The 5-HT6 receptor antagonist idalopirdine potentiates the effects of donepezil on gamma oscillations in the frontal cortex of anesthetized and awake rats without affecting sleep-wake architecture. Neuropharmacology. 2017 Feb;113(Pt A):45-59.
Additional Infomation	SGS518, a novel antagonist for the 5HT6 subtype of the serotonin receptor, is being developed as a treatment for Cognitive Impairment Associated with Schizophrenia (CIAS). Idalopirdine has been used in trials studying the treatment of Cognition, Schizophrenia, and Alzheimer's Disease. Drug Indication Investigated for use/treatment in neurologic disorders and schizophrenia and schizoaffective disorders. Mechanism of Action SGS518 is a selective antagonist of the 5-Hydroxytryptamine-6 (5-HT6) serotonin receptor believed to act by enhancing transmission of chemicals in the brain.

Solubility Data

Solubility (In Vitro)

DMSO: >10 mM in DMSO Water: <1 mg/mL Ethanol:

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	2.5102 mL	12.5511 mL	25.1023 mL
	5 mM	0.5020 mL	2.5102 mL	5.0205 mL
	10 mM	0.2510 mL	1.2551 mL	2.5102 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.