Synonym
Lu AE58054; Lu AE-58054; Lu AE 58054; Idalopirdine; Iladopirdine HCl; Iladopirdine hydrochloride
IUPAC/Chemical Name
2-(6-fluoro-1H-indol-3-yl)-N-(3-(2,2,3,3-tetrafluoropropoxy)benzyl)ethanamine hydrochloride
InChi Key
KXOQNPANAFXKTN-UHFFFAOYSA-N
InChi Code
InChI=1S/C20H19F5N2O.ClH/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;1H
SMILES Code
FC1=CC2=C(C=C1)C(CCNCC3=CC=CC(OCC(F)(F)C(F)F)=C3)=CN2.[H]Cl
Appearance
White to off-white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Idalopirdine Hydrochloride (Lu AE58054 Hydrochloride) is a potent and selective 5-HT6 receptor antagonist with a Ki of 0.83 nM.
In vitro activity:
The binding of [3H]LSD to membranes from BHK cells expressing human 5-HT6Rs was inhibited in a concentration-dependent fashion by Lu AE58054. The affinity (Ki) of Lu AE58054 calculated for human 5-HT6Rs was 0.83 nM. The affinity of Lu AE58054 for 5-HT2ARs was 100-fold lower than for 5-HT6Rs and Lu AE58054 had over 400-fold lower affinity for the other 5-HTR subtypes examined (Table 1). Selectivity profiling in more than 80 binding as well as in 20 enzyme assays indicated >50 fold selectivity except for the adrenergic hα1A and hα1B receptors. Affinity and efficacy profiling for the hα1A and hα1B receptors demonstrated that Lu AE58054 displayed an affinity (Ki) of 21 and 22 nM, respectively, and inhibited epinephrine-induced activation of both receptors (Cerep Contract Facility and Lundbeck, data on file).
Reference: Int J Neuropsychopharmacol. 2010 Sep;13(8):1021-33. https://academic.oup.com/ijnp/article-lookup/doi/10.1017/S1461145710000659
In vivo activity:
The activity of idalopirdine was measured in the rat model of excessive eating. Animals were on a high caloric diet that consisted of milk chocolate with nuts, cheese, salted peanuts and condensed milk. During a four-week experiment, the rats had constant access to standard feed and water ad libitum. Idalopirdine was administered intraperitoneally at a dose 5 mg/kg b.w./day. To establish whether idalopirdine would effectively suppress the rebound hyperphagia that accompanies refeeding, it was administered after a 20 h food deprivation period. Pica behavior was evaluated after the administration of idalopirdine to confirm that the suppression of food intake was not caused by visceral illness. The effect of the four-week treatment with idalopirdine on the amount of peritoneal adipose tissue, and on lipid and carbohydrate profiles in rats was also examined. The statistical significance was calculated using the one-way ANOVA post-hoc Tukey Multiple Comparison Test or the two-way ANOVA post-hoc Bonferroni Multiple Comparison Test. Idalopirdine significantly reduced caloric intake and prevented the development of obesity in tested animals. Rats, that received idalopirdine, had a smaller amount of adipose tissue in the peritoneum as well as lower glucose, triglyceride and cholesterol levels in comparison to the control group. Moreover, an anorectic action was not caused by abnormalities of the gastrointestinal tract, such as nausea. The obtained results indicate that idalopirdine reduces caloric intake and could be considered for further tests as a potential treatment of obesity.
Reference: Metab Brain Dis. 2018 Jun;33(3):733-740. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29297106/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
25.0 |
57.49 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
434.84
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Arnt J, Bang-Andersen B, Grayson B, Bymaster FP, Cohen MP, DeLapp NW, Giethlen B, Kreilgaard M, McKinzie DL, Neill JC, Nelson DL, Nielsen SM, Poulsen MN, Schaus JM, Witten LM. Lu AE58054, a 5-HT6 antagonist, reverses cognitive impairment induced by subchronic phencyclidine in a novel object recognition test in rats. Int J Neuropsychopharmacol. 2010 Sep;13(8):1021-33. doi: 10.1017/S1461145710000659. Epub 2010 Jun 23. PMID: 20569520.
2. Kotańska M, Lustyk K, Bucki A, Marcinkowska M, Śniecikowska J, Kołaczkowski M. 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. doi: 10.1007/s11011-017-0175-1. Epub 2018 Jan 3. PMID: 29297106; PMCID: PMC5956042.
3. Dudek M, Marcinkowska M, Bucki A, Olczyk A, Kołaczkowski M. Idalopirdine - a small molecule antagonist of 5-HT6 with therapeutic potential against obesity. Metab Brain Dis. 2015 Dec;30(6):1487-94. doi: 10.1007/s11011-015-9736-3. Epub 2015 Sep 29. PMID: 26419385; PMCID: PMC4642593.
In vitro protocol:
1. Arnt J, Bang-Andersen B, Grayson B, Bymaster FP, Cohen MP, DeLapp NW, Giethlen B, Kreilgaard M, McKinzie DL, Neill JC, Nelson DL, Nielsen SM, Poulsen MN, Schaus JM, Witten LM. Lu AE58054, a 5-HT6 antagonist, reverses cognitive impairment induced by subchronic phencyclidine in a novel object recognition test in rats. Int J Neuropsychopharmacol. 2010 Sep;13(8):1021-33. doi: 10.1017/S1461145710000659. Epub 2010 Jun 23. PMID: 20569520.
In vivo protocol:
1. Kotańska M, Lustyk K, Bucki A, Marcinkowska M, Śniecikowska J, Kołaczkowski M. 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. doi: 10.1007/s11011-017-0175-1. Epub 2018 Jan 3. PMID: 29297106; PMCID: PMC5956042.
2. Dudek M, Marcinkowska M, Bucki A, Olczyk A, Kołaczkowski M. Idalopirdine - a small molecule antagonist of 5-HT6 with therapeutic potential against obesity. Metab Brain Dis. 2015 Dec;30(6):1487-94. doi: 10.1007/s11011-015-9736-3. Epub 2015 Sep 29. PMID: 26419385; PMCID: PMC4642593.
1: Witten L, Bang-Andersen B, Nielsen SM, Miller S, Christoffersen CT, Stensbøl TB, Brennum LT, Arnt J. Characterization of [³H]Lu AE60157 ([³H]8-(4-methylpiperazin-1-yl)-3-phenylsulfonylquinoline) binding to 5-hydroxytryptamine₆ (5-HT₆) receptors in vivo. Eur J Pharmacol. 2012 Feb 15;676(1-3):6-11. doi: 10.1016/j.ejphar.2011.11.029. Epub 2011 Dec 4. PubMed PMID: 22155399.
2: Arnt J, Bang-Andersen B, Grayson B, Bymaster FP, Cohen MP, DeLapp NW, Giethlen B, Kreilgaard M, McKinzie DL, Neill JC, Nelson DL, Nielsen SM, Poulsen MN, Schaus JM, Witten LM. Lu AE58054, a 5-HT6 antagonist, reverses cognitive impairment induced by subchronic phencyclidine in a novel object recognition test in rats. Int J Neuropsychopharmacol. 2010 Sep;13(8):1021-33. doi: 10.1017/S1461145710000659. Epub 2010 Jun 23. PubMed PMID: 20569520.
