Art. -Nr.: HY-14557

Pimavanserin

(Synonyms: ACP-103)

12 Cited Publications

Kundenbewertung

Based on 12 publication(s) in Google Scholar

Pimavanserin is a selective, brain-penetrant, inverse agonist of the 5-HT2A receptor with pIC₅₀ and pK_d of 8.73 and 9.3, respectively.

Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.

Reinheit: 99.86%
CAS. Nr.: 706779-91-1
Formel: C₂₅H₃₄FN₃O₂
Molecular Weight:427.55

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year

Pimavanserin Chemical Structure

CAS. Nr.: 706779-91-1

Größe

Preis

Verfügbarkeit

Menge

Sample (0.1mg)

In-stock

(In Japan)

Apply Now

Angebot einholen Ask For Quote & Lead Time Consult sales personnel for more information Check price and availability Angebot einholen Ask For Quote & Lead Time Consult sales personnel for more information Check price and availability

Massenanfrage

Amount: USD 0.00

* Bitte wählen Sie Menge, bevor Sie Artikel hinzufügen.

Top Publications Citing

Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
- Clinical Trial
Chemical Information
Publications (12)
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Protokoll
Reinheit & Dokumentation
Verweise
Help & FAQs
Bioz

Biologische Aktivität

Beschreibung

Pimavanserin is a selective, brain-penetrant, inverse agonist of the 5-HT2A receptor with pIC₅₀ and pK_d of 8.73 and 9.3, respectively.

IC₅₀ & Target^[1]

5-HT_2A Receptor

8.7 (pIC₅₀)

5-HT_2A Receptor

Alle 5-HT Receptor Isoform-spezifische Produkte anzeigen :

Cellular Effect

Cell Line	Type	Value	Description	References
HEK293	IC₅₀	22 nM Compound: 1	Antagonist activity at 5HT2A receptor (unknown origin) expressed in HEK293 cells assessed as inhibition of serotonin hydrochloride-induced calcium flux preincubated for 1 hr followed by serotonin hydrochloride addition by calcium 6 dye based FLIPR assay Antagonist activity at 5HT2A receptor (unknown origin) expressed in HEK293 cells assessed as inhibition of serotonin hydrochloride-induced calcium flux preincubated for 1 hr followed by serotonin hydrochloride addition by calcium 6 dye based FLIPR assay	[PMID: 32285676]

In Vitro

Pimavanserin (ACP-103) competitively antagonizes the binding of [³H]ketanserin to heterologously expressed human 5-HT_2A receptors with a mean pK_i of 9.3 in membranes and 9.70 in whole cells. Pimavanserin demonstrates lesser affinity (mean pK_i of 8.80 in membranes and 8.00 in whole cells, as determined by radioligand binding) and potency as an inverse agonist (mean pIC₅₀ 7.1 in R-SAT) at human 5-HT_2C receptors, and lacked affinity and functional activity at 5-HT_2B receptors, dopamine D₂ receptors, and other human monoaminergic receptors^[1]. Pimavanserin (ACP-103) is highly selective for 5-HT_2A receptors, lacking affinity for other receptors in a broad profile screen including 65 different molecular targets; the only other receptor for which Pimavanserin demonstrates affinity is 5-HT_2C, and Pimavanserin is approximately 30-fold selective for 5-HT_2A receptors over 5-HT_2C receptors depending on the assay^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Pimavanserin (ACP-103) is a potent, efficacious, orally active 5-HT_2A receptor inverse agonist with a behavioral pharmacological profile consistent with utility as an antipsychotic agent. Pimavanserin attenuates head-twitch behavior (3 mg/kg p.o.), and prepulse inhibition deficits (1-10 mg/kg s.c.) induced by the 5-HT_2A receptor agonist (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride in rats and reduces the hyperactivity induced in mice by the N-methyl-D-aspartate receptor noncompetitive antagonist 5H-dibenzo[a,d]cyclohepten-5,10-imine (dizocilpine maleate; MK-801) (0.1 and 0.3 mg/kg s.c.; 3 mg/kg p.o.), consistent with a 5-HT_2A receptor mechanism of action in vivo and antipsychotic-like efficacy. Pimavanserin demonstrates >42.6% oral bioavailability in rats^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

Chemical Information

CAS. Nr. 706779-91-1
Appearance Solid
Molecular Weight 427.55
Formel C₂₅H₃₄FN₃O₂
Color White to off-white
SMILES

CC(C)COC1=CC=C(CNC(N(CC2=CC=C(F)C=C2)C3CCN(C)CC3)=O)C=C1
Synonyms

ACP-103
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Publications (12)

All

Sort by:

Journal Impact Factor

Nat Commun

Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential. [Abstract]

2023 Dec 15;14(1):8221. PMID: 38102107
Proc Natl Acad Sci U S A

Metformin rescues Parkinson's disease phenotypes caused by hyperactive mitochondria. [Abstract]

2020 Oct 20;117(42):26438-26447. PMID: 33024014
J Med Chem

Design, Synthesis, Molecular Docking, and Biological Evaluation of Novel Pimavanserin-Based Analogues as Potential Serotonin 5-HT2A Receptor Inverse Agonists. [Abstract]

2023 Jul 13;66(13):9057-9075. PMID: 37378639
Sci Rep

Mechanisms of 5-HT receptor antagonists in the regulation of fibrosis in a 3D human liver spheroid model. [Abstract]

2024 Jan 16;14(1):1396. PMID: 38228622
ACS Chem Neurosci

Big Data Challenges Targeting Proteins in GPCR Signaling Pathways; Combining PTML-ChEMBL Models and [35S]GTPγS Binding Assays. [Abstract]

2019 Nov 20;10(11):4476-4491. PMID: 31618004
Int J Neuropsychopharmacol

A Complex Impact of Systemically Administered 5-HT2A Receptor Ligands on Conditioned Fear. [Abstract]

2021 Sep 21;24(9):749-757. PMID: 34228806
Food Chem Toxicol

Non-clinical pharmacology and toxicology studies of LPM6690061, a novel 5-hydroxytryptamine (5-HT)2A receptor inverse agonist. [Abstract]

2023 Jun:176:113800. PMID: 37100235
Int J Clin Exp Med

2019;12(8):10342-10349
bioRxiv

Identification of 5-HT2A Receptor Signaling Pathways Responsible for Psychedelic Potential. [Abstract]

2023 Jul 31:2023.07.29.551106. PMID: 37577474
Patent

US20200352950A1.
bioRxiv

2020 Feb.
Virginia Commonwealth University

2016 Oct.

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : 50 mg/mL (116.95 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

2.3389 mL

11.6945 mL

23.3891 mL

5 mM

0.4678 mL

2.3389 mL

4.6778 mL

10 mM

0.2339 mL

1.1695 mL

2.3389 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 2.5 mg/mL (5.85 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)

Solubility: ≥ 2.5 mg/mL (5.85 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (5.85 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Protokoll

Kinase Assay^[1]

For the membrane binding, NIH-3T3 cells are grown to 70% confluence in 15 cm² dishes and transfected with 10 μg of receptor plasmid DNA using Polyfect transfection reagent. Two days after transfection, cells expressing the desired serotonin receptor are homogenized in 20 mM HEPES/10 mM EDTA and spun down at 11,000g at 4°C for 30 min. The supernatant is discarded, and the pellet is resuspended in 20 mM HEPES/1 mM EDTA and spun down at the same setting. The pellet is then resuspended in 20 mM HEPES/0.5 mM EDTA, and membranes are used for binding assays. Bradford analysis is used to determine total membrane protein. K_d and B_max values are derived from 12-point concentration experiments using 1 nM [³H]ketanserin for the 5-HT_2A receptor and 3 nM [³H]mesulergine for the 5-HT_2B and 5-HT_2C receptors. Membranes are incubated at room temperature for 3 h with various concentrations of test ligand in the presence of a fixed concentration of radioligand. The suspension is filtered as explained below for whole-cell binding, washed with ice-cold buffer, and dried, and radioactivity is determined using TopCount^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay^[1]

For the whole-cell binding, 6 million human embryonic kidney 293T cells are plated in 10-cm dishes and transfected with 5 μg of plasmid DNA using Polyfect. Two days after transfection, cells are harvested with 10 mM EDTA, washed, and resuspended in binding buffer (1× DMEM with 0.1% bovine serum albumin). Then, 60,000 cells transfected with the 5-HT_2A receptor or 20,000 cells transfected with the 5-HT_2C-INI receptor are incubated at 37°C for 3 h in the presence of 5 nM radioligand ([³H]ketanserin for 5-HT_2A receptors and [³H]mesulergine for 5-HT_2C-INI receptors) and varying concentrations of ligands (total volume 100 μL in a 96-well plate). Cells are filtered onto a 96-well GF/B filter plate and washed with 300 mL of wash buffer (25 mM HEPES, 1 mM CaCl₂, 5 mM MgCl₂, and 0.25 M NaCl) using a Filtermate 196 harvester. The filter plates are dried under a heat lamp before addition of 50 μL of scintillation fluid to each well. Plates are counted on a TopCount. Separately, the hydrochloride salt form of Pimavanserin (10 μM) is evaluated at MDS Pharma Services for activity in a broad screen of radioligand binding assays at 65 different receptors^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration^[1]

Mice^[1]
Non-Swiss albino mice are used for locomotor activity experiments. For determination of spontaneous activity, Pimavanserin is administered alone (s.c. 60 min before session start or p.o. 60 min before session start). For hyperactivity experiments, mice are treated with 0.3 mg/kg MK-801 (i.p.) 15 min presession (the peak dose for producing hyperactivity in an inverted-U dose-effect curve as determined in pilot experiments) in combination with vehicle or Pimavanserin. Motor activity data are collected during a 15-min session in a lit room. Mice had no prior exposure to the motor cages. Immediately before placing the mice in the locomotor chambers, effects on myorelaxation/ataxia are determined by placing each of the mouse's forepaws in contact with a horizontal wire while holding the mouse by the base of the tail. Mice are required to bring at least one hindpaw in contact with the wire within 10 s to be scored as a “pass” and failure to do so is considered ataxic. Each dose or dose combination is tested in a separate group of mice (n=8).
Rats^[1]
For DOI head-twitch experiments in rats, vehicle or a dose of Pimavanserin is administered orally 120 min before DOI administration. DOI HCl (2.5 mg/kg i.p.) is administered immediately before observations. After injection of DOI, each rat is placed into an empty cage and observed. Latency to the first head twitch and the number of head twitches occurring over 5 min are recorded. Each rat is used only once with eight to 16 rats per dose group.

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (279 KB)
SDS (396 KB)
- English - EN (396 KB)
- Français - FR (396 KB)
- Deutsch - DE (396 KB)
- Norwegian - NO (396 KB)
- Español - ES (396 KB)
- Swedish - SV (396 KB)
- Italian - IT (396 KB)
- Portuguese - PT (396 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Vanover KE, et al. Pharmacological and behavioral profile of N-(4-fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl) carbamide (2R,3R)-dihydroxybutanedioate (2:1) (ACP-103), a novel 5-hydroxytryptamine(2A) receptor inverse agonist. J Pharmacol Exp Ther. 2006 May;317(2):910-8. [Content Brief]

[2]. Vanover KE, et al. A 5-HT2A receptor inverse agonist, ACP-103, reduces tremor in a rat model and levodopa-induced dyskinesias in a monkey model. Pharmacol Biochem Behav. 2008 Oct;90(4):540-4. [Content Brief]

[3]. Ezzeldin E, et al. A rapid, simple and highly sensitive UPLC-MS/MS method for quantitation of pimavanserin in plasma and tissues: Application to pharmacokinetics and brain uptake studies in mice. J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Apr 15;1143:122015. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	2.3389 mL	11.6945 mL	23.3891 mL	58.4727 mL
	5 mM	0.4678 mL	2.3389 mL	4.6778 mL	11.6945 mL
	10 mM	0.2339 mL	1.1695 mL	2.3389 mL	5.8473 mL
	15 mM	0.1559 mL	0.7796 mL	1.5593 mL	3.8982 mL
	20 mM	0.1169 mL	0.5847 mL	1.1695 mL	2.9236 mL
	25 mM	0.0936 mL	0.4678 mL	0.9356 mL	2.3389 mL
	30 mM	0.0780 mL	0.3898 mL	0.7796 mL	1.9491 mL
	40 mM	0.0585 mL	0.2924 mL	0.5847 mL	1.4618 mL
	50 mM	0.0468 mL	0.2339 mL	0.4678 mL	1.1695 mL
	60 mM	0.0390 mL	0.1949 mL	0.3898 mL	0.9745 mL
	80 mM	0.0292 mL	0.1462 mL	0.2924 mL	0.7309 mL
	100 mM	0.0234 mL	0.1169 mL	0.2339 mL	0.5847 mL

Keywords

Pimavanserin

12 Cited Publications

100 mg Angebot einholen

Subscribe to the

MedChemExpress

Newsletter

Produktname:
Art. -Nr.:
Menge:
MCE Japan Authorized Agent:

Produktname:
CAS. Nr.:
Species:
Reinheit:
Menge:

Pimavanserin

GPCR/G Protein Compound Library

Neuronal Signaling Compound Library

FDA-Approved Drug Library

CNS-Penetrant Compound Library

Drug Repurposing Compound Library

Orally Active Compound Library

Neurotransmitter Receptor Compound Library

FDA Approved & Pharmacopeial Drug Library

Anti-Alzheimer's Disease Compound Library

Anti-Parkinson's Disease Compound Library

Neurodegenerative Disease-related Compound Library

Rare Diseases Drug Library

5-HT Receptor Compound Library

Human Metabolite Library

Coagulation and Anti-coagulation Compound Library

Heterocyclic Compound Library

Off-patent Drug Library

Membrane Protein-targeted Compound Library

Membrane Receptor-targeted Compound Library

Highly Selective Inhibitors Library

Multi-Target Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Drug Repurposing Compound Library Plus

FDA-Approved Drug Library Plus

FDA-Approved Drug Library Mini

Bioactive Compound Library

High-Throughput Bioactive Compound Library

Mass Spectrometry Human Metabolite Library

Lactylation Compound Library

Publications Citing Use of MedChemExpress (MCE) Pimavanserin

Alle 5-HT Receptor Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Publications (12)

Lösungsmittel & Löslichkeit

Protokoll

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

Pimavanserin Related Classifications

Art. -Nr.: HY-14557