Art. -Nr.: HY-14539

Clozapine

(Synonyms: HF 1854; ZINC000019796155)

11 Cited Publications

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Based on 11 publication(s) in Google Scholar

Clozapine (HF 1854) is an antipsychotic used for the research of schizophrenia. Clozapine has high affinity for a number of neuroreceptors. Clozapine is a potent antagonist of dopamine D2 with a K_i of 75 nM. Clozapine inhibits the muscarinic M1 receptor and serotonin 5HT2A receptor with K_is of 9.5 nM and 4 nM, respectively. Clozapine is also a potent and selective agonist at the muscarinic M4 receptor (EC₅₀=11 nM).

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Reinheit: 99.84%
CAS. Nr.: 5786-21-0
Formel: C₁₈H₁₉ClN₄
Molecular Weight:326.83

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 1 year , -20°C, 6 months

Clozapine Chemical Structure

CAS. Nr.: 5786-21-0

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Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Publications (11)
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Reinheit & Dokumentation
Verweise
Help & FAQs
Bioz

Biologische Aktivität

Beschreibung

Clozapine (HF 1854) is an antipsychotic used for the research of schizophrenia. Clozapine has high affinity for a number of neuroreceptors. Clozapine is a potent antagonist of dopamine D2 with a K_i of 75 nM. Clozapine inhibits the muscarinic M1 receptor and serotonin 5HT2A receptor with K_is of 9.5 nM and 4 nM, respectively^[1]^[2]^[3]. Clozapine is also a potent and selective agonist at the muscarinic M4 receptor (EC₅₀=11 nM)^[4].

IC₅₀ & Target^[1]^[4]

5-HT_2A Receptor

4 nM (Ki, Inhibitor)

5-HT_2A Receptor

5-HT₆ Receptor

5-HT₇ Receptor

mAChR1

9.5 nM (Ki, Antagonist)

mAChR4

11 nM (EC₅₀, Agonist)

α2-adrenergic receptor

51 nM (Ki, Inhibitor)

D₂ Receptor

75 nM (Ki, Antagonist)

Alle Dopamine Receptor Isoform-spezifische Produkte anzeigen :

Alle mAChR Isoform-spezifische Produkte anzeigen :

Alle Adrenergic Receptor Isoform-spezifische Produkte anzeigen :

Alle 5-HT Receptor Isoform-spezifische Produkte anzeigen :

Alle Ligands for E3 Ligase Isoform-spezifische Produkte anzeigen :

Cellular Effect

Cell Line	Type	Value	Description	References
CHO	EC₅₀	56 μM Compound: clozapine	Cytotoxicity against CHO cells by MTT assay Cytotoxicity against CHO cells by MTT assay	[PMID: 17870534]
CHO	IC₅₀	206 nM Compound: 1	Inhibition of human dopamine D2L receptor expressed in intact CHO FlpIn cells assessed as inhibition of receptor-mediated mediated ERK1/2 phosphorylation by Alpha-Screen plate-based assay Inhibition of human dopamine D2L receptor expressed in intact CHO FlpIn cells assessed as inhibition of receptor-mediated mediated ERK1/2 phosphorylation by Alpha-Screen plate-based assay	[PMID: 22243698]
CHO	IC₅₀	3.6 μM Compound: clozapine	Inhibition of Cav1.2 current measured using QPatch automatic path clamp system in CHO cells expressing Cav1.2, beta-2 and alpha-2/delta-1 subunits Inhibition of Cav1.2 current measured using QPatch automatic path clamp system in CHO cells expressing Cav1.2, beta-2 and alpha-2/delta-1 subunits	[PMID: 23812503]
CHO	IC₅₀	4.1 x 10^-8 M Compound: Clozapine	Displacement of [3H]methylspiperone from human recombinant Dopamine D4.4 receptor expressed in CHO cells Displacement of [3H]methylspiperone from human recombinant Dopamine D4.4 receptor expressed in CHO cells	[PMID: 26988801]
CHO	IC₅₀	4.1 x 10^-8 M Compound: Clozapine	Displacement of [3H]methyl-spiperone from human recombinant dopamine D4.4 receptor expressed in CHO cells measured after 60 mins by scintillation counting method Displacement of [3H]methyl-spiperone from human recombinant dopamine D4.4 receptor expressed in CHO cells measured after 60 mins by scintillation counting method	[PMID: 27876250]
CHO	IC₅₀	4.1 x 10^-2 μM Compound: Clozapine	Displacement of [3H]methyl-spiperone from human recombinant dopamine D4.4 receptor expressed in CHO cells measured after 60 mins by scintillation counting method Displacement of [3H]methyl-spiperone from human recombinant dopamine D4.4 receptor expressed in CHO cells measured after 60 mins by scintillation counting method	[PMID: 27876250]
CHO	IC₅₀	0.058 μM Compound: clozapine	Inhibitory concentration against human Dopamine receptor D4.2 in CHO cells Inhibitory concentration against human Dopamine receptor D4.2 in CHO cells	[PMID: 8831770]
CHO-K1	IC₅₀	9.4 nM Compound: 4	Inhibition of binding of 1.0 nM [3H]pirenzepine to cloned human Muscarinic acetylcholine receptor M1 expressed in membranes from CHO-K1 cells Inhibition of binding of 1.0 nM [3H]pirenzepine to cloned human Muscarinic acetylcholine receptor M1 expressed in membranes from CHO-K1 cells	[PMID: 10377229]
CHO-K1	IC₅₀	9.4 nM Compound: 1	Inhibitory binding of [3H]pirenzepine to human Muscarinic acetylcholine receptor M1 in membranes from CHO-K1 cells Inhibitory binding of [3H]pirenzepine to human Muscarinic acetylcholine receptor M1 in membranes from CHO-K1 cells	[PMID: 9406603]
HEK293	IC₅₀	650 nM Compound: Clozapine	Inhibition of human ERG expressed in HEK293 cells by electrophysiology assay Inhibition of human ERG expressed in HEK293 cells by electrophysiology assay	[PMID: 23675993]
HeLa	IC₅₀	17 nM Compound: Clozapine	Displacement of [3H]LSD from human cloned 5-HT6 receptor expressed in HeLa cells Displacement of [3H]LSD from human cloned 5-HT6 receptor expressed in HeLa cells	[PMID: 24495863]
Sf21	IC₅₀	126.1 μM Compound: Clozapine	Inhibition of human BSEP expressed in plasma membrane vesicles of Sf21 cells assessed as inhibition of ATP-dependent [3H]taurocholate uptake Inhibition of human BSEP expressed in plasma membrane vesicles of Sf21 cells assessed as inhibition of ATP-dependent [3H]taurocholate uptake	[PMID: 21965623]
Sf21	IC₅₀	196.5 μM Compound: Clozapine	Inhibition of Sprague-Dawley rat Bsep expressed in plasma membrane vesicles of Sf21 cells assessed as inhibition of ATP-dependent [3H]taurocholate uptake Inhibition of Sprague-Dawley rat Bsep expressed in plasma membrane vesicles of Sf21 cells assessed as inhibition of ATP-dependent [3H]taurocholate uptake	[PMID: 21965623]
WI-38	CC₅₀	40 μM Compound: Clozapine	Cytotoxicity against human WI38 cells assessed as reduction in cellular DNA level preincubated for 2 hrs before viral infection measured after 7 days by real time PCR assay Cytotoxicity against human WI38 cells assessed as reduction in cellular DNA level preincubated for 2 hrs before viral infection measured after 7 days by real time PCR assay	[PMID: 17893158]
WI-38	EC₅₀	23.26 μM Compound: Clozapine	Antiviral activity against BKV Gardner ATCC VR837 infected in human WI38 cells assessed as reduction in viral DNA level preincubated for 2 hrs before viral infection measured after 7 days by real time PCR assay Antiviral activity against BKV Gardner ATCC VR837 infected in human WI38 cells assessed as reduction in viral DNA level preincubated for 2 hrs before viral infection measured after 7 days by real time PCR assay	[PMID: 17893158]

In Vitro

Clozapine (HF 1854) is a D2 receptor antagonist with a K_i of 75 nM, blocks the serotonin 5HT2A receptor with a K_i of 4 nM, inhibits the muscarinic M1 receptor with a K_i of 9.5 nM, blocks α2-adrenoceptor with a K_i value of 51 nM^[1].
Clozapine (0-1 μM; 24 h) downregulates 5-HT₆ and upregulates 5-HT₇ receptors in HeLa cells^[2].
Clozapine is a full agonist at the muscarinic M4 receptor (EC₅₀=11 nM) expressed in CHO cells^[4].

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

In Vivo

Clozapine (HF 1854) (25 mg/kg/day; i.p.; 21 days) shows antipsychotic effects in lysergic acid diethylamide-induced psychosis mouse model^[3].

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

Animal Model:

Male 129 S6/Sv mice, lysergic acid diethylamide (LSD)-induced psychosis model^[3]
Dosage:

25 mg/kg/day
Administration:

Intraperitoneal injection, 21 days
Result:

Decreased head-twitch response, reduced 5-HT_2A mRNA, rescued induction of c-fos, but not egr-1 and egr-2.

Chemical Information

CAS. Nr. 5786-21-0
Appearance Solid
Molecular Weight 326.83
Formel C₁₈H₁₉ClN₄
Color Light yellow to yellow
SMILES

CN1CCN(CC1)C2=NC3=CC(Cl)=CC=C3NC4=CC=CC=C42
Synonyms

HF 1854; ZINC000019796155
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	1 year
	-20°C	6 months

Publications (11)

All Cell Imaging/StainingBio/Physico-chemical AssayIn Vivo Efficacy Study

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Journal Impact Factor

Nat Commun

Norepinephrine-mediated arousal fluctuations drive inverted U-shaped functional connectivity dynamics. [Abstract]

2025 Dec 13;16(1):11318. PMID: 41390822

Clozapine purchased from MedChemExpress. Usage Cited in: Nat Commun. 2025 Dec 13;16(1):11318. [Abstract]

In isoflurane anesthetized mice, the injection of Clozapine (0.03 mg/kg; i.p.) significantly increased EEG-based arousal index, but from a low to middle arousal level.
Nat Commun

Feedforward inhibition of stress by brainstem neuropeptide Y neurons. [Abstract]

2024 Sep 1;15(1):7603. PMID: 39217143

Clozapine purchased from MedChemExpress. Usage Cited in: Nat Commun. 2024 Sep 1;15(1):7603. [Abstract]

Representative current clamp recording of a NPY^DRN/vlPAG-hM4Di neuron with the bath of Clozapine (5 μM). Average membrane potential and firing frequency before and after Clozapine application to inhibit NPY ^DRN/vlPAGneurons were also recorded. Clozapine effectively inhibited hM4Di⁺ NPY^DRN/vlPAG neurons with decreased neuronal membrane potential and firing frequency.

Clozapine purchased from MedChemExpress. Usage Cited in: Nat Commun. 2024 Sep 1;15(1):7603. [Abstract]

Percentage of body weight changes, daily food intake and its area under curve (AUC) of mCherry-restraint and hM4Di-restraint mice. Clozapine (i.p.; 0.2mg/kg; 30 min before restraint for 14 d) caused NPY^hM4Di mice to consume less food and lost more body weight than NPY^mCherry mice during chronic restraint stress.
Mol Psychiatry

ZFP804A mutant mice display sex-dependent schizophrenia-like behaviors. [Abstract]

2021 Jun;26(6):2514-2532. PMID: 33303946

Clozapine purchased from MedChemExpress. Usage Cited in: Mol Psychiatry. 2021 Jun;26(6):2514-2532. [Abstract]

The administration of Clozapine (i.p.; 2 d) restored impaired PPI in female ZFP804A mutant mice.
Commun Med (Lond)

AI-enabled drug prediction and gene network analysis reveal therapeutic use of vorinostat for Rett Syndrome in preclinical models. [Abstract]

2025 Jul 1;5(1):249. PMID: 40595330
Eur J Pharm Sci

Investigating the relevance of CYP2J2 inhibition for drugs known to cause intermediate to high risk torsades de pointes. [Abstract]

2023 Aug 1:187:106475. PMID: 37225005
Eur J Pharm Sci

Atypical kinetics of cytochrome P450 2J2: Epoxidation of arachidonic acid and reversible inhibition by xenobiotic inhibitors. [Abstract]

2021 Sep 1:164:105889. PMID: 34044117
Cell Rep Methods

RECOVER identifies synergistic drug combinations in vitro through sequential model optimization. [Abstract]

2023 Oct 23;3(10):100599. PMID: 37797618
FEBS J

TRPM7 controls skin keratinocyte senescence by targeting intracellular calcium signaling. [Abstract]

2024 Nov;291(21):4680-4695. PMID: 39185948

Clozapine purchased from MedChemExpress. Usage Cited in: FEBS J. 2024 Nov;291(21):4680-4695. [Abstract]

HaCaT cells were transfected with siNC or siRNA against TRPM7 and then treated with Clozapine (Clo) (10 μM; 6 d) the next day. Clozapine (Clo) promoted activation of TRPM7 and increased SA-b-Gal activity.
Biochem Biophys Res Commun

Dual-cardiotoxicity evaluation of torsadogenic risk drugs using human iPSC-derived cardiomyocytes. [Abstract]

2025 Oct 30:786:152756. PMID: 41043280
bioRxiv

2024 November 03.
bioRxiv

Functional coupling between MC4R and Kir7.1 contributes to clozapine-induced hyperphagia. [Abstract]

2024 Jun 8:2024.06.07.597973. PMID: 38895206

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : 50 mg/mL (152.98 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

3.0597 mL

15.2985 mL

30.5969 mL

5 mM

0.6119 mL

3.0597 mL

6.1194 mL

10 mM

0.3060 mL

1.5298 mL

3.0597 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, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

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 (7.65 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 (7.65 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 (7.65 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

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (282 KB)
SDS (644 KB)
- English - EN (644 KB)
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- Deutsch - DE (644 KB)
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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]. Seeman P, et al. Clozapine, a fast-off-D2 antipsychotic. ACS Chem Neurosci. 2014 Jan 15;5(1):24-9. [Content Brief]

[2]. Zhukovskaya NL, et al. Clozapine downregulates 5-hydroxytryptamine6 (5-HT6) and upregulates 5-HT7 receptors in HeLa cells. Neurosci Lett. 2000 Jul 21;288(3):236-40. [Content Brief]

[3]. Moreno JL, et al. Persistent effects of chronic clozapine on the cellular and behavioral responses to LSD in mice. Psychopharmacology (Berl). 2013 Jan;225(1):217-26. [Content Brief]

[4]. Zorn SH, et al. Clozapine is a potent and selective muscarinic M4 receptor agonist. Eur J Pharmacol. 1994 Nov 15;269(3):R1-2. [Content Brief]

[5]. Takano R, et al. Clozapine as an E3 Ligand for PROTAC Technology. ACS Med Chem Lett. 2025 Jan 8;16(2):258-262. [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, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	3.0597 mL	15.2985 mL	30.5969 mL	76.4924 mL
	5 mM	0.6119 mL	3.0597 mL	6.1194 mL	15.2985 mL
	10 mM	0.3060 mL	1.5298 mL	3.0597 mL	7.6492 mL
	15 mM	0.2040 mL	1.0199 mL	2.0398 mL	5.0995 mL
	20 mM	0.1530 mL	0.7649 mL	1.5298 mL	3.8246 mL
	25 mM	0.1224 mL	0.6119 mL	1.2239 mL	3.0597 mL
	30 mM	0.1020 mL	0.5099 mL	1.0199 mL	2.5497 mL
	40 mM	0.0765 mL	0.3825 mL	0.7649 mL	1.9123 mL
	50 mM	0.0612 mL	0.3060 mL	0.6119 mL	1.5298 mL
	60 mM	0.0510 mL	0.2550 mL	0.5099 mL	1.2749 mL
	80 mM	0.0382 mL	0.1912 mL	0.3825 mL	0.9562 mL
	100 mM	0.0306 mL	0.1530 mL	0.3060 mL	0.7649 mL

Clozapine

11 Cited Publications

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Clozapine

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Publications Citing Use of MedChemExpress (MCE) Clozapine

Alle Dopamine Receptor Isoform-spezifische Produkte anzeigen

Alle mAChR Isoform-spezifische Produkte anzeigen

Alle Adrenergic Receptor Isoform-spezifische Produkte anzeigen

Alle 5-HT Receptor Isoform-spezifische Produkte anzeigen

Alle Ligands for E3 Ligase Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Publications (11)

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

Clozapine Related Classifications

Art. -Nr.: HY-14539