Compound Detail

CHEMBL42

CLOZAPINE

💊 Approved Drug

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💊 Approved Drug

CN1CCN(C2=Nc3cc(Cl)ccc3Nc3ccccc32)CC1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL42
Name	CLOZAPINE
Phase	Approved
Structure Type	MOL
InChI Key	QZUDBNBUXVUHMW-UHFFFAOYSA-N
Therapeutic	✓ Yes

Known Names

Clozapina Clozapine Clozapine (caraco) Clozapine (clozaril) Clozapine (fazaclo) Clozapine (ivax) Clozapine (mylan) Clozapine (teva) Clozapine (udl) Clozapine (versacloz) Clozapine resolution mixture Clozaril +8 more

103

Targets

861

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

326.8

MW (Da)

3.72

ALogP

HBA

HBD

30.9

PSA (Å²)

0.80

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
First Approval	1989
Availability	Prescription
Chirality	Achiral

Routes of Administration

Oral

Flags

Black Box Warning Natural Product

USAN Stem	-pine
USAN Year	1969

Extended Properties

Molecular Formula	C18H19ClN4
MW	326.83
Aromatic Rings	2
Heavy Atoms	23
NP-Likeness	-0.78

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Serotonin 2a (5-HT2a) receptor antagonist	ANTAGONIST	5-hydroxytryptamine receptor 2A	✓	✓
Dopamine D2 receptor antagonist	ANTAGONIST	D(2) dopamine receptor	✓	✓

Indications

Psychotic Disorders Psychotic Disorders Schizophrenia Anxiety Bipolar Disorder Dementia Depressive Disorder Developmental Disabilities Intellectual Disability

ATC Classification

N05AH02

clozapine

Level 1: NERVOUS SYSTEM

Level 2: PSYCHOLEPTICS

Drug Warnings

Black Box Warning

hematological toxicity

Country: United States

Black Box Warning

cardiotoxicity

Country: United States

Black Box Warning

vascular toxicity

Country: United States

Black Box Warning

neurotoxicity

Country: United States

Black Box Warning

infectious disease

Country: United States

Activity Summary

Ki 634 meas. best 9.24

IC50 204 meas. best 8.52

Kd 16 meas. best 9.16

EC50 7 meas. best 9.4

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Histamine H1 receptor CHEMBL231	EC50	9.4	9.4	0.4	1
Histamine H1 receptor CHEMBL231	Ki	9.24	8.675	0.6	10
5-hydroxytryptamine receptor 2A CHEMBL322	Kd	9.16	8.89	0.7	2
Unchecked CHEMBL612545	Kd	9.16	9.16	0.7	1
Muscarinic acetylcholine receptor M1 CHEMBL216	Ki	9.01	8.3833	1.0	6
Alpha-2C adrenergic receptor CHEMBL1916	Ki	8.94	8.16	1.1	3
5-hydroxytryptamine receptor 2A CHEMBL224	Ki	8.92	8.0605	1.2	41
Adrenergic receptor alpha-1 CHEMBL1907610	Ki	8.85	8.0133	1.4	18
Unchecked CHEMBL612545	Ki	8.85	7.31	1.4	15
5-hydroxytryptamine receptor 2A CHEMBL322	Ki	8.8	8.0062	1.6	29
Serotonin 2 (5-HT2) receptor CHEMBL2093870	Ki	8.74	8.15	1.8	10
Muscarinic acetylcholine receptor M1 CHEMBL276	Ki	8.68	7.7367	2.1	3
5-hydroxytryptamine receptor 2C CHEMBL225	Ki	8.54	7.91	2.9	26
Histamine H1 receptor CHEMBL4701	Ki	8.54	8.23	2.9	3
5-hydroxytryptamine receptor 2A CHEMBL3446	IC50	8.52	8.52	3.0	1
Histamine H1 receptor CHEMBL231	Kd	8.51	8.51	3.1	1
5-hydroxytryptamine receptor 2B CHEMBL1833	Ki	8.5	8.26	3.2	3
Alpha-1B adrenergic receptor CHEMBL315	Ki	8.45	7.8775	3.6	4
Adrenergic receptor alpha-1 CHEMBL2094251	Ki	8.43	7.8375	3.7	4
Histamine H1 receptor CHEMBL3943	Ki	8.42	8.138	3.8	5
Adrenergic receptor alpha-1 CHEMBL1907610	IC50	8.4	7.5717	4.0	12
Alpha adrenergic receptor 1A and 1B CHEMBL2111476	Ki	8.4	8.4	4.0	1
5-hydroxytryptamine receptor 6 CHEMBL3371	Ki	8.4	8.1044	4.0	16
5-hydroxytryptamine receptor 2A CHEMBL224	IC50	8.38	8.15	4.2	2
Histamine H1 receptor CHEMBL231	IC50	8.31	8.31	4.9	1
Serotonin 2 (5-HT2) receptor CHEMBL2095200	Ki	8.3	8.11	5.0	2
5-hydroxytryptamine receptor 7 CHEMBL3155	Ki	8.26	7.6026	5.5	31
5-hydroxytryptamine receptor 2C CHEMBL225	IC50	8.22	8.11	6.0	2
Muscarinic acetylcholine receptor M4 CHEMBL1821	Ki	8.2	7.7	6.3	3
5-hydroxytryptamine receptor 1A CHEMBL214	Ki	8.2	6.8747	6.4	15
5-hydroxytryptamine receptor 7 CHEMBL3223	Ki	8.2	7.7667	6.3	3
Alpha-1B adrenergic receptor CHEMBL315	IC50	8.19	8.19	6.5	1
Homo sapiens CHEMBL372	EC50	8.19	8.19	6.4	1
D(2) dopamine receptor CHEMBL217	Ki	8.15	7.0024	7.1	80
D(1A) dopamine receptor CHEMBL2056	Ki	8.12	7.044	7.5	15
Serotonin 2 (5-HT2) receptor CHEMBL2093870	IC50	8.11	7.585	7.8	10
5-hydroxytryptamine receptor 2A CHEMBL322	IC50	8.11	7.76	7.8	6
Alpha-2C adrenergic receptor CHEMBL1916	IC50	8.1	8.1	7.9	1
5-hydroxytryptamine receptor 2C CHEMBL324	Ki	8.1	7.7483	8.0	6
D(2) dopamine receptor CHEMBL217	IC50	8.05	6.556	9.0	10
D(4) dopamine receptor CHEMBL3361	Ki	8.05	7.6967	9.0	3
Histamine H1 receptor CHEMBL4701	IC50	8.05	7.7767	9.0	3
Muscarinic acetylcholine receptor M1 CHEMBL216	IC50	8.03	8.02	9.4	3
Muscarinic acetylcholine receptor M5 CHEMBL2035	Ki	8.02	7.51	9.5	2
D(4) dopamine receptor CHEMBL219	Ki	8.0	7.5778	10.0	55
Alpha-1A adrenergic receptor CHEMBL229	Ki	8.0	7.8133	10.0	3
Alpha-1B adrenergic receptor CHEMBL232	Ki	8.0	8.0	10.0	1
Hypothalamus CHEMBL613575	EC50	8.0	8.0	10.0	1
5-hydroxytryptamine receptor 2B CHEMBL1833	IC50	7.96	7.96	11.0	1
Alpha-2B adrenergic receptor CHEMBL1942	Ki	7.96	7.48	11.0	2

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	1761.94	ng.hr.mL-1	Rattus norvegicus
AUC	14.49	ng.hr.mL-1	Rattus norvegicus
CL	2.5	mL.min-1.kg-1	Homo sapiens
CL	2.5	mL.min-1.kg-1	Homo sapiens
CL	2.5	mL.min-1.kg-1	Homo sapiens
CL	2.5	mL.min-1.kg-1	Homo sapiens
CL	6.76	uL.min-1.(10^6cells)-1	Homo sapiens
CL	15.14	mL.min-1.g-1	Homo sapiens
CL	150.0	uL.min-1.(10^6cells)-1	Rattus norvegicus
CL	0.000147	mL.min-1.g-1	Homo sapiens
CL	1.2e-05	mL.min-1.g-1	Homo sapiens
CL	0.44	mL.min-1.g-1	Rattus norvegicus
CL	0.07	mL.min-1.g-1	Rattus norvegicus
CL	2006.0	mL.min-1.kg-1	Rattus norvegicus
CL	98.0	mL.min-1.kg-1	Homo sapiens
CL	0.1	mL.min-1.kg-1	Homo sapiens
CL	5.4	mL.min-1.kg-1	Homo sapiens
CL	0.159	uL/min	Homo sapiens
CL	17.4	mL.min-1.g-1	Homo sapiens
CL	10.3	mL.min-1.kg-1	Homo sapiens
CL	82.4	mL.min-1.kg-1	Mus musculus
CL	6.8	mL.min-1.g-1	Mus musculus
CL	5.8	mL.min-1.g-1	Homo sapiens
CL	20.4	mL.min-1.g-1	Rattus norvegicus
CL	35.9	mL.min-1.g-1	Mus musculus
CL	55.1	mL.min-1.kg-1	Mus musculus
CL	142.0	mL.min-1.kg-1	Mus musculus
Cmax	6.0	nM	Rattus norvegicus
Cmax	3490.0	nM	Homo sapiens
F	79.0	%	Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Histamine H1 receptor	EC50	=	0.4	nM	9.4	Inverse agonist activity at human histamine H1 receptor by R-SAT assay	-
Histamine H1 receptor	Ki	=	0.571	nM	9.24	DRUGMATRIX: Histamine H1, Central radioligand binding (ligand: [3H] Pyrilamine)	-
5-hydroxytryptamine receptor 2A	Kd	=	0.6918	nM	9.16	Negative log concentration of antagonist on 5-hydroxytryptamine 2A receptor in r...	11754579
Unchecked	Kd	=	0.6918	nM	9.16	pA2 value was evaluated by measuring the inhibition of the 5-HT-induced contract...	10425088
Muscarinic acetylcholine receptor M1	Ki	=	0.98	nM	9.01	Binding affinity towards human M1 muscarinic receptor.	11170639
Histamine H1 receptor	Ki	=	1.0	nM	9.0	Binding Assay: Binding assay using 5-HT2A, Dopamine D2, SERT, αA1, 5-HT2C and H1...	-
Histamine H1 receptor	Ki	=	1.0	nM	9.0	Inhibition of histamine H1 receptor (unknown origin)	24559051
Histamine H1 receptor	Ki	=	1.1	nM	8.96	Inhibition of [3H]pyrilamine binding to human Histamine H1 receptor	15771415
Alpha-2C adrenergic receptor	Ki	=	1.144	nM	8.94	DRUGMATRIX: Adrenergic Alpha-2C radioligand binding (ligand: [3H] MK-912)	-
5-hydroxytryptamine receptor 2A	Ki	=	1.199	nM	8.92	DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2A radioligand binding (ligand: ...	-
Adrenergic receptor alpha-1	Ki	=	1.4	nM	8.85	Binding affinity against Alpha-1 adrenergic receptor from rat cerebral cortex	9622541
Adrenergic receptor alpha-1	Ki	=	1.4	nM	8.85	Binding affinity towards alpha-1 adrenergic receptors in rat brain synaptosomal ...	7909336
Adrenergic receptor alpha-1	Ki	=	1.4	nM	8.85	Evaluated for binding affinity against alpha-1 adrenergic receptor	10893315
Unchecked	Ki	=	1.4	nM	8.85	Binding affinity to adrenergic alpha1 receptor	18378462
5-hydroxytryptamine receptor 2A	Ki	=	1.4	nM	8.85	Binding affinity to human 5HT2A receptor	32976928
5-hydroxytryptamine receptor 2A	Ki	=	1.585	nM	8.8	Affinity at 5-hydroxytryptamine 2A receptor of the rat brain cortex was assessed...	10821703
Histamine H1 receptor	Ki	=	1.8	nM	8.74	Displacement of [3H]pyrilamine from human H1 receptor by liquid scintillation co...	22245230
Serotonin 2 (5-HT2) receptor	Ki	=	1.8	nM	8.74	Binding affinity determined in radioreceptor binding assay by using [3H]ketanser...	1346653
Muscarinic acetylcholine receptor M1	Ki	=	1.8	nM	8.74	Displacement of [3H]QNB from human M1 receptor by liquid scintillation counting	22245230
Muscarinic acetylcholine receptor M1	Ki	=	1.8	nM	8.74	Binding affinity to human cloned muscarinic M1 receptor	18595716

Literature References

PubMed	DOI	Target Context	# Activities
-	10.6019/CHEMBL3885881	Rattus norvegicus	199
-	10.5281/zenodo.13943903	ADMET	89
31158845	10.1038/s41586-019-1291-3	ADMET	62
-	10.6019/CHEMBL4295262	Unchecked	36
2571727	10.1021/jm00130a003	Mus musculus	27
23297297	10.1124/dmd.112.050484	Cytochrome P450 3A4	25
17360666	10.1073/pnas.0611417104	Mus musculus	22
23297297	10.1124/dmd.112.050484	Liver microsome	19
16472241	10.2174/1570163043334794	Hepatotoxicity	18
23297297	10.1124/dmd.112.050484	Cytochrome P450 2D6	16
22194678	10.1371/journal.pcbi.1002310	Hepatotoxicity	14
11392544	10.1016/s0960-894x(01)00200-1	Mus musculus	14
2571727	10.1021/jm00130a003	Rattus norvegicus	11
18024584	10.1073/pnas.0709695104	H4	11
15646539	10.1016/s0399-8320(04)95062-2	Unchecked	11
2891853	10.1021/jm00396a016	Mus musculus	10
8831770	10.1021/jm960268u	Rattus norvegicus	10
15771414	10.1021/jm049629t	Rattus norvegicus	10
34721	10.1021/jm00190a009	Mus musculus	10
16854056	10.1021/jm051008s	Histamine H4 receptor	9

Data from ChEMBL 36 via Core Engine