Compound Detail

CHEMBL344159

TOLVAPTAN

💊 Approved Drug

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💊 Approved Drug

Cc1ccccc1C(=O)Nc1ccc(C(=O)N2CCCC(O)c3cc(Cl)ccc32)c(C)c1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL344159
Name	TOLVAPTAN
Phase	Approved
Structure Type	MOL
InChI Key	GYHCTFXIZSNGJT-UHFFFAOYSA-N
Therapeutic	✓ Yes

Known Names

Jinarc Jynarque OPC-41061 OPC-41061(TOLVAPTAN) Samsca Tolvaptan Tolvaptan accord

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

448.9

MW (Da)

5.68

ALogP

HBA

HBD

69.6

PSA (Å²)

0.54

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
First Approval	2009
Availability	Prescription
Chirality	Racemic

Routes of Administration

Oral

Flags

Black Box Warning Natural Product

USAN Stem	-vaptan
USAN Year	1999

Extended Properties

Molecular Formula	C26H25ClN2O3
MW	448.95
Aromatic Rings	3
Heavy Atoms	32
NP-Likeness	-1.43

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Vasopressin V2 receptor antagonist	ANTAGONIST	Vasopressin V2 receptor	✓	✓

Indications

Cardiovascular Diseases Heart Failure Heart Failure Hyponatremia Inappropriate ADH Syndrome Polycystic Kidney Diseases Polycystic Kidney, Autosomal Dominant Dyspnea Edema, Cardiac Liver Cirrhosis Carcinoma Kidney Diseases Kidney Failure, Chronic

ATC Classification

C03XA01

tolvaptan

Level 1: CARDIOVASCULAR SYSTEM

Level 2: DIURETICS

Drug Warnings

Black Box Warning

hepatotoxicity

Country: United States

Activity Summary

Ki 11 meas. best 9.37

IC50 5 meas. best 8.35

EC50 4 meas. best 5.47

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Vasopressin V2 receptor CHEMBL1790	Ki	9.37	8.94	0.4	4
Unchecked CHEMBL612545	Ki	9.1	9.1	0.8	1
Vasopressin V2 receptor CHEMBL1790	IC50	8.35	8.15	4.5	2
Vasopressin V1a receptor CHEMBL1889	Ki	7.5	7.015	32.0	2
Mu-type opioid receptor CHEMBL233	Ki	6.39	6.39	410.0	1
Vasopressin V1a receptor CHEMBL1889	IC50	6.33	6.33	470.0	1
Sigma intracellular receptor 2 CHEMBL4105907	Ki	5.99	5.99	1031.2	1
Beta-2 adrenergic receptor CHEMBL210	EC50	5.47	5.47	3400.0	1
Glucose-dependent insulinotropic receptor CHEMBL5652	EC50	5.4	5.4	4018.7	1
Glucagon-like peptide 1 receptor CHEMBL1784	EC50	5.33	5.33	4643.6	1
5-hydroxytryptamine receptor 2C CHEMBL225	Ki	5.31	5.31	4856.2	1
Free fatty acid receptor 4 CHEMBL5339	EC50	5.29	5.29	5108.1	1
Histamine H1 receptor CHEMBL231	Ki	5.17	5.17	6687.3	1
Bile salt export pump CHEMBL6020	IC50	5.0	5.0	9990.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	4262.33	ng.hr.mL-1	Homo sapiens
AUC	824.0	ng.hr.mL-1	Mus musculus
AUC	961.0	ng.hr.mL-1	Mus musculus
AUC	967.0	ng.hr.mL-1	Mus musculus
CL	164.0	ml/min	Rattus norvegicus
Cmax	877.6	nM	Mus musculus
Cmax	1951.22	nM	Mus musculus
T1/2	0.3833	hr	Rattus norvegicus
T1/2	4.1	hr	Mus musculus
T1/2	2.23	hr	Mus musculus
Tmax	0.83	hr	Mus musculus
Tmax	0.33	hr	Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Vasopressin V2 receptor	Ki	=	0.43	nM	9.37	Concentration which inhibit [3H]AVP binding to human Vasopressin V2 receptor cod...	11087564
Unchecked	Ki	=	0.79	nM	9.1	Binding affinity towards AVP receptor	11087564
Vasopressin V2 receptor	Ki	=	1.0	nM	9.0	Displacement of [3H]-arginine-vasopressin from human V2 receptor expressed in hu...	34255509
Vasopressin V2 receptor	Ki	=	1.7	nM	8.77	Displacement of conivaptan-red from SNAP-tagged V2 receptor (unknown origin) exp...	35363466
Vasopressin V2 receptor	Ki	=	2.4	nM	8.62	Displacement of conivaptan-red from SNAP-tagged human V2 receptor expressed in H...	35579344
Vasopressin V2 receptor	IC50	=	4.502	nM	8.35	GPCR PRESTO-Tango dose-response in antagonist mode with target: AVPR2	-
Vasopressin V2 receptor	IC50	=	11.22	nM	7.95	Antagonist activity at human V2 receptor expressed in CHO cells assessed as redu...	35363466
Vasopressin V1a receptor	Ki	=	32.0	nM	7.5	Displacement of [3H]-arginine-vasopressin from human V1A receptor expressed in h...	34255509
Vasopressin V1a receptor	Ki	=	296.0	nM	6.53	Displacement of [3H]-vasopressin from human V1A receptor expressed in CHO cells ...	35579344
Mu-type opioid receptor	Ki	=	410.01	nM	6.39	PDSP Secondary Binding target: OPRM1 - Compounds are tested at 10 uM concentrati...	-
Vasopressin V1a receptor	IC50	=	470.0	nM	6.33	Inhibition of human V1A receptor expressed in human 1321N1 cells assessed as cal...	34255509
Sigma intracellular receptor 2	Ki	=	1031.22	nM	5.99	PDSP Secondary Binding target: TMEM97 - Compounds are tested at 10 uM concentrat...	-
Beta-2 adrenergic receptor	EC50	=	3400.0	nM	5.47	GPCR PRESTO-Tango dose-response in antagonist mode with target: ADRB2	-
Glucose-dependent insulinotropic receptor	EC50	=	4018.74	nM	5.4	GPCR PRESTO-Tango dose-response in antagonist mode with target: GPR119	-
Glucagon-like peptide 1 receptor	EC50	=	4643.58	nM	5.33	GPCR PRESTO-Tango dose-response in antagonist mode with target: GLP1R	-
5-hydroxytryptamine receptor 2C	Ki	=	4856.23	nM	5.31	PDSP Secondary Binding target: HTR2C - Compounds are tested at 10 uM concentrati...	-
Free fatty acid receptor 4	EC50	=	5108.13	nM	5.29	GPCR PRESTO-Tango dose-response in antagonist mode with target: FFAR4	-
Histamine H1 receptor	Ki	=	6687.29	nM	5.17	PDSP Secondary Binding target: HRH1 - Compounds are tested at 10 uM concentratio...	-
Bile salt export pump	IC50	=	9990.0	nM	5.0	Inhibition of human BSEP overexpressed in Sf9 cell membrane vesicles assessed as...	23956101

Literature References

PubMed	DOI	Target Context	# Activities
-	10.6019/CHEMBL4689842	HEK-293T	10
35363466	10.1021/acs.jmedchem.2c00011	Vasopressin V2 receptor	9
-	10.6019/CHEMBL4689842	Fibroblast	9
-	10.6019/CHEMBL4689842	U2OS	8
35363466	10.1021/acs.jmedchem.2c00011	ADMET	7
38509003	10.1021/acs.jmedchem.4c00217	ADMET	5
-	10.6019/CHEMBL5209801	Apelin receptor	5
-	10.6019/CHEMBL5209801	Free fatty acid receptor 4	5
-	10.6019/CHEMBL5209801	Adhesion G-protein coupled receptor F1	5
-	10.6019/CHEMBL5209801	N-formyl peptide receptor 2	5
-	10.6019/CHEMBL5209801	Glucagon-like peptide 1 receptor	5
-	10.6019/CHEMBL5209801	Type-1 angiotensin II receptor	5
35579344	10.1021/acs.jmedchem.2c00567	ADMET	5
35579344	10.1021/acs.jmedchem.2c00567	Mus musculus	5
-	10.6019/CHEMBL5209801	CX3C chemokine receptor 1	5
-	10.6019/CHEMBL5209801	Alpha-2A adrenergic receptor	5
-	10.6019/CHEMBL5209801	C5a anaphylatoxin chemotactic receptor 1	5
-	10.6019/CHEMBL5209801	Sphingosine 1-phosphate receptor 1	5
-	10.6019/CHEMBL5209801	Beta-2 adrenergic receptor	5
-	10.6019/CHEMBL5209801	Glucose-dependent insulinotropic receptor	5

Data from ChEMBL 36 via Core Engine