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Compound Detail

CHEMBL779

TADALAFIL
💊 Approved Drug
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💊 Approved Drug
CN1CC(=O)N2[C@H](c3ccc4c(c3)OCO4)c3[nH]c4ccccc4c3C[C@@H]2C1=O

Basic Information

ChEMBL ID CHEMBL779
Name TADALAFIL
Phase Approved
Structure Type MOL
InChI Key WOXKDUGGOYFFRN-IIBYNOLFSA-N
Therapeutic ✓ Yes

Known Names

Adcirca Adcirca (previously tadalafil lilly) Chewtadzy Cialis IC-351 IC351 LY-450190 LY450190 NSC-750236 NSC-759172 Tadalafil Tadalafil component of entadfi +7 more
23
Targets
93
Activities
4
Assay Types
11
PK Parameters
20
Publications
19
Known Names
20
Indications
1
Mechanisms

Molecular Properties

389.4
MW (Da)
2.21
ALogP
4
HBA
1
HBD
74.9
PSA (Ų)
0.69
QED
0
Ro5 Violations
1
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2002
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral

Flags

Natural Product
USAN Stem -afil
USAN Year 2001

Extended Properties

Molecular Formula C22H19N3O4
MW 389.41
Aromatic Rings 3
Heavy Atoms 29
NP-Likeness -0.17

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Phosphodiesterase 5A inhibitor INHIBITOR cGMP-specific 3',5'-cyclic phosphodiesterase

Indications

Erectile Dysfunction Erectile Dysfunction Hypertension, Pulmonary Hypertension, Pulmonary Prostatic Hyperplasia Pulmonary Arterial Hypertension Glucose Intolerance Heart Defects, Congenital Insulin Resistance Lung Diseases, Interstitial Muscular Dystrophy, Duchenne Premature Ejaculation Raynaud Disease Transposition of Great Vessels Carcinoma, Non-Small-Cell Lung Carcinoma, Squamous Cell Cushing Syndrome Dementia, Vascular Diabetes Mellitus, Type 2 Eisenmenger Complex

ATC Classification

G04BE08
tadalafil
Level 1: GENITO URINARY SYSTEM AND SEX HORMONES
Level 2: UROLOGICALS

Activity Summary

IC50 79 meas. best 9.08
EC50 7 meas. best 7.11
Ki 4 meas. best 8.92
Kd 3 meas. best 8.72

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
ADMET
CHEMBL612558
IC50 9.08 9.08 0.8 1
cGMP-specific 3',5'-cyclic phosphodiesterase
CHEMBL1827
IC50 8.92 8.2426 1.2 19
Unchecked
CHEMBL612545
Ki 8.92 8.92 1.2 1
Unchecked
CHEMBL612545
IC50 8.92 6.83 1.2 2
cGMP-specific 3',5'-cyclic phosphodiesterase
CHEMBL1827
Kd 8.72 8.67 1.9 2
cGMP-specific 3',5'-cyclic phosphodiesterase
CHEMBL3478
IC50 8.48 8.2033 3.3 6
cGMP-specific 3',5'-cyclic phosphodiesterase
CHEMBL4567
Ki 8.3 8.3 5.0 1
cGMP-specific 3',5'-cyclic phosphodiesterase
CHEMBL1827
Ki 8.28 8.14 5.2 2
Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A
CHEMBL2717
IC50 8.0 6.9817 10.0 12
cGMP-specific 3',5'-cyclic phosphodiesterase
CHEMBL4567
EC50 7.11 7.11 78.0 1
Rattus norvegicus
CHEMBL376
EC50 6.82 6.56 150.0 2
Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha'
CHEMBL3977
IC50 6.4 6.4 402.0 1
Phosphodiesterase 6
CHEMBL2097163
IC50 6.01 5.634 980.0 5
Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha
CHEMBL3741
IC50 5.52 5.52 3000.0 1
Nuclear receptor subfamily 2 group E member 1
CHEMBL1961788
EC50 5.3 5.3 5000.0 1
Phosphodiesterase 6
CHEMBL2096979
IC50 5.29 5.29 5100.0 1
cGMP-specific 3',5'-cyclic phosphodiesterase
CHEMBL1827
EC50 5.24 5.24 5810.0 1
NCI-H1299
CHEMBL612255
IC50 5.11 5.09 7800.0 2
Trypanosoma cruzi
CHEMBL368
IC50 5.07 5.07 8600.0 1
Phosphodiesterase 4
CHEMBL2093863
IC50 5.04 5.04 9200.0 1
NCI-H661
CHEMBL1075544
IC50 5.0 4.84 9900.0 2
Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A
CHEMBL4295711
EC50 4.96 4.81 11000.0 2
A549
CHEMBL392
IC50 4.91 4.5567 12200.0 3
Acetylcholinesterase
CHEMBL3199
IC50 4.58 4.58 26159.0 1
Acetylcholinesterase
CHEMBL220
IC50 4.58 4.58 26100.0 1
Leishmania donovani
CHEMBL367
IC50 4.4 4.4 40060.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 4.1 4.0333 79432.8 3
Trypanosoma brucei rhodesiense
CHEMBL612348
IC50 4.01 4.01 97580.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 5.1 mL.min-1.kg-1 Rattus norvegicus
CL 49.0 mL.min-1.g-1 Homo sapiens
CL 5.167 mL.min-1.kg-1 Rattus norvegicus
F 63.0 % Rattus norvegicus
F 63.0 % Rattus norvegicus
T1/2 2.4 hr Rattus norvegicus
T1/2 17.0 hr -
T1/2 2.4 hr Rattus norvegicus
T1/2 17.5 hr Homo sapiens
T1/2 17.5 hr Mus musculus
Vd 5.2 kg-1 Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
ADMET IC50 = 0.84 nM 9.08 Drug concentration in C57B6 mouse brain at 15 mg/kg, po via gavage measured afte... 35144038
Unchecked Ki = 1.2 nM 8.92 Binding affinity to MT1 receptor (unknown origin) assessed as inhibition constan... 38516587
cGMP-specific 3',5'-cyclic phosphodiesterase IC50 = 1.2 nM 8.92 Inhibition of PDE5 (unknown origin) using FAM-cGMP as substrate after 60 mins by... 23313637
cGMP-specific 3',5'-cyclic phosphodiesterase IC50 = 1.2 nM 8.92 Inhibition of PDE5A (unknown origin) 29363967
Unchecked IC50 = 1.2 nM 8.92 Inhibition of PDE5 (unknown origin) 35144038
cGMP-specific 3',5'-cyclic phosphodiesterase IC50 = 1.3 nM 8.89 Inhibition of Phosphodiesterase 5 from human platelets 12570368
cGMP-specific 3',5'-cyclic phosphodiesterase IC50 = 1.8 nM 8.74 Affinity Biochemical interaction: ([3H]cGMP-Binding Assay) EUB0002731a PDE5A -
cGMP-specific 3',5'-cyclic phosphodiesterase Kd = 1.9 nM 8.72 Affinity Biochemical interaction: ([3H] inhibitor exchange-dissociation kinetics... -
cGMP-specific 3',5'-cyclic phosphodiesterase IC50 = 2.35 nM 8.63 Inhibition of N-terminal GST-tagged human PDE5A1 expressed in baculovirus infect... 31021628
cGMP-specific 3',5'-cyclic phosphodiesterase Kd = 2.4 nM 8.62 Affinity Biochemical interaction: (competitive binding assay with radiolabelled ... -
cGMP-specific 3',5'-cyclic phosphodiesterase IC50 = 3.0 nM 8.52 Inhibition of human recombinant PDE5A-mediated hydrolysis of cGMP after 30 mins ... 21189023
cGMP-specific 3',5'-cyclic phosphodiesterase IC50 = 3.162 nM 8.5 Inhibition of PDE5 (unknown origin) 29620890
cGMP-specific 3',5'-cyclic phosphodiesterase IC50 = 3.3 nM 8.48 Inhibition of bovine PDE5 after 24 hrs by HTRF 17107795
cGMP-specific 3',5'-cyclic phosphodiesterase IC50 = 4.0 nM 8.4 Inhibition of PDE5A1 (unknown origin) using [3H]-cGMP substrate incubated for 15... 38614063
cGMP-specific 3',5'-cyclic phosphodiesterase IC50 = 4.0 nM 8.4 Inhibition of human phosphodiesterase 5 15837326
cGMP-specific 3',5'-cyclic phosphodiesterase IC50 = 4.0 nM 8.4 Inhibition of human recombinant PDE5 after 1.5 hrs by fluorescent polarization a... 20206015
cGMP-specific 3',5'-cyclic phosphodiesterase IC50 = 4.0 nM 8.4 Inhibition of PDE5A1 (unknown origin) by immobilized metal ion affinity-based fl... 31103902
cGMP-specific 3',5'-cyclic phosphodiesterase IC50 = 4.67 nM 8.33 Inhibition of full length recombinant human N-terminal GST-tagged PDE5A1 express... 30245400
cGMP-specific 3',5'-cyclic phosphodiesterase IC50 = 5.0 nM 8.3 Inhibition of bovine PDE5 after 24 hrs by time-resolved fluorescence resonance e... 22204607
cGMP-specific 3',5'-cyclic phosphodiesterase IC50 = 5.0 nM 8.3 Inhibition of PDE5A (unknown origin) 32171616

Literature References

PubMed DOI Target Context # Activities
- 10.5281/zenodo.13943903 ADMET 89
39149110 10.1039/d4md00364k A549 17
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
39149110 10.1039/d4md00364k NCI-H1299 14
39149110 10.1039/d4md00364k NCI-H661 13
31021628 10.1021/acs.jmedchem.9b00123 Unchecked 10
23313637 10.1016/j.ejmech.2012.12.009 Unchecked 10
37862143 10.1021/acs.jmedchem.3c01088 Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A 6
27606546 10.1021/acs.jmedchem.6b00908 NON-PROTEIN TARGET 6
14521415 10.1021/jm0300577 Rattus norvegicus 5
29549837 10.1016/j.ejmech.2018.03.005 Unchecked 5
15771456 10.1021/jm0401098 Unchecked 5
31021628 10.1021/acs.jmedchem.9b00123 ADMET 4
27606546 10.1021/acs.jmedchem.6b00908 Histone deacetylase 6 4
12570368 10.1021/jm0256068 Unchecked 4
30245400 10.1016/j.ejmech.2018.09.028 cGMP-specific 3',5'-cyclic phosphodiesterase 3
37468498 10.1038/s41467-023-40064-9 5-hydroxytryptamine receptor 2A 3
37468498 10.1038/s41467-023-40064-9 Cannabinoid receptor 1 3
30245400 10.1016/j.ejmech.2018.09.028 Unchecked 3
25087753 10.1016/j.vascn.2014.07.002 Voltage-gated inwardly rectifying potassium channel KCNH2 3

Data from ChEMBL 36 via Core Engine