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Compound Detail

CHEMBL6

INDOMETHACIN
💊 Approved Drug
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💊 Approved Drug
COc1ccc2c(c1)c(CC(=O)O)c(C)n2C(=O)c1ccc(Cl)cc1

Basic Information

ChEMBL ID CHEMBL6
Name INDOMETHACIN
Phase Approved
Structure Type MOL
InChI Key CGIGDMFJXJATDK-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

Aconip Artracin Artracin sr Berlind 75 ret Durametacin Flexin-25 continus Flexin-50 continus Flexin-75 continus Imbrilon Indo-lemmon Indo-paed Indocid ret +18 more
67
Targets
572
Activities
4
Assay Types
30
PK Parameters
20
Publications
30
Known Names
20
Indications
1
Mechanisms

Molecular Properties

357.8
MW (Da)
3.93
ALogP
4
HBA
1
HBD
68.5
PSA (Ų)
0.77
QED
0
Ro5 Violations
4
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1965
Availability Prescription
Chirality Achiral

Routes of Administration

Oral Parenteral Topical

Flags

Black Box Warning Natural Product
USAN Year 1963

Extended Properties

Molecular Formula C19H16ClNO4
MW 357.79
Aromatic Rings 3
Heavy Atoms 25
NP-Likeness -0.72

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Cyclooxygenase inhibitor INHIBITOR Cyclooxygenase

Indications

Acute Pain Arthralgia Arthritis, Gouty Arthritis, Rheumatoid Cardiovascular Diseases Ductus Arteriosus, Patent Eye Diseases Myalgia Osteoarthritis Rheumatic Diseases Spondylitis Spondylitis, Ankylosing Alzheimer Disease Hemorrhage Inflammation Pancreatitis Pancreatitis Premature Birth Renal Colic Severe Acute Respiratory Syndrome

ATC Classification

C01EB03
indometacin
Level 1: CARDIOVASCULAR SYSTEM
Level 2: CARDIAC THERAPY
M01AB01
indometacin
Level 1: MUSCULO-SKELETAL SYSTEM
Level 2: ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS
M01AB51
indometacin, combinations
Level 1: MUSCULO-SKELETAL SYSTEM
Level 2: ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS
M02AA23
indometacin
Level 1: MUSCULO-SKELETAL SYSTEM
Level 2: TOPICAL PRODUCTS FOR JOINT AND MUSCULAR PAIN
S01BC01
indometacin
Level 1: SENSORY ORGANS
Level 2: OPHTHALMOLOGICALS

Drug Warnings

Black Box Warning
neurotoxicity
Country: United States
Black Box Warning
gastrointestinal toxicity
Country: United States
Black Box Warning
cardiotoxicity
Country: United States

Activity Summary

IC50 541 meas. best 9.85
Ki 19 meas. best 9.82
EC50 7 meas. best 9.85
Kd 5 meas. best 7.04

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Prostaglandin G/H synthase 1
CHEMBL221
IC50 9.85 6.9899 0.1 78
Prostaglandin G/H synthase 2
CHEMBL230
IC50 9.85 6.1744 0.1 123
Androgen receptor
CHEMBL1871
EC50 9.85 9.85 0.1 1
Nicotinate phosphoribosyltransferase
CHEMBL4523354
Ki 9.82 9.82 0.1 1
Prostaglandin G/H synthase 1
CHEMBL2649
IC50 8.7 8.7 2.0 1
Cyclooxygenase
CHEMBL2095157
IC50 8.54 6.6988 2.9 8
THP-1
CHEMBL614245
IC50 8.44 7.1967 3.6 3
Prostaglandin G/H synthase 1
CHEMBL2949
IC50 8.4 6.9105 4.0 80
Prostaglandin G/H synthase 1
CHEMBL2860
IC50 8.39 6.314 4.1 5
Unchecked
CHEMBL612545
IC50 8.3 6.27 5.0 18
Prostaglandin G/H synthase 1
CHEMBL4042
IC50 8.22 7.72 6.0 3
Prostaglandin G/H synthase 2
CHEMBL4321
IC50 8.19 6.9789 6.4 9
Prostaglandin G/H synthase 2
CHEMBL2977
IC50 8.0 7.5533 10.0 3
Cyclooxygenase
CHEMBL2094253
IC50 8.0 8.0 10.0 1
Cyclooxygenase
CHEMBL2096674
IC50 7.96 6.3911 11.0 9
Prostaglandin G/H synthase (cyclooxygenase)
CHEMBL2111349
IC50 7.7 7.7 20.0 1
Prostaglandin D2 receptor 2
CHEMBL5071
Ki 7.3 6.2 50.0 2
Interleukin-8
CHEMBL2157
IC50 7.3 7.3 50.0 1
RAW264.7
CHEMBL612557
IC50 7.28 4.8065 52.8 49
Cytochrome c oxidase subunit 2
CHEMBL6174
IC50 7.16 6.685 70.0 2
Prostaglandin G/H synthase 2
CHEMBL4102
IC50 7.06 5.5748 87.0 25
Prostaglandin G/H synthase 2
CHEMBL230
Kd 7.04 7.04 92.0 1
Aldo-keto reductase family 1 member C3
CHEMBL4681
IC50 7.0 5.6513 100.0 8
Platelet
CHEMBL4296519
IC50 7.0 6.1825 100.0 4
Thromboxane-A synthase
CHEMBL1835
IC50 7.0 7.0 100.0 1
Blood
CHEMBL613416
IC50 6.92 6.66 120.0 2
NON-PROTEIN TARGET
CHEMBL3879801
IC50 6.85 4.9878 140.0 9
Prostaglandin G/H synthase (cyclooxygenase)
CHEMBL2111358
IC50 6.82 6.0333 150.0 3
Mus musculus
CHEMBL375
IC50 6.62 6.535 240.0 6
Prostaglandin G/H synthase 1
CHEMBL221
Kd 6.6 6.6 253.0 1
Homo sapiens
CHEMBL372
IC50 6.6 6.025 250.0 10
Mononuclear cell line
CHEMBL614723
IC50 6.52 6.52 300.0 1
Prostaglandin D2 receptor 2
CHEMBL5071
EC50 6.41 6.41 389.0 1
Prostaglandin-H2 D-isomerase
CHEMBL4334
IC50 6.3 6.3 500.0 1
Albumin
CHEMBL3253
Kd 6.16 6.16 700.0 1
Rattus norvegicus
CHEMBL376
IC50 6.1 5.16 800.0 2
Prostaglandin G/H synthase 2
CHEMBL230
Ki 5.82 5.82 1500.0 1
Solute carrier family 22 member 6
CHEMBL1641347
IC50 5.52 5.52 3000.0 1
Aldo-keto reductase family 1 member B1
CHEMBL2622
IC50 5.44 5.44 3631.0 1
Solute carrier family 22 member 6
CHEMBL1777665
Ki 5.38 5.19 4200.0 2
Nitric oxide synthase, inducible
CHEMBL3464
IC50 5.35 4.718 4500.0 5
Zingiber officinale
CHEMBL2366941
IC50 5.31 5.31 4900.0 1
Canine coronavirus
CHEMBL5291668
IC50 5.3 5.3 5000.0 1
Aldo-keto reductase family 1 member B1
CHEMBL3081
IC50 5.3 5.3 5000.0 1
ATP-binding cassette sub-family C member 4
CHEMBL1743128
IC50 5.24 5.24 5800.0 1
Organic anion transporter 3
CHEMBL1641348
Ki 5.22 5.22 5950.0 1
Aldo-keto reductase family 1 member B1
CHEMBL1900
IC50 5.22 5.22 6000.0 1
Polyunsaturated fatty acid 5-lipoxygenase
CHEMBL215
IC50 5.16 5.16 7000.0 1
BV-2
CHEMBL614781
IC50 5.15 4.678 7100.0 5
Prostaglandin G/H synthase 1
CHEMBL2949
Ki 5.1 5.1 7900.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 93771.0 ng.hr.mL-1 Rattus norvegicus
AUC 97096.0 ng.hr.mL-1 Rattus norvegicus
AUC 279.8 - Chlorocebus sabaeus
CL 2.24 mL.min-1.kg-1 Homo sapiens
CL 1.3 mL.min-1.kg-1 Homo sapiens
CL 1.1 mL.min-1.kg-1 Homo sapiens
CL 1.3 mL.min-1.kg-1 Homo sapiens
CL 0.002 mL.min-1.kg-1 Canis lupus familiaris
CL 0.43 mL.min-1.kg-1 Rattus norvegicus
CL 1.3 mL.min-1.kg-1 Homo sapiens
CL 2.0 mL.min-1.kg-1 Homo sapiens
CL 13.0 mL.min-1.kg-1 Macaca
CL 1e-06 mL.min-1.g-1 Homo sapiens
CL 0.21 mL.min-1.kg-1 Homo sapiens
CL 1.4 mL.min-1.kg-1 Homo sapiens
CL 4.2 mL.min-1.g-1 Homo sapiens
CL 5.2 mL.min-1.g-1 Homo sapiens
CL - - Homo sapiens
CL 1.58 mL.min-1.kg-1 Homo sapiens
CL 1.58 mL.min-1.kg-1 Homo sapiens
CL 0.001 uL/min Homo sapiens
Cmax 29011.43 nM Rattus norvegicus
Cmax 2794.94 nM Homo sapiens
Cmax 5589.87 nM Homo sapiens
Cmax 25.0 nM Homo sapiens
F 80.0 % Homo sapiens
F 98.0 % Homo sapiens
F 99.0 % Homo sapiens
F 100.0 % Homo sapiens
Fu 0.01 - Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Androgen receptor EC50 = 0.14 nM 9.85 Agonist activity at androgen receptor (unknown origin) expressed in HeLa cells c... 23432095
Prostaglandin G/H synthase 1 IC50 = 0.14 nM 9.85 Inhibition of COX1 (unknown origin) 38516587
Prostaglandin G/H synthase 2 IC50 = 0.14 nM 9.85 Inhibition of COX-2 (unknown origin) using arachidonic acid as substrate preincu... 38516587
Nicotinate phosphoribosyltransferase Ki = 0.15 nM 9.82 Inhibition of NAPRT (unknown origin) -
Prostaglandin G/H synthase 1 IC50 = 2.0 nM 8.7 In vitro inhibitory activity against human Prostaglandin G/H synthase 1 (COX-1) ... 12877584
Prostaglandin G/H synthase 1 IC50 = 2.0 nM 8.7 In vitro inhibitory activity against Prostaglandin G/H synthase 1 in murine J774... 15857149
Cyclooxygenase IC50 = 2.9 nM 8.54 In vitro inhibitory effect on production of prostaglandin E2 (PGE2) in rat synov... 10821716
Prostaglandin G/H synthase 1 IC50 = 3.0 nM 8.52 Inhibition of arachidonic acid induced TXB2 generation in isolated human platele... 11906281
Prostaglandin G/H synthase 1 IC50 = 3.0 nM 8.52 Inhibition of Prostaglandin G/H synthase 1 in U-937 cells from human histiocytic... 11462976
THP-1 IC50 = 3.6 nM 8.44 Effect on production of eicosanoids from THP-1 cells stimulated with A-23187 usi... 10737736
THP-1 IC50 = 3.6 nM 8.44 Concentration required to inhibit production of PGE-2 from THP-1 cells stimulate... 11229777
Prostaglandin G/H synthase 1 IC50 = 4.0 nM 8.4 Inhibition of ovine COX1 16814546
Prostaglandin G/H synthase 1 IC50 = 4.1 nM 8.39 Inhibition of bovine COX1 assessed as inhibition of calcium ionophore A23187-ind... 22749420
Prostaglandin G/H synthase 1 IC50 = 5.0 nM 8.3 Inhibition of COX1 assessed as TBX2 production in human whole blood 16814546
Unchecked IC50 = 5.0 nM 8.3 Inhibition of LPS-induced PGE2 production in C57BL6 mouse peritoneal cells measu... 30006172
Prostaglandin G/H synthase 2 IC50 = 5.9 nM 8.23 Inhibition of PGE-2 generation in LPS-stimulated human monocytes (Prostaglandin ... 11906281
Prostaglandin G/H synthase 1 IC50 = 6.0 nM 8.22 Inhibition of ovine COX1 after 5 mins 20503989
Prostaglandin G/H synthase 1 IC50 = 6.0 nM 8.22 Inhibition of COX1 17341061
Prostaglandin G/H synthase 1 IC50 = 6.0 nM 8.22 In vitro inhibition of Prostaglandin G/H synthase 1 -
Prostaglandin G/H synthase 1 IC50 = 6.0 nM 8.22 Inhibition of Prostaglandin G/H synthase 1 using whole cell assay -

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL3885861 Rattus norvegicus 2115
- 10.6019/CHEMBL3885881 Rattus norvegicus 1348
31158845 10.1038/s41586-019-1291-3 ADMET 99
- 10.5281/zenodo.13943903 ADMET 89
36170566 10.1021/acs.jmedchem.2c01355 H9c2 33
8071938 10.1021/jm00044a011 Rattus norvegicus 30
26117820 10.1016/j.ejmech.2015.06.020 Rattus norvegicus 26
3669013 10.1021/jm00394a020 Rattus norvegicus 20
17945398 10.1016/j.ejmech.2007.08.008 Rattus norvegicus 19
17964781 10.1016/j.bmcl.2007.10.037 Rattus norvegicus 19
16472241 10.2174/1570163043334794 Hepatotoxicity 18
2115585 10.1021/jm00170a003 Rattus norvegicus 17
17166724 10.1016/j.bmc.2006.11.029 Mus musculus 16
21800856 10.1021/np200343t Mus musculus 16
32485533 10.1016/j.ejmech.2020.112438 Rattus norvegicus 15
23687559 10.1021/ml400066a Unchecked 15
31803395 10.1039/C9MD00228F ADMET 15
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
- 10.1007/s00044-011-9707-0 Mus musculus 13
22197135 10.1016/j.ejmech.2011.12.008 Mus musculus 13

Data from ChEMBL 36 via Core Engine