Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C19H16ClNO4 |
| Molecular Weight | 357.788 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC2=C(C=C1)N(C(=O)C3=CC=C(Cl)C=C3)C(C)=C2CC(O)=O
InChI
InChIKey=CGIGDMFJXJATDK-UHFFFAOYSA-N
InChI=1S/C19H16ClNO4/c1-11-15(10-18(22)23)16-9-14(25-2)7-8-17(16)21(11)19(24)12-3-5-13(20)6-4-12/h3-9H,10H2,1-2H3,(H,22,23)
| Molecular Formula | C19H16ClNO4 |
| Molecular Weight | 357.788 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionCurator's Comment: description was created based on several sources, including
https://clinicaltrials.gov/ct2/show/NCT02183168 | https://clinicaltrials.gov/ct2/show/NCT02770950 | https://www.ncbi.nlm.nih.gov/pubmed/20503989 | https://www.ncbi.nlm.nih.gov/pubmed/14056924 | https://www.ncbi.nlm.nih.gov/pubmed/27988363
Curator's Comment: description was created based on several sources, including
https://clinicaltrials.gov/ct2/show/NCT02183168 | https://clinicaltrials.gov/ct2/show/NCT02770950 | https://www.ncbi.nlm.nih.gov/pubmed/20503989 | https://www.ncbi.nlm.nih.gov/pubmed/14056924 | https://www.ncbi.nlm.nih.gov/pubmed/27988363
Indometacin (INN and BAN) or indomethacin (AAN, USAN, and former BAN) is a nonsteroidal anti-inflammatory drug (NSAID) commonly used as a prescription medication to reduce fever, pain, stiffness, and swelling from inflammation. Indomethacin has analgesic, anti-inflammatory, and antipyretic properties. The mechanism of action of Indometacin, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2). Indomethacin is a potent inhibitor of prostaglandin synthesis in vitro. Indomethacin concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because indomethacin is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues. Indometacin is indicated for: Moderate to severe rheumatoid arthritis including acute flares of chronic disease, Moderate to severe ankylosing spondylitis, Moderate to severe osteoarthritis, Acute painful shoulder (bursitis and/or tendinitis), Acute gouty arthritis. In general, adverse effects seen with indomethacin are similar to all other NSAIDs. For instance, indometacin inhibits both cyclooxygenase-1 and cyclooxygenase-2, it inhibits the production of prostaglandins in the stomach and intestines, which maintain the mucous lining of the gastrointestinal tract. Indometacin, therefore, like other non-selective COX inhibitors can cause peptic ulcers. These ulcers can result in serious bleeding and/or perforation requiring hospitalization of the patient. To reduce the possibility of peptic ulcers, indomethacin should be prescribed at the lowest dosage needed to achieve a therapeutic effect, usually between 50–200 mg/day. It should always be taken with food. Nearly all patients benefit from an ulcer protective drug (e.g. highly dosed antacids, ranitidine 150 mg at bedtime, or omeprazole 20 mg at bedtime). Other common gastrointestinal complaints, including dyspepsia, heartburn and mild diarrhea are less serious and rarely require discontinuation of indomethacin.
CNS Activity
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11906281 |
3.0 nM [IC50] | ||
Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20503989 |
10.0 nM [IC50] | ||
Target ID: CHEMBL4681 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23432095 |
100.0 nM [IC50] | ||
Target ID: CHEMBL1835 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2547071 |
100.0 nM [IC50] | ||
Target ID: CHEMBL221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12142058 |
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Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12142058 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | INDOCIN Approved UseTIVORBEX is indicated for treatment of mild to moderate acute pain in adults. TIVORBEX is a NSAID indicated for treatment of mild to moderate acute pain in adults (1). Launch Date1965 |
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| Primary | INDOCIN Approved UseTIVORBEX is indicated for treatment of mild to moderate acute pain in adults. TIVORBEX is a NSAID indicated for treatment of mild to moderate acute pain in adults (1). Launch Date1965 |
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| Primary | INDOCIN Approved UseTIVORBEX is indicated for treatment of mild to moderate acute pain in adults. TIVORBEX is a NSAID indicated for treatment of mild to moderate acute pain in adults (1). Launch Date1965 |
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| Primary | INDOCIN Approved UseTIVORBEX is indicated for treatment of mild to moderate acute pain in adults. TIVORBEX is a NSAID indicated for treatment of mild to moderate acute pain in adults (1). Launch Date1965 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2 μg/mL |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
INDOMETHACIN plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
2369 ng/mL |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
INDOMETHACIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
7762 ng × h/mL |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
INDOMETHACIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
7.22 h |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
INDOMETHACIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1% |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
INDOMETHACIN plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Stimulation of cyclooxygenase-2-activity by nitric oxide-derived species in rat chondrocyte: lack of contribution to loss of cartilage anabolism. | 2001-04-15 |
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| Inactivation of creatine kinase during the interaction of indomethacin with horseradish peroxidase and hydrogen peroxide: involvement of indomethacin radicals. | 2001-03-14 |
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| Indomethacin prevents the induction of inducible nitric oxide synthase in murine peritoneal macrophages and decreases their nitric oxide production. | 2001-03-09 |
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| Haloperidol-stomach lesions attenuation by pentadecapeptide BPC 157, omeprazole, bromocriptine, but not atropine, lansoprazole, pantoprazole, ranitidine, cimetidine and misoprostol in mice. | 2001-03-09 |
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| Comparative effects of indomethacin on cell proliferation and cell cycle progression in tumor cells grown in vitro and in vivo. | 2001-03-01 |
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| Agonist-specific regulation of monocyte chemoattractant protein-1 expression by cyclooxygenase metabolites in hepatic stellate cells. | 2001-03 |
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| Effect of indomethacin on gallbladder inflammation and contractility during acute cholecystitis. | 2001-03 |
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| Methotrexate and early postoperative complications in patients with rheumatoid arthritis undergoing elective orthopaedic surgery. | 2001-03 |
|
| Increased 15-HPETE production decreases prostacyclin synthase activity during oxidant stress in aortic endothelial cells. | 2001-02-01 |
|
| Indomethacin increases 15-PGDH mRNA expression in HL60 cells differentiated by PMA. | 2001-02 |
|
| Does exposure to magnesium sulfate in utero decrease the risk of necrotizing enterocolitis in premature infants? | 2001-02 |
|
| Upregulation of angiotensin-converting enzyme by vascular endothelial growth factor. | 2001-02 |
|
| Lack of small intestinal ulcerogenecity of nitric oxide-releasing indomethacin, NCX-530, in rats. | 2001-02 |
|
| Protective role of cyclooxygenase inhibitors in the adverse action of passive cigarette smoking on the initiation of experimental colitis in rats. | 2001-01-05 |
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| An investigation into the thermal behaviour of an amorphous drug using low frequency dielectric spectroscopy and modulated temperature differential scanning calorimetry. | 2001-01 |
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| Effect of Lactobacillus ingestion on the gastrointestinal mucosal barrier alterations induced by indometacin in humans. | 2001-01 |
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| Review article: the gastrointestinal safety profile of rofecoxib, a highly selective inhibitor of cyclooxygenase-2, in humans. | 2001-01 |
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| Effect of the nonsteroidal anti-inflammatory drug indomethacin on proliferation and apoptosis of colon carcinoma cells. | 2001 |
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| Risk of upper gastrointestinal bleeding and perforation associated with low-dose aspirin as plain and enteric-coated formulations. | 2001 |
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| Salicylate-induced growth arrest is associated with inhibition of p70s6k and down-regulation of c-myc, cyclin D1, cyclin A, and proliferating cell nuclear antigen. | 2000-12-08 |
|
| Non-steroidal anti-inflammatory drugs with different cyclooxygenase inhibitory profiles that prevent aberrant crypt foci formation but vary in acute gastrotoxicity in a rat model. | 2000-12 |
|
| Inhibition of inducible nitric oxide synthase gene expression by indomethacin or ibuprofen in beta-amyloid protein-stimulated J774 cells. | 2000-11-17 |
|
| Role of BAX in the apoptotic response to anticancer agents. | 2000-11-03 |
|
| Role of endothelin-converting enzyme-1 in the suppression of constitutive nitric oxide synthase in rat gastric mucosal injury by indomethacin. | 2000-11 |
|
| Effect of indomethacin on blood pressure in elderly people with essential hypertension well controlled on amlodipine or enalapril. | 2000-11 |
|
| Inhibition of proteolysis by a cyclooxygenase inhibitor, indomethacin. | 2000-11 |
|
| Keratinocyte growth factor-2 (FGF-10) promotes healing of experimental small intestinal ulceration in rats. | 2000-11 |
|
| Indomethacin inhibits the accumulation of tumor cells in mouse lungs and subsequent growth of lung metastases. | 2000-10-29 |
|
| A case of living-related kidney transplantation in Bartter's syndrome. | 2000-10 |
|
| Indomethacin-induced apoptosis in esophageal adenocarcinoma cells involves upregulation of Bax and translocation of mitochondrial cytochrome C independent of COX-2 expression. | 2000-09-27 |
|
| Two opposing effects of non-steroidal anti-inflammatory drugs on the expression of the inducible cyclooxygenase. Mediation through different signaling pathways. | 2000-09-08 |
|
| A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus. | 2000-09-07 |
|
| Suppressed injury-induced rise in spinal prostaglandin E2 production and reduced early thermal hyperalgesia in iNOS-deficient mice. | 2000-09-01 |
|
| Protection by polaprezinc, an anti-ulcer drug, against indomethacin-induced apoptosis in rat gastric mucosal cells. | 2000-09 |
|
| Indomethacin inhibits endothelial cell proliferation by suppressing cell cycle proteins and PRB phosphorylation: a key to its antiangiogenic action? | 2000-08 |
|
| Chronic intrathecal cannulation enhances nociceptive responses in rats. | 2000-08 |
|
| Ibuprofen as effective as indomethacin for patent ductus arteriosus. | 2000-07-25 |
|
| Transcriptional induction of Nur77 by indomethacin that results in apoptosis of colon cancer cells. | 2000-07 |
|
| Indomethacin decreases insulin secretion in patients with type 2 diabetes mellitus. | 2000-07 |
|
| Regrowth of 5-fluorouracil-treated human colon cancer cells is prevented by the combination of interferon gamma, indomethacin, and phenylbutyrate. | 2000-06-15 |
|
| The influence of indomethacin on the acth secretion induced by central stimulation of adrenergic receptors. | 2000-06 |
|
| Effects of hydrogen peroxide scavenger Catalase on villous microcirculation in the rat small intestine in a model of inflammatory bowel disease. | 2000-05 |
|
| The role of nitric oxide and prostaglandin E2 on the hyperalgesia induced by excitatory amino acids in rats. | 2000-04 |
|
| Persistent pulmonary hypertension after maternal naproxen ingestion in a term newborn: a case report. | 2000 |
|
| [Effect of carrageenan and indomethacin on the growth of a murine fibrosarcoma]. | 2000 |
|
| Matrix metalloproteinases 2 and 9 in indomethacin-induced rat gastric ulcer. | 2000 |
|
| Premature onset of labor, neonatal patent ductus arteriosus, and prostaglandin synthetase antagonists--a rat model of a human problem. | 1979-09-15 |
|
| [Intrahepatic cholestasis following treatment with penicillamine D and indomethacine]. | 1976-05-28 |
|
| Letter: Aspirin sensitivity: other drugs. | 1975-02 |
|
| [Clinical results of a multicentral double-blind examination of naproxen compared to indomethacin in chronic rheumatoid arthritis, ankylosing spondylitis, and osteoarthrosis]. | 1975-02 |
Patents
Sample Use Guides
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27988363
U251 cells were incubated for 24 h with different concentrations of indomethacin (0.03, 0.06, 0.13, 0.25, 0.5, 1 mkM), diclofenac (DIC),naproxen (NAP), or ketoprofen (KET), and the cell viability was assessed by MTT or crystal violet (CV) tests.
| Substance Class |
Chemical
Created
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| Record UNII |
XXE1CET956
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| Record Status |
Validated (UNII)
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| Classification Tree | Code System | Code | ||
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NDF-RT |
N0000000160
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NCI_THESAURUS |
C1323
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WHO-VATC |
QS01BC01
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WHO-VATC |
QC01EB03
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NCI_THESAURUS |
C54677
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NDF-RT |
N0000175721
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LIVERTOX |
NBK548001
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WHO-ATC |
M02AA23
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NDF-RT |
N0000175722
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WHO-VATC |
QM01AB01
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WHO-ATC |
M01AB01
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WHO-ATC |
S01BC01
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WHO-VATC |
QM02AA23
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WHO-ATC |
S01CC02
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WHO-VATC |
QM01AB51
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WHO-ATC |
M01AB51
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WHO-ATC |
C01EB03
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| Code System | Code | Type | Description | ||
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CHEMBL6
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PRIMARY | |||
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DB00328
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m6279
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PRIMARY | Merck Index | ||
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5781
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PRIMARY | RxNorm | ||
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D007213
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PRIMARY | |||
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Indomethacin
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XXE1CET956
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DTXSID9020740
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SUB08180MIG
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100000092758
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49662
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757061
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XXE1CET956
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1524
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77541
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1341001
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3101
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3715
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INDOMETHACIN
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PRIMARY | Description: A white or a pale yellow, crystalline powder; odourless or almost odourless. Solubility: Practically insoluble in water; sparingly soluble in ethanol (~750 g/l) TS and ether R. Category: Analgesic; anti-inflammatory. Storage: Indometacin should be kept in a well-closed container, protected from light. Additional information: Indometacin exhibits polymorphism. The polymorph specified in the monograph corresponds to the crystal form of indometacin RS.Definition: Indometacin contains not less than 98.0% and not more than 101.0% of C19H16ClNO4, calculated with reference to the dried substance. | ||
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1440
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C576
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53-86-1
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1909
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200-186-5
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INDOMETACIN
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| Related Record | Type | Details | ||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR | |||
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BASIS OF STRENGTH->SUBSTANCE |
ASSAY (HPLC)
USP
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BASIS OF STRENGTH->SUBSTANCE |
ASSAY (TITRATION)
EP
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR | |||
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DEGRADENT -> PARENT |
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TARGET -> INHIBITOR |
IC50
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SALT/SOLVATE -> PARENT |
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SALT/SOLVATE -> PARENT |
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TARGET -> INHIBITOR |
IC50
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| Related Record | Type | Details | ||
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METABOLITE -> PARENT |
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PRODRUG -> METABOLITE ACTIVE |
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METABOLITE -> PARENT |
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METABOLITE -> PARENT |
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METABOLITE -> PARENT |
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PARENT -> IMPURITY |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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ACTIVE MOIETY |
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