Synonym
Indomethacin; Indometacin; Indocin.
IUPAC/Chemical Name
2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetic acid
InChi Key
CGIGDMFJXJATDK-UHFFFAOYSA-N
InChi Code
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)
SMILES Code
O=C(O)CC1=C(C)N(C(C2=CC=C(Cl)C=C2)=O)C3=C1C=C(OC)C=C3
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Indometacin (INN and BAN) or indomethacin (AAN, USAN and former BAN) is a non-steroidal anti-inflammatory drug (NSAID) commonly used as a prescription medication to reduce fever, pain, stiffness, and swelling. It works by inhibiting the production of prostaglandins, molecules known to cause these symptoms. It is marketed under more than twelve different trade names.
Clinical indications for indometacin include:
Hemicrania continua
ankylosing spondylitis
arthritic gout
Bartter syndrome
bursitis
cryoglobulinemia
dysmenorrhea (menstrual cramps)
exertion headache
fever and pain associated with malignant diseases (especially tumor fever associated with liver involvement, lymphogranulomatosis)
hemicrania continua
hypnic headache
juvenile arthritis
migraine
patent ductus arteriosus
nephrogenic diabetes insipidus (prostaglandin inhibits vasopressin's action in the kidney)
osteoarthritis
Paget's disease of bone
paroxysmal hemicrania
pericarditis
primary stabbing headaches
pseudogout
psoriatic arthritis
Reactive arthritis
renal colic (pain due to kidney stones)
retinopathy of prematurity
rheumatoid arthritis
tendinitis
trigeminal autonomic cephalgias
Headaches induced by or otherwise a result of Valsalva maneuver
Indomethacin has also been used clinically to delay premature labor, reduce amniotic fluid in polyhydramnios, and to close patent ductus arteriosus.
Indomethacin is a potent drug with many serious side effects and should not be considered an analgesic for minor aches and pains or fever. The medication is better described as an anti-inflammatory, rather than an analgesic. Indomethacin can also affect warfarin and subsequently raise INR.
Biological target:
Indomethacin (Indometacin) is a blood-brain permeable and nonselective inhibitor of COX1 and COX2, with IC50s of 18 nM and 26 nM for human COX-1 and COX-2, respectively, in CHO cells.
In vitro activity:
A panel of cell lines which express Shc were serum-starved overnight in the presence of indomethacin at varying concentrations. Cells were then stimulated with 10 ng/ml EGF for 2 min. Amongst the cell lines this study chose two breast cancer cell lines, MCF7 and SkBr3, due to the strong link between Shc expression status and breast cancer progression. This study also tested carcinoma cell lines derived from skin (A431), kidney (A498) and cervix (HeLa). The effects of indomethacin on EGFR signalling were examined by immunoblotting. In all cell lines used, the phosphorylation of Erk upon EGF stimulation was down-regulated upon indomethacin treatment (Fig. 5).
Reference: Cancer Lett. 2019 Aug 10; 457: 86–97. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584941/
In vivo activity:
REH cells transduced with the firefly luciferase-EGFP vector were injected into NSG mice. Indomethacin or vehicle was administered in the drinking water every second day throughout the entire experiment, and the growth of the cancer cells was followed by noninvasive in vivo imaging from 1 week after IT injection. As shown in Figure 3A-B, the luminescence from the leukemic cells treated with indomethacin was reduced by 81% 3 weeks after initiating the experiment. At 4 weeks after IT injection, the reduced growth of indomethacin-treated REH cells persisted, whereas the growth of REH cells in mice exposed to vehicle substantially increased.
Reference: Blood Adv. 2019 Nov 12; 3(21): 3181–3190. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855122/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
56.4 |
157.63 |
| Ethanol |
15.3 |
42.71 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
357.79
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Mirshahidi S, de Necochea-Campion R, Moretta A, Williams NL, Reeves ME, Otoukesh S, Mirshahidi HR, Khosrowpour S, Duerksen-Hughes P, Zuckerman LM. Inhibitory Effects of Indomethacin in Human MNNG/HOS Osteosarcoma Cell Line In Vitro. Cancer Invest. 2020 Jan;38(1):23-36. doi: 10.1080/07357907.2019.1698592. Epub 2019 Dec 16. PMID: 31770037.
2. Lin CC, Suen KM, Stainthorp A, Wieteska L, Biggs GS, Leitão A, Montanari CA, Ladbury JE. Targeting the Shc-EGFR interaction with indomethacin inhibits MAP kinase pathway signalling. Cancer Lett. 2019 Aug 10;457:86-97. doi: 10.1016/j.canlet.2019.05.008. Epub 2019 May 14. PMID: 31100409; PMCID: PMC6584941.
3. Overby H, Yang Y, Xu X, Wang S, Zhao L. Indomethacin promotes browning and brown adipogenesis in both murine and human fat cells. Pharmacol Res Perspect. 2020 Jun;8(3):e00592. doi: 10.1002/prp2.592. PMID: 32430973; PMCID: PMC7237299.
4. Richartz N, Duthil E, Ford A, Naderi EH, Bhagwat S, Gilljam KM, Burman MM, Ruud E, Blomhoff HK, Skah S. Targeting cyclooxygenase by indomethacin decelerates progression of acute lymphoblastic leukemia in a xenograft model. Blood Adv. 2019 Nov 12;3(21):3181-3190. doi: 10.1182/bloodadvances.2019000473. PMID: 31698450; PMCID: PMC6855122.
In vitro protocol:
1. Mirshahidi S, de Necochea-Campion R, Moretta A, Williams NL, Reeves ME, Otoukesh S, Mirshahidi HR, Khosrowpour S, Duerksen-Hughes P, Zuckerman LM. Inhibitory Effects of Indomethacin in Human MNNG/HOS Osteosarcoma Cell Line In Vitro. Cancer Invest. 2020 Jan;38(1):23-36. doi: 10.1080/07357907.2019.1698592. Epub 2019 Dec 16. PMID: 31770037.
2. Lin CC, Suen KM, Stainthorp A, Wieteska L, Biggs GS, Leitão A, Montanari CA, Ladbury JE. Targeting the Shc-EGFR interaction with indomethacin inhibits MAP kinase pathway signalling. Cancer Lett. 2019 Aug 10;457:86-97. doi: 10.1016/j.canlet.2019.05.008. Epub 2019 May 14. PMID: 31100409; PMCID: PMC6584941.
In vivo protocol:
1. Overby H, Yang Y, Xu X, Wang S, Zhao L. Indomethacin promotes browning and brown adipogenesis in both murine and human fat cells. Pharmacol Res Perspect. 2020 Jun;8(3):e00592. doi: 10.1002/prp2.592. PMID: 32430973; PMCID: PMC7237299.
2. Richartz N, Duthil E, Ford A, Naderi EH, Bhagwat S, Gilljam KM, Burman MM, Ruud E, Blomhoff HK, Skah S. Targeting cyclooxygenase by indomethacin decelerates progression of acute lymphoblastic leukemia in a xenograft model. Blood Adv. 2019 Nov 12;3(21):3181-3190. doi: 10.1182/bloodadvances.2019000473. PMID: 31698450; PMCID: PMC6855122.
1: Nalamachu S, Wortmann R. Role of indomethacin in acute pain and inflammation management: a review of the literature. Postgrad Med. 2014 Jul;126(4):92-7. doi: 10.3810/pgm.2014.07.2787. Review. PubMed PMID: 25141247.
2: Pacifici GM. Differential renal adverse effects of ibuprofen and indomethacin in preterm infants: a review. Clin Pharmacol. 2014 Jul 31;6:111-6. doi: 10.2147/CPAA.S59376. eCollection 2014. Review. PubMed PMID: 25114597; PubMed Central PMCID: PMC4124049.
3: Sethi S, Sethi N, Wadhwa V, Garud S, Brown A. A meta-analysis on the role of rectal diclofenac and indomethacin in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis. Pancreas. 2014 Mar;43(2):190-7. doi: 10.1097/MPA.0000000000000090. Review. PubMed PMID: 24518496.
4: Pacifici GM. Clinical pharmacology of indomethacin in preterm infants: implications in patent ductus arteriosus closure. Paediatr Drugs. 2013 Oct;15(5):363-76. doi: 10.1007/s40272-013-0031-7. Review. PubMed PMID: 23754139.
5: Summ O, Evers S. Mechanism of action of indomethacin in indomethacin-responsive headaches. Curr Pain Headache Rep. 2013 Apr;17(4):327. doi: 10.1007/s11916-013-0327-x. Review. PubMed PMID: 23423598.
6: Chiba H, Masutani S, Toyoshima K, Mori R. Indomethacin for preterm infants with intracranial hemorrhage. Pediatr Int. 2013 Feb;55(1):124-6. doi: 10.1111/ped.12037. Review. PubMed PMID: 23409994.
7: Bonzi M, Fiorelli EM; Gruppo di Autoformazione Metodologica (GrAM). Indomethacin prevents post-ERCP pancreatitis in selected high-risk patients. Intern Emerg Med. 2012 Dec;7(6):557-8. doi: 10.1007/s11739-012-0872-z. Epub 2012 Nov 2. Review. PubMed PMID: 23117274.
8: Szabó IL, Czimmer J, Szolcsányi J, Mózsik G. Molecular pharmacological approaches to effects of capsaicinoids and of classical antisecretory drugs on gastric basal acid secretion and on indomethacin-induced gastric mucosal damage in human healthy subjects (mini review). Curr Pharm Des. 2013;19(1):84-9. Review. PubMed PMID: 22946903.
9: Neumann R, Schulzke SM, Bührer C. Oral ibuprofen versus intravenous ibuprofen or intravenous indomethacin for the treatment of patent ductus arteriosus in preterm infants: a systematic review and meta-analysis. Neonatology. 2012;102(1):9-15. doi: 10.1159/000335332. Epub 2012 Mar 8. Review. PubMed PMID: 22414850.
10: Johnston PG, Gillam-Krakauer M, Fuller MP, Reese J. Evidence-based use of indomethacin and ibuprofen in the neonatal intensive care unit. Clin Perinatol. 2012 Mar;39(1):111-36. doi: 10.1016/j.clp.2011.12.002. Epub 2012 Jan 13. Review. PubMed PMID: 22341541; PubMed Central PMCID: PMC3598606.
11: Anabrees JA, Aifaleh KM. Fluid restriction and prophylactic indomethacin in extremely low birth weight infants. J Clin Neonatol. 2012 Jan;1(1):1-5. doi: 10.4103/2249-4847.92228. Review. PubMed PMID: 24027673; PubMed Central PMCID: PMC3761987.
12: Anabrees J, Alfaleh K. Fluid restriction and prophylactic indomethacin versus prophylactic indomethacin alone for prevention of morbidity and mortality in extremely low birth weight infants. Cochrane Database Syst Rev. 2011 Jul 6;(7):CD007604. doi: 10.1002/14651858.CD007604.pub2. Review. PubMed PMID: 21735414.
13: Longhi A, Errani C, Battaglia M, Alberghini M, Ferrari S, Mercuri M, Molinari M. Aggressive fibromatosis of the neck treated with a combination of chemotherapy and indomethacin. Ear Nose Throat J. 2011 Jun;90(6):E11-5. Review. PubMed PMID: 21674455.
14: Fujino H, Murayama T. [Novel anti-cancer effects of indomethacin: exploring the cyclooxygenase-inhibition-independent effects]. Nihon Yakurigaku Zasshi. 2011 Apr;137(4):177-81. Review. Japanese. PubMed PMID: 21478637.
15: Hoy SM, Scott LJ. Indomethacin/prochlorperazine/caffeine: a review of its use in the acute treatment of migraine and in the treatment of episodic tension-type headache. CNS Drugs. 2011 Apr;25(4):343-58. doi: 10.2165/11206740-000000000-00000. Review. PubMed PMID: 21425885.
16: Jones LJ, Craven PD, Attia J, Thakkinstian A, Wright I. Network meta-analysis of indomethacin versus ibuprofen versus placebo for PDA in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2011 Jan;96(1):F45-52. doi: 10.1136/adc.2009.168682. Epub 2010 Sep 27. Review. PubMed PMID: 20876595.
17: Prakash S, Shah ND, Chavda BV. Cluster headache responsive to indomethacin: Case reports and a critical review of the literature. Cephalalgia. 2010 Aug;30(8):975-82. doi: 10.1177/0333102409357642. Epub 2010 Mar 12. Review. PubMed PMID: 20656709.
18: Fowlie PW, Davis PG, McGuire W. Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants. Cochrane Database Syst Rev. 2010 Jul 7;(7):CD000174. doi: 10.1002/14651858.CD000174.pub2. Review. PubMed PMID: 20614421.
19: Suleyman H, Albayrak A, Bilici M, Cadirci E, Halici Z. Different mechanisms in formation and prevention of indomethacin-induced gastric ulcers. Inflammation. 2010 Aug;33(4):224-34. doi: 10.1007/s10753-009-9176-5. Review. PubMed PMID: 20084447.
20: Prakash S, Shah ND, Bhanvadia RJ. Hemicrania continua unresponsive or partially responsive to indomethacin: does it exist? A diagnostic and therapeutic dilemma. J Headache Pain. 2009 Feb;10(1):59-63. doi: 10.1007/s10194-008-0088-9. Epub 2008 Dec 19. Review. PubMed PMID: 19096758; PubMed Central PMCID: PMC3451756.
