3-Indolepropionic acid

3-indolepropionic acid
Clinical data
Trade namesOxigon[2]
Other namesConjugate acid:
 • 1H-Indole-3-propanoic acid
 • Indole-3-propionic acid
Conjugate base:
 • Indole-3-propionate
ATC code
  • none
Legal status
Legal status
  • US: Unscheduled
  • UN: Unscheduled
Identifiers
  • 3-(1H-Indol-3-yl)propanoic acid
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEBI
CompTox Dashboard (EPA)
ECHA InfoCard100.011.455 Edit this at Wikidata
Chemical and physical data
FormulaC11H11NO2
Molar mass189.214 g·mol−1
3D model (JSmol)
Melting point134 to 135 °C (273 to 275 °F) [3]
  • C1=CC=C2C(=C1)C(=CN2)CCC(=O)O
  • InChI=1S/C11H11NO2/c13-11(14)6-5-8-7-12-10-4-2-1-3-9(8)10/h1-4,7,12H,5-6H2,(H,13,14)
  • Key:GOLXRNDWAUTYKT-UHFFFAOYSA-N
  (verify)

3-Indolepropionic acid (IPA), or indole-3-propionic acid, has been studied for its therapeutic value in the treatment of Alzheimer's disease. As of 2022[4] IPA shows potential in the treatment of this disease, though the therapeutic effect of IPA depends on dose and time of therapy initiation.

Though promising in some historical clinical trials, IPA is not clinically listed as a useful therapeutic in managing Alzheimer's as of 2023.[5]

This compound endogenously produced by human microbiota and has only been detected in vivo when the species Clostridium sporogenes is present in the gastrointestinal tract.[6][7][8] As of April 2016, C. sporogenes, which uses tryptophan to synthesize IPA, is the only species of bacteria known to synthesize IPA in vivo at levels which are subsequently detectable in the blood plasma of the host.[6][7][8][9]

IPA is an even more potent scavenger of hydroxyl radicals than melatonin, the most potent scavenger of hydroxyl radicals that is synthesized by human enzymes.[3][9] Similar to melatonin but unlike other antioxidants, it scavenges radicals without subsequently generating reactive and pro-oxidant intermediate compounds.[3][9][10] In 2017, elevated concentrations of IPA in human blood plasma were found to be correlated with a lower risk of type 2 diabetes and higher consumption of fiber-rich foods.[3][11][12]

  1. ^ Galligan JJ (February 2018). "Beneficial actions of microbiota-derived tryptophan metabolites". Neurogastroenterology and Motility. 30 (2): e13283. doi:10.1111/nmo.13283. PMID 29341448. S2CID 39904059.
  2. ^ Bendheim PE, Poeggeler B, Neria E, Ziv V, Pappolla MA, Chain DG (October 2002). "Development of indole-3-propionic acid (OXIGON) for Alzheimer's disease". Journal of Molecular Neuroscience. 19 (1–2): 213–217. doi:10.1007/s12031-002-0036-0. PMID 12212784. S2CID 31107810. The accumulation of amyloid-beta and concomitant oxidative stress are major pathogenic events in Alzheimer's disease. Indole-3-propionic acid (IPA, OXIGON) is a potent anti-oxidant devoid of pro-oxidant activity. IPA has been demonstrated to be an inhibitor of beta-amyloid fibril formation and to be a potent neuroprotectant against a variety of oxidotoxins. This review will summarize the known properties of IPA and outline the rationale behind its selection as a potential disease-modifying therapy for Alzheimer's disease.
  3. ^ a b c d e Cite error: The named reference Human metabolome IPA was invoked but never defined (see the help page).
  4. ^ Jiang H, Chen C, Gao J (December 2022). "Extensive Summary of the Important Roles of Indole Propionic Acid, a Gut Microbial Metabolite in Host Health and Disease". Nutrients. 15 (1): 151. doi:10.3390/nu15010151. PMC 9824871. PMID 36615808.
  5. ^ "How Alzheimer's drugs help manage symptoms". Mayo Clinic. Retrieved 3 November 2023.
  6. ^ a b Cite error: The named reference Microbiome IPA was invoked but never defined (see the help page).
  7. ^ a b Cite error: The named reference Microbial biosynthesis of bioactive compounds was invoked but never defined (see the help page).
  8. ^ a b Attwood G, Li D, Pacheco D, Tavendale M (June 2006). "Production of indolic compounds by rumen bacteria isolated from grazing ruminants". Journal of Applied Microbiology. 100 (6): 1261–1271. doi:10.1111/j.1365-2672.2006.02896.x. PMID 16696673. S2CID 35673610.
  9. ^ a b c Cite error: The named reference Indolepropionic acid scavenging was invoked but never defined (see the help page).
  10. ^ Reiter RJ, Guerrero JM, Garcia JJ, Acuña-Castroviejo D (November 1998). "Reactive oxygen intermediates, molecular damage, and aging. Relation to melatonin". Annals of the New York Academy of Sciences. 854 (1): 410–424. Bibcode:1998NYASA.854..410R. doi:10.1111/j.1749-6632.1998.tb09920.x. PMID 9928448. S2CID 29333394.
  11. ^ de Mello VD, Paananen J, Lindström J, Lankinen MA, Shi L, Kuusisto J, et al. (April 2017). "Indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the Finnish Diabetes Prevention Study". Scientific Reports. 7: 46337. Bibcode:2017NatSR...746337D. doi:10.1038/srep46337. PMC 5387722. PMID 28397877.
  12. ^ Tuomainen M, Lindström J, Lehtonen M, Auriola S, Pihlajamäki J, Peltonen M, et al. (May 2018). "Associations of serum indolepropionic acid, a gut microbiota metabolite, with type 2 diabetes and low-grade inflammation in high-risk individuals". Nutrition & Diabetes. 8 (1): 35. doi:10.1038/s41387-018-0046-9. PMC 5968030. PMID 29795366.