Indole-3-pyruvic acid

• CAS: 392-12-1
• Catalog Number: ACM392121
• Category: Main Products
• Molecular Weight: 203.19
• Molecular Formula: C₁₁H₉NO₃
• Synonyms: Indole-3-pyruvic acid; 3-(1H-Indol-3-yl)-2-oxopropanoic acid; 3-(1H-indol-3-yl)-2-oxopropanoic acid
• IUPAC Name: 3-(1H-indol-3-yl)-2-oxopropanoicacid
• SMILES: C1=CC=C2C(=C1)C(=CN2)CC(=O)C(=O)O
• InChI Key: RSTKLPZEZYGQPY-UHFFFAOYSA-N
• Boiling Point: 445.2ºC at 760 mmHg
• Melting Point: 215ºC
• Flash Point: 223ºC
• Density: 1.421 g/cm³
• Appearance: solid
• EC Number: 206-874-1
• Exact Mass: 203.05800
• Hazard Statements: Xi:Irritant
• Safety Description: S26-S36
• Stability: Stable under normal temperatures and pressures. Air sensitive Light sensitive.
• WGK Germany: 3

Case Study

Antioxidant, Anti-Mutagenic and Neuroregulatory Properties of Indole-3-pyruvic Acid

Politi V, D'Alessio S, Di Stazio G, et al. Advances in Tryptophan Research, 1996: 291-298.

Indole-3-pyruvic acid (IPA) exhibited prominent antioxidant activity by scavenging reactive oxygen species: As a key indole derivative and tryptophan metabolite, IPA featured a conjugated planar enol structure that enhanced its reactivity toward oxygen free radicals. It neutralized oxidative substances, underwent ring-opening reactions and converted into kynurenic acid, oxalic acid and other metabolites, effectively mitigating oxidative damage in cells and tissues. It demonstrated strong anti-mutagenic effects in the Ames test using Salmonella typhimurium TA 100: With 1 mg IPA added per plate, the revertant colony numbers induced by 4NQO, 2-NF, Captan and Folpet were drastically reduced close to blank control levels. IPA showed no inhibitory impact on mutagens acting through non-radical mechanisms such as methyl methanesulfonate. Additionally, IPA exerted comprehensive neuroregulatory properties: In mammalian bodies, it inhibited liver tryptophan-2,3-dioxygenase to elevate circulating tryptophan content, promoted the synthesis of serotonin and melatonin in the brain, and increased endogenous kynurenic acid to suppress excessive neuronal excitation. In stress model rats, IPA lowered serum corticosterone, relieved stress responses and improved sleep quality, while also presenting anxiolytic, sedative and analgesic effects. These studies demonstrate that indole-3-pyruvic acid possesses significant antioxidant, anti-mutagenic and neuroregulatory properties.
A series of in vitro biochemical assays, microbial mutagenicity tests and in vivo animal experiments were conducted. Ames test was adopted to evaluate anti-mutagenic capacity with multiple radical-based mutagens. Biochemical analyses were used to detect enzyme activity and metabolite changes in liver and brain tissues. Rodent stress and sleep models were established to assess IPA's physiological effects on nervous system functions. Metabolic pathways and product formation of IPA under oxidative attack were also analyzed. The results verified that IPA protects organisms against oxidative stress and mutagenic damage via radical scavenging, and modulates tryptophan metabolism to regulate neural activity and related physiological functions.

Tautomeric Stabilizing, Kynurenic Acid-Promoting and Stress-Regulating Properties of Indole-3-Pyruvic Acid

Bartolini B, Comiello C, Sella A, et al. Related Pharmacological Research

Indole-3-pyruvic acid (IPA) presented distinct tautomeric conversion characteristics in different solution environments: Freshly prepared IPA mainly existed as the enol tautomer, while it rapidly transformed into the keto form and gem-diol derivatives within one hour in phosphate buffer; borate buffer effectively maintained the stability of enol-IPA for a long time. Endogenous tautomerases in animal tissues further prevented this tautomeric shift, allowing enol-IPA to be detected in plasma and organ homogenates for hours. It demonstrated potent kynurenic acid (KA) promoting activity: Enol-IPA served as a direct precursor of KA. Under the action of oxygen free radicals, it was converted into KA without relying on tryptophan ring-opening enzymes, and stabilized enol-IPA increased KA production by up to 10% in animal bodies. Additionally, IPA exerted prominent stress-regulating and neuroprotective effects: In repeated stress rat models, IPA lowered serum glucocorticoid levels and suppressed excessive stress responses. It also relieved anxiety, improved sleep quality in human subjects, and reduced hypertension symptoms in stress-related animal models. Mechanistically, IPA interacted with macrophage migration inhibitory factor (MIF) and other tautomerases, forming a regulatory loop to balance glucocorticoid and inflammatory reactions. These studies demonstrate that indole-3-pyruvic acid has remarkable tautomeric stabilizing, kynurenic acid-promoting and stress-regulating properties.
The experiment adopted HPLC to monitor the keto-enol tautomer equilibrium of IPA in various buffer solutions over time. In vitro biochemical tests were used to analyze the conversion pathway from IPA to KA. In vivo stress animal models and human clinical observations were applied to evaluate the physiological effects of IPA. The interactions between IPA, tautomerases and stress-related cytokines were also explored via biochemical analysis. The results verified that the enol tautomer of IPA is the main bioactive form, which regulates stress responses and neural activities by boosting KA synthesis and modulating the endocrine and immune systems.

Feedback-Regulating, Reversible Enzymatic and Auxin-Modulating Properties of Indole-3-Pyruvic Acid

Sato A, Soeno K, Kikuchi R, et al. PNAS, 2022, 119(25): e2203633119.

Indole-3-pyruvic acid (IPyA) exhibited prominent product feedback-regulating activity on tryptophan aminotransferase (TAA1): In in vitro enzymatic assays, IPyA acted as a natural inhibitor of TAA1. With a \(K_m\) value of 0.7 μM, it competed with L-tryptophan (\(K_m = 43.6\) μM) for the enzyme active site and suppressed TAA1 catalytic activity in a concentration-dependent manner. The IPyA analog KOK2099 also produced strong competitive inhibition against TAA1, further verifying this feedback mechanism. It demonstrated notable reversible enzymatic reaction characteristics: TAA1 catalyzed the forward reaction converting tryptophan to IPyA, and also facilitated the reverse reaction transforming IPyA back into tryptophan, with alanine serving as the preferred amino acid substrate for the reverse process. This reversible reaction maintained IPyA at a low steady concentration and prevented non-enzymatic overproduction of indole-3-acetic acid (IAA). Additionally, IPyA exerted key auxin homeostatic effects coordinated with YUCCA enzymes: YUCCAs continuously consumed IPyA to synthesize IAA, which relieved TAA1 from feedback inhibition and reactivated the enzyme. This "push-pull" regulatory loop stably controlled endogenous IAA levels. In Arabidopsis seedling tests, IPyA analogs inhibited root elongation and lateral root formation by lowering in vivo IAA content, and the growth defects could be rescued by exogenous IAA supplementation. These studies demonstrate that indole-3-pyruvic acid possesses significant feedback-regulating, reversible enzymatic and auxin-modulating properties in plant auxin biosynthesis.The experiment adopted recombinant TAA1 and YUCCA proteins for in vitro enzymatic reaction tests. HPLC and fluorescence detection were used to quantify tryptophan consumption and IAA production. Dixon plots were applied to analyze enzyme inhibition types and kinetic parameters. Wild-type Arabidopsis thaliana seedlings were used for in vivo functional verification, with different IPyA analogs applied to observe plant growth changes and measure endogenous IAA concentrations via UPLC-MS/MS. Comparative assays were also conducted on TAR homologs from rice and tomato. The results verified that the IPyA-mediated feedback regulation mechanism is conserved across monocots and eudicots, and it precisely balances the two-step auxin biosynthesis pathway to maintain plant hormone homeostasis.

Anti-Arthritic, Immunomodulatory and AhR-Activating Properties of Indole-3-Pyruvic Acid

Huang T, Cheng L, Jiang Y, et al. Annals of Translational Medicine, 2023, 11(5): 213.

Indole-3-pyruvic acid (IPA) exerted remarkable anti-arthritic activity in collagen-induced arthritis (CIA) SD rats: Oral administration of 20 mg/kg/d IPA for consecutive days obviously relieved paw redness and swelling, and lowered clinical arthritis scores. Radiological and histological examinations revealed decreased bone erosion and inflammatory cell infiltration in joint tissues compared with the untreated CIA control group. It demonstrated potent immunomodulatory effects by restoring the Th17/Treg cell balance: IPA significantly inhibited the differentiation of pro-inflammatory Th17 cells and down-regulated the expression of RORγt and pro-inflammatory cytokines including IL-17A, TNF-α and IL-1β. Meanwhile, it promoted the differentiation of immune-suppressive Treg cells, up-regulated Foxp3 expression and increased the level of anti-inflammatory IL-10. Additionally, IPA showed distinct aryl hydrocarbon receptor (AhR) activating properties: As an endogenous AhR ligand, IPA upregulated AhR and its downstream target CYP1A expression. When the AhR antagonist CH223191 was applied together with IPA, the therapeutic and immunoregulatory effects of IPA were markedly weakened, confirming that IPA functions mainly through the AhR pathway. Clinical metabolomics analysis also proved IPA content was negatively correlated with rheumatoid arthritis (RA) disease activity scores. These studies demonstrate that indole-3-pyruvic acid possesses significant anti-arthritic, immunomodulatory and AhR-activating properties.
The experiment enrolled 14 rheumatoid arthritis patients and 14 healthy volunteers for plasma metabolomics analysis via LC-MS. In vitro assays used human peripheral blood mononuclear cells (PBMCs) to evaluate the influence of IPA on Th17 and Treg differentiation, with CH22319 set as the AhR inhibitor. A total of 42 male SD rats were randomly divided into seven groups: normal control, CIA model, methotrexate control, low-dose IPA (10 mg/kg), high-dose IPA (20 mg/kg), CH223191 group and combined treatment group. CIA was established via bovine type II collagen immunization. Drugs were given by intragastric or intraperitoneal administration after modeling. Joint conditions were regularly observed, and blood samples, spleen tissues and joint specimens were collected for ELISA, flow cytometry, qPCR, X-ray and HE staining detection. The results verified that IPA alleviates rheumatoid arthritis symptoms and regulates immune homeostasis primarily by activating the AhR signaling pathway to rebalance Th17/Treg cells.

Custom Q&A

What is the molecular formula of Indole-3-pyruvic acid?

The molecular formula of Indole-3-pyruvic acid is C11H9NO3.

What are the synonyms of Indole-3-pyruvic acid?

The synonyms of Indole-3-pyruvic acid include indole-3-pyruvic acid, indol-3-yl pyruvic acid, and beta-Indolepyruvic acid, among others.

What is the CAS number of Indole-3-pyruvic acid?

The CAS number of Indole-3-pyruvic acid is 392-12-1.

What is the IUPAC name of Indole-3-pyruvic acid?

The IUPAC name of Indole-3-pyruvic acid is 3-(1H-indol-3-yl)-2-oxopropanoic acid.

What is the InChIKey of Indole-3-pyruvic acid?

The InChIKey of Indole-3-pyruvic acid is RSTKLPZEZYGQPY-UHFFFAOYSA-N.

What is the Canonical SMILES of Indole-3-pyruvic acid?

The Canonical SMILES of Indole-3-pyruvic acid is C1=CC=C2C(=C1)C(=CN2)CC(=O)C(=O)O.

What is the European Community Number of Indole-3-pyruvic acid?

The European Community Number of Indole-3-pyruvic acid is 206-874-1.

What is the DSSTox Substance ID of Indole-3-pyruvic acid?

The DSSTox Substance ID of Indole-3-pyruvic acid is DTXSID3042053.

What is the Wikidata ID of Indole-3-pyruvic acid?

The Wikidata ID of Indole-3-pyruvic acid is Q23905803.

What is the molecular formula and structure of Indole-3-pyruvic acid?

The molecular formula of Indole-3-pyruvic acid is C11H9NO3. The structure can be visualized in the 2D and 3D images provided in the reference.