Purine Metabolism

Xanthine, a plant alkaloid found in tea, coffee, and cocoa, is a mild stimulant of the central nervous system. Xanthine also acts as an intermediate product on the pathway of purine degradation.

Hippuric Acid is an orally active metabolite. Hippuric Acid can be produced by intestinal microorganisms from the metabolism of polyphenols, benzoic acid. Hippuric Acid decreases NRF2, MMP9 and leads to ROS accumulation. Hippuric Acid activates TGFβ/SMAD signaling. Hippuric Acid improves hyperuricemia and colitis. Hippuric Acid can also be used in cardiovascular disease research. .

Adrenocorticotropic hormone (ACTH; Adrenocorticotrophic hormone) is a polypeptide tropic hormone produced by the anterior pituitary gland. Adrenocorticotropic hormone stimulates cortisol secretion from the adrenal cortex via the hypothalamic-pituitary-adrenal (HPA) axis. Adrenocorticotropic hormone regulates cortisol and androgen production. Adrenocorticotropic hormone can promote the development of spermatogenesis. Adrenocorticotropic hormone can relieve acute inflammation in gout models by inhibiting the polarization of macrophages to M1 type, inhibiting ROS and proinflammatory factor production and protecting mitochondrial function. Adrenocorticotropic hormone can be used for the researches of inflammation, endocrinology, metabolic disease, such as gout and nephrotic syndrome.

Homogentisic acid is an orally active, blood-brain barrier-permeable amyloidogenic compound that functions as both an amyloid component and a pigment precursor. Accumulation of homogentisic acid downregulates tight junction proteins (such as claudin-5, occludin, ZO-1) and impairs blood-brain barrier integrity. Homogentisic acid and its oxidation product benzoquinone acetic acid not only induce the aggregation and fibrosis of multiple proteins (such as Aβ_1-42, α-synuclein, SAA, Transthyretin (TTR), atrial natriuretic peptide), but also trigger oxidative stress, damage to the Wnt/β-catenin pathway, and neurotoxicity, leading to ochronosis pigment deposition and synaptic dysfunction. At specific concentrations, homogentisic acid exerts no cytotoxicity or genotoxicity on human peripheral blood lymphocytes, and even counteracts the genotoxicity induced by Irinotecan (HY-16562). Homogentisic acid serves as an important tool molecule for investigating the mechanisms of diseases including ochronosis, secondary amyloidosis, Alzheimer's disease, and colorectal cancer.

Uricase, Microorganism (Uox, Microorganism) is a uricase (urate oxidase) derived from Microorganism. Uricase, Microorganism converts uric acid into allantoin. The absence of Uricase in mammals causes kidney diseases resulting from uric acid accumulation. Uricase, Microorganism can be used for research on chronic refractory gout and hyperuricemia.

Erythronic acid potassium is a urinary metabolite that serves as a diagnostic marker for transaldolase (TALDO) deficiency. Erythronic acid potassium is a differential urinary metabolite associated with renal injury in hyperuricemic rats. Erythronic acid potassium can be used in studies related to transaldolase deficiency and hyperuricemia.

Erythronic acid is a urinary metabolite that serves as a diagnostic marker for transaldolase (TALDO) deficiency. Erythronic acid is a differential urinary metabolite associated with renal injury in hyperuricemic rats. Erythronic acid can be used in studies related to transaldolase deficiency and hyperuricemia.

Xanthine oxidase-IN-24 is an orally active mixed-type inhibitor of xanthine oxidase, with an IC₅₀ of 0.051 μM and a K_i of 0.162 μM. Xanthine oxidase-IN-24 interacts with both free xanthine oxidase and the xanthine-xanthine oxidase complex, and reduces uric acid production in vivo. In a rat model of hyperuricemia induced by Potassium oxonate (HY-17511), Xanthine oxidase-IN-24 dose-dependently lowers serum uric acid levels, improves renal function-related biochemical parameters such as creatinine and urea nitrogen, and alleviates histopathological damage to liver and kidney tissues. Xanthine oxidase-IN-24 can be used in the research of hyperuricemia.

Adrenocorticotropic hormone (ACTH; Adrenocorticotrophic hormone) TFA is a polypeptide tropic hormone produced by the anterior pituitary gland. Adrenocorticotropic hormone TFA stimulates cortisol secretion from the adrenal cortex via the hypothalamic-pituitary-adrenal (HPA) axis. Adrenocorticotropic hormone TFA regulates cortisol and androgen production. Adrenocorticotropic hormone TFA can promote the development of spermatogenesis. Adrenocorticotropic hormone TFA can relieve acute inflammation in gout models by inhibiting the polarization of macrophages to M1 type, inhibiting ROS and proinflammatory factor production and protecting mitochondrial function. Adrenocorticotropic hormone TFA can be used for the researches of inflammation, endocrinology, metabolic disease, such as gout and nephrotic syndrome.

Ulodesine (BCX4208) is a purine nucleoside phosphorylase (PNP) inhibitor, with an IC₅₀ of 2.293 nM against human PNP, and low nanomolar IC₅₀ values against mouse, rat and monkey PNP. Ulodesine blocks the production of uric acid precursors, reduces serum uric acid levels, clears accumulated uric acid in the blood, and elevates the levels of purine nucleosides including guanosine. Ulodesine reduces the counts of total lymphocytes, T lymphocytes and lymphocyte subsets, inhibits the proliferation of cancer cells and activated lymphocytes, and enhances vaccine immune responses. Ulodesine can be used in research related to hyperuricemia and gout.

5-O-Methylvisammioside (4'-O-β-D-Glucosyl-5-O-methylvisamminol) is an orally active natural chromone glycoside and multiple biological activities. 5-O-Methylvisammioside inhibits ferroptosis by activating the Nrf2/HO-1 signaling axis. 5-O-Methylvisammioside alleviates intestinal barrier damage by inhibiting the ROS/NF-κB/NLRP3 pathway. 5-O-Methylvisammioside exerts a protective effect against acute liver injury by reducing ALT/AST, decreasing inflammatory infiltration, and inhibiting IκB-α phosphorylation and NF-κB nuclear translocation. 5-O-Methylvisammioside blocks the HMGB1/RAGE/MEK/ERK signaling axis to exert anti-tumor and anti-angiogenic effects. 5-O-Methylvisammioside improves depression-like behaviors by inhibiting Src kinase and the NF-κB pathway.

Antrafenine (Stakane) is a derivative of 2-(quinolin-4-ylamino) benzoate, and is an orally active anti-inflammatory and analgesic agent. Antrafenine protects mammalian epithelial cells from cell death upon exposure to influenza A virus A/WSN/33 (H1N1). Antrafenine inhibits carrageenan-induced paw swelling in rats, and reduces exudate volume and total leukocyte infiltration in carrageenan- and calcium pyrophosphate dihydrate crystal-induced pleurisy in rats. Antrafenine can be used in studies related to influenza and pseudogout.

Uricase (Recombinant) (Uox (Recombinant)) is a uricase (urate oxidase). Uricase (Recombinant) converts uric acid into allantoin. The deficiency of Uricase in mammals causes kidney diseases resulting from uric acid accumulation. Uricase (Recombinant) can be used for research on chronic refractory gout and hyperuricemia.

Xanthine oxidoreductase-IN-6 (Compound 4) is an orally active xanthine oxidoreductase (XOR) inhibitor with an IC₅₀ of 170 nM. Xanthine oxidoreductase-IN-6 can block the final step of uric acid biosynthesis and lower serum uric acid levels. Xanthine oxidoreductase-IN-6 also shows Cytochrome P450 3A4 (CYP3A4) inhibitory activity. Xanthine oxidoreductase-IN-6 can be used for the research of hyperuricemia.

Azaleatin is an orally active inhibitor of hQC, NS2B-NS3 protease and E. coli β-glucuronidase, with IC₅₀ values of 1.1 μM, 38.00 μg/mL and 0.57 μM, respectively. Azaleatin inhibits the activities of NF-κB, MyD88, JAK1, TLR4, STAT3, IL-1β, IL-6, COX-2, TNF-α and β-glucuronidase, blocks pro-inflammatory signaling pathways, reduces the levels of ROS, MDA and uric acid, elevates the levels of GPx, GSR, GST, SOD, CAT, HO-1 and GSH, scavenges free radicals and exerts reducing capacity. Azaleatin inhibits the expression of pro-apoptotic proteins Bax, Caspase-9 and Caspase-3, and upregulates the expression of anti-apoptotic protein Bcl-2. Azaleatin reduces the levels of cardiac injury markers, restores cardiac histological structure, inhibits Aβ aggregation, dengue protease activity, hepatic stellate cell proliferation and cancer cell growth, and also exhibits antibacterial activity. Azaleatin can be used in studies related to subchronic cardiotoxicity, Alzheimer's disease, dengue fever, hyperuricemia, liver fibrosis, gastric cancer and bacterial infections.

Strictinin is an orally active phenolic compound. Strictinin reduces xanthine oxidase activity, uric acid production, and the activation of ERK1/2, JNK, NF-κB, and NLRP3 inflammasome components in hepatocytes treated with Xanthine (HY-W017389). Strictinin decreases elevated serum uric acid levels and enhanced xanthine oxidase activity in mice treated with potassium oxonate. Strictinin acts as a ROR1 inhibitor and exhibits anticancer activity against highly aggressive non-androgen-dependent prostate cancer. Strictinin induces cancer cell apoptosis (apoptosis), arrests cell cycle, and inhibits cancer cell migration, invasion, and epithelial-mesenchymal transition. Strictinin modulates gut microbiota, inhibits bacterial growth and biofilm formation, accelerates small intestinal transit, and blocks viral entry and replication. Strictinin can be used in research related to hyperuricemia, androgen receptor-negative non-androgen-dependent prostate cancer, triple-negative breast cancer, bacterial infections, constipation, coronavirus infections, dental caries, and infections caused by influenza A, influenza B, and human parainfluenza virus type 1.

Xininurad is a potent orally active URAT1 inhibitor with an IC₅₀ of 7.17 nM. Xininurad inhibits URAT1 activity to reduce serum uric acid levels and increase urinary uric acid excretion. Xininurad can be used for the research of hyperuricemia and gout.

Procyanidin B2 3′-O-gallate (B2-3′-G), isolated from Rhodiola crenulata extracts, is a potent xanthine oxidase (XO) inhibitor (IC₅₀ = 24.24 μM, K_i = 6.16 μM). Procyanidin B2 3′-O-gallate has antioxidant activity and reduces the formation of UV-induced α-tocopheroxyl. Procyanidin B2 3′-O-gallate can be used for hyperuricemia and gout research.

Uricase, candida utilis (Uox, candida utilis) is a uricase (urate oxidase) derived from Candida utilis. Uricase, candida utilis converts uric acid into allantoin. The absence of Uricase in mammals causes kidney diseases resulting from uric acid accumulation. Uricase, candida utilis can be used for research on chronic refractory gout and hyperuricemia.

7DG (7-Desacetoxy-6,7-dehydrogedunin) is a PKR inhibitor, P2X7 purinergic receptor inhibitor, and skin-lightening agent. 7DG binds outside the ATP-catalytic domain of PKR, blocks the kinase activity-independent protein-protein interactions of PKR, inhibits the phosphorylation and activity of PKR, disrupts ASC assembly and caspase-1 activation, and suppresses the activation of the NLRP1 inflammasome. 7DG inhibits pyroptosis, suppresses the ATP-P2X7 signaling pathway, and abolishes ATP-induced increases in the expression levels of MITF, tyrosinase, PMEL/gp100, and melanin content. 7DG exerts skin-lightening effects in cultured skin in vitro. 7DG can be used in research related to chronic obstructive pulmonary disease, gout, type 2 diabetes, Alzheimer's disease, and hyperpigmentary skin disorders.