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.

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.

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.

URAT1-IN-16 is an orally active URAT1 inhibitor with an IC₅₀ value of 0.19 μM. URAT1-IN-16 also functions as an NLRP3 inflammasome pathway inhibitor by effectively suppressing mature IL-1β secretion (IC₅₀ = 2.52 μM). URAT1-IN-16 exhibits remarkable serum uric acid-lowering and anti-inflammatory activities in vivo, and can be used for hyperuricemia and gout research.

URAT1/GLUT9-IN-2 is a selective, orally active URAT1/GLUT9 inhibitor, with an IC₅₀ of 2.81 μM against URAT1 and an IC₅₀ of 12.53 μM against GLUT9. URAT1/GLUT9-IN-2 reduces serum uric acid levels and protects renal function. URAT1/GLUT9-IN-2 can be used in research related to hyperuricemia and hyperuricemic nephropathy.

URAT1/GLUT9-IN-3 is an orally active URAT1/GLUT9 dual inhibitor with IC₅₀ values of 4.01 and 1.60 μM. URAT1/GLUT9-IN-3 inhibits URAT1-mediated uric acid uptake and GLUT9-mediated uric acid transport, reducing renal urate reabsorption. URAT1/GLUT9-IN-3 reduces serum uric acid levels in hyperuricemic mice. URAT1/GLUT9-IN-3 can be used for the researches of gout and hyperuricemia.

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.

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.

Xanthine oxidase-IN-23 (Compound BPF) is an orally active, reversible, mixed-type Xanthine oxidase inhibitor with an IC₅₀ of 3.33 μM. Xanthine oxidase-IN-23 directly binds to XOD in a reversible mixed-type manner to inhibit its catalytic activity. Xanthine oxidase-IN-23 upregulates ABCG2 and downregulates GLUT9 to promote renal urate excretion. Xanthine oxidase-IN-23 reduces serum urate levels and improves renal function in hyperuricemic mice. Xanthine oxidase-IN-23 can be used in the research of hyperuricemia.

Pantothenate kinase-IN-3 is an orally active PANK3-selective binder and CoA biosynthesis activator with a human PANK3 K_i of 9.1 nM, human PANK3 K_a of 1.8 nM, human PANK1β K_i of 113 nM, human PANK1β K_a of 23.4 nM, and oral effectiveness.Pantothenate kinase-IN-3 binds PANK3 via a water-mediated interaction between its sulfonamide NH and Gly193, elevates cellular, hepatic, and forebrain CoA levels, and shows improved metabolic stability in mouse and human microsomes.Pantothenate kinase-IN-3 has solubility properties favorable at pH 7.Pantothenate kinase-IN-3 can be used for the research of hepatic metabolic CoA deficiencies (acidemias).

PDE4-IN-33 is a phosphodiesterase 4 (PDE4) inhibitor. PDE4-IN-33 reduces uric acid levels. PDE4-IN-33 PDE4-IN-33 can be used for the research of hyperuricemia and gout.