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.

Smilaxchinoside A is an orally active steroidal glycoside found in the roots of S. riparia. Smilaxchinoside A reduces serum uric acid levels and shows potent uricosuric activity. Smilaxchinoside A inhibits XOD activity and downregulates renal mURAT1 expression. Smilaxchinoside A can be used for the research of hyperuricemia.

Ligusticum cycloprolactam is a potent, orally active, and CNS-penetrant TLR4/NF-κB inhibitor, exhibiting anti-inflammatory and neuroprotective activity. Ligusticum cycloprolactam reduces FPR1 expression, inhibits NLRP3 inflammasome, TLR4/NF-κB, hepatic MAPK and TGF-β signaling, and selectively activates hepatic FXR. Ligusticum cycloprolactam attenuates pro-inflammatory mediator production, enhances anti-inflammatory cytokine secretion, regulates renal uric acid transporters, and preserves intestinal microbiota composition. Ligusticum cycloprolactam can be used for the research of ischemic stroke, hyperuricemic nephropathy, neuroinflammation, and metabolic dysfunction-associated fatty liver disease.

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

Xanthine oxidase-IN-20 is a potent and orally active xanthine oxidase (XO) inhibitor with an IC₅₀ of 1.7 nM. Xanthine oxidase-IN-20 exhibits outstanding serum uric acid (SUA)-lowering efficacy in both mouse and rat acute hyperuricemia models. Xanthine oxidase-IN-20 shows favorable safety profile. Xanthine oxidase-IN-20 can be used for hyperuricemia and gout research.

AA 193 is an orally active uricosuric agent. AA 193 inhibits the net reabsorption of uric acid in nephrons, regulates the renal reabsorption process of filtered uric acid, promotes uric acid excretion in a dose-dependent manner, and reduces serum uric acid levels. AA 193 mildly inhibits the activity of xanthine dehydrogenase (XDH). AA 193 can be used in studies related to hyperuricemia.

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

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

JN-170 is a potent and highly selective inhibitor and transport corrector of human SLC6A19 (IC₅₀=47 nM). Furthermore, at a concentration of 35 μM, JN-170 exhibits no activity against SLC1A5, SLC7A5, or SLC6A8. JN-170 is applicable to research on phenylketonuria (PKU) and hyperphenylalaninemia. JN-170 is also suitable for studies related to various metabolic disorders, including tyrosinemia, maple syrup urine disease, urea cycle disorders, and hyperammonemia.

XO/COX/LOX-IN-1 is a XO/COX/LOX inhibitor with an IC₅₀ of 3.2 μM against rat XO, 10.83 μM against 5-LOX, 12.67 μM against COX-1, and 8.31 μM against COX-2. XO/COX/LOX-IN-1 binds to the active sites of XO, 5-LOX, COX-1 and COX-2, thereby blocking enzyme activities associated with uric acid, leukotriene, prostaglandin synthesis and inflammatory pathways. XO/COX/LOX-IN-1 can be used in the research of hyperuricemia and inflammation.

Ulodesine succinate (BCX4208 succinate) 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 succinate 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 succinate 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 succinate can be used in research related to hyperuricemia and gout.

HYJ-2 is a URAT1 inhibitor and urate-lowering agent. HYJ-2 inhibits URAT1-mediated urate transport and interacts with key residues within the URAT1 binding pocket. HYJ-2 reduces serum urate levels in hyperuricemic mice without inducing liver or kidney injury. HYJ-2 shows low cytotoxicity to hepatocytes and renal cells. HYJ-2 does not significantly induce hepatocyte apoptosis or mitochondrial dysfunction. HYJ-2 can be used in studies related to hyperuricemia and gout.

Xanthine oxidase-IN-22 is an orally active inhibitor of xanthine oxidase (XO) (IC₅₀: 0.0034 μM). Xanthine oxidase-IN-22 exhibits a mixed-type inhibition mode against XO. Xanthine oxidase-IN-22 reduces serum uric acid levels in mice. Xanthine oxidase-IN-22 can be used in research related to hyperuricemia and gout.

URAT1-IN-15 (Compound 9) is an orally active, selective URAT1 inhibitor with an IC₅₀ of 69.81 nM. URAT1-IN-15 inhibits CYP2C9 (IC₅₀ = 8.39 μM). URAT1-IN-15 shows uricosuric activity. URAT1-IN-15 can be used in the research of hyperuricemia.

Xanthine oxidase-IN-21, a Genipin (HY-17389) derivative, is an orally active mixed competitive xanthine oxidase (XOD) inhibitor with an IC₅₀ of 0.68 μM. Xanthine oxidase-IN-21 reduces renal fibrosis by decreasing α-SMA expression and suppresses pro-inflammatory cytokines IL-1β, IL-6, and TNF-α through NF-κB pathway regulation. Xanthine oxidase-IN-21 also inhibits URAT1 and GLUT9 expression, promoting uric acid excretion and lowering serum uric acid levels. Xanthine oxidase-IN-21 shows significantly hepatorenal protection activity. Xanthine oxidase-IN-21 can be used for the research of hyperuricemia.