uremic

Iptacopan hydrochloride (LNP023 hydrochloride) is an orally bioavailable, highly potent and highly selective factor B inhibitor with an IC50 of 10 nM. Iptacopan hydrochloride shows direct, reversible, and high-affinity binding to human factor B with a KD of 7.9 nM.

N-Acetyl-L-arginine (Ac-Arg-OH), an N-acyl-L-alpha-amino acid with a strong basic nature (based on its pKa), has elevated serum levels in hyperargininemic patients and is associated with several diseases, including uremia and colorectal cancer. In untreated hyperargininemic patients, it reaches its highest levels in cerebrospinal fluid. It has also been detected in apples and loquats, suggesting it could be a potential biomarker for consumption of these foods. Additionally, a low-arginine diet combined with sodium benzoate therapy leads to a marked decrease in plasma N-acetyl-L-arginine concentrations.

N-Acetyl-L-arginine dihydrate (N-Ac-L-arg-OH) is one of the guanidino compounds found elevated in the serum of a hemodialyzed renal insufficient (uremic) pediatric population.

pTH (1-37) (human), a fragment of parathyroid hormone (PTH), promotes cAMP formation and enhances alkaline phosphatase activity. Additionally, it fosters growth, elevates bone calcium content, and augments bone mineral density (BMD) in uremic animals. This compound shows promise for osteoporosis research [1] [2] [3].

p-Cresyl Sulfate is the major uremic toxin present in the blood of patients with chronic kidney disease and is derived from the metabolites of tyrosine and phenylalanine in the liver.

Danicopan (ACH-4471) (ACH-4471) is a selective, orally active small molecule factor D inhibitor with high binding affinity to human factor D, with a Kd value of 0.54 nM. Danicopan (ACH-4471) inhibits the activity of the complement replacement pathway (APC) and may block the complement replacement pathway in paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS).

p-Cresyl sulfate potassium (p-Tolyl sulfate potassium salt) is a prototype protein-bound uremic toxin derived from the metabolites of tyrosine and phenylalanine through liver.

Indoxyl sulfate-d5 is intended for use as an internal standard for the quantification of indoxyl sulfate by GC- or LC-MS. Indoxyl sulfate is a uremic toxin and a metabolite of tryptophan. It is formed via sulfation of indole, an intermediate generated from tryptophan by intestinal bacteria, by the sulfotransferase (SULT) isoform 1A1 variant 2 (SULT1A1*2) in the liver. Indoxyl sulfate activates the aryl hydrocarbon receptor (AhR) in HepG2 40 6 hepatoma cells (EC50 = 12.1 nM in a reporter assay). It also inhibits the organic anion transporter (OAT) isoforms OAT1 and OAT3 (Kis = 34.2 and 74.4 µM, respectively for the rat transporters) in S2 proximal tubule cells. Indoxyl sulfate (0.2 and 1 mM) increases superoxide anion and nitric oxide levels in isolated human mononuclear blood cells. It increases serum creatinine and blood urea nitrogen (BUN) levels in the 5 6 nephrectomized rat model of chronic renal failure when administered at a dose of 50 mg kg.

P-CRESOL-d3 (METHYL-d3) is a deuterated compound of P-CRESOL. P-CRESOL has a CAS number of 106-44-5. p-Cresol (4-methylphenol) is a partially lipophilic moiety which strongly binds to plasma protein (close to 100%) under normal conditions. p-Cresol is metabolized through conjugation, mainly sulphation and glucuronization, but removal of the unconjugated p-cresol is, at least in part, via the urine. Therefore it is not surprising that this compound, together with several other phenoles, is retained when the kidneys fail. P-Cresol is an end-product of protein breakdown, and an increase of the nutritional protein load in healthy individuals results in enhanced generation and urinary excretion. The serum p-cresol concentration in uremic patients can be decreased by changing to a low-protein diet. p-Cresol is one of the metabolites of the amino acid tyrosine, and to a certain extent also of phenylalanine, which are converted to 4-hydroxyphenylacetic acid by intestinal bacteria, before being decarboxylated to p-cresol (putrefaction).

4-Ethylphenyl sulfate, a gut microbial metabolite, is also a protein-bound uremic toxin and a xenobiotic substrate that causes endothelial dysfunction [1].

Potassium 1H-indol-3-yl sulfate (Potassium 3-indoxyl sulfate) is an agonist for the human Aryl Hydrocarbon Receptor (AhR), a key regulator of immune-inflammatory conditions. A metabolite of tryptophan derived from dietary protein, it is produced by intestinal bacteria and metabolized in the liver. In chronic kidney disease patients with impaired renal function, it accumulates in serum as a uremic toxin, inducing oxidative stress and accelerating disease progression. At 250 μM, it activates NF-Κb, promoting TGF-β1 and Smad3 expression in rat proximal tubular cells, which is associated with profibrotic activity.

Guanidinosuccinic acid (GSA) has been identified as a uremic toxin, is a nitrogenous metabolite isolated in excess from serum and urine.

Indican (Indoxyl-β-D-glucoside) is a natural protective compound that is used to protect the liver.

Ravulizumab (ALXN1210) is a humanized monoclonal antibody that specifically binds to human complement protein C5 with high affinity, targeting complement factor 5 to block complement activation. It can be used for the prevention and treatment of paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, and myasthenia gravis.

Phytic acid dipotassium salt is an endogenous metabolite that inhibits β-secretase 1 (BACE1).