Chronic Kidney Disease

Mito-TEMPO is a mitochondria-targeted antioxidant. Mito-TEMPO induces mitophagy by activating the PINK1/Parkin pathway, inhibits NLRP3 inflammasome activation, restores mitochondrial membrane potential, and improves renal function and podocyte injury. Mito-TEMPO regulates Ca²⁺ homeostasis, inhibits Bnip3 overexpression, shortens action potential duration, and exerts antiarrhythmic effects. Mito-TEMPO reverses premature senescence, reduces trabecular bone loss, and decreases cell apoptosis. Mito-TEMPO can be used in studies of chronic kidney disease, age-related cardiac dysfunction, postmenopausal osteoporosis, and ischemic stroke.

Bardoxolone methyl (RTA 402) is an orally active and blood-brain-barrier-penetrant activator of Nrf2 and an inhibitor of SARS-CoV-2 3CL protease. Bardoxolone methyl inhibits SARS-CoV-2 replication in Vero cells with an EC₅₀ value of 0.29 μM. Bardoxolone methyl increases levels of pNrf2 and HO-1, inhibits inflammatory mediators like pNFκB and MCP-1. Bardoxolone methyl activates the Nrf2 pathway to enhance antioxidant and anti-inflammatory responses, inhibits viral replication, and improves mitochondrial function. Bardoxolone methyl can be used in research on chemotherapy-induced neuropathic pain (CINP), COVID-19, and chronic kidney disease (CKD).

Eplerenone (Epoxymexrenone) is a selective, highly specific and orally active aldosterone blocker (SAB). Eplerenone also is a selective mineralocorticoid receptor antagonist (MRA) with IC₅₀ value of 0.081 μM. Eplerenone can be used for the research of hypertension, atherosclerosis, chronic systolic heart failure (HF) and cardiovascular (CV).

Zigakibart (BION-1301) is an IgG4-kappa, humanized monoclonal antibody against TNFSF13 (tumor necrosis factor (TNF) superfamily member 13, APRIL, CD256). Zigakibart exhibits anti-inflammatory activity.

(+)-Magnoflorine (α-Magnoflorine) is an orally active aporphine alkaloid with multiple biological activities. (+)-Magnoflorine promotes Parkin/PINK1 -mediated mitochondrial autophagy, inhibits the activation of NLRP3/Caspase-1 pathway, regulates the intestinal microbiota, and exhibits significant anti-inflammatory and immunomodulatory activities. (+)-Magnoflorine inhibits JNK and TLR4/NF-κB signaling pathways, activates Sirt1/AMPK pathway, alleviates neuronal oxidative stress and apoptosis. Magnoflorine upregulates miR-410-3p, inhibits HMGB1/NF-κB pathway, and has anti-tumor activity. (+)-Magnoflorine also has significant antifungal activity.

(+)-Magnoflorine (α-Magnoflorine) iodide is an orally active aporphine alkaloid with multiple biological activities. (+)-Magnoflorine iodide promotes Parkin/PINK1 -mediated mitochondrial autophagy, inhibits the activation of NLRP3/Caspase-1 pathway, regulates the intestinal microbiota, and exhibits significant anti-inflammatory and immunomodulatory activities. (+)-Magnoflorine iodide inhibits JNK and TLR4/NF-κB signaling pathways, activates Sirt1/AMPK pathway, alleviates neuronal oxidative stress and apoptosis. Magnoflorine upregulates miR-410-3p, inhibits HMGB1/NF-κB pathway, and has anti-tumor activity. (+)-Magnoflorine iodide also has significant antifungal activity.

2,8-Dihydroxyadenine is an endogenous metabolite that forms crystals in urine, leading to kidney stone formation and crystal deposition in the kidney. 2,8-Dihydroxyadenine induces crystal-induced tubular injury, inflammation, and fibrosis through crystal deposition in renal tubules, where crystals are excreted in urine, internalized by tubular epithelial cells, and transported to the interstitium. 2,8-Dihydroxyadenine upregulates CD44 expression near crystals, TNF-α signaling through NF-κB, and mTORC1 signaling, while inducing actin stress fiber formation and cytoskeletal remodeling. 2,8-Dihydroxyadenine downregulates epithelial-mesenchymal transition pathways and oxidative phosphorylation, and induces changes affecting inflammation, metabolism, and cell cycle regulation. 2,8-Dihydroxyadenine can be used in research on kidney disease, adenine phosphoribosyltransferase deficiency, and kidney stone disease.

Hydroxycotinine is a nicotine metabolite commonly found in the urine of smokers. Hydroxycotinine is the primary biomarker of tobacco/nicotine vapor exposure, formed from the conversion of nicotine via cotinine. Hydroxycotinine serum levels in rodents are influenced by sex and co-exposure to nicotine vapor and ethanol. Hydroxycotinine elevation is associated with decreased eGFR and increased risk of chronic kidney disease. Hydroxycotinine can be used in research related to chronic kidney disease.

Atidafonat is an orally active sodium-dependent phosphate transporter inhibitor, with IC₅₀ values of 6.8, 1.5, and 1.7 μM against human NaPi-IIb, PiT-1, PiT-2, respectively; and IC₅₀ values of 3.9, 1.9, and 1.7 μM against rat NaPi-IIb, PiT-1, PiT-2, respectively. Atidafonat inhibits intestinal phosphate absorption, increases fecal phosphate excretion, reduces urinary phosphate excretion, and decreases the levels of serum phosphate, FGF23, and adult parathyroid hormone. Atidafonat ameliorates ectopic thoracic aortic calcification, renal injury and hyperphosphatemia, and inhibits the expression of fibrosis markers. Atidafonat can be used for the research of hyperphosphatemia and chronic kidney disease-mineral and bone disorder (CKD-MBD).

Saikosaponin C is an orally active MMP-2 inducer. Saikosaponin C induces the survival, growth, migration and capillary tube formation of endothelial cells. Saikosaponin C inhibits the early stage of hepatitis C virus infection. Saikosaponin C can be used in research related to ischemic tissue diseases, chronic kidney diseases and hepatitis C virus infection.

THR-123 TFA is an orally active ALK3 peptide agonist. THR-123 TFA has a relatively weak binding to ALK2, but does not bind to ALK6. THR-123 TFA suppresses inflammation, Apoptosis and the epithelial-to-mesenchymal transition program and reverses established fibrosis in five mouse models of acute and chronic renal injury. THR-123 TFA can be used for the study of kidney fibrosis.

VTP-27999 Hydrochloride is an orally active renin inhibitor. VTP-27999 Hydrochloride functionally inhibits renin and acid-activated prorenin, suppresses plasma renin activity and modulates plasma and urinary aldosterone levels. VTP-27999 Hydrochloride reduces mean arterial blood pressure, induces plasma renin concentration increases, decreases plasma angiotensin II levels and enhances renin immunoreactivity. VTP-27999 (Hydrochloride) can be used for the research of hypertension and chronic renal disease.

Ebribafusp alfa (ADX-097) comprising a humanized anti-C3d monoclonal antibody linked to two moieties of the first five consensus repeats of factor H (fH1-5). Ebribafusp alfa binds C3d and related fragments, catalyzes AP convertase dissociation, acts as a factor I co-factor for C3b cleavage, and delivers fH1-5 moieties to C3d-deposited tissues for local complement inhibition without systemic blockade. Ebribafusp alfa reduces glomerular C3 deposition, proteinuria, urine albumin-creatinine ratios, and urine soluble C5b-9 levels, preserves podocyte foot-process architecture, inhibits skin complement activation, and localizes to UVB-damaged primate skin. Ebribafusp alfa can be used for the research of membranous nephropathy, bullous pemphigoid, discoid lupus erythematosus, C3 glomerulopathy, IgA nephropathy, and lupus nephritis.

Pedalitin is a tyrosinase and α-glucosidase inhibitor with IC₅₀ values of 0.28 mM and 0.29 mM, respectively, and can be isolated and extracted from Rabdosia serra. Pedalitin is a xanthine oxidase (Xanthine Oxidase) (IC₅₀ = 3.7 µM) and myeloperoxidase (MPO) (IC₅₀ = 3.8 nM) inhibitor. Pedalitin ameliorates NAFLD by downregulating the EGFR/IRS1/AKT1/FOXO1 signaling pathway and related inflammatory and lipid metabolism factors. Pedalitin reduces the risk of urinary tract infection and stones by inhibiting the expression of the urease UreC gene in Proteus mirabilis. Pedalitin also exhibits antifungal activity, with a MIC of 3.9 mg/L against Cryptococcus neoformans. Pedalitin can be used for research on non-alcoholic fatty liver disease, chronic kidney disease, kidney stones, cryptococcosis, and abdominal pain.

MRS2768 tetrasodium salt is a potent, selective, and metabolically stable P2Y₂ receptor agonist with an EC₅₀ of 1.89 μM for the human P2Y₂ receptor. MRS2768 tetrasodium salt activates Gq/PLC/PKC signaling, leading to downstream phosphorylation of Akt, eNOS, and ERK, with effects varying by cell type. MRS2768 tetrasodium salt inhibits ENaC via Gq/PKC/Src/Akt to promote natriuresis and lower blood pressure in the kidney. MRS2768 tetrasodium salt activates eNOS to increase NO secretion in endothelial cells. MRS2768 tetrasodium salt drives proliferation via PI3K/Akt in fibroblasts and cancer cells. MRS2768 tetrasodium salt exerts anti-apoptotic effects through PKC/Src/Akt in cardiomyocytes. MRS2768 tetrasodium salt can be applied to investigate P2Y₂-dependent pathological processes, including acute kidney injury, chronic kidney disease and renal fibrosis, DOCA-salt induced hypertension, myocardial infarction, pulmonary arterial hypertension, pancreatic cancer, cardiac fibrosis, dry eye disease, as well as shear stress-mediated vascular remodeling and atherosclerosis.

PAI-1 is a serine protease inhibitor (SERPIN). PAI-1 binds to and irreversibly inhibits uPA, tPA and furin; it also interacts with vitronectin, α1-acid glycoprotein, CRT, TLR4, proteasome α-3 subunit, uPAR, LRP1, Integrin αvβ3 and thrombin. PAI-1 regulates fibrinolysis, extracellular matrix turnover, cell migration, angiogenesis, inflammatory response and tissue remodeling; it mediates epithelial-mesenchymal transition (EMT)/endothelial-mesenchymal transition (EndMT), apoptosis and thrombus stabilization. PAI-1 can be used in research related to sepsis, acute lung injury, cardiovascular diseases, tissue fibrosis, diabetic nephropathy, obstructive nephropathy and non-insulin-dependent diabetes mellitus.

pUR4 is a recombinant peptide that acts as a fibronectin (FN) inhibitor. pUR4 binds to the N-terminal type I modules of fibronectin, inhibiting the polymerization of soluble fibronectin and its deposition into the extracellular matrix (ECM). pUR4 reduces β1 integrin activation by depleting ECM fibronectin and disrupting FN-β1 integrin coupling. pUR4 attenuates TNF-α-induced endothelial hyperpermeability, maintains endothelial monolayer integrity, and reduces TNF-α-induced cell morphological changes. pUR4 decreases neutrophil adhesion to cardiac endothelial cells, T cell interstitial migration, immune cell infiltration, collagen deposition, and fibroblast activation. pUR4 can be used in research on pathological vascular leakage, heart failure, inflammation, chronic kidney disease, liver fibrosis, and intestinal fibrosis.

Hydroxycotinine-d₃ is the d₃-labeled Hydroxycotinine (HY-113239). Hydroxycotinine is a nicotine metabolite commonly found in the urine of smokers. Hydroxycotinine is the primary biomarker of tobacco/nicotine vapor exposure, formed from the conversion of nicotine via cotinine. Hydroxycotinine serum levels in rodents are influenced by sex and co-exposure to nicotine vapor and ethanol. Hydroxycotinine elevation is associated with decreased eGFR and increased risk of chronic kidney disease. Hydroxycotinine can be used in research related to chronic kidney disease.

rel-Hydroxycotinine-d₃ is the d₃-labeled Hydroxycotinine (HY-113239). Hydroxycotinine is a nicotine metabolite commonly found in the urine of smokers. Hydroxycotinine is the primary biomarker of tobacco/nicotine vapor exposure, formed from the conversion of nicotine via cotinine. Hydroxycotinine serum levels in rodents are influenced by sex and co-exposure to nicotine vapor and ethanol. Hydroxycotinine elevation is associated with decreased eGFR and increased risk of chronic kidney disease. Hydroxycotinine can be used in research related to chronic kidney disease.

PXS 64, a mannose-6-phosphate (M6P) analogue. a lipophilic prodrug of PXS 25 (HY-181430). PXS 64 is an effective anti-fibrotic agent by inhibiting the activation of latent TGF-β1. PXS64, inhibits fibrosis via TGF-β1 pathway in human lung fibroblasts. PXS 64 reduces TGFβ-mediated collagen IV, fibronectin, MCP-1, and phospho-smad2 expression in kidney cells. PXS 64 reduces collagen deposition in dermal scar fibroblasts. PXS 64 can be used for the research of chronic kidney disease, idiopathic pulmonary fibrosis, scarring.