Nephritis

Sulfamethoxypyridazine is an orally active and brain-penetrant sulfonamide antibiotic. Sulfamethoxypyridazine exhibits antibacterial activity and inhibits growth of susceptible bacterial strains. Sulfamethoxypyridazine can be used for the research of pyelonephritis, urinary tract infections, and dermatitis herpetiformis.

AZM198 is an orally active myeloperoxidase (MPO) inhibitor. AZM198 irreversibly inactivates MPO (IC₅₀=0.015 μM) via covalent binding to the heme prosthetic group, preferentially targets extracellular MPO activity, and reduces neutrophil extracellular trap formation, reactive oxygen species production and degranulation. AZM198 increases the fibrous cap thickness of atherosclerotic plaques, reduces lesion area, ameliorates hepatic steatosis and fibrosis in non-alcoholic steatohepatitis, and alleviates proteinuria and inflammatory infiltration associated with glomerulonephritis. AZM198 also decreases circulating levels of high-sensitivity Cardiac Troponin I and IL-1β, and mitigates endothelial cell injury. Therefore, AZM198 is suitable for research on various MPO-related diseases, including atherosclerotic cardiovascular disease, myocardial infarction, ischemic stroke, non-alcoholic steatohepatitis and crescentic glomerulonephritis.

Imidapril hydrochloride (TA-6366) is an orally active dual inhibitor of angiotensin-converting enzyme (ACE) and MMP-9. Imidapril hydrochloride inhibits lipopolysaccharide-induced phosphorylation of c-Jun, MKK4 and JNK in monocytes, and downregulates the production of specific inflammatory factors such as TNF-α and IP-10, thereby exerting anti-inflammatory activity. Imidapril hydrochloride also effectively ameliorates mesangial expansion and reduces urinary albumin excretion by inhibiting angiotensin AngII production, lowering glomerular pressure and oxidative stress, thus delaying disease progression. Imidapril hydrochloride can also directly bind to the active site of MMP-9 to inhibit gelatinase activity, and suppress the enlargement of cerebral aneurysms without altering systemic blood pressure. Imidapril hydrochloride is widely applicable to related studies on autoimmune glomerulonephritis, diabetic nephropathy, cerebral aneurysms and other conditions.

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.

MEDI-579 is a fully human monoclonal antibody against PAI-1, with a K_D value of 6 pM for human PAI-1 and 105 pM for rat PAI-1. MEDI-579 restores renal plasmin activity and inhibits PAI-1-mediated intracellular signal transduction. MEDI-579 reduces albuminuria, glomerulosclerosis severity, TGF-β1 expression level, and phosphorylated Smad2 level induced in diabetic mice. MEDI-579 decreases the levels of active PAI-1 in plasma and kidneys, and increases plasma plasmin level in a mouse model of lupus nephritis. MEDI-579 can be used in research related to diabetic nephropathy and lupus nephritis. The recommended isotype control is human IgG1 kappa (HY-P99001).

BMS-986184 is a fully human monoclonal antibody targeting interferon gamma-induced protein 10 (IP-10)/CXCL10. BMS-986184 can be used for the research of lupus nephritis.

TJN-331 is a potent and orally active TGF-β1 Inhibitor. TJN-331 ameliorates anti-glomerular basement membrane (GBM) nephritis in rats by inhibitng TGF-β1 production, thereby reducing extracapillary proliferation in glomeruli. TJN-331 inhibits mesangial expansion in experimental IgA nephropathy in ddY mice. TJN-331 can be used for the research of nephritis and IgA nephropathy.

Rhodojaponin VI is an orally active diterpenoid compound found in hododendron molle G. Don
(Ericaceae) (RM). Rhodojaponin VI binds rat N-Ethylmaleimide-sensitive fusion (NSF) with a Kd of 1.03 μM. Rhodojaponin VI blocks the MDM2-Notch1 signalling pathway by reducing MDM2 and Notch1 expression. Rhodojaponin VI indirectly reduces Cav_2.2 current intensity by inhibiting NSF-mediated Cav2.2 trafficking. Rhodojaponin VI alleviates glomerulonephritis progression and podocyte injury in passive heymann nephritis rats. Rhodojaponin VI also has antinociceptive effects. Rhodojaponin VI can be used for the researches of heymann nephritis and pain.

mNOX-E36 is a murine-specific analogue of NOX-E36 (HY-148100), an anti-CCL-2 L-RNA aptamer that binds and neutralises the mouse chemokine CCL-2. mNOX-E36 reduces scarring in an experimental murine model of glaucoma filtration surgery (GFS). mNOX-E36 ameliorates lupus nephritis in mice. mNOX-E36 can be used for GFS and lupus nephritis research.

19-epi-Scholaricine is an orally active indole alkaloid. 19-epi-Scholaricine downregulates the expression of profibrotic/apoptotic proteins (HRAS, HSP90AA1, KDR) and upregulates the expression of cell cycle-related protein (CDK2). 19-epi-Scholaricine suppresses ROS production and reduces the release of inflammatory mediators, thereby attenuating podocyte apoptosis, renal inflammation and oxidative stress by inhibiting AKT/mTOR. 19-epi-Scholaricine can be used in the research of chronic glomerulonephritis and membranous nephropathy.