renal injury

Djenkolic Acid (S,S'-Methylenebiscysteine) is a naturally occurring sulfur-containing amino acid extracted from djenkol beans(Archidendron pauciflorum), which is native to Southeast Asia. It is an uncommon but important cause of acute kidney injury in human.

Irbesartan (SR-47436) is an Angiotensin 2 Receptor Blocker whose mechanism of action involves antagonizing the Angiotensin 2 Receptor.

Doxorubicin hydrochloride is an anthracycline antibiotic with cytotoxic and antitumor activity. It is an effective inhibitor of human DNA topoisomerase I and II, with IC50 values of 0.8 μM and 2.67 μM, respectively. In addition to inhibiting DNA topoisomerases, it can reduce the phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase. Doxorubicin hydrochloride also induces apoptosis and autophagy. In animal studies, it is commonly used to induce models of acute renal failure, chronic kidney injury, and heart failure.

Cisplatin (CDDP) is a chemotherapeutic agent with antitumor activity and is a classic DNA crosslinker. It inhibits DNA synthesis and induces DNA damage in cancer cells by forming DNA adducts, ultimately leading to cell death. In addition, Cisplatin can activate ferroptosis and induce autophagy. In animal studies, it is commonly used to establish models of chronic kidney injury and acute renal failure.

Immethridine dihydrobromide is a novel, highly potent and selective histamine H3 receptor (H3R) agonist that inhibits dendritic cell function and alleviates experimental autoimmune encephalomyelitis.Immethridine dihydrobromide MesV induces depolarization of neurons and the MMN and prevents cardiorenal and renal injury. injury.

JP1302 is a selective α2C adrenoceptor antagonist with a Kb value of 16 nM and a Ki of 28 nM for human α2C receptors.JP1302 has antidepressant activity, disrupts the FACT complex and degrades histone H1.JP1302 has been used in the study of neuropsychiatric disorders, acute renal failure, and renal injury.

α-NETA is a potent choline acetyltransferase (ChA) inhibitor and an ALDH1A1 and chemokine-like receptor 1 (CMKLR1) antagonist.Anti-cancer activity,Cholinesterase and acetylcholinesterase (AChE) inhibition,Dose-dependent reduction of body weight and fasting blood glucose levels in STZ-induced diabetic mice,Significantly reduced expression of renal injury markers,May be CEP-9722 can be used for the study of diabetic nephropathy.

5-Hydroxy-1-methylhydantoin (HD-003) is an antioxidant potentially for the treatment of renal failure. A creatinine metabolite, 5-Hydroxy-1-methylhydantoin , a hydroxyl radical scavenger, has previously been shown to confer renoprotection by inhibiting the progression of chronic kidney disease in rats. 5-Hydroxy-1-methylhydantoin is a novel anti-oxidant drug completely suppressed the expression of B2-kinin receptors (B2KR) in response to high glucose (25 mM) stimulation in VSMC and was also shown to attenuate the effects of BK on VSMC remodeling. 5-Hydroxy-1-methylhydantoin inhibited the BK-induced increase in MAPK phosphorylation and attenuated the increase in connective tissue growth factor (CTGF) protein levels in VSMC. These findings suggest that 5-Hydroxy-1-methylhydantoin may confer vascular protection against high glucose concentrations and BK-stimulation to ameliorate vascular injury and remodeling through its anti-oxidant properties.

4-Hydroxychalcone (P-Cinnamoylphenol) attenuates hyperaldosteronism, inflammation, and renal injury in cryptochrome-null mice.

Deoxycorticosterone acetate (DOCA) is a steroid hormone produced by the adrenal glands, possessing mineralocorticoid activity and serving as a precursor to aldosterone. As an agonist of the mineralocorticoid receptor, DOCA can induce severe kidney damage, including inflammation, fibrosis, glomerular injury, and proteinuria. It is commonly used to establish animal models of chronic kidney injury and hypertension.

SIRT5 inhibitor 6 is a novel and potent Sirtuin 5 inhibitor with an IC50 = 310 nM for the treatment of sepsis-associated acute kidney injury (AKI) that modulates protein succinylation and pro-inflammatory cytokine release in the kidney and attenuates renal dysfunction and pathologic injury.

SIRT5 inhibitor 7 (compound 58), a substrate-competitive and selective SIRT5 inhibitor with IC 50 = 310 nM, significantly attenuated renal dysfunction and pathological damage in lipopolysaccharide (LPS)- and cecum ligation/perforation (CLP)-induced septic AKI mice, and modulated proteinsuccinimidylation and proinflammatory cytokine release and pro-inflammatory cytokine release in the kidneys of acute kidney injury (AKI) mice.

GW274150 phosphate is a selective, orally active iNOS inhibitor with an IC50 of 0.2 μM in J774 cells. It mitigates experimental renal ischaemia-reperfusion injury and exhibits analgesic effects in rat models of inflammatory and neuropathic pain.

Ferroptosis-IN-12 (Cpd-A1) is an inhibitor of ferroptosis. It effectively suppresses ferroptosis in mouse renal tubular epithelial cells (mTECs) treated with Erastin and improves renal function in dose-dependent manners in mouse models of acute kidney injury (AKI) induced by ischemia/reperfusion (I/R) or cecal ligation and puncture (CLP). This compound also reduces renal tubular damage and eliminates inflammation. Exhibiting good plasma stability and high distribution in renal tissues during pharmacokinetic studies in mice, Ferroptosis-IN-12 shows promising potential for research in the field of AKI.

PROTACSTING degrader-3 (Compound ST9) is a STINGPROTAC-type degrader with a DC50 of 0.62 μM. It induces STING degradation via the ubiquitin-proteasome pathway. This compound exerts anti-inflammatory effects by inhibiting the STING/TBK1/NF-κB signaling. Additionally, it offers renal protection and can be used in research on acute kidney injury.

PROTACSTING degrader-4 is a covalent STINGPROTAC degrader free of nitro groups, exhibiting a DC50 of 3.23 μM. It effectively inhibits STING and its downstream signaling pathways, including p-TBK1 and p-NF-κB (p-P65), as well as immune-inflammatory cytokines. Additionally, PROTACSTING degrader-4 mitigates renal and blood inflammation in mouse models of Cisplatin-induced acute kidney injury (AKI).

Magnesium Lithospermate B is a natural product activates eNOS and ameliorates endothelial dysfunction in diabetes by enhancing vasodilation in addition to reducing oxidative stress, it can protecte cardiomyocytes from ischemic injury through specific inhibition of TAB1-p38 apoptosis signaling.improves renal failure.

STING-IN-17 is an orally active inhibitor of STING (human STING IC50= 29 nM, murine STING IC50= 15 nM). It effectively suppresses the phosphorylation of STING, TBK1, and IRF3. The compound inhibits the expression of IP10, IFNB1, and ISG56 mRNA in a dose-dependent manner. Additionally, STING-IN-17 reduces ROS and inhibits the expression of cleaved-PARP/caspase-3. It shows potential for improving renal function and can be utilized in research on inflammatory diseases such as acute kidney injury.

Ferroptosis-IN-21 is an inhibitor of ferroptosis that combats renal ischemia-reperfusion injury by directly scavenging peroxy free radicals to prevent cell death. It demonstrates broad-spectrum, nanomolar-level inhibitory potency against various ferroptosis inducers in renal tubular epithelial cells and effectively suppresses the accumulation of lipid reactive oxygen species (ROS). Additionally, Ferroptosis-IN-21 significantly alleviates renal ischemia-reperfusion injury in mice, as evidenced by improved histological damage and functional impairment, reduced expression of inflammatory cytokines, and decreased levels of lipid peroxidation biomarkers such as 4-hydroxynonenal. Ferroptosis-IN-21 is a potential candidate in research for developing ferroptosis-targeted therapeutics.

XRF-1021 is an orally active HIPK2 inhibitor with an IC50 value of 0.18 μM. It reduces the expression of fibrosis markers such as fibronectin, type I collagen, and α-SMA in NRK-49F and HK-2 cells stimulated by TGF-β1. XRF-1021 blocks signaling pathways including TGF-β, NF-κB, p53, Wnt/β-catenin, and Notch. Additionally, it alleviates renal injury and fibrosis in vivo and can be utilized for research in chronic kidney disease.

H36-E4 is an inhibitor of the E3 ubiquitin ligase 27 containing WW domains (WWP2), with a KD value of 6.25 μM. In a unilateral renal ischemia-reperfusion (UIR) mouse model, H36-E4 suppresses WWP2 expression, restores levels of succinate dehydrogenase complex subunit C (SDHC), and slows the transition from acute kidney injury (AKI) to chronic kidney disease (CKD). This compound is useful for research on the progression of AKI to CKD.

AMPKα1 activator 1 is a selective and orally active activator of AMPKα1 with an EC50 of 35.1 nM. It exhibits a selectivity for AMPKα1 over AMPKα2 by 176-fold. This compound serves as a cytoprotective and renoprotective agent. In models of renal ischemia-reperfusion injury, AMPKα1 activator 1 reduces elevated serum creatinine and blood urea nitrogen levels, alleviates kidney damage, and decreases cellular infiltration in renal tissues. It is applicable for research related to renal ischemia-reperfusion injury.

High affinity JNK inhibitor (Ki values are 25-50 nM). Inhibits JNK via competitive binding of the ATP-binding site of active, phosphorylated JNK. Exhibits > 40-fold selectivity for JNK over p38, ERK, IKK2, protein kinase C, Lck and ZAP70. Hepatoprotective. Also inhibits HCMV replication. Uehara et al (2004) c-Jun N-terminal kinase mediates hepatic injury after rat liver transplantation. Transplantation. 78 324 PMID:15316358 |Uehara et al (2005) JNK mediates hepatic ischemia reperfusion injury. J.Hepatol. 42 850 PMID:15885356 |Ma et al (2007) A pathogenic role for c-Jun amino-terminal kinase signaling in renal fibrosis and tubular cell apoptosis. J.Am.Soc.Nephrol. 18 472 PMID:17202416 |Ma et al (2009) Blockade of the c-Jun amino terminal kinase prevents crescent formation and halts established anti-GBM glomerulonephritis in the rat. Lab.Invest. 89 470 PMID:19188913 |Zhang et al (2015) The c-Jun N-terminal kinase inhibitor SP600125 inhibits human cytomegalovirus replication. J.Med.Virol. 87 2135 PMID:26058558 |Vasilevskaya et al (2015) Inhibition of JNK sensitizes hypoxic colon cancer cells to DNA-damaging agents. Clin.Cancer.Res. 21 4143 PMID:26023085

Cinnamtannin A2 is a natural product and procyanidin tetramer that enhances GLP-1 and insulin secretion in mice. It protects against renal injury by reducing KIM-1 and NGAL expression and exhibits antioxidant activity.