renal fibrosis

R-268712 is a specific activin receptor-like kinase 5 (ALK5) inhibitor(IC50 of 2.5 nM). It is also an orally active transforming growth factor-β type I receptor inhibitor.

PFI-2 is an effective, specific and cell-active lysine methyltransferase SETD7 inhibitor (Ki/IC50: 0.33/2 nM), 1000-fold selectivity over other methyltransferases and other non-epigenetic targets.

PFI-2 hydrochloride ((R)-PFI-2 hydrochloride) is a potent, highly selective, and cell-active inhibitor of the methyltransferase activity of SETD7 (IC50: 2 nM), 500 fold active than (S)-PFI-2.

Angiotensin II is a major biologically active vasoconstrictor peptide that regulates blood pressure by binding to AT1R and AT2R receptors. It stimulates the sympathetic nervous system, promotes aldosterone synthesis, and enhances renal function. Additionally, it induces vascular smooth muscle cell proliferation and increases collagen synthesis, leading to vascular and myocardial hypertrophy and fibrosis. It also promotes apoptosis and endothelial capillary formation. Angiotensin II is commonly used to induce hypertension and cardiac hypertrophy animal models.

Sinefungin (Adenosyl-Ornithine) belongs to natural products and is an mRNA methyltransferase inhibitor with broad-spectrum antiviral activity. This compound possesses cell permeability and is commonly used in antiviral mechanism research and antiviral drug development.

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.

AZ12601011 is an orally active, selective and potent TGFBR1 kinase inhibitor.AZ12601011 inhibits the release of inflammatory factors, interleukin (IL)-1β, IL-6 and tumor necrosis factor-α, and inhibits the growth of breast tumors.AZ12601011 directly binds to TGF-βR1 and blocks downstream Smad3 activation, which can be used to prevent renal fibrosis.

Fezagepras (Setogepram) is an orally active GPR40 agonist and is an antagonist or inverse agonist of GPR84 with anti-inflammatory, anti-fibrotic, and anti-proliferative actions.

Resorcinolnaphthalein is a specific enhancer of angiotensin-converting enzyme 2 (ACE2) (EC50 value of 19.5 μM).

A-839977 is a selective P2X7 receptor antagonist with anti-inflammatory and analgesic properties, inhibiting BzATP-induced calcium efflux from the P2X7 receptor, and is used in the study of renal fibrosis.

Fluorofenidone (AKF-PD) attenuates the progression of renal interstitial fibrosis partly by suppressing NADPH oxidase and extracellular matrix (ECM) deposition via the PI3K/Akt signalling pathway. Fluorofenidone is an analogue of AMR69. Which displays equivalent lower toxicity, antifibrotic activity, and longer half-life.

TRPC6 antagonist-1 (X26) is a TRPC6 inhibitor with IC50 values of 0.97 μM for TRPC6, 3.93 μM for TRPC3, 5.77 μM for TRPC5, and 4.37 μM for TRPC7. Additionally, TRPC6 antagonist-1 hinders TGF-β1-induced myofibroblast differentiation, thereby mitigating renal fibrosis.

Linvemastat (Compound FC-4) is an orally active MMP-12 inhibitor with an IC50 of less than 10 nM and demonstrates high selectivity over MMP-1, -2, -3, -7, -9, -10, and -14. It significantly reduces lung fibrosis in a mouse model of bleomycin-induced unilateral pulmonary fibrosis and effectively alleviates kidney damage, interstitial inflammation, or fibrosis in a unilateral ureteral obstruction renal fibrosis model. Linvemastat is suitable for research into inflammatory diseases such as idiopathic pulmonary fibrosis (IPF), inflammatory bowel disease (IBD), and asthma.

Xanthine oxidase-IN-21, a Genipin derivative, is an orally effective mixed competitive inhibitor of xanthine oxidase (XOD) with an IC50 of 0.68 μM. It alleviates renal fibrosis by reducing α-SMA expression and modulates the NF-κB pathway to inhibit pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Additionally, Xanthine oxidase-IN-21 suppresses the expression of URAT1 and GLUT9, promoting uric acid excretion and lowering serum uric acid levels. This compound exhibits significant hepatorenal protective effects and can be used in research on hyperuricemia.

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.

PI3K/mTOR-IN-20 is a selective dual inhibitor of PI3K/mTOR. It demonstrates nanomolar anti-proliferative effects in MRC-5 and Mlg2908 cells with IC50 values of 0.380 and 0.090 μM, respectively. In a Bleomycin-induced pulmonary fibrosis model, PI3K/mTOR-IN-20 reduces Ashcroft scores, decreases hydroxyproline content and collagen deposition, downregulates fibrosis-related protein expression, and aids in the repair of lung tissue structure. This compound exhibits good safety, as indicated by stable weight recovery in mice without significant hepatic or renal toxicity. PI3K/mTOR-IN-20 is useful for research on pulmonary fibroblasts.

KS370G (Caffeic Acid Phenethyl Amide) inhibits UUO-induced renal fibrosis marker expression. KS370G is an orally active hypoglycemic and cardioprotective agent that reduces collagen deposition in obstructed kidneys and significantly decreases renal expression of inflammatory chemokines/adhesion molecules and monocyte markers and improves left ventricular hypertrophy and function in the heart of pressure-overloaded mice.KS370G can be used to study renal obstructive nephropathy.

SLM6031434 HCl is a SphK2 inhibitor with anti-fibrotic effects that reduces LPS-induced TNFα and IL-1β production and can be used to study renal fibrosis.

Dracorhodin perchlorate inhibits cell growth, and induces apoptosis in fibroblasts in a dose-and time-dependent manner, arresting cell cycle at G1 phase, may as a candidate for anti-breast cancer. Dracorhodin perchlorate can inhibit high glucose-induced serum and glucocorticoid induced protein kinase 1 (SGK1) and fibronectin(FN) expression in human mesangial cells, and this may be part of the mechanism of preventing and treating renal fibrosis of DN.

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

1.Aristolactam I (Aristololactum) has cytotoxic potency, mediated through the induction of apoptosis in a caspase 3-dependent pathway. 2. The effects of Aristololactam I may be mediated by different mechanisms except TGF-beta1 pathway. 3. Aristololactam I may be one of toxic metabolites in Chinese herbs containing AA which participate in renal damage and fibrosis.

Evogliptin (DA-1229) is a DPP4 inhibitor with oral activity. Evogliptin has significant and lasting hypoglycemic effect in mouse model. Evogliptin inhibits the production of the fibrosis and inflammatory in hepatocytes signals by inducing autophagy. Evogliptin can be used to study type 2 diabetes, chronic liver inflammation, osteoporosis and renal impairment.

SGC agonist 2 is a potent soluble guanylate cyclase (SGC) agonist with potential therapeutic applications for cardiovascular diseases (heart failure, angina, pulmonary hypertension, myocardial infarction) and fibrotic diseases (renal fibrosis, systemic sclerosis).

3-Deazaneplanocin A (DZNep) is a dual inhibitor of histone methyltransferase (EZH2) and S-adenosylhomocysteine hydrolase (AHCY) with antipoxidative activity that inhibits hepatic, renal, peritoneal, and airway fibrosis by inducing proteasomal degradation of its targets and reducing toxicity in animal models.