Table 14.
Targeting dysregulated epigenetic and posttranslational modification by small molecule compounds to treat CNS, cardiovascular, liver, lung, and kidney diseases
| Diseases | Compounds | Modification | Targets | Biological functions | Ref |
|---|---|---|---|---|---|
| ICH | Paeonol | Ubiquitination | ACSL4 | Paeonol inhibits ferroptosis of neurons in ICH through downregulating HOTAIR-dependant UPF1-mediated degradation of ACSL4. | 312 |
| ICH | Isorhynchophylline | ncRNA | p53/SLC7A11 | Isorhynchophylline attenuates cell damage through inhibiting ferroptosis via upregulating miR-122-5p and SLC7A11 mRNA, and inhibiting p53 expression in ferric ammonium citrate-treated hippocampal HT-22 cells. The protective effects of IRN against FAC-induced ferroptosis were weakened by miR-122-5p knockdown. | 313 |
| PD | (-)-Clausenamide | Phosphorylation | ALOX5 | Clau directly interactes with the Ser663 of ALOX5, the PKCα-phosphorylation site, and thus prevented the nuclear translocation of ALOX5. | 240 |
| TBI | Melatonin | ncRNA | 5-LOX | Melatonin improves brain function of mice after TBI through inhibiting ferroptosis and endoplasmic reticulum (ER) stress via reducing circPtpn14 (mmu_circ_0000130), which sponge miR-351-5p to downregulate 5-LOX. | 589 |
| MS | UNC0642 | Methylation | GPX4 | G9a inhibitor restored anti-ferroptotic gene expression, reduced inflammation-induced neuronal loss, and improved clinical outcome. Similarly, neuronal anti-ferroptotic gene expression was reduced in MS brain tissue and was boosted by G9a inhibition in human neuronal cultures. | 378 |
| Aortic dissection | BRD4770 | Methylation | System Xc--GPX4; FSP1-CoQ10; GCH1-BH4 | BRD4770 attenuated aortic dilation through inhibiting the inflammatory response and ferroptosis. | 590 |
| Aortic dissection | Liproxstatin-1 | Phosphorylation | ALOX5 | Liproxstatin-1 largely abrogates BAPN-induced AAD in mice. These results suggest that inhibition of METTL3 or ferroptosis is an effective intervention strategy for AD. | 422 |
| Fer-1 | Methylation | Fer-1 abolishes detrimental role of PRMT4-mediated ferroptosis in DIC. | 411 | ||
| DIC | Metformin | phosphorylation | AMPKα2 | metformin (MET) treatment could inhibit ferroptosis and improve cardiac function via activating AMPKα2 phosphorylation. | 412 |
| DIC | Ferrostatin-1 | Ubiquitination | Ferrostatin-1 suppresses exacerbation of DOX-induced myocardial damage in MITOL-knockout hearts. | 414 | |
| Cardiac Fibrosis | C646 | Acetylation | p53 | Inhibition of p53 acetylation by C646 significantly alleviated ferroptosis in H9c2 myofibroblasts. | 416 |
| Cardiac Fibrosis | Ferrostatin-1 | Acetylation | p53 | Treatment of SIRT3-cKO mice with ferrostatin-1 led to a significant reduction in ferroptosis and cardiac fibrosis. | 416 |
| Cardiac Fibrosis | Ferrostatin-1 | ncRNA | GPX4 | Fer-1 promotes the antioxidant capacity of cardiac fibroblasts, reduced GPX4-mediated ferroptosis and alleviated I/R-induced CF. | 417 |
| HFD-induced cardiac injury | Celastrol | Phosphorylation | AKT/GSK3β | Celastrol confers ferroptosis resistance via AKT/GSK3β signaling in high-fat diet-induced cardiac injury. | 591 |
| HFD-induced cardiac injury | Piperlongumine | Phosphorylation | STAT3 | Piperlongumine protects cardiomyocytes from ferritinophagy-mediated ferroptosis both in vitro and in vivo through reducing phosphorylated STAT3 levels. | 420 |
| MIRI | Compound 968 | ncRNA | GLS2 | Inhibition of miR-190a-5p caused upregulation of GLS2, resulting in decreased ferroptosis, which could be blocked by GLS2 inhibitor compound 968. | 399 |
| Acute liver injury | Sulforaphane | Phosphorylation | BECN1 | Nrf2-dependent autophagy activation by sulforaphane disrupted SLC7A11 binding to S93-phosphorylated BECN1 and increased SLC7A11 membrane transfer to inhibit ferroptosis. Activation of Nrf2 not only upregulates the expression of SLC7A11, GPX-4 and autophagy-related proteins, but also destroys the binding of SLC7A11 and BECN1 by inducing autophagy, thereby promoting SLC7A11 membrane transfer and GSH synthesis, and finally suppressing ferroptosis. | 441 |
| Liver fibrosis | Berberine | Ubiquitination | ferritin | Berberine alleviates mouse liver fibrosis by inducing ferrous redox to activate ROS-mediated HSC ferroptosis. | 592 |
| Liver fibrosis | Recombinant FGF21 | Ubiquitination | Recombinant FGF21 inhibits liver fibrosis by inhibiting hepatocytes ferroptosis through promotiing HO-1 ubiquitination and degradation and Nrf2 activation. | 593 | |
| Liver fibrosis | Artemether | Phosphorylation | AMPKα2 | Artemether alleviates liver fibrosis in vivo and in vitro through inducing HSC ferroptosis via inhibiting the ubiquitination of IRP2, thereby inducing the increase of iron in HSC. | 594 |
| NAFLD | Urolithin C | Phosphorylation | AMPK | Urolithin C inhibits NAFLD via regulating AMPK-ferroptosis axis, maintaining intestinal mucosal barrier and counteracting gut dysbiosis. | 595 |
| Toxin -mediated hepatic toxicity | Fer-1 and tBHQ | Phosphorylation | Nrf2 | Ethyl carbamate-induced liver dysfunction and inflammation, accompanied with oxidative stress, ferroptosis and downregulated Nrf2 signaling in Balb/c mice, which could be effectively reversed by Fer-1 and tBHQ pretreatment. | 464 |
| Toxin -mediated hepatic toxicity | Fer-1 or tBHQ | Phosphorylation | Nrf2 | Fer-1 or tBHQ inhibit Glyphosate triggered ferroptosis-induced liver damage in a mouse mode | 465 |
| Acute liver failure | AGK2 | Phosphorylation | MFN2/GPX4 | AGK2 inhibits thioacetamide-induced acute liver failure via regulating the MFN2-PERK axis and ferroptosis signaling pathway. | 596 |
| Acute lung injury | MitoQ | Phosphorylation | - | MitoQ pretreatment countered As-induced pulmonary ferroptosis and ALI. | 469 |
| Acute lung injury | Fer-1 | Ubiquitination | - | Arsenic-triggered mitochondria damage and ferroptosis were mitigated in Fer-1 pretreated-MLE-12 cells. | 469 |
| Acute lung injury | PERK inhibitor | Phosphorylation | PERK | PERK inhibitor and Mfn-2-overexpression all mitigated As-induced ferroptosis in MLE-12 cells. | 469 |
| Acute lung injury | Ferrostatin-1 | - | - | Ferrostatin-1 alleviates lung injury and pulmonary edema. | 470 |
| Sepsis-Induced Acute Lung Injury | Obacunone | Ubiquitination | Nrf2 | Obacunone alleviates lipopolysaccharide-induced acute lung injury through inhibiting ferroptosis via inhibiting Nrf2 ubiquitinated proteasome degradation, thereby upregulating GPX4 and SLC7A11. | 597 |
| Pulmonary epithelial senescence | Melatonin | Acetylation | SIRT3/p53 | SIRT3 activation by melatonin deacetylated P53 at lysines 320 (K320), thus blocking senescence and ferroptosis. | 598 |
| COPD | rhMFG-E8 | Ubiquitination | MFG-E8 | rhMFG-E8 ameliorates ferroptosis induced by cigarette smoke extract in BEAS-2B cells and HBE cells. | 483 |
| Diabetic nephropathy | Germacrone | - | - | Germacrone inhibits DN through inhibiting ferroptosis via mmu_circRNA_0000309 silence or miR-188-3p mimics abrogated the antiapoptosis and anti-injury effects of germacrone through aggravating mitochondria damage, and elevating reactive oxygen species and ferroptosis-related protein levels. | 486 |
| Renal IRI | IU1 | Ubiquitination | USP14 | IU1, a small molecule inhibitor of USP14 and NAC effectively alleviated renal injury of I/R mice. | 490 |
| Renal IRI | Fedratinib | Ubiquitination | GPX4 | A JAK2 inhibitor Fedratinib downregulates TRIM21 expression and reduce damage both in vivo and in vitro, which is correlated with the upregulation of GPX4. | 491 |
| Toxin-mediated kidney toxicity | SB431542 or SB505124 | - | ALK4/5 | ALK4/5 kinase inhibitors, SB431542 or SB505124, suppressed cadmium-induced HK-2 cell death | 494 |
| Toxin-mediated kidney toxicity | SIS3 | Phosphorylation | TGFβ1 | Cadmium-induced cell death was attenuated by treatment with SIS3, a selective inhibitor of TGFβ1-dependent Smad3 phosphorylation. | 494 |
| Folic Acid-Induced Kidney Injury | Roxadustat (FG-4592) | Phosphorylation | Akt/GSK-3β/Nrf2 | Roxadustat (FG-4592) attenuates Folic Acid-Induced Kidney Injury through inhibitng ferroptosis via Akt/GSK-3β-mediated Nrf2 activation. | 599 |
| Acute kidney injury | Baicalein | Acetylation | p53 | Baicalein ameliorates polymyxin B-induced acute renal injury through inhibiting ferroptosis via reducing p53 K382 acetylation via upregulation of SIRT1 expression. | 600 |
| Acute kidney injury | Dihydromyricetin | - | - | Dihydromyricetin attenuates cisplatin-induced acute kidney injury by inhibiting ferroptosis via | 601 |
| Acute kidney injury | myo-inositol | Ubiquitination | NOX4 | myo-inositol ameliorates cisplatin-induced acute kidney injury through inhibitng ferroptosis via promotes CHIP-mediated ubiquitination of NOX4. | 602 |
| Diabetic kidney disease | Dapagliflozin | Ubiquitination | SLC40A1 | Dapagliflozin ameliorated tubular injury by inhibiting ferroptosis through stabilize SLC40A1 via reduce ubiquitination degradation. | 603 |
| Diabetic kidney disease | Ginkgolide B | Ubiquitination | GPX4 | Ginkgolide B alleviates diabetic kidney disease through inhibiting ferroptosis by inhibiting GPX4 ubiquitination. | 604 |
| Diabetic kidney disease | Schisandrin A | - | - | Schisandrin A attenuates diabetic kidney disease Ferroptosis and NLRP3 Inflammasome-Mediated Pyroptosis in Diabetic Nephropathy through Mitochondrial Damage by AdipoR1 Ubiquitination | 605 |
| Adriamycin-Induced Renal Damage | Astragaloside IV | Phosphorylation | PI3K/Akt /Nrf2 | Astragaloside IV attenuates Adriamycin-Induced Renal Damage through inhibiting ferroptosis via activations of the PI3K/Akt and Nrf2 | 606 |
AGK2 an inhibitor for SIRT2, BECN1 coiled-coil myosin-like BCL2-interacting protein