NecroX-7 (LC28-0126) / LG Chem - LARVOL DELTA

NecroX-7 Ameliorate FK506-Induced Nephrotoxicity in LLC-PK1 Cells (Pig Kidney Epithelial Cells) (ATC 2022) - "These results collectively provide therapeutic evidence that necrox-7 ameliorates the FK506-induced renal damage via antioxidant effect and inhibiting apoptosis and inflammation."

IO biomarker • Immunology • Inflammation • Nephrology • Oncology • Renal Disease • Transplantation • ANXA5 • BAX • BCL2 • CASP3 • HMGB1 • IL6 • KIM1 • TLR4 • TNFA

Clinical Trial to Evaluate Pharmacokinetic Characteristics of MIT-001 After SC and IV Administration in Healthy Subjects (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: MitoImmune Therapeutics

New P1 trial

Pharmacokinetics and Tolerability of LC28-0126, a Novel Necrosis Inhibitor, After Multiple Ascending Doses: A Phase I Randomized, Double-Blind, Placebo-Controlled Study in Healthy Male Subjects. (PubMed, Clin Ther) - P1 | "Multiple administrations of LC28-0126 exhibited a dose-proportional pharmacokinetic profile and were well tolerated at a dose range of 3-30 mg. ClinicalTrials.gov identifier: NCT03196804."

Clinical • Journal • P1 data • PK/PD data • Cardiovascular • Graft versus Host Disease • Immunology • Mucositis • Myocardial Infarction • Reperfusion Injury • Stomatitis

Protective Effect of a Novel Clinical-grade Small Molecule Necrosis Inhibitor Against Oxidative Stress and Inflammation During Islet Transplantation. (PubMed, Am J Transplant) - "Supplementation with NecroX-7 during isolation or serum-deprived culture of hIAPP mouse and NHP islets also improved posttransplant glycemia in the recipient streptozotocin-induced diabetic hIAPP mice and BALB/c-nu/nu mice, respectively. In conclusion, pretransplant administration of NecroX-7 during islet isolation and serum-deprived culture suppressed mitochondrial ROS injury, generation of DAMPs-induced proinflammatory responses, and accumulation of toxic IAPP oligomers ex vivo, and improved posttransplant glycemia in vivo."

Clinical • Journal • Immunology • Inflammation • Transplantation • HMGB1 • IL1B • IL6 • MAPK8 • TNFA

Regulation of HMGB1 release protects chemoradiotherapy-associated mucositis. (PubMed, Mucosal Immunol) - "Additionally, NecroX-7 inhibited the HMGB1-induced release of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and macrophage inflammatory protein (MIP)-1β, as well as the expression of p53-upregulated modulator of apoptosis (PUMA) and the excessive inflammatory microenvironment, including nuclear factor-kB (NF-kB) pathways. In conclusion, our findings suggest that HMGB1 plays a key role in the pathogenesis of OM; therefore, blockade of HMGB1 by NecroX-7 may be a novel therapeutic strategy for OM."

Journal

The Indole Derivative NecroX Blocks Th17 Cell Differentiation and Fibroblast-like Synoviocytes-mediated Th1/Th17 Responses in Rheumatoid Arthritis (ACR-ARHP 2019) - "When RA-FLS were co-cultured with CD4+ T cells, NecroX-7 inhibited RA-FLS-mediated Th1 and Th17 cell expansion both in cell-cell contact-dependent and inflammatory cytokine-dependent manners. NecroX could be an immune regulator of inflammatory arthritis by suppressing Th17 cell differentiation and RA-FLS activation and inhibiting the pro-inflammatory feedback loop between Th17 cell and RA-FLS. These observations suggest that NecroX might be useful for the development of anti-inflammatory agents."

"LC28-0126, a new anti-inflammatory agent from @LG Life Sciences, was successfully evaluated in humans after multiple doses #ASCPT2019" (@Cortellis)

The protective effect of necrosis inhibition on acute murine colitis induced by dextran sulphate sodium (ECCO-IBD 2019) - "...The aim of this study investigated the effect of necrosis inhibition using a novel necrosis inhibitor (NI, NecroX-7) in acute murine colitis model and in vitro study...Conclusion A necrosis inhibition effectively reduced DSS-induced colitis and inflammatory cytokines. Necrosis inhibition might be a new approach to treat inflammatory bowel disease."

PARP Biomarker • Preclinical