LJP 1207 / Innoviva - LARVOL DELTA

Protective Effect of Selegiline (R-deprenyl) in Aminoglycoside-Induced Hearing Loss. (PubMed, Neurochem Res) - "The reversibility or lack of MAO-B inhibition in safinamide and LJP-1207, respectively, as well as the absence of the propargylamine moiety with known intrinsic neuroprotective activity in both molecules, may explain their ineffectiveness. Selegiline, or certain propargylamine analogues of it, offer a promising therapy against AGIHL by addressing its multifactorial pathology through antioxidant, antiapoptotic, neuroprotective, and anti-inflammatory actions, while enhancing endogenous DAergic protective mechanisms."

Journal • CNS Disorders • Inflammation • Movement Disorders • Otorhinolaryngology • Parkinson's Disease • AOC3

Increased atherosclerotic plaque in AOC3 knock-out in ApoE mice and characterization of AOC3 in atherosclerotic human coronary arteries. (PubMed, Front Cardiovasc Med) - "Human VSMCs, treated or not with LJP1586, an AOC3 inhibitor, were used to measure differentiation markers by qPCR...This suggests that AOC3 may have an important role in atherosclerosis independent of its canonical inflammatory effect. The dual role of AOC3 impacts therapeutic strategies using pharmacological regulators of SSAO activity."

Journal • Preclinical • Atherosclerosis • Cardiovascular • Dyslipidemia • Immunology • Inflammation • AOC3 • APOE

Protective effects of the novel amine-oxidase inhibitor multi-target drug SZV 1287 on streptozotocin-induced beta cell damage and diabetic complications in rats. (PubMed, Biomed Pharmacother) - "We aimed to explore the effects of AOC3 inhibition and to test the actions of our novel AOC3 inhibitor multi-target drug candidate, SZV 1287, compared to a selective reference compound, LJP 1207, in an 8-week long insulin-controlled streptozotocin (STZ)-induced (60 mg/kg i.p.) rat diabetes model...We provide the first evidence for protective effects of AOC3 inhibition on STZ-induced pancreatic beta cell damage, neuropathic cold hypersensitivity and diabetic retinal dysfunction. Long-term treatment with our novel multi-target analgesic candidate, SZV 1287, is safe and effective also under diabetic conditions."

Journal • Diabetes • Diabetic Neuropathy • Diabetic Retinopathy • Immunology • Metabolic Disorders • Pain • Retinal Disorders • AOC3

Comparison of Inhibitor and Substrate Selectivity between Rodent and Human Vascular Adhesion Protein-1. (PubMed, Mediators Inflamm) - "Human VAP-1 was more sensitive compared to rat or mouse VAP-1 (lowest IC concentration) to semicarbazide but was least sensitive to hydralazine and LJP-1207...The larger hydrophobic compounds from Astellas (compound 35c) and Boehringer Ingelheim (PXS-4728A) were hypothesized to have higher binding affinity for human VAP-1 compared to rodent VAP-1 since the channel in human VAP-1 is larger and more hydrophobic than that in rodent VAP-1...Rat VAP-1 had the highest affinity for all three substrates and mouse VAP-1 had intermediate affinity for BA and phenylethylamine, but tyramine was not a substrate for mouse VAP-1 under these assay conditions. These results suggest that comparing oxidative deamination in mouse and rat VAP-1 may be important if using these species for preclinical efficacy models."

Journal • Preclinical • Immunology • AOC3

Semicarbazide-Sensitive Amine Oxidase Increases in Calcific Aortic Valve Stenosis and Contributes to Valvular Interstitial Cell Calcification. (PubMed, Oxid Med Cell Longev) - "Calcification of VIC was inhibited in the presence of the specific SSAO inhibitor LJP1586. The association of SSAO expression and activity with valvular calcification and oxidative stress as well as the decreased VIC calcification by SSAO inhibition points to SSAO as a possible marker and therapeutic target to be further explored in CAVS."

Journal • Diabetes • Metabolic Disorders • AOC3 • PARP • PARP1