AEOL 10113 / Aeolus - LARVOL DELTA

Thermal Stability Kinetics and Shelf Life Estimation of the Redox-Active Therapeutic and Mimic of Superoxide Dismutase Enzyme, Mn(III) meso-Tetrakis(N-ethylpyridinium-2-yl)porphyrin Chloride (MnTE-2-PyPCl, BMX-010). (PubMed, Oxid Med Cell Longev) - "Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin chloride (MnTE-2-PyPCl, BMX-010, and AEOL10113) is among the most studied superoxide dismutase (SOD) mimics and redox-active therapeutics, being currently tested as a drug candidate in a phase II clinical trial on atopic dermatitis and itch. According to the R1 modelling of the isothermal decomposition data, the estimated shelf life value for 10% decomposition (t ) of MnTE-2-PyPCl at 25°C was approximately 17 years, which is consistent with the high solid-state stability of the compound. These results represent the first study on the solid-state decomposition kinetics of Mn(III) 2-N-alkylpyridylporphyrins, contributing to the development of this class of redox-active therapeutics and SOD mimics and providing supporting data to protocols on purification, handling, storage, formulation, expiration date, and general use of these compounds."

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Ortho Isomeric Mn(III) N-Alkyl- and Alkoxyalkylpyridylporphyrins-Enhancers of Hyaluronan Degradation Induced by Ascorbate and Cupric Ions. (PubMed, Int J Mol Sci) - "The ortho compounds MnTE-2-PyP (BMX-010, AEOL10113), MnTnBuOE-2-PyP (BMX-001) and MnTnHex-2-PyP are able to redox cycle with ascorbate whereby producing HO which is subsequently coupled with Cu(I) to produce the OH radical essential for HA degradation. The impact of different Mn(III)-porphyrins on the HA decay was further clarified by electron paramagnetic resonance spectrometry. The ability to catalyze the degradation of HA in a biological milieu, in the presence of cupric ions and ascorbate under the conditions of high tumor oxidative stress provides further insight into the anticancer potential of redox-active ortho isomeric Mn(III) porphyrins."

Journal • Oncology

HO-Driven Anticancer Activity of Mn Porphyrins and the Underlying Molecular Pathways. (PubMed, Oxid Med Cell Longev) - "The lead Mn porphyrins, namely, MnTE-2-PyP (BMX-010, AEOL10113), MnTnBuOE-2-PyP (BMX-001), and MnTnHex-2-PyP, were tested in numerous injuries of normal tissue and cellular and animal cancer models. The wealth of the data led to the progression of MnTnBuOE-2-PyP into four Phase II clinical trials on glioma, head and neck cancer, anal cancer, and multiple brain metastases, while MnTE-2-PyP is in Phase II clinical trial on atopic dermatitis and itch."

Journal • Review • Anal Carcinoma • Atopic Dermatitis • Brain Cancer • Dermatitis • Dermatology • Gastrointestinal Cancer • Glioma • Head and Neck Cancer • Immunology • Oncology • Solid Tumor • BCL2

Redox-Active Drug, MnTE-2-PyP, Prevents and Treats Cardiac Arrhythmias Preserving Heart Contractile Function. (PubMed, Oxid Med Cell Longev) - "Herein, we describe the effects of the redox-active therapeutic Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin, AEOL10113, BMX-010 (MnTE-2-PyP), on rat heart as an entry to new strategies to circumvent cardiomyopathies. MnTE-2-PyP prevents and treats cardiac arrhythmias in rats. In contrast to most antiarrhythmic drugs, MnTE-2-PyP preserves cardiac contractile function, arising, thus, as a prospective therapeutic for improvement of cardiac arrhythmia treatment."

Journal • Atrial Fibrillation • Cardiomyopathy • Cardiovascular

Reduction of peroxynitrite by some manganoporphyrins of AEOL series: DFT approach with dispersion correction and NBO analysis. (PubMed, J Inorg Biochem) - "Reductive oxygen atom cleavage from peroxynitrite (ONOO) to form NO in aqueous solution by some AEOL compounds (AEOL-10113, AEOL-10150, AEOL-11114 and AEOL-11203) was studied by DFT/M06-2X computations with D3 dispersion correction and gCP (geometrical counterpoise correction) for basis set superposition error. In AEOL compounds and their association complexes with ONOO, Mn atom prefered the high spin state (S = 2) to the intermediate spin state (S = 1). Natural bond orbital analysis showed that electron transfer from the most negative oxygen atom in ONOO to Mn atom in MnP has the biggest interaction energy among all kinds of donor-acceptor interactions between ONOO and MnP."

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Mn porphyrins as a novel treatment targeting sickle cell NOXs to reverse and prevent acute vaso-occlusion in vivo. (PubMed, Blood Adv) - "We show for the first time the therapeutic effectiveness of the redox-active manganese (Mn) porphyrins MnTnBuOE-2-PyP5+ (MnBuOE; BMX-001) and MnTE-2-PyP5+ (MnE; BMX-010, AEOL10113) to treat established vaso-occlusion in a humanized sickle mouse model of an acute vaso-occlusive crisis using intravital microscopy. Our data suggest that Mn porphyrins, likely by repressing NOX-mediated adhesive function of SSRBCs and activated leukocytes, could represent a novel, safe therapeutic intervention to treat or prevent the establishment of acute pain crises. These NOX-targeted antioxidants merit further assessment in SCD clinical trials."

Journal • Preclinical • Gene Therapies • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

Mn porphyrin-based redox-active drugs - Differential effects as cancer therapeutics and protectors of normal tissue against oxidative injury. (PubMed, Antioxid Redox Signal) - "Studies that simultaneously explore differential effects in same animal are lacking, while they are essential for understanding of extremely intricate interactions of metal-based drugs with complex cellular networks of normal and cancer cells/tissues."

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