Aerucin (aerubumab) / Aridis - LARVOL DELTA

Hotspot Mutagenesis Strategy Yielding a Highly Sensitive Nanobody against Parathion for Immunoassay Development. (PubMed, Anal Chem) - "Specifically, seven residues Ser28, Tyr29, Ser32, Lys102, Phe103, Arg105, and Ala106 encoded by two AGY and two RGYW codons were selected and randomized to construct a saturation mutation library...The average recoveries in vegetable and fruit samples ranged from 87.0% to 113.0%. In summary, this work demonstrated that hotspot mutagenesis is effective for maximizing the efficiency to obtain Nbs with improved sensitivity, and the developed BA-ELISA is a robust tool for the routine screening of parathion."

Journal

Presence of EGF ligand restricts the binding ability of EgB4 nanobody to EGFR extracellular domain. (PubMed, Sci Rep) - "Our computed results showed that, in addition to the residues asp98 and asp110 that were previously reported, two other residues, arg105 and asp108, are also highly interactive with the EGFR extracellular domain...When EGF stabilizes the dimerization of EGFR, there is less opportunity for EgB4 to bind. This crucial aspect has not been reported before."

Journal • Oncology • EGFR

Clothianidin Exposure Induces Cell Apoptosis via Mitochondrial Oxidative Damage. (PubMed, Environ Toxicol) - "Amino acid sites Arg105, Arg130, and Leu373 in CYP3A4, and nitro group and chlorothiazole group in CLO structure might be the potential binding action target. These results indicated that CLO exposure could induce an apoptotic effect on Caco-2 cells, possibly acting through combining and inhibiting its metabolic enzyme CYP3A4, and then leading to oxidative stress and mitochondrial damage. Thus, CLO exposure might be a potential risk factor for human intestinal health."

Journal • CASP3 • CASP9 • CYP3A4

Drug-induced enzyme activity inhibition and CYP3A4 genetic polymorphism significantly shape the metabolic characteristics of furmonertinib. (PubMed, Toxicology) - "It was found that telmisartan significantly inhibited the metabolism of furmonertinib, as demonstrated by a significant increase in the AUC of furmonertinib when co-administered with telmisartan, compared to the furmonertinib-alone group. The key loci affecting the inhibitory effect were identified as ARG105, ILE301, ALA370, and LEU373. Collectively, these data would provide a reference for the quantitative application of furmonertinib."

Journal • CYP3A4

Core antibiotic resistance genes mediate gut microbiota to intervene in the treatment of major depressive disorder. (PubMed, J Affect Disord) - "Our findings suggest that ARGs play a role in the interplay between major depressive disorder and gut microbiota. The role of ARGs should be taken into account when understanding the relationship between depression and gut microbiota."

Journal • CNS Disorders • Depression • Gastrointestinal Disorder • Major Depressive Disorder • Mood Disorders • Psychiatry

Identification of functional modulators of coactivator hub proteins using changes in conformational stability (ACS-Sp 2024) - "Additionally, there are many dynamic domains like CBP KIX that have no established probes, so this method will also be applied to new target coactivators TRRAP(cancer) and ARC105(metabolic disorders). At the conclusion of this work, a suite of chemical probes for high value targets will be discovered, characterized and available for broad usage. Further, the approach can be translated to the many dynamic hub proteins in the human proteome."

Metabolic Disorders • Oncology

CYTOGENETIC DIAGNOSIS WITH NEXT-GENERATION CYTOGENETICS BY OPTICAL GENOME MAPPING IN PATIENTS WITH MYELOFIBROSIS. (EHA 2022) - "NGS detected pathogenic mutations in JAK2 (p.Val617Phe, VAF 41%), SRSF2 (p.Pro95His, VAF 42%) and ETV6 (p.Arg105*, VAF 41%) and likely pathogenic mutation in ASXL1 (p.?; c.1720-2A>G, VAF 45%)...Conclusion Optical Genome Mapping suggest to be very promising diagnostic tool that can complete the study of patients with myelofibrosis, especially in those with non-assessable karyotype. The extension to a larger number of patients will confirm the results obtained and detect variables that remain cryptic to the karyotype."

Clinical • Hematological Malignancies • Immunology • Inflammatory Arthritis • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • ASXL1 • CALR • ETV6 • FGFR1 • JAK2 • PDGFRA • PDGFRB • SRSF2

In silico design based on quantum chemical, molecular docking studies and ADMET predictions of ciprofloxacin derivatives as novel potential antibacterial and antimycrobacterium agents. (PubMed, J Biomol Struct Dyn) - "The results of the docking studies indicate that one pharmacophore designed presents a great inhibition behavior against gram-positive organism (4QGG) and significant interactions observed between the compound and ARG48, GLN101, ARG105 and GLU37 residues of 4QGG. Natural bonding orbital analysis, reactivity indices and molecular electrostatic potential were carried out. The research finding of this study can be helpful to design a new potent antibacterial, antimycrobacterium candidate's drugs that will serve as the basis for future in vitro and in vivo research.Communicated by Ramaswamy H. Sarma."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Structural basis for an unprecedented enzymatic alkylation in cylindrocyclophane biosynthesis. (PubMed, Elife) - "We use a mutagenic screening approach to locate CylK's active site at its domain interface, identifying two residues, Arg105 and Tyr473, that are required for catalysis...Bioinformatic analysis of CylK homologs from other cyanobacteria establishes that they conserve these key catalytic amino acids but they are likely associated with divergent reactivity and altered secondary metabolism. By gaining a molecular understanding of this unusual biosynthetic transformation, this work fills a gap in our understanding of how alkyl halides are activated and used by enzymes as biosynthetic intermediates, informing enzyme engineering, catalyst design, and natural product discovery."

Journal

Structure and mechanism of Mycobacterium smegmatis polynucleotide phosphorylase. (PubMed, RNA) - "Alanine mutagenesis pinpointed RNA and phosphate contacts as essential (Arg105, Arg431, Lys534, Thr470+Ser471), important (Arg112, Arg430), or unimportant (Phe68) for PNPase activity. Severe phosphorolysis and polymerase defects accompanying alanine mutations of the enzymic metal ligands suggest a two-metal mechanism of catalysis by MsmPNPase."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Molecular Dynamics Simulation Framework to Probe the Binding Hypothesis of CYP3A4 Inhibitors. (PubMed, Int J Mol Sci) - "The results indicate the importance of binding pocket residues including Phe57, Arg105, Arg106, Ser119, Arg212, Phe213, Thr309, Ser312, Ala370, Arg372, Glu374, Gly481 and Leu483 for interaction with CYP3A4 inhibitors. The WaterSwap binding energies were further complemented with the MM(GB/PB)SA results and it was observed that the binding energies calculated by both methods do not differ significantly. Overall, our results could guide towards the use of multiple computational approaches to achieve a better understanding of CYP3A4 inhibition, subsequently leading to the design of highly specific and efficient new chemical entities with suitable ADMETox properties and reduced side effects."

Journal

Pre-Clinical and Phase I Safety Data for Anti-Pseudomonas aeruginosa Human Monoclonal Antibody AR-105 (IDWeek 2019) - "In the Phase 1 clinical study, AR‑105 was shown to be safe and well-tolerated, with a PK profile similar to that of other IgG1 mAbs. AR-105 is a promising drug candidate for therapy of PA pneumonia."

P1 data