Article
Chemistry, Medicinal
Zsolt Szeleczky, Zoltan Szakacs, Eva Bozo, Ferenc Baska, Krisztina Vukics, Sandor Levai, Krisztina Temesvari, Elemer Vass, Zoltan Beni, Balazs Kramos, Ildiko Magdo, Csaba Szantay, Janos Koti, Katalin Domany-Kovacs, Istvan Greiner, Imre Bata
Summary: A new class of selective vasopressin receptor 1A (V-1A) antagonists has been identified, with the synthesis of four atropisomeric stereoisomers characterized by chiral axis and a stereogenic center. In vitro pharmacological profiles show that the human V-1A receptor strongly prefers the isomers with aR axial chirality, with the most active isomer being the aR,5S form. The structure-activity relationships for the isomers and newly synthesized analogues could be tentatively explained by an in silico study.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Pradeep Paudel, Dong Hyun Kim, Jieun Jeon, Se Eun Park, Su Hui Seong, Hyun Ah Jung, Jae Sue Choi
Summary: Aurantio-obtusin in Cassia seeds showed specific neuroprotective effects by targeting V1AR receptors, reducing neuronal damage in a transient brain ischemia/reperfusion injury mouse model.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Kateryna Che, Markus Muttenthaler, Dennis Kurzbach
Summary: This study utilized virtual screening strategies and experimental nuclear magnetic resonance data to reveal the conformational selectivity features of VP-V1aR complex formation. The conformation of VP's three-residue tail significantly modulated the complex dissociation constants, with solvent-exposed and more flexible structures binding to the receptor with enhanced affinities. This research provides insights into the evolutionary selected conformational properties of VP and guides the design of more potent and selective VP analogues.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Multidisciplinary Sciences
Adrien Flahault, Pierre-Emmanuel Girault-Sotias, Mathilde Keck, Rodrigo Alvear-Perez, Nadia De Mota, Lucie Esteoulle, Sridevi M. Ramanoudjame, Xavier Iturrioz, Dominique Bonnet, Catherine Llorens-Cortes
Summary: In this study, LIT01-196 was shown to be a promising treatment for AVP-induced hyponatremia by activating apelin-R, reducing the antidiuretic effect of AVP, and increasing aqueous diuresis.
NATURE COMMUNICATIONS
(2021)
Article
Entomology
Nikoletta A. Nagy, Zoltan Nemeth, Edit Juhasz, Szilard Poliska, Rita Racz, Johanna Kiss, Andras Kosztolanyi, Zoltan Barta
Summary: In the beetle Lethrus apterus, inotocin may be involved in the regulation of parental care, as its expression levels increase over the reproductive season, with no differences found between sexes.
JOURNAL OF INSECT PHYSIOLOGY
(2021)
Article
Endocrinology & Metabolism
Shruti Mohan, Peter R. Flatt, Nigel Irwin, R. Charlotte Moffett
Summary: Novel analogues of the nonapeptide hormone arginine vasopressin were generated and screened for their metabolic effects in rodent models. One analogue, Ac3IV, showed potential for antidiabetic efficacy in high-fat-fed mice by reducing body weight, glucose levels, and improving insulin sensitivity. These analogues also improved cholesterol levels and decreased islet cell proliferation and apoptosis.
DIABETES OBESITY & METABOLISM
(2021)
Article
Health Care Sciences & Services
Hilda T. Maibach, Michael J. Brownstein, Steven M. Hersch, Karen E. Anderson, Debra E. Itzkowitz, Eve M. Damiano, Neal G. Simon
Summary: SRX246, an orally available V1a receptor antagonist, was found to reduce aggressive behavior in HD patients and was well tolerated.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Review
Chemistry, Medicinal
Ferenc Baska, Eva Bozo, Tamas Patocs
Summary: This manuscript summarizes recent patent activity related to vasopressin receptor antagonists, focusing on selective V1a or V2 antagonists and dual-acting V1a/V2 antagonists. Despite unsuccessful clinical trials in many cases, there is still potential in the research of vasopressin receptor antagonists, as evidenced by several ongoing clinical trials.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2023)
Article
Pharmacology & Pharmacy
Hiroyuki Fujiki, Masayuki Matsunaga, Masayuki Furukawa, Tatsuya Yamashita, Shigeki Nakamura, Toshiki Miyazaki, Hiroshi Mizuguchi, Yasuhiro Menjo, Takakuni Matsuda, Yoshihisa Yamada
Summary: OPC-61815 is a pro-drug of tolvaptan, which can be converted into tolvaptan after intravenous administration. It has good water solubility and diuretic effect.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2022)
Article
Multidisciplinary Sciences
Masahiko Tosaka, Rei Yamaguchi, Yutaro Itabashi, Naoto Mukada, Haruka Tsuneoka, Kentaro Takahashi, Shunsuke Nakamura, Takahiko Nakazawa, Yuhei Yoshimoto
Summary: Oral tolvaptan administration is effective in treating hyponatremia with SIAD in patients after pituitary surgery. It significantly increases serum sodium concentration, decreases urine osmolality and urinary sodium concentration, and increases urine output.
Article
Cardiac & Cardiovascular Systems
Thomas Mondritzki, Thuy Anh Mai, Julia Vogel, Elisabeth Pook, Pierre Wasnaire, Carsten Schmeck, Joerg Hueser, Wilfried Dinh, Hubert Truebel, Peter Kolkhof
Summary: The novel dual V1a/V2 receptor antagonist pecavaptan efficiently induces aquaresis and counteracts AVP-mediated haemodynamic aggravation in heart failure models.
EUROPEAN JOURNAL OF HEART FAILURE
(2021)
Article
Endocrinology & Metabolism
Salwa Afifi, Azizia Wahedi, Jean -Paul Paluzzi
Summary: This study investigates the distribution and physiological roles of adipokinetic hormone/corazonin-related peptide (ACP) in Aedes aegypti mosquitoes. The results suggest that ACP may function as a neurotransmitter and/or neuromodulator, facilitating communication between the brain and posterior regions of the nervous system. Additionally, ACP has a role in regulating energy substrates, particularly in the degradation of fat in female mosquitoes.
GENERAL AND COMPARATIVE ENDOCRINOLOGY
(2023)
Article
Pharmacology & Pharmacy
R. Bhandari, A. Kuhad
Summary: Autism spectrum disorder (ASD) lacks approved drugs for core symptom treatment, but vasopressin receptor antagonists show potential as therapeutics, influencing social behavior and potentially improving symptoms.
DRUGS OF THE FUTURE
(2021)
Article
Transplantation
Roman-Ulrich Mueller, A. Lianne Messchendorp, Henrik Birn, Giovambattista Capasso, Emilie Cornec-Le Gall, Olivier Devuyst, Albertien van Eerde, Patrick Guirchoun, Tess Harris, Ewout J. Hoorn, Nine V. A. M. Knoers, Uwe Korst, Djalila Mekahli, Yannick Le Meur, Tom Nijenhuis, Albert C. M. Ong, John A. Sayer, Franz Schaefer, Aude Servais, Vladimir Tesar, Roser Torra, Stephen B. Walsh, Ron T. Gansevoort
Summary: Approval of tolvaptan for ADPKD has transformed patient care and shifted focus from general measures to targeting disease-specific mechanisms. Evidence-based approaches are crucial due to long-term nature of treatment and potential side effects.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2022)
Article
Chemistry, Medicinal
Guanglin Luo, Xiang-Jun Jiang, Ling Chen, Charles M. Conway, Michael Gulianello, Walter Kostich, Deborah Keavy, Laura J. Signor, Ping Chen, Carl Davis, Valerie J. Whiterock, Richard Schartman, Kimberly A. Widmann, John E. Macor, Gene M. Dubowchik
Summary: Researchers identified a series of high-affinity heterocycle derivatives as CGRP receptor antagonists, some of which showed good oral exposure and reduced time-dependent CYP3A4 inhibition. However, challenges remained in improving the oral bioavailability of these compounds.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Hematology
Johannes Schmoellerl, Ines A. M. Barbosa, Martina Minnich, Florian Andersch, Leonie Smeenk, Marije Havermans, Thomas Eder, Tobias Neumann, Julian Jude, Michaela Fellner, Anja Ebert, Monika Steininger, Ruud Delwel, Florian Grebien, Johannes Zuber
Summary: Chromosomal rearrangements involving the MDS1 and EVI1 complex locus (MECOM) on chromosome 3q26 define an aggressive subtype of acute myeloid leukemia (AML) that is associated with chemotherapy resistance and dismal prognosis. EVI1 controls the expression of ERG and occupies a conserved intragenic enhancer region in AML, and interfering with this regulatory axis may provide entry points for the development of rational targeted therapies.
Article
Pharmacology & Pharmacy
Lisa Pallareti, Tine F. Rath, Boris Trapkov, Tsonko Tsonkov, Anders Thorup Nielsen, Kasper Harpsoe, Patrick R. Gentry, Hans Brauner-Osborne, David E. Gloriam, Simon R. Foster
Summary: This study used virtual screening, analog searches, and pharmacological assays to investigate GPR139 signaling and identify improved compounds. The rank order of potency of reference agonists was consistent across assays, and several new agonists and antagonists were identified. These findings contribute to the GPR139 tool compound repertoire.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Christian R. O. Bartling, Flora Alexopoulou, Sarah Kuschert, Yanni K. -Y. Chin, Xinying Jia, Vita Sereikaite, Dennis Ozcelik, Thomas M. Jensen, Palash Jain, Mads M. Nygaard, Kasper Harpsoe, David E. Gloriam, Mehdi Mobli, Kristian Stromgaard
Summary: Peptides targeting disease-relevant protein-protein interactions have limitations in terms of metabolic stability and membrane permeability. Peptide cyclization, particularly hydrocarbon stapling, offers a valuable approach to develop metabolically stable and cell-permeable cyclic leads with improved affinity and stability. In this study, a comprehensive examination of cyclization strategies led to the identification of cyclic APP dodecamer peptides that target the phosphotyrosine binding domain of Mint2 with significantly improved properties.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Jimmy Caroli, Alibek Mamyrbekov, Kasper Harpsoe, Sahar Gardizi, Linda Doerries, Eshan Ghosh, Alexander S. Hauser, Albert J. Kooistra, David E. Gloriam
Summary: Biased signaling allows hormones, probes, or drugs to produce different functional outcomes through the same receptor. The Biased Signaling Atlas provides a community platform for data and tools to advance this concept, potentially leading to the development of safer and more potent drugs.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Medicinal
Emil Marcher-Rorsted, Jitka Nykodemova, Kasper Harpsoe, Anders A. Jensen, Jesper L. Kristensen
Summary: This article discusses a class of compounds with selective activity on the serotonin 2A receptor and synthesizes and characterizes the structures of these compounds. The results show that one stereoisomer exhibits activity and shares a common binding mode with known compounds.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Biotechnology & Applied Microbiology
Rocio Olmo, Stefanie Urimare Wetzels, Gabriele Berg, Luca Cocolin, Moritz Hartmann, Marta Hugas, Tanja Kostic, Thomas Rattei, Manfred Ruthsatz, Daria Rybakova, Angela Sessitsch, Colette Shortt, Kenneth Timmis, Evelyne Selberherr, Martin Wagner
Summary: Within the MicrobiomeSupport project funded by the European Union, the workshop 'Education in Food Systems Microbiome Related Sciences' brought together researchers, public health experts, and industry partners from around the world to address the educational needs in microbiome-related sciences in food systems. This publication provides a summary of the discussions and recommendations from the workshop.
MICROBIAL BIOTECHNOLOGY
(2023)
Article
Genetics & Heredity
Tamara Halter, Stephan Koestlbacher, Thomas Rattei, Frederik Hendrickx, Alejandro Manzano-Marin, Matthias Horn
Summary: This study explores a unique system where the dwarf spider Oedothorax gibbosus is co-infected with multiple endosymbionts, including Wolbachia, 'Candidatus Tisiphia', Cardinium, and Rhabdochlamydia. Through genome sequencing, the researchers reconstructed these endosymbiont genomes and analyzed their interactions and evolutionary relationships with the spider host.
MICROBIAL GENOMICS
(2023)
Article
Infectious Diseases
Lukas Lueftinger, Peter Majek, Thomas Rattei, Stephan Beisken
Summary: This study investigates the performance of in-silico antimicrobial susceptibility testing (AST) from clinical metagenomic data. Using simulated metagenomes with known resistance phenotype, the impact of various factors on AST accuracy is explored. The results show that an optimized metagenomics assembly and binning workflow can improve AST accuracy, and machine learning-based methods outperform rule-based approaches on simulated patient samples.
Review
Pharmacology & Pharmacy
Icaro A. Simon, Walden E. Bjorn-Yoshimoto, Kasper Harpsoe, Stylianos Iliadis, Bo Svensson, Anders A. Jensen, David E. Gloriam
Summary: This article investigates the structure and selectivity hotspots of serotonin receptors, explores the mechanism of interaction between drugs and receptors, and emphasizes the importance of integrating knowledge.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2023)
Article
Microbiology
Sarah P. Esser, Janina Rahlff, Weishu Zhao, Michael Predl, Julia Plewka, Katharina Sures, Franziska Wimmer, Janey Lee, Panagiotis S. Adam, Julia McGonigle, Victoria Turzynski, Indra Banas, Katrin Schwank, Mart Krupovic, Till L. V. Bornemann, Perla Abigail Figueroa-Gonzalez, Jessica Jarett, Thomas Rattei, Yuki Amano, Ian K. Blaby, Jan-Fang Cheng, William J. Brazelton, Chase L. Beisel, Tanja Woyke, Ying Zhang, Alexander J. Probst
Summary: CRISPR spacers in DPANN archaea can target chromosomal DNA of their episymbionts, and this phenomenon is widespread across different archaeal lineages. Using metagenomics, metatranscriptomics, and single-cell genomics, researchers found that CRISPR spacers in Candidatus Altiarchaeum crystalense and Ca. A. horonobense match putative essential genes in their episymbionts' genomes. Metabolic interaction modeling also indicates that episymbionts can be either parasitic or mutualistic depending on the host genotype. Moreover, CRISPR-Cas targeting of genomes associated with symbiotic archaea is independently evolved in various archaeal lineages, as suggested by an analysis of 7,012 archaeal genomes.
NATURE MICROBIOLOGY
(2023)
Review
Chemistry, Multidisciplinary
Jessica Taylor, Andrew Sharp, Steve P. Rannard, Sarah Arrowsmith, Tom O. McDonald
Summary: The WHO estimates that 15 million babies are born preterm each year, resulting in 1 million infant mortalities and long-term health issues. While progress has been made in understanding the causes of preterm birth and developing therapeutic options such as progesterone or uterine contraction suppressants, the number of preterm births continues to rise. This review highlights the urgent need for alternative and improved therapeutic systems for preterm birth, specifically focusing on the potential of nanomedicine to enhance the efficacy and address current drawbacks of existing therapeutics. Different nanomedicines, including liposomes, lipid-based carriers, polymers, and nanosuspensions, are discussed, along with their significance in improving existing therapeutic agents in obstetrics. The review also explores the potential repurposing of other pharmaceutical agents with tocolytic properties for preterm birth treatment.
NANOSCALE ADVANCES
(2023)