Anna Vulpetti
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View article: Fragment-based discovery enables direct targeting of the melanoma oncogene MITF
Fragment-based discovery enables direct targeting of the melanoma oncogene MITF Open
Despite the improvement of therapeutic options, melanoma patients with advanced metastatic disease are still in high need of durable treatments. Analysis of clinical data from patients receiving targeted and/or immunotherapy, along with ge…
View article: Ligandability Assessment of IL-1β by Integrated Hit Identification Approaches
Ligandability Assessment of IL-1β by Integrated Hit Identification Approaches Open
Human interleukin-1β (IL-1β) is a pro-inflammatory cytokine that plays a critical role in the regulation of the immune response and the development of various inflammatory diseases. In this publication, we disclose our efforts toward the d…
View article: DCAF1-based PROTACs with activity against clinically validated targets overcoming intrinsic- and acquired-degrader resistance
DCAF1-based PROTACs with activity against clinically validated targets overcoming intrinsic- and acquired-degrader resistance Open
Targeted protein degradation (TPD) mediates protein level through small molecule induced redirection of E3 ligases to ubiquitinate neo-substrates and mark them for proteasomal degradation. TPD has recently emerged as a key modality in drug…
View article: Design, Synthesis, In Vitro and In Vivo Evaluation of Cereblon Binding Bruton’s Tyrosine Kinase (BTK) Degrader CD79b targeted Antibody Drug Conjugates
Design, Synthesis, In Vitro and In Vivo Evaluation of Cereblon Binding Bruton’s Tyrosine Kinase (BTK) Degrader CD79b targeted Antibody Drug Conjugates Open
Antibody-drug conjugates (ADCs) are an established modality which allows for targeted delivery of a potent molecule, or payload, to a desired site of action. ADCs, wherein the payload is a targeted protein degrader is an emerging area in t…
View article: Discovery of Ligands for TRIM58, a Novel Tissue-Selective E3 Ligase
Discovery of Ligands for TRIM58, a Novel Tissue-Selective E3 Ligase Open
Redirecting E3 ligases to neo-substrates, leading to their proteasomal disassembly, known as targeted protein degradation (TPD), has emerged as a promising alternative to traditional, occupancy-driven pharmacology. Although the field has e…
View article: QM Assisted ML for 19F NMR Chemical Shift Prediction
QM Assisted ML for 19F NMR Chemical Shift Prediction Open
Ligand-observed 19F NMR detection is an efficient method for screening libraries of fluorinated molecules in fragment-based drug design campaigns. Screening fluorinated molecules in large mixtures makes 19F NMR a high-throughput method. Ty…
View article: Discovery of a selective and biologically active low-molecular weight antagonist of human interleukin-1β
Discovery of a selective and biologically active low-molecular weight antagonist of human interleukin-1β Open
Human interleukin-1β (hIL-1β) is a pro-inflammatory cytokine involved in many diseases. While hIL-1β directed antibodies have shown clinical benefit, an orally available low-molecular weight antagonist is still elusive, limiting the applic…
View article: QM Assisted ML for 19F NMR Chemical Shift Prediction
QM Assisted ML for 19F NMR Chemical Shift Prediction Open
Ligand-observed 19F NMR detection is an efficient method for screening libraries of fluorinated molecules in fragment-based drug design campaigns. Screening fluorinated molecules in large mixtures makes 19F NMR a high-throughput method. Ty…
View article: Discovery of New Binders for DCAF1, an Emerging Ligase Target in the Targeted Protein Degradation Field
Discovery of New Binders for DCAF1, an Emerging Ligase Target in the Targeted Protein Degradation Field Open
In this study, we describe the rapid identification of potent binders for the WD40 repeat domain (WDR) of DCAF1. This was achieved by two rounds of iterative focused screening of a small set of compounds selected on the basis of internal W…
View article: Reinstating targeted protein degradation with DCAF1 PROTACs in CRBN PROTAC resistant settings
Reinstating targeted protein degradation with DCAF1 PROTACs in CRBN PROTAC resistant settings Open
Targeted protein degradation (TPD) of neo-substrates with proteolysis targeting chimeras (PROTACs) or molecular glues has emerged as a key modality in exploring new biology as well as designing new drug candidates where catalytic inhibitio…
View article: Inside Cover: Comprehensive and High‐Throughput Exploration of Chemical Space Using Broadband <sup>19</sup>F NMR‐Based Screening (Angew. Chem. Int. Ed. 35/2020)
Inside Cover: Comprehensive and High‐Throughput Exploration of Chemical Space Using Broadband <sup>19</sup>F NMR‐Based Screening (Angew. Chem. Int. Ed. 35/2020) Open
19F NMR-based fragment screening is an effective approach in pharmaceutical research to explore the chemical space for specific target–ligand interactions. In their Research Article on page 14809, A. Lingel, A. O. Frank, and co-workers rep…
View article: Innentitelbild: Comprehensive and High‐Throughput Exploration of Chemical Space Using Broadband <sup>19</sup>F NMR‐Based Screening (Angew. Chem. 35/2020)
Innentitelbild: Comprehensive and High‐Throughput Exploration of Chemical Space Using Broadband <sup>19</sup>F NMR‐Based Screening (Angew. Chem. 35/2020) Open
19F-NMR-basiertes Fragmentscreening ist ein effektiver Ansatz in der pharmazeutischen Forschung zur Untersuchung des chemischen Substanzraums für spezifische Target-Ligand-Wechselwirkungen. In ihrem Forschungsartikel auf S. 14919 berichten…
View article: Discovery of LOU064 (Remibrutinib), a Potent and Highly Selective Covalent Inhibitor of Bruton’s Tyrosine Kinase
Discovery of LOU064 (Remibrutinib), a Potent and Highly Selective Covalent Inhibitor of Bruton’s Tyrosine Kinase Open
Bruton's tyrosine kinase (BTK), a cytoplasmic tyrosine kinase, plays a central role in immunity and is considered an attractive target for treating autoimmune diseases. The use of currently marketed covalent BTK inhibitors is limited to on…
View article: Design of Potent and Selective Covalent Inhibitors of Bruton’s Tyrosine Kinase Targeting an Inactive Conformation
Design of Potent and Selective Covalent Inhibitors of Bruton’s Tyrosine Kinase Targeting an Inactive Conformation Open
Bruton's tyrosine kinase (BTK) is a member of the TEC kinase family and is selectively expressed in a subset of immune cells. It is a key regulator of antigen receptor signaling in B cells and of Fc receptor signaling in mast cells and mac…
View article: Design, Synthesis, and Preclinical Characterization of Selective Factor D Inhibitors Targeting the Alternative Complement Pathway
Design, Synthesis, and Preclinical Characterization of Selective Factor D Inhibitors Targeting the Alternative Complement Pathway Open
Complement factor D (FD), a highly specific S1 serine protease, plays a central role in the amplification of the alternative complement pathway (AP) of the innate immune system. Dysregulation of AP activity predisposes individuals to diver…
View article: Ligand-Based Fluorine NMR Screening: Principles and Applications in Drug Discovery Projects
Ligand-Based Fluorine NMR Screening: Principles and Applications in Drug Discovery Projects Open
Ligand-based fluorine NMR screening has gained popularity in drug discovery projects during the past decade and has become a powerful methodology to produce high quality hits. Its high sensitivity to protein binding makes it particularly s…
View article: Optimizing a Weakly Binding Fragment into a Potent RORγt Inverse Agonist with Efficacy in an in Vivo Inflammation Model
Optimizing a Weakly Binding Fragment into a Potent RORγt Inverse Agonist with Efficacy in an in Vivo Inflammation Model Open
The transcription factor RORγt is an attractive drug-target due to its role in the differentiation of IL-17 producing Th17 cells that play a critical role in the etiopathology of several autoimmune diseases. Identification of starting poin…
View article: Discovery and Design of First Benzylamine-Based Ligands Binding to an Unlocked Conformation of the Complement Factor D
Discovery and Design of First Benzylamine-Based Ligands Binding to an Unlocked Conformation of the Complement Factor D Open
Complement Factor D, a serine protease of the S1 family and key component of the alternative pathway amplification loop, represents a promising target for the treatment of several prevalent and rare diseases linked to the innate immune sys…
View article: Discovery of Highly Potent and Selective Small-Molecule Reversible Factor D Inhibitors Demonstrating Alternative Complement Pathway Inhibition <i>in Vivo</i>
Discovery of Highly Potent and Selective Small-Molecule Reversible Factor D Inhibitors Demonstrating Alternative Complement Pathway Inhibition <i>in Vivo</i> Open
The highly specific S1 serine protease factor D (FD) plays a central role in the amplification of the complement alternative pathway (AP) of the innate immune system. Genetic associations in humans have implicated AP activation in age-rela…
View article: Structure-Based Library Design and Fragment Screening for the Identification of Reversible Complement Factor D Protease Inhibitors
Structure-Based Library Design and Fragment Screening for the Identification of Reversible Complement Factor D Protease Inhibitors Open
Chronic dysregulation of alternative complement pathway activation has been associated with diverse clinical disorders including age-related macular degeneration and paroxysmal nocturnal hemoglobinurea. Factor D is a trypsin-like serine pr…