Join Novalix at Discovery on Target 2024 in Boston, MA, from October 1st to 3rd!
Our experts will be present at this leading event on novel drug targets and technologies. The symposium will spotlight advancements in both current and emerging fields, with a focus on target validation strategies for the discovery and development of innovative therapeutic agents from biologics to small molecules.
Organized by CHI, Discovery on Target 2024 will cover popular topics like kinases, immunomodulation, and degraders, while also introducing new areas such as covalent chemistries, synthetic biology, cancer antibodies, generative AI, and translational models.
NovAliX will present three cutting-edge scientific posters.
Identification and characterization of small molecules inhibiting RNA targets: miRNA
This poster #A39 will be presented by Paola Ciapetti, PhD, Director Alliance Management, in Session A from October 1st to 2nd a.m.
Abstract: RNA plays a key role in transcription and translation: gene regulation, proliferation, apoptosis, and development. The biological function is linked to the unique secondary and tertiary structures. Many diseases are associated with dysregulation of RNA functions, so there is a growing interest in RNAs as drug targets for novel therapies or targeting undruggable proteins. The most used modalities are antisense oligonucleotides (ASOs), CRISPR gene editing, and more recently small molecules.
Although ASOs and CRISPR are highly specific, they bring some significant challenges such as delivery and adverse reactions. Small molecules are attractive because drug-like properties can be optimized by classical medicinal chemistry.
Targeting RNAs with small molecules is a promising modality for oncology, cardiovascular diseases and CNS disorders. In particular, dys-regulation of microRNAs play key roles in the genesis of the different diseases and thus have been targeted by small molecule inhibitors recently. Here, we describe the setup of a flowchart to identify and optimize new efficient inhibitors of microRNA. Starting with SPR to select and characterize a group of small molecules that bind specifically to pre-miR with high affinities, we validated their inhibitory activity on miR maturation and function with biochemical and cellular assays. The approach demonstrates a miRNA targeting platform that could be applied to other oncogenic miRNA targets.
PCKD, the Most Relevant Model for ADPKD
This poster #A40 will be presented by Laurent Saniere, PhD, Senior Vice-President Pharmacology & DMPK, in Session A from October 1st to 2nd a.m.
Abstract: Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder, affecting 12 million people globally. It is characterized by the development of fluid-filled kidney cysts, which often leads to kidney failure. The vasopressin receptor 2 antagonist, Tolvaptan, is the only approved treatment that slows the progression of ADPKD. Nevertheless, there is still a high unmet need for treatment options for patients with ADPKD because Tolvaptan has limited efficacy and non-negligible side effects.
Integrating Single-Particle Cryo-Electron Microscopy and Hydrogen/ Deuterium Exchange Mass Spectrometry to Elucidate the Structure and Dynamics of G-Protein Coupled Receptors
This poster #B39 will be presented by Paola Ciapetti, PhD, Director Alliance Management, in Session B from October 2nd p.m. to 3rd.
Abstract: Single-Particle Cryo-Electron Microscopy (cryo-EM) has revolutionized the structural biology field by allowing high-resolution imaging of challenging macromolecules, such as membrane proteins, in their native lipid environment.
Among these membrane proteins, G protein-coupled receptors (GPCRs) play a key role in cell signaling pathways and thus represent a target for developing new drugs. TGR5, a member of the GPCR family, plays a pivotal role in bile acid signaling and has emerged as a promising therapeutic target for various metabolic and inflammatory diseases. We showcase how cryo-EM has enabled us to obtain atomic-level insights into the architecture of TGR5, shedding light on its ligand binding sites, conformational changes, and membrane interactions. Complementing cryo-EM, HDX-MS offers a unique perspective on protein dynamics by measuring the exchange rates of hydrogen and deuterium atoms in proteins.
We present our findings on applying HDX-MS to probe the flexibility and conformational dynamics of TGR5. By mapping regions of TGR5 susceptible to deuterium exchange, we gain insights into the conformational changes associated with ligand binding, activation, and signal transduction. The integration of cryo-EM and HDX-MS represents a powerful approach to comprehensively characterize the structure-function relationship of TGR5 and membrane proteins in the broadest sense. We highlight the significance of combining cutting-edge structural and dynamic techniques in unraveling the mysteries of membrane proteins, with implications for drug discovery and precision medicine.
Join us on our booth number 508
If you are attending, do not miss the poster sessions! Contact our team to set up a meeting on our booth number 508:
Frank Moffatt, PhD, Senior Director of Business Development
Paola Ciapetti, PhD, Director Alliance Management
Sabine Gratzer, PhD, Drug Discovery, Distinguished Research Fellow
Laurent Saniere, PhD, Senior Vice-President Pharmacology & DMPK
