Posters

Coronaviruses replicate their large RNA genomes through a conserved discontinuous transcription mechanism that generates the subgenomic RNAs required for viral assembly, making the process an attractive target for broad-spectrum antivirals. This poster presents IRBM's integrated screening platform, which pairs a phenotypic campaign on a stable SARS-CoV replicon cell line with an RNA-targeted approach directed at conserved stem-loop elements in the SARS-CoV-2 5'UTR. Mechanistic follow-up, surface plasmon resonance and NMR studies converge on chemically unrelated small molecules that preferentially interfere with subgenomic RNA synthesis and on validated RNA binders refined by structure-guided optimization. Download the poster to explore the screening cascade, mechanistic data and binding studies in detail.

Peptides offer clear advantages as a therapeutic modality, but drug-like properties often require non-natural amino acids, whose computational handling remains a major challenge. This poster presents iPeptides, IRBM's in-house Python toolkit that operates directly on the molecular chemical graph, treating natural and non-natural residues with the same rigor. Its extensible design connects HELM sequence notation to atomistic 3D models and integrates combinatorial enumeration of imported monomer libraries, machine-learning-based prioritization, and downstream modeling, including cross-link and cycle-size optimization. The result is a unified framework for systematically exploring peptide chemical space across diverse design challenges. Download the poster to explore the workflow in detail.

Achieving sufficient unbound brain exposure while maintaining potent target inhibition is a major challenge in small-molecule drug discovery. This poster presents IRBM's integrated medicinal chemistry, pharmacology, and drug metabolism and pharmacokinetics strategy for an SHP2 inhibitor program. Compounds progress through a cascade that links CNS-relevant physicochemical design, complementary in vitro blood-brain barrier models, and in vivo rodent pharmacokinetics, using unbound brain exposure rather than potency alone to guide prioritization. This resource-efficient approach supported the selection of I-1000233, a brain-penetrant allosteric SHP2 inhibitor that achieves CNS exposure and efficacy in an orthotopic glioblastoma model. Download the poster to explore the optimization cascade, exposure data, and in vivo results in detail.

De-risking CNS drug discovery depends on translational models that can reliably predict whether a compound will cross the blood-brain barrier (BBB), a structure that both protects the brain and blocks most therapeutics from reaching it. This poster describes IRBM's validated human BBB model, generated from iPSC-derived brain-like microvascular endothelial cells in a 2.5-dimensional, non-contact culture and benchmarked against key features of the in vivo barrier. It outlines how the system characterizes barrier integrity, polarized transporter activity, and receptor-mediated transcytosis, then links in vitro permeability readouts to unbound drug exposure measured in rodent brain and cerebrospinal fluid. The approach improves selection of CNS-penetrant candidates and strengthens translational relevance beyond animal models. Download the poster to explore the model characterization, functional assays, and in vitro/in vivo correlation data in detail.

Reliable preclinical models represent one of the biggest limits in brain tumor drug discovery: classical 2D cell cultures rarely reproduce the cellular architecture and spatial organization of glioblastoma, so encouraging readouts often fail to translate. This poster outlines Complex 3D Patient Organoids (C3POs), engineered ex vivo spheroids that assemble patient-derived glioma stem-like cells with astrocytes and microglia in defined proportions, each population followed by fluorescent labeling and high-content imaging across a panel of molecular subtypes. Rebuilding this cellular context reshapes measured drug sensitivity and brings potency closer to tumor in vivo behavior, strengthening lead optimization, combination work, and subtype-specific testing. Download the poster to explore the model design and comparative drug-response data. A variant of this poster was presented at AACR 2026 and can be found further down this page.

SHP2 is a validated regulator of the RAS-MAPK pathway in oncology, yet no SHP2 inhibitor is approved and no active clinical trial currently addresses brain cancers, where poor CNS exposure continues to constrain therapeutic outcomes. This poster presents IRBM's focused multiparameter optimization (MPO) strategy, integrating structure-based design, in silico property prediction, and iterative in vitro/in vivo ADME profiling, which converted potent, peripherally restricted inhibitors into the brain-penetrant candidate I-1000233 while preserving cellular activity. The work provides a practical framework for enabling CNS exposure in small molecules, with relevance for primary brain tumors and metastatic disease. Download the poster to explore the SAR, design strategy, and full in vivo characterization in detail.

Pyroglutamate (Pgl) formation is a temperature-driven side reaction that compromises the efficiency of lactam-bridged peptide synthesis under MW-assisted SPPS. Here, IRBM systematically evaluates both process parameters and sequence determinants governing intramolecular Pgl formation. Integration of protocol optimization with CD spectroscopy and residue-scanning identifies the key conformational states enabling N-terminal cyclization. These findings establish a defined structure–reactivity framework and deliver a validated synthetic protocol for constrained peptides and macrocyclic therapeutics.

Drug metabolism and pharmacokinetics (DMPK) often enter drug discovery too late, allowing potent compounds with poor exposure to advance and fail in later stages. This poster presents IRBM's exposure-driven DMPK framework, which integrates early in vitro profiling and in vivo pharmacokinetics into a structured, multiparametric decision process that weighs unbound exposure and developability criteria alongside potency. Applied to a small-molecule SHP2 inhibitor program, the approach supported the assessment of CNS potential and guided optimization toward a CNS-active candidate with efficacy in an orthotopic glioblastoma model. Download the poster to explore the decision framework and in vivo characterization in detail.

Helicases are essential enzymes in coronavirus replication but have historically proven difficult to drug. The SARS-CoV-2 NSP13 helicase, conserved across coronaviruses and central to viral RNA synthesis, represents a compelling antiviral target that remains largely unexploited. This poster describes a multi-assay screening campaign conducted by IRBM, combining ATPase and unwinding assays to screen the IRBM small molecule library, followed by dose-response profiling and counter-screens to triage hits. Confirmed inhibitors display a time-dependent, irreversible inhibition profile, supported by jump dilution experiments and HRMS intact mass analysis, with selectivity over human helicases and key SARS-CoV-2 enzymes. Download the poster to explore the screening funnel, mechanistic characterization data, and structure-activity findings in detail.

Bicyclic peptides enhance receptor binding and proteolytic stability through conformational constraint, but their synthesis typically requires multistep assembly, orthogonal protection strategies, and repeated purification. This poster presents IRBM's one-pot solution-phase route via bis-lactam cyclization, pairing head-to-tail macrolactamization with in situ Allyl/Alloc deprotection and spontaneous cross-link formation in a single vessel. A screen of coupling reagents and solvents reduces resin handling, reaction time, and solvent use while supporting reproducible scale-up. Download the poster to explore the reagent-solvent screen and cyclization workflow in detail.