Medicinal Chemistry Philosophy & Approach
•Medchem is about multi-parameter optimization: focus on solving the relevant problems
•Identify rapidly potential bottlenecks, make designs towards addressing the most critical project issues
•Spend enough time on data analysis to understand how each parameter is modulated within a chemotype
•In structurally enabled projects, compchem and medchem need to work very closely
•Brainstorming sessions with experienced medicinal chemists for ideas, progress assessment, blindspots
•Monitoring chemistry outsourcing and synthesis
•Each new design should have a rationale to justify synthesis, balance between exploration and fine-tuning
•Close monitoring of performance and target prioritization increases bandwidth
•Synthesis of compound in library-mode can help rapidly explore chemical space
•Leverage multiple CROs for their strengths (throughput, libraries, synthesis, medchem)
•Managing expectations with stakeholders
•Transparent communication with management to convey progress against the goals, key challenges
•Achieving in vivo POC requires optimizing potency and ADME/PK in parallel
•Team should take appropriate risks to accelerate timelines as project evolves and resources are limited
Vast experience in drug discovery with fragments, covalent, molecular glues, bifunctional, inhibitors of kinases, PPI, peptides across oncology, rare diseases and virology
Key contributions to drug discovery across pharma and biotech
During the last 17 years working as a medicinal chemist in drug discovery, I learned that to impact a project you need to focus on addressing the often difficult key challenges. My experience spans from small molecule inhibitors (viral enzymes, kinases), ligands (fragments, RNA-targeted, PPI disruption), new modalities (molecular glues, splicing inhibitors) to beyond Ro5 molecules (bifunctional molecules, peptide conjugates). I learned to optimize efficiently potency (affinity, enzymatic, cellular) in parallel with ADME/PK properties to progress projects rapidly towards the next milestone. I have performed hit triaging, analog by catalog, fragment growing, modelling, virtual screens, multi-parameter optimization and built compound profiling workflows.
I was fortunate to work within strong multidisciplinary teams to contribute to building platforms and to the identification of several development candidates in multiple therapeutic areas (virology, oncology, rare genetic disease, CNS). I was directly involved with the discovery of development candidates for HCV protease, HCV NS5A, HCMV polymerase, next-generation platinum, SSTR2-targeting conjugate, MYB splicing modulator and HTT splicing modulator.
Contact me to see how I can impact your drug discovery project: benoit@mapleseedtx.com
Remix Therapeutics
Syros Pharmaceuticals
Tarveda Therapeutics
Boehringer Ingelheim
