Computational Drug Discovery Consulting
Turn Unexplained Small-Molecule Behavior into Structure-Driven Design Decisions
No viable hits? Stalled SAR? Potency–ADME tradeoffs? No clear path forward?
When hits are missing or SAR is stalled, I decode the structural and biological signals to prioritize the next compounds worth making.
20+ Years | Scripps · Celgene · Incyte · Startups | Trusted by Dozens of Drug Discovery Teams
Small-Molecule Discovery Bottlenecks I Help Resolve
Failed Screen / No Hits
Tractable Hits
Find Tractable Hits Even When Screening Fails
Uncover druggable and allosteric opportunities when standard screens fail to yield viable starting points.
- Identify druggable and allosteric sites from sequence, structure, and dynamics
- Mine validated chemotypes across mechanistically related targets
False SAR / No Progress
New Lead Direction
Rescue Lead Series Misled by Non-Specific SAR
Expose misleading SAR and promiscuous chemotypes before they consume additional optimization cycles.
- Reset program direction with binding-mode and cheminformatic analyses
- Redirect screening and design towards tractable lead series
Stalled SAR
Productive Vectors
Clarify Stalled SAR via Function-Weighted Residue Analysis
Decode inconsistent SAR by weighting interactions according to biological and mechanistic relevance.
- Map conserved, catalytic, and gating residues to guide docking and SAR interpretation
- Separate critical from incidental interactions to define productive design vectors
Potency-ADME Conflict
Developable Leads
Untangle Potency–ADME Tradeoffs With Molecular Insight
Direct early leads to chemical space where potency and ADME coexist.
- Avoid the corner trap where potency gains close off viable ADME space
- Provide structural rationale to balance potency and ADME before committing to costly synthesis routes
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Stalled SAR or unclear next compounds?
Share your SAR question or compound series and get a practical next-design recommendation.
✓ fully confidential and fast NDA turn aroud
James Zapf, Ph.D.
Founder and Principal Scientist
Z Molecular Insights
Scientific judgment for small-molecule discovery decisions
James Zapf, Ph.D. brings 20+ years of small-molecule drug discovery experience across Scripps Research, Celgene, Incyte, Mitsubishi Tanabe, and startup programs.
He helps pharma and biotech teams identify tractable hits, resolve stalled SAR, and define compound design strategies grounded in structure, ligand behavior, and biological function.
The focus is practical: reduce uncertainty, prioritize the next compounds to make, and avoid costly cycles around non-productive design ideas
Ready for a Fresh Read on Your Program?
Need tractable hits, a way through stalled SAR, or a clearer structural rationale?
I help define the next compounds worth making by connecting structural, ligand, and biological evidence to practical design decisions.
✓ 12+ Client Programs
✓ CDA in 24 hrs