A computational pipeline that takes a drug payload and a biomolecular target, scores conjugation sites on the protein surface, and executes the conjugation chemistry between them. Successfully replicated the chemistry of 10 FDA-approved Antibody-Drug Conjugates.
Antibody-Drug Conjugates are among the most promising classes of precision oncology therapeutics. They combine the specificity of monoclonal antibodies with the cytotoxic potency of small-molecule drugs. But the chemistry that links them — the conjugation — is where most design failures occur.
Choosing the right linker, the right reactive handles, the right conjugation site on the antibody — these decisions are typically made through expensive, iterative trial-and-error in the wet lab. ClickChem replaces that with computation.
ClickChem is a fully automated computational pipeline that analyses the molecular structure of any drug payload, identifies its reactive functional groups, selects the optimal conjugation chemistry, and generates the complete payload-linker-antibody conjugate — including 3D conformers — in seconds.
It doesn't just suggest — it executes. The pipeline runs real reaction templates (SMARTS-based), validates products with cheminformatics, and exports production-ready molecular files (SMILES, SDF, PDB).
Seven reaction families supported: SPAAC, IEDDA, CuAAC, Thiol-Maleimide, NHS-ester Amidation, Oxime Ligation, and Hydrazone Formation — covering bioorthogonal click chemistry, classical ADC conjugation, and carbonyl-based ligation strategies.
ClickChem processes each conjugation through a deterministic pipeline with built-in validation at every step.
Analyses the payload molecule to identify all reactive functional groups: thiols, primary amines, azides, alkynes, tetrazines, strained alkenes, carboxylic acids, NHS esters, and more.
SMARTS Pattern MatchingAnalyses the 3D structure of the target protein to identify the most accessible residues for conjugation. Generates multiple conformations of the antibody and measures solvent exposure across all of them, so the ranking reflects how accessible each site really is — not just one static snapshot.
Multi-Conformer Surface AnalysisSelects the optimal conjugation chemistry based on detected handles, scored sites, target type, and preset mode. Ranks candidate reactions by selectivity and clinical precedent across all seven supported families.
Biomolecule-Aware PlannerSelects and attaches the appropriate bifunctional linker from a curated library of ADC-grade linkers — including mc-VC-PABC, SMCC, PEG-azides, and DBCO-based crosslinkers.
Linker CatalogRuns the selected conjugation reaction using validated SMARTS templates. Generates the covalent bond between payload-linker and the biomolecular target. Full atom-mapping and stereochemistry preservation.
RDKit EngineConfirms the conjugate is chemically valid — correct molecular weight, expected bond formation, sanitisation checks. Then generates 3D conformers (ETKDG) and exports SMILES, SDF, and PDB files ready for downstream docking, MD simulation, or interactive visualisation in the browser.
Cheminformatics QC · Production-Ready FilesClickChem supports dual operation modes to cover both established clinical practice and cutting-edge bioorthogonal chemistry. The pipeline selects the appropriate mode based on the conjugation site and target type.
Native mode replicates the exact conjugation strategies used in FDA-approved ADCs — Thiol-Maleimide for cysteine-conjugated drugs, NHS-ester Amidation for lysine sites. Engineered mode opens the door to modern bioorthogonal reactions that require no natural amino acid handles.
Uses Thiol-Maleimide and NHS-ester Amidation — the conjugation chemistry behind Adcetris, Kadcyla, Enhertu, and every other approved ADC. Proven clinical pathways, reproduced computationally.
Applies SPAAC (azide-DBCO), IEDDA (tetrazine-TCO), CuAAC (azide-alkyne), Oxime Ligation (aminooxy-aldehyde), and Hydrazone Formation (hydrazine-aldehyde). Designed for engineered antibodies and carbonyl-bearing targets.
Conjugates two different drug payloads onto the same antibody using orthogonal chemistries. Enables dual-payload ADC design — a frontier in combination therapy.
ClickChem has successfully replicated the conjugation chemistry of 10 FDA-approved Antibody-Drug Conjugates spanning 2000–2021. Each case produces a complete, valid conjugate using the same reaction family as the real drug.
What takes weeks of empirical screening in a medicinal chemistry lab, ClickChem resolves in seconds. Researchers can explore dozens of conjugation strategies computationally before committing to synthesis.
The pipeline checks every product against cheminformatics rules. Failed reactions are caught in silico — not after expensive wet-lab experiments.
With dual-click and engineered bioorthogonal modes, ClickChem supports ADC architectures that don't yet exist in the clinic — opening new design space for pharmaceutical R&D.
The ClickChem Conjugation Designer is a live, interactive demo. Input any payload SMILES, select a target, and watch the full pipeline execute in real time.