TP53 Y163C discovery programme
One cancer mutation.
One pocket it created.
Oncivra turns the TP53 Y163C mutant structure, its surface lesion and internal scoring models into a diverse shortlist of testable molecules — designed to hold the mutant protein in its working shape, and to leave the normal protein alone.
1.65 Å
Mutant crystal structure, PDB 8QWL
0.68
PockDrug score of the lesion
0
Clinical programmes on this mutation
Pipeline
From one target to a small set of testable molecules.
Target gate
Score candidate mutations before spending a campaign.
Dossier
Assemble the biology, competition and unmet need.
Structure
Start from the deposited mutant coordinates, not a model.
Pockets
Carry every pocket state, and say which one is observed.
Design
Independent generative campaigns for chemical breadth.
Filter
Remove what nobody could make or develop.
Dock
Keep multiple plausible poses per molecule.
Verify
Re-test survivors with a second, independent model.
Selectivity
Compare the mutant against wild type and other mutants.
Diversity
Cluster, then pick one representative per series.
Shortlist
A diverse candidate set with full computational provenance.
Lab
Experimental testing, then recalibrate on what comes back.
The target
Why this mutation.
The platform scores the target from the evidence it actually holds — structures, pocket residues, pocket druggability, citations and known chemical matter — and reports the terms that score badly alongside the ones that score well.
The score is computed live from the evidence records, not fixed here. Full scorecard inside the platform.
A pocket the mutation made
Replacing Tyr163 with cysteine leaves a cavity on the surface of the p53 DNA-binding domain that healthy protein does not have. That difference is the whole basis for selectivity.
A real structure, not a model
PDB 8QWL is a 1.65 Å crystal structure of this exact mutant. The pocket residues used here are computed from those deposited coordinates.
A handle for chemistry
The introduced cysteine is a covalent attachment point, and simulation work reports the cavity enlarges once a nearby salt bridge opens. Both are carried as hypotheses, labelled as such.
An open field
The neighbouring Y220C mutation already has a clinical-stage stabiliser, which proves this class of pocket is druggable. Nothing is in the clinic for Y163C.
Platform
Four engines, running together.
Find
Which target deserves the campaign. Genomic and variant reasoning, human evidence, druggability, competition.
Design
What could attack it. Parallel generative campaigns around the chosen pocket, filtered for real chemistry.
Verify
Which molecules our internal scoring models agree on. Pose generation, affinity prediction, selectivity, developability.
Learn
What the bench taught us. Measured results recalibrate the models and steer the next generation.
Evidence
Everything traces back to a source.
Structures, assays, compounds and clinical programmes are drawn from public scientific records, and every candidate carries the models that supported it.
- Mutant structure
PDB 8QWL — p53 Y163C, 1.65 Å
- Selectivity
PDB 2J1X, 2VUK — Y220C counter-target
- Structure
PDB 2OCJ, 1TSR — wild-type reference
- Sequence
UniProt P04637
- Mutation frequency
cBioPortal, GDC, OncoKB
- Target and chemistry
Open Targets, ChEMBL, PubChem
About
A discovery engine, honestly described.
Oncivra uses generative and structural models to design and prioritise novel small molecules against a pocket created by a recurrent cancer mutation, for experimental testing.
It does not claim a finished medicine. The campaign ends with a small, diverse set of candidates and the package a laboratory needs to test them.
Open the platform