Small molecules against intrinsically disordered proteins, advancing from discovery toward the clinic.
Peptone designs fully synthetic small molecules against intrinsically disordered proteins. We measure the transient pockets across a target's conformational ensemble, then design binders that hold it in a state that cannot drive disease. The same platform advances programs across oncology, immunology and inflammation, and CNS.
Each program advances across six development stages, from discovery to the clinic. Select a program to expand its target, approach, and development detail.
Target
The androgen receptor N-terminal domain (AR-NTD) carries the receptor's main transcriptional activation function and stays intrinsically disordered in isolation. Because approved antiandrogens bind the ligand-binding domain, splice variants and ligand-independent signalling through the NTD remain a driver of resistance in castration-resistant disease.
Approach
Peptone maps the transient pockets that appear across the AR-NTD ensemble using HDX-MS and GPU-accelerated modelling, then designs binders that stabilise a conformation which cannot recruit the transcriptional machinery. The result is a fully synthetic small molecule rather than a biologic.
Preclinical
In illustrative preclinical models the program shows target-dependent suppression of AR-driven transcription in cell lines that no longer respond to ligand-binding-domain inhibitors, with activity retained against common AR splice variants.
Development Plan
This example program is positioned at IND-enabling studies, with toxicology and formulation work preceding a first planned clinical entry.
Target
Alpha-synuclein is a small intrinsically disordered protein whose misfolding and aggregation into oligomers and fibrils is a hallmark of Parkinson's disease and other synucleinopathies. Its lack of a stable fold has made it a classic undruggable target for conventional structure-based design.
Approach
Rather than chasing a fixed pocket, Peptone measures the transient contacts that precede aggregation and designs binders that stabilise non-amyloidogenic states of the monomer, lowering the population of aggregation-prone conformers.
Preclinical
Illustrative biophysical and cellular assays show reduced aggregation and preserved physiological behaviour of the target, supporting progression of the chemical series.
Development Plan
This example program sits in lead optimization, where potency, selectivity, and central nervous system exposure are being refined ahead of candidate selection.
Target
Tau is a microtubule-associated protein with long intrinsically disordered regions. In tauopathies it detaches, becomes hyperphosphorylated, and assembles into filaments, making the disordered form itself the object of interest for therapeutic design.
Approach
Peptone profiles the aggregation-nucleating segments of tau and screens for binders that engage these transient motifs, aiming to keep tau in soluble, assembly-incompetent states.
Preclinical
Illustrative screening has produced confirmed hits with target engagement in biophysical assays; the series is being characterised for selectivity and cellular activity.
Development Plan
This example program is at the hit-to-lead stage, where early chemical matter is being triaged into a lead series.
Target
c-Myc is a transcription factor that is disordered outside of its complex with MAX and is deregulated across a broad range of cancers. Direct pharmacological control of c-Myc has been considered undruggable because it presents no classical binding pocket.
Approach
Peptone applies its disorder-first platform to characterise the conformational ensemble of c-Myc and to search for binders that disrupt its productive interactions, extending the platform beyond aggregation targets into transcriptional biology.
Preclinical
As a discovery-stage example, work is focused on target validation and early hit finding against defined disordered regions.
Development Plan
This example program is run as a strategic collaboration, with the partner responsible for later preclinical and clinical development.
The programs shown here are illustrative examples used to present pipeline structure and staging. They are not approved or actual Peptone programs. Confirmed programs, targets, and stages will be published once approved.