# AR-NTD antagonist

> A small molecule that engages the intrinsically disordered N-terminal domain of the androgen receptor to shut down transcriptional signalling that current therapies leave intact.

[View this page on Peptone](https://peptone.io/pipeline/ar-ntd-antagonist/)

## Program facts

- Target: AR-NTD
- Modality: Small molecule
- Indication: Metastatic castration-resistant prostate cancer
- Stage: DC

## 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

Preclinical work 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. Mechanism-of-action studies are advanced with academic partners at IOR and The Royal Marsden.

## Development Plan

The program is at the development candidate stage, where candidate characterisation and development planning precede IND-enabling studies. Collaborations continue to deepen disease biology and MoA understanding.

Peptone's AR-NTD antagonist program is advanced with academic collaborations at
the Institute of Oncology Research (Andrea Alimonti) and The Royal Marsden /
ICR (Johann de Bono). See Partnering and Collaborations on the pipeline page
for detail.