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.
IND Enabling
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.
- Target
- AR-NTD
- Modality
- Small molecule
- Indication
- Metastatic castration-resistant prostate cancer
- Stage
- IND Enabling
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 IND-enabling studies, with toxicology and formulation work preceding planned clinical entry. Collaborations deepen disease biology and MoA understanding ahead of first-in-human studies.
Collaborations
-
IOR
Bellinzona and Zurich, Switzerland
Prof. Andrea Alimonti
Director of IOR and professor at ETH Zurich
Deepening AR-NTD mechanism of action with prostate cancer resistance biology at IOR in Bellinzona.
View collaboration -
Royal Marsden
London, United Kingdom
Prof. Johann de Bono
Regius Professor of Cancer Research
Advancing AR-NTD disease biology with clinical prostate cancer leadership at The Royal Marsden and ICR.
View collaboration