Helicon Allosteric ARON degrader

Helicon Allosteric ARON degrader is a first-in-class bifunctional helically-constrained (Helicon) peptide designed to selectively target and degrade the transcriptionally active, agonist-bound conformation of the androgen receptor (ARON). Developed by Parabilis Medicines, these degraders utilize a novel mechanism of action by binding to the AF2 coactivator site, an allosteric site distinct from the traditional androgen binding pocket targeted by current standard-of-care AR inhibitors and other degraders in development. By specifically targeting the active state of the receptor, this therapeutic approach aims to overcome resistance mechanisms such as AR mutations and gene amplifications that drive disease progression in castration-resistant prostate cancer (CRPC). Preclinical data demonstrate that these Helicon degraders achieve potent AR protein reduction, suppress transcriptional targets like PSA (KLK3) and TMPRSS2, and exhibit significant tumor growth inhibition in AR-amplified xenograft models.

Other names

Helicon Allosteric ARON binders