CTS2190 is an orally available small molecule that specifically inhibits PRMT1, an enzyme heavily overexpressed in advanced metastatic prostate cancer and linked to poor prognosis in metastatic castrate-resistant prostate cancer (mCRPC).

PRMT1 plays a critical role in epigenetic regulation by asymmetrically dimethylating arginine residues on histones and other proteins. Inhibiting PRMT1 with CTS2190 disrupts cancer-driving processes through dual mechanisms: altering gene expression and inducing DNA damage repair deficiencies and cell cycle arrest.

Preclinical studies show that CTS2190 leads to significant degradation of the androgen receptor (AR), including therapy-resistant AR-V7 variants, and suppression of key cancer genes like PSA and MYC. In models like 22RV1, CTS2190 outperformed standard treatments such as docetaxel, enzalutamide, and even advanced AR-targeting PROTACs.

Researchers propose that CTS2190 could be effective as a standalone therapy or combined with existing treatments, enhancing outcomes especially for patients resistant to AR pathway inhibitors. CTS2190 is now advancing through a Phase I/II clinical trial, with a special focus on patients with ARPI-resistant mCRPC.

Source.

Clinical trial.