OPN-6602 regulates gene transcription via chromatin remodeling

E1A binding protein p300 (EP300) and CREB-binding protein (CBP) are paralog histone acetyltransferases (HAT) bearing bromodomains that are involved in transcription and cell growth, survival, apoptosis and DNA repair. EP300/CBP are master regulators of oncogenic signaling and immune evasion.

Inhibition of EP300/CBP bromodomains blocks HAT activity, reducing gene expression and tumor growth, potentially delaying or preventing tumor growth and drug resistance.

OPN-6602 is a potent and selective EP300/CBP bromodomain inhibitor. OPN-6602 blocks signaling involved in cell growth and tumorigenesis by modulation of histone acetylation and the recruitment of EP300/CBP bromodomains.

OPN-6602 reduces androgen receptor (AR)-driven and MYC gene expression while acting through a distinct mechanism from BET bromodomain inhibitors. Inhibition of AR signaling with OPN-6602 has been shown to reduce tumor growth in metastatic castration resistant prostate cancer (mCRPC) xenograft and PDX models.

Interferon regulatory factor 4 (IRF4) is a highly expressed transcription factor responsible for regulating lymphocyte differentiation, and is overexpressed in multiple myelomas. OPN-6602 downregulates IRF4/MYC through EP300/CBP inhibition. OPN-6602 shows differentiated potency and efficacy in multiple myeloma xenograft models. As an epigenetic modulator, OPN-6602 has potential therapeutic benefit across numerous indications.