CSRM617 is an ONECUT2 (OC2) inhibitor that directly targets OC2 HOX domain (KD = 7.43 μM) and disrupts OC2 target genes promoter binding. CSRM617 blocks OC2-dependent prostate cancer growth in cultures (IC50 = 4-50 μM; 48 h) via apoptosis induction (fold of untreated annexin V population = 2.3/10 μM, 3.5/20 μM; 22Rv1) and exhibits in vivo efficacy against metastases as well as the growth of established 22Rv1 tumor in mice in vivo (50 mg/kg/day ip.).
HOX domain-targeting ONECUT2 (OC2) inhibitor against OC2-dependent prostate cancer growth in vitro and in vivo.
Tumor heterogeneity complicates patient treatment and can be due to transitioning of cancer cells across phenotypic cell states. This process is associated with the acquisition of independence from an oncogenic driver, such as the estrogen receptor (ER) in breast cancer
Treatment of prostate cancer (PC) by androgen suppression promotes the emergence of aggressive variants that are androgen receptor (AR) independent. Here we identify the transcription factor ONECUT2 (OC2) as a master regulator of AR networks in metastatic castration-resistant prostate cancer
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