Metarrestin

Metarrestin is a first-in-class pyrrole–pyrimidine-derived small molecule that selectively targets the perinucleolar compartment (PNC), a subnuclear structure predominantly found in solid tumor cells and associated with metastatic potential[1][8]. It acts as an orally available inhibitor of the PNC and has demonstrated potent antineoplastic activity by disrupting nucleolar structure and inhibiting RNA polymerase I transcription[1][6][8]. Metarrestin’s mechanism involves interaction with eukaryotic translation elongation factor 1 alpha 2 (eEF1A2), which plays a role in PNC assembly and metastasis progression; its disruption leads to collapse of the nucleolus and inhibition of ribosome biogenesis critical for metastatic cancer cell survival[8][6]. Preclinical studies show that metarrestin blocks invasion and metastasis across multiple cancer models—including pancreatic cancer—and prolongs survival without significant toxicity[5][8]. The drug was developed through collaboration involving researchers at Northwestern University Feinberg School of Medicine and the National Cancer Institute Center for Cancer Research[8][5].

Other names

trans-4-(7-benzyl-4-imino-5,6-diphenyl-4,7-dihydro-3H-pyrrolo(2,3-d)pyrimidin-3-yl) cyclohexanol(1r,4r)-4-{7-benzyl-4-imino-5,6-diphenyl-3H,4H,7H-pyrrolo[2,3-d]pyrimidin-3-yl}cyclohexan-1-olCyclohexanol 4-(4,7-dihydro-4-imino-5,6-diphenyl–7-(phenylmethyl)-3H-pyrrolo(2,3-d)pyrimidin–3–yl)-trans-trans–4-(4.7-Dihydro– ̶ ̶imino–5.6 diphenyI – 7 – (phenymethyl) – 3 H pyrrolo(2.3 d)pyrimidi n - 31 ) cyclohexanol)