metarrestin (ML-246) / National Cancer Institute - Bethesda - LARVOL DELTA

Metarrestin (ML-246) in Subjects With Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=116 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2027 ➔ Dec 2028 | Trial primary completion date: Dec 2026 ➔ Dec 2027

Trial completion date • Trial primary completion date • Brain Cancer • Breast Cancer • Colorectal Cancer • Hormone Receptor Positive Breast Cancer • Neurofibrosarcoma • Oncology • Pancreatic Cancer • Pediatrics • Solid Tumor

Development and characterization of endolysosomal trafficking targeting chimera degraders of α1A-adrenergic receptor. (PubMed, J Adv Res) - "Proof-of-concept studies of the ETTAC degraders for GPCR successfully elucidate the roles of post-endocytic sorting proteins and applied to directing the lysosomal degradation of α1A-ARs. Consequently, the ETTAC strategy represents a promising approach for the selective degradation of GPCRs and paves the way for future drug development."

Journal • Benign Prostatic Hyperplasia • Oncology • Prostate Cancer • Targeted Protein Degradation

Optimizing and integrating high-throughput cell-based assays to enable SAR studies of metarrestin to target cancer metastasis (AACR 2025) - "For detection of rRNA inhibition and PNC disassembly in cells, we utilized a rRNA selective fluorescent probe (Probe 1) and a GFP-based reporter of the PNC, respectively, followed by confocal microscopy using an Opera Phenix. Using this suite of cell-based assays, we evaluated the compound of ~160 metarrestin derivatives and performed comparative analyses of compound activities in measurements of PNC disassembly, rRNA synthesis inhibition, and cytostatic growth effect in PANC1 and PC3M cells."

Genito-urinary Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor

Metarrestin, a Perinucleolar Compartment Inhibitor, Effectively Suppresses Metastasis (CRD 2024) - No abstract available

Oncology

Dynamic chromosome association with nuclear organelles in living cells. (PubMed, Histochem Cell Biol) - "Interestingly, when cells were treated with a low concentration of actinomycin D that inhibits Pol I transcription through intercalating GC-rich DNA, chromosome movement was significantly blocked. Treatment with another Pol I inhibitor, metarrestin, which does not impact DNA, had little effect on the movement, suggesting that the DNA structure itself plays a role in chromosome dynamics. Furthermore, inhibition of Pol II transcription with α-amanitin also reduced the chromosome movement, demonstrating that Pol II, but not Pol I transcription, is important for chromosome dynamics in the nucleus."

Journal

The eEF1A Protein in Cancer: Clinical Significance, Oncogenic Mechanisms, and Targeted Therapeutic Strategies. (PubMed, Pharmacol Res) - "Among them, plitidepsin was approved for the treatment of multiple myeloma whereas metarrestin was currently under clinical development. Despite significant achievements in these two interrelated fields, hitherto there lacks a systematic examination of the eEF1A protein in the context of cancer research. Therefore, the present work aims to delineate its clinical implications, molecular oncogenic mechanisms, and targeted therapeutic strategies as reflected in the ever expanding body of literature, so as to deepen mechanistic understanding of eEF1A-involved tumorigenesis and inspire the development of eEF1A-targeted chemotherapeutics and biologics."

Journal • Review • Hematological Malignancies • Multiple Myeloma • Oncology • EEF1A1

Metarrestin (ML-246) in Subjects With Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=98 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2024 ➔ Dec 2027 | Trial primary completion date: Dec 2024 ➔ Dec 2026

Metastases • Trial completion date • Trial primary completion date • Brain Cancer • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Neurofibrosarcoma • Oncology • Pancreatic Cancer • Pediatrics • Solid Tumor

Metarrestin (ML-246) in Subjects With Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=98 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Metastases • Trial completion date • Trial primary completion date • Brain Cancer • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Neurofibrosarcoma • Oncology • Pancreatic Cancer • Pediatrics • Solid Tumor