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Cancer Target Rationale

GSK is investigating the activity of two compounds that target protein arginine methyltransferases (PRMTs).1

PRMT5 is overexpressed in multiple tumor types, including lymphoma, breast, lung, and bladder cancers, and regulates splicing, gene expression, and activation of p53.2,3

Overview

GSK3326595, a selective inhibitor of PRMT5, is being investigated as a monotherapy in solid tumors and in combination with other therapies in various hematologic malignancies.1

GSK3368715, a type 1 PRMT inhibitor, is being investigated in phase I trials for patients with diffuse large B-cell lymphoma and solid tumors.1,4

References

  1. ClinicalTrials.gov. Accessed June 14, 2021. www.clinicaltrials.gov/
  2. Smith E, Zhou W, Shindiapina P, Sif S, Li C, Baiocchi RA. Recent advances in targeting protein arginine methyltransferase enzymes in cancer therapy. Expert Opin Ther Targets. 2018;22(6):527-545.
  3. Poulard C, Corbo L, Le Romancer M. Protein arginine methylation/demethylation and cancer. Oncotarget. 2016;7(41):67532-67550.
  4. Fedoriw A, Rajapurkar SR, O’Brien S, et al. Anti-tumor activity of the type I PRMT inhibitor, GSK3368715, synergizes with PRMT5 inhibition through MTAP loss. Cancer Cell. 2019;36(1):100-114.