GSK3326595 — Investigational Agent
Other · Phase 1/2 · GlaxoSmithKline
Mechanism of Action
Selective inhibitor of PRMT5 (protein arginine methyltransferase 5), an enzyme that symmetrically dimethylates arginine residues on histone and non-histone substrates, regulating splicing, transcription, and cell survival. Exploits synthetic lethality in MTAP-deleted cancers: homozygous MTAP deletion (found in ~15% of all cancers) causes accumulation of the metabolite MTA (methylthioadenosine), which is an endogenous partial inhibitor of PRMT5. MTAP-deleted tumor cells are therefore already partially PRMT5-suppressed and are exquisitely sensitive to further pharmacologic PRMT5 inhibition,…
Investigational Indications
- MTAP-deleted mesothelioma
- MTAP-deleted glioblastoma (GBM)
- MTAP-deleted urothelial/bladder cancer
- MTAP-deleted pancreatic ductal adenocarcinoma (PDAC)
- MTAP-deleted NSCLC
- Other MTAP-deleted solid tumors