TNG-462 is an orally active and selective PRMT5 inhibitor with anti-tumor activity against metlthioadenosine phosphorylase (MTAP) deficiency and/or metlthioadenosine (MTA) accumulation cancers.
TNG-462 (0-1 μM) exhibits selectivity and inhibition of cell viability in MTAP deficient tumor cells (NSCLC, PDAC, bladder, hematological malignancies), with IC50values less than 1 μM[1].
TNG-462 (40, 100 mg/kg; once daily (100 mg/kg) or b.i.d (40 mg/kg); 21 days; p.o.) has anti-tumor activity in a xenograft mouse model derived from MTAP deficient cell lines[1].TNG-462 (30 mg/kg; twice daily; 5 weeks; p.o.) in combination with osimertinib (EGFR inhibitor) (1 mg/kg; once daily; 5 weeks) has synergistic anti-tumor activity in MTAP-deficient cell line-derived xenograft mouse model[1].
References:
[1]. Briggs K, et al. TNG462 is a potential best-in-class MTA-cooperative PRMT5 inhibitor for the treatment of MTAP-deleted solid tumors[J]. Cancer Research, 2023, 83(7_Supplement): 4970-4970. [2]. Kevin M Cottrell, et al. Piperidin-1- yl-n-pyrydi ne-3-yl-2-oxoacet am ide derivatives useful for the treatment of mtap-deficient and/or mt a-accumulating cancers. Patent WO2022026892A1.