MRTX-1719 is a potent and selective inhibitor of the PRMT5/MTA complex with an IC50 value of <10 nM against PRMT5/MTAMTAPDELSDMA cell lines.

PRMT5/MTAMTAPDELSDMA cells:<10 nM (IC50)

METHODS: To study the selectivity of MRTX1719 in reducing MTAP del tumor cell viability, 70 MTAP del and 26 MTAP WT human cancer cell lines were evaluated in a 5-day CellTiter-Glo (CTG) viability assay. RESULTS MRTX1719 selectively reduced the viability of MTAP del cell line, with minimal impact on MTAP WT cells. The median IC50 value of MRTX1719 in MTAP del cell line was 90 nmol/L, while the median IC50 value of MRTX1719 in MTAP WT cell line was IC50 is 2.2 μmol/L. [1] METHODS: MRTX1719 was studied in MTAP-del SDMA cells and MTAP-del active cell experiments. RESULTS IC50 = 8 nM in the MTAP-del SDMA experiment and IC50 = 12 nM in the MTAP-del activity experiment, with 82-fold and 74-fold selectivity over the corresponding MTAPWT experiment. [2]

METHODS: MRTX1719 was studied in selected MTAP del cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models for ∼3 weeks at 100 mg/kg orally. RESULTS MRTX1719 showed significant anti-tumor activity in all models tested. [1] METHODS: Lu-99 is a human lung cancer cell line lacking MTAP/cdkn2a. When tumors reached ~200 mm3, MRTX1719 was administered by gavage (12.5, 25, 50, and 100 mg/kg) once daily until day 21. Tumor volumes were measured throughout the study. RESULTS MRTX1719 can inhibit the growth of Lu-99 cells in a concentration-dependent manner. [2]