PRMT1-IN-3 is a potent inhibitor of protein arginine methyltransferase 1 (PRMT1) with an IC50 of 4.11 μM. It also inhibits PRMT6 and PRMT8, with IC50 values of 23.3 and 30.1 μM, respectively. In triple-negative breast cancer (TNBC) cells, PRMT1-IN-3 reduces asymmetric dimethylarginine (ADMA) levels and the histone modification H4R3me2a. It induces cell cycle arrest and apoptosis in MDA-MB-231 cells and inhibits cell migration and colony formation. Furthermore, PRMT1-IN-3 serves as a chemosensitizer for Paclitaxel and is applicable in TNBC research.

PRMT1:4.11 μM

PRMT1-IN-3 (Compound YH-4) significantly enhances the thermal stability of PRMT1 (ΔTm = +5.2°C) at concentrations of 10 μM between 37-65°C, with minimal effect on other PRMT subtypes. It inhibits the growth of MDA-MB-231, HCT116, HeLa, and A549 cells over a 48-hour period with IC50 values of 6.38 μM, 15.29 μM, 12.97 μM, and 9.187 μM, respectively. In a dose-dependent manner, PRMT1-IN-3 (1.25-10 μM, 48 hours) reduces ADMA levels and H4R3me2a modifications in MDA-MB-231 cells. Furthermore, PRMT1-IN-3 (0-20 μM, 72 hours) exhibits synergistic effects with Paclitaxel (PTX) in MDA-MB-231 and MDA-MB-231/Taxol resistant cells, with resistance indices of 9.0 and 92.7, respectively. The compound also induces G0/G1 phase arrest, apoptosis, and inhibits cell migration in MDA-MB-231 cells at concentrations of 0-40 μM over 0-48 hours. Finally, PRMT1-IN-3 at 20 μM concentration almost completely suppresses colony formation of MDA-MB-231 cells over a 10-day period.

PRMT1-IN-3 (Compound YH-4) administered at 30 mg/kg via intraperitoneal injection for 7 consecutive days, followed by a 3-day drug-free period over a total of 21 days, acts as a chemosensitizer for PTX. It enhances the therapeutic efficacy and markedly reduces the required dosage and side effects in a TNBC mouse model.