**4.3 Small molecule inhibitors of PRMT5**

PRMT5 is overexpressed in a several types of cancers. There are currently over 50 PRMT5 small molecule inhibitors, and PRMT5 is emerging as a hotspot for cancer targeted therapy [144]. Some small molecule inhibitors of PRMT5 are currently undergoing assessment in phase 1 clinical trial for non-Hodgkin lymphomas and solid cancers include GSK3326595 and JNJ-64619178 (**Table 1**). PRMT5 has also been implicated in the progression and metastasis of pancreatic and colon cancer. As a result, a lead compound, PR5-LL-CM01 (**Table 1**), has been discovered by our group to have more potent inhibitory properties compared to EPZ015666 in pancreatic and colon cancer cells [114]. However, EPZ015666 showed high potency *in vitro* and in mantle lymphoma cells with an IC50 of 22nM (**Table 1**) [145]. Another potent inhibitor of PRMT5, LLY-283 (IC50 = 20 nM) (**Table 1**) showed an outstanding inhibition of breast, lung, skin, ovarian, and hematological cancer cells' proliferation [142].
