PRMT5 Inhibitor

GSK3326595 is a protein arginine methyltransferase 5 (PRMT5) inhibitor. GSK3326595 decreases SARS-CoV-2 infection, inhibits cancer cell proliferation and induces pro-inflammatory macrophage polarization and increases hepatic triglyceride levels without affecting atherosclerosis. GSK3326595 can be used for research of relapsed/refractory mantle cell lymphoma.

Navlimetostat is a potent, orally active, selective PRMT5-MTA complex inhibitor, with IC₅₀ of 3.6 and 20.5 nM for PRMT5-MTA and PRMT5. Navlimetostat binds to the PRMT5-MTA complex, with KD value of 0.14 pM. Navlimetostat shows antineoplastic activity in vitro and in vivo, and can be used for cancer study.

EPZ015666 (GSK3235025) is an orally available inhibitor of PRMT5 with an IC₅₀ of 22 nM.

Onametostat (JNJ-64619178) is a selective, orally active and pseudo-irreversible protein arginine methyltransferase 5 (PRMT5) inhibitor with an IC₅₀ of 0.14 nM. Onametostat has potent activity in lung cancer.

GSK591 (EPZ015866), a chemical probe, is a potent and selective inhibitor of protein methyltransferase 5 (PRMT5) with an IC₅₀ of 4 nM.

WX2-43 is a PRMT5-KLF4 inhibitor (K_d of 11.0 nM). WX2-43 binds to the region between amino acids L400-M500 on PRMT5. WX2-43 efficiently intercepts the interaction between KLF4 and PRMT5, and blocks KLF4 methylation. WX2-43 decreases p21 levels and increases Bax levels. WX2-43 suppresses triple negative breast tumor progression. WX2-43 can be used in the research of triple-negative breast cancer and colorectal cancer.

MC4491 is a selective LSD1/PRMT5 inhibitor, with an IC₅₀ of 0.152 μM against the LSD1/CoREST complex and an IC₅₀ of 0.043 μM against the PRMT5/MEP50 complex. MC4491 induces transcriptomic changes and splicing alterations in AML cells. MC4491 is applicable for the research of acute myeloid leukemia.

LLY-283, a chemical probe, is a potent, selective and oral protein arginine methyltransferase 5 (PRMT5) inhibitor, with an IC₅₀ of 22 nM and a K_d of 6 nM for PRMT5:MEP50 complex, and shows antitumor activity.

PF-06939999 (PRMT5-IN-3) is a SAM-competitive, orally active PRMT5 inhibitor that inhibits the expression of SDMA protein (IC₅₀ in A427 is 1.1 nM). PF-06939999 exhibits antitumor effect.

TNG908 is a MTAP synergistic PRMT5 inhibitor. TNG908 crosses the blood-brain barrier and is orally active. TNG908 could be used in cancer research.

DS-437 is a dual PRMT5/7 inhibitor (IC₅₀s of PRMT5/7=6 μM). DS-437 is selective for PRMT5 and PRMT7 over 29 other human protein-, DNA-, and RNA-methyltransferases. DS-437 is a S-adenosylmethionine (SAM)-competitive inhibitor of PRMT5. DS-437 also inhibits DNMT3A and DNMT3B, with IC₅₀s of 52 and 62 μM, respectively. DS-437 inhibits the methylation of FOXP3.

HLCL-61 hydrochloride is a first-in-class inhibitor of protein arginine methyltransferase 5 (PRMT5).

BRD0639 is a first-in-class inhibitor of the PRMT5-substrate adaptor interaction. BRD0639 is a PRMT5 binding motif (PBM)-competitive agent that can support studies of PBM dependent PRMT5 activities.

MRTX9768 is a potent, selective, orally active, first-in-class PRMT5-MTA complex inhibitor.

Navlimetostat hydrochloride is a potent, orally active, selective PRMT5-MTA complex inhibitor, with IC₅₀s of 3.6 and 20.5 nM for PRMT5-MTA and PRMT5. Navlimetostat hydrochloride binds to the PRMT5-MTA complex, with KD value of 0.14 pM. Navlimetostat shows antineoplastic activity in vitro and in vivo, and can be used for cancer study.

AM-9747 (compound 503) is a potent PRMT5 inhibitor with an K_i value of 0.06 nM. AM-9747 shows antiproliferative.

PR5-LL-CM01 is a potent protein arginine methyltransferase 5 (PRMT5) inhibitor (IC₅₀= 7.5 μM). Anti-tumor activies.

PRMT5-IN-30 (compound 17) is a potent and selective protein arginine methyltransferase 5 (PRMT5) inhibitor with an IC₅₀ of 0.33 μM and a K_d of 0.987 μM. PRMT5-IN-30 exhibits a broad selectivity against a panel of other methyltransferases. PRMT5-IN-30 inhibits PRMT5 mediated SmD3 methylation.

(S)-Navlimetostat (example 16-7) is the S-enantiomer of Navlimetostat. (S)-Navlimetostat is a PRMT5/MTA complex inhibitor, with an IC₅₀ of 7070 nM.

CMP-5 is a potent, specific, and selective PRMT5 inhibitor, while displays no activity against PRMT1, PRMT4, and PRMT7 enzymes. CMP-5 selectively blocks S2Me-H4R3 by inhibiting PRMT5 methyltransferase activity on histone preparations. CMP-5 prevents Epstein-Barr virus (EBV)-driven B-lymphocyte transformation but leaving normal B cells unaffected.