HuR Inhibitor

MS-444 (BE-34776) is a HuR (ELAVL1) inhibitor that blocks the cytoplasmic translocation of HuR and inhibits its dimerization. MS-444 reduces cytoplasmic HuR levels by preventing the binding of HuR to ARE-mRNA, without altering the total expression of HuR. MS-444 induces apoptosis, inhibits cell growth, angiogenesis and invasion, and also regulates immune function and microbiota. MS-444 effectively alters the number, size and invasiveness of tumors in various cancer models. MS-444 is tolerable to intraperitoneal injection in vivo and can be applied to research related to colorectal cancer, familial adenomatous polyposis, colitis-associated cancer and glioblastoma.

CMLD-2, an inhibitor of HuR-ARE interaction, competitively binds HuR protein disrupting its interaction with adenine-uridine rich elements (ARE)-containing mRNAs (K_i=350 nM). CMLD-2 induces apoptosis exhibits antitumor activity in different cancer cells as colon, pancreatic, thyroid and lung cancer cell lines. Hu antigen R (HuR) is an RNA binding protein, can regulate target mRNAs stability and translation.

KH-3 is a potent RNA-binding protein Hu antigen R (HuR) inhibitor with an IC₅₀ value of 0.35 μM. KH-3 has anti-proliferative activity. KH-3 suppresses breast cancer cell invasion as well as delays the initiation of lung colonies by disrupting HuR-FOXQ1 mRNA interaction.

SRI-42127 is a HuR translocation inhibitor. HuR is an RNA regulator that binds to AREs, and HuR translocations promote the production of inflammatory cytokines in glial cells. However, SRI-42127 can destroy mRNA stability and inhibit gene promoter activation. SRI-42127 also inhibits microglial cell activation and attenuates recruitment/chemotaxis of neutrophils and monocytes.

SRI-43265 (compound 40) is an inhibitor of human antigen R protein (HuR) dimerization, and HuR multimers have been implicated in cancer and inflammatory pathogenesis.

TM11, a Tanshinone mimic, is a potent HuR inhibitor that can inhibit HuR-RNA complex formation. TM11 reduces LPS-induced inflammatory response in murine macrophages.

ZM-32 is an inhibitor for human antigen R (HuR), that downregulates the expression of VEGF-A and MMP9, and thus inhibits breast cancer tumor angiogenesis. ZM-32 exhibits broad-spectrum anti-proliferative effects in a variety of cancer cell lines, and exhibits antitumor efficacy against MDA-MB-231 in mouse models.

Azaphilone-9 (AZA-9) is an inhibitor of HuR-ARE RNA interaction (IC₅₀=1.2 μM) by binding RNA-binding protein Hu antigen R (HuR). The HuR-RNA interactions stabilize many oncogenic mRNAs in tumors. Thus Azaphilone-9 potentially inhibit cancer cell growth and progression.

Okicenone is a Hu protein R (HuR) inhibitor. Okicenone inhibits HuR oligomerization, interferes with HuR RNA binding, HuR trafficking, cytokine expression and T-cell activation.