EPZ031686 / Ipsen - LARVOL DELTA

Loss of histone methyltransferase Smyd3 triggers WAT browning and adaptive thermogenesis via enhancing PPARγ expression in a H4K20me3-dependent manner. (PubMed, J Transl Med) - "Collectively, our findings identify Smyd3 as a potential therapeutic target for modulating adaptive thermogenesis. Pharmacological inhibition of Smyd3 with EPZ031686 represents a promising strategy to promote WAT browning and adaptive thermogenesis, offering a potential therapeutic avenue for combating obesity."

Journal • Cardiovascular • Genetic Disorders • Obesity • PPARG • SMYD3

Discovery of the 4-aminopiperidine-based compound EM127 for the site-specific covalent inhibition of SMYD3. (PubMed, Eur J Med Chem) - "In enzymatic assays, 11C showed a stronger SMYD3 inhibitory effect compared to the reference inhibitor EPZ031686...Furthermore, 11C (5 μM) strongly decreased the steady-state mRNA levels of genes important for tumor biology such as cyclin dependent kinase 2, c-MET, N-cadherin and fibronectin 1, all known to be regulated, at least in part, by SMYD3. Thus, 11C is as a first example of second generation SMYD3 inhibitors; this agent represents a covalent and a site specific SMYD3 binder capable of potent and prolonged attenuation of methyltransferase activity."

Journal • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CDH2 • CDK2 • FN1 • MET • NECTIN1 • SMYD3

Novel insights into SMYD2 and SMYD3 inhibitors: from potential anti-tumoural therapy to a variety of new applications. (PubMed, Mol Biol Rep) - "In addition to their oncogenic roles, SMYD2 and SMYD3 are involved in many other physiopathological conditions. In this review we will focus on the advances made in the last five years in the field of pharmacology regarding drugs targeting SMYD2 (such as LLY-507 or AZ505) and SMYD3 (such as BCI-121 or EPZ031686) and their potential cellular and molecular mechanisms of action and application in anti-tumoural therapy and/or against other diseases."

Journal • Review • Oncology • SMYD3

SMYD3 inhibition induces protective autophagy in bladder cancer via mTOR pathway (AUA 2019) - "...The combined administration of SMYD3 inhibitor EPZ031686 and 3-MA could inhibit mTOR signaling pathway synergically and show a dramatic anti-tumor effect. SMYD3 has a potential to be a biomarker of invasive bladder cancer. Combined inhibition of SMYD3 and autophagy might be a treatment strategy for bladder cancer."