Relevant sirtuin publications

A PubMed search for “sirtuin” yields nearly 2000 publications.

 What we are providing here is a curated selection of reports with relevance to Evrys Bio’s proprietary SIRT2 inhibitors follows.

Sirtuins regulate viral replication

SIRT control of viral growth is conserved from bacteria to humans.

• Budayeva, Rowland and Cristea 2016. Anti-viral activities of SIRTs.
• Koyuncu, Budayeva, Miteva, Ricci et al 2014. All seven SIRTs modulate the replication of bacterial and human viruses, revealing that the SIRTs are elements of an evolutionarily conserved viral regulatory system.

Anti-viral activities of sirtuin 2 inhibitors

SIRT2 inhibitors block replication and spread of multiple RNA and DNA viral pathogens.

• Acosta, Bowlin, Brooks, Chiang et al 2020. The clinical path for new anti-cytomegalovirus drugs, and the potential of SIRT2 inhibitors for this application. Lillian Chiang, Evrys co-founder and CEO, is a co-author.
• Piracha, Saeed, Kim, Kwon et al 2020. SIRT2 isoforms are recruited to the hepatitis B virus cccDNA, modulating epigenetic marks on the viral minichromosome and controlling its transcriptional output.
• Hackett, Dittmar, Segrist, Pittenger et al 2019. Tenovin-2 (SIRT1/SIRT2/SIRT3 inhibitor) and sirtinol (SIRT1/SIRT2 inhibitor) inhibit representative alphaviruses, bunyaviruses and flaviviruses.
• Cheng, Ren, Cai Jiang and Chen 2018. The hepatitis B virus HBx protein elevates SIRT2, which in turn promotes viral replication and hepatocarcinogenesis.
• Piracha, Kwon, Saeed, Kim et al 2018. SIRT2 enhances hepatitis B virus transcription through the AKT pathway.
• Yu, Jiang, Cheng, Hu et al 2018. The SIRT2 inhibitor, AGK2, inhibits hepatitis B virus replication in vitro and in vivo.
• Mao, Li, Ding, Meng et al 2016. Sirtinol (SIRT1/SIRT2 inhibitor) inhibits the production of cytomegalovirus progeny in cultured fibroblasts.
• Kanda, Sasaki, Nakamoto, Haga et al 2015. Sirtinol (SIRT1/SIRT2 inhibitor) blocks hepatitis A virus replication by antagonizing function of its internal ribosomal entry site (IRES).

Anti-microbial activities of sirtuin 2 inhibitors

SIRT2 inhibitors block replication of multiple intracellular microbial pathogens.

• Bhaskar, Kumar, Khan, Singh et al 2020. Inhibition of SIRT2 restricts the intracellular growth of Mycobacterium tuberculosis and enhances efficacy of the anti-TB drug Isoniazid in the murine model of infection.
• Pereira, Chevalier, Chaze, Gianetto et al 2018. Listeria induces phosphorylation and nuclear localization of SIRT2, which then supports its replication.
• Gogoi, Chandra, Sarikhani, Ramani et al 2018. SIRT2 inhibition reduces pathogen organ burden and associated tissue damage in a mouse model of Salmonella infection.

Anti-cancer activities of sirtuin 2 inhibitors

SIRT2 inhibitors block cancer cell growth and activate T cells in the tumor microenvironment.

• Haimadi, Zhang, Kim, Wang et al 2020. SIRT2 suppresses T cell metabolism and inhibition of SIRT2 endows human TILs with superior metabolic fitness and effector functions.

(Cell Metab. 2020 Sep 1;32(3):420-436.e12. doi: 10.1016/j.cmet.2020.07.008. Epub 2020 Aug 7. PMID: 32768387)

• Jing, Hu, Negron Abril, Stupinski et al 2016. SIRT2 inhibitors induce degradation of c-Myc in some tumor cells, markedly inhibiting tumor xenograft growth.
• Hoffmann, Breitenbucher, Schuler and Ehrenhofer-Murray 2014. SIRT2 inhibitors induce hyperacetylation and activation of p53 in tumor cells.
• Ramakrishnan, Davaakhuu, Kaplun, Chung et al 2014. SIRT2 inhibitors block full activation of AKT.
• Liu, Xu, Malukova, Scarlett et al 2013. c-Myc and N-myc upregulate SIRT2, which then inhibits expression of the NEDD4 ubiquitin ligase, stabilizing Myc proteins.

Sirtuin 2-null mice predict that SIRT2 inhibitors will be well tolerated

• Ciarlo, Heinonen, Théroude, Herderschee et al 2017. SIRT2 knockout mice are healthy and immunocompetent and resistant to chronic staphylococcal infection.