TET2 Activator GLIX1

**Semantic type:** Nucleic Acid, Nucleoside, or Nucleotide|Pharmacologic Substance

**Definition:** An orally bioavailable, small molecule, blood brain barrier (BBB) penetrant and activator of the enzyme Tet methylcytosine dioxygenase 2 (TET2), with potential antineoplastic activity. Upon oral administration, TET2 activator GLIX1 selectively binds to and agonizes TET2, thereby increasing TET2 activity in cancer cells. This allows for an increase in DNA oxidation at 5-methylcytosine (5mC) residues, thereby forming 5-hydroxymethylcytosine (5hmC). High 5hmC production leads to excessive base excision repair (BER) and results in numerous single-strand DNA breaks (SSBs) in close proximity, which eventually form double-strand DNA breaks (DSBs). The abundance of DSBs overwhelm the DNA damage response (DDR) pathway in these cancer cells, resulting in the induction of apoptotic cell death. In many cancer cells, TET2 activity is inhibited, which results in reduced levels of genomic 5hmC. Normal, healthy cells have normal TET2 activity and normal levels of 5hmC and in which the SSBs can be efficiently processed by DDR.

**Synonyms:** - GLIX 1 - GLIX-1 - GLIX1 - TET2 Agonist GLIX1