DP68

DP68 is an experimental small molecule and an analogue of the alkylating agent temozolomide (TMZ), specifically developed for the treatment of glioblastoma multiforme (GBM). Unlike temozolomide, which primarily induces DNA methylation at the O6 position of guanine—a lesion easily repaired by O-6-methylguanine-DNA methyltransferase (MGMT)—DP68 functions as a DNA cross-linking agent. It induces interstrand DNA cross-links (ICLs), which allows it to bypass common resistance mechanisms such as MGMT overexpression and mismatch repair (MMR) deficiencies. DP68 triggers a robust DNA damage response, characterized by the phosphorylation of ATM, Chk1, Chk2, and H2AX, leading to a distinct S-phase cell cycle arrest. Preclinical data suggest that DP68 is significantly more potent than TMZ and is effective against TMZ-resistant GBM cell lines and neurosphere models.

Other names

temozolomide analogue DP68