Lenvatinib–temozolomide drug–drug cocrystal (LEN-TMZ cocrystal)

The Lenvatinib–temozolomide drug–drug cocrystal is a pharmaceutical solid-state complex consisting of two active pharmaceutical ingredients (APIs) within a single crystalline lattice. It is not a biological target but rather a therapeutic agent designed to treat aggressive malignancies, such as glioblastoma, by combining the anti-angiogenic properties of Lenvatinib with the cytotoxic effects of Temozolomide. Lenvatinib functions by inhibiting multiple receptor tyrosine kinases involved in tumor angiogenesis and proliferation, including vascular endothelial growth factor receptors (VEGFR) and fibroblast growth factor receptors (FGFR). Temozolomide is an oral alkylating agent that crosses the blood-brain barrier and causes DNA fragmentation, leading to cell cycle arrest. By formulating these two drugs as a cocrystal, researchers aim to enhance the pharmacokinetic profile and therapeutic efficacy of the combination therapy compared to individual administration. This approach targets both the tumor's genetic stability and its supporting microvasculature to overcome resistance mechanisms in difficult-to-treat cancers.

Other names

Lenvatinib-temozolomide cocrystalLEN-TMZ drug-drug cocrystal

The Lenvatinib–temozolomide drug–drug cocrystal is a multi-component crystalline system where Lenvatinib acts as a multi-kinase inhibitor (targeting VEGFR1-3, FGFR1-4, PDGFRα, KIT, and RET) and Temozolomide acts as an alkylating agent that delivers a methyl group to DNA (primarily at the O6 and N7 positions of guanine), leading to DNA damage and cell death. The cocrystal form is designed to improve the physicochemical properties, such as solubility or stability, of the individual components while providing synergistic antitumor activity by simultaneously inhibiting pro-angiogenic pathways and inducing cytotoxic DNA damage.