TTL1177

TTL1177 is a selective small molecule antagonist of voltage-gated T-type calcium channels, developed by TAU Therapeutics in collaboration with the University of Virginia for the treatment of glioblastoma multiforme (GBM). T-type calcium channels are often overexpressed in various cancers, including GBM, where they contribute to cell proliferation and resistance to therapy. TTL1177 works by inducing cell cycle arrest in the G1/G0 phase and promoting cell death through the extrinsic apoptotic pathway, characterized by the activation of caspase-8 and the cleavage of Bid protein. Furthermore, TTL1177 has been shown to induce autophagy and significantly sensitize GBM cells to the effects of ionizing radiation and chemotherapy (such as temozolomide), suggesting its potential as both a monotherapy and a sensitizing agent in combination regimens.