MTI-101 (Voronoi)

MTI-101 (formerly VOR-101) is an orally bioavailable, potent, and selective **Type II pan-RAF inhibitor** being developed for the treatment of advanced solid tumors. Originally discovered by **Voronoi** and licensed to **Metis Therapeutics**, MTI-101 is designed to inhibit both monomeric and dimeric forms of **BRAF** and **CRAF** (RAF1) kinases. This mechanism is intended to overcome the 'paradoxical activation' of the MAPK pathway often observed with first-generation BRAF inhibitors, which can lead to treatment resistance and secondary malignancies. By targeting a broad range of RAF isoforms and conformations, MTI-101 aims to provide therapeutic benefit in tumors harboring various RAS or RAF mutations, including those in colorectal cancer, melanoma, and non-small cell lung cancer. The drug is currently being evaluated in Phase 1 clinical trials to determine its safety, tolerability, and preliminary efficacy in patients with advanced solid tumors characterized by mutations in the RAS-MAPK pathway.