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**ELV-3111** is a first-in-class Type 1 pan-RAF inhibitor (αC-helix-in, DFG-in binding mode) developed by Enliven Therapeutics with potent activity against ARAF, BRAF, and CRAF. It demonstrates exceptional kinome selectivity, superior ERK pathway suppression, and antiproliferative effects in BRAFV600E, NRAS-mutant, and BRAF inhibitor-resistant cell lines, including Class I/II/III BRAF mutants, both alone and in combination with MEK inhibitors like binimetinib. ELV-3111 exhibits favorable drug-like properties, including excellent predicted human pharmacokinetics, low plasma protein binding, and good kinetic solubility, enabling safe combination therapy with reduced paradoxical activation and toxicity in normal tissues. It has completed all IND-enabling studies and shows robust antitumor activity in NRASQ61K xenograft models, positioning it for expanded use in BRAF/NRAS-mutant cancers beyond limitations of Type 1.5/2 RAF inhibitors.
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