Drug intelligence / Profile preview

ELV-3111

Development stage
Preclinical
Lead developer
Enliven Therapeutics
Modality
Small Molecules
01

Overview

**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.

02

Targets

ARAF (Proto-oncogene serine/threonine-protein kinase A-Raf)LCK (Proto-oncogene tyrosine-protein kinase Lck)BRAF (B-Raf proto-oncogene, serine/threonine kinase)BLK (B lymphoid tyrosine kinase)SIK3PTK6 (Protein-tyrosine kinase 6)SIK1 (Salt-inducible kinase 1)ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase)YES1 (YES proto-oncogene 1 tyrosine kinase)RAF1 (c-Raf-1 (Y340D/Y341D))HCK (Haematopoietic Cell Kinase)DDR1 (Discoidin domain receptor 1)

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