LY4286533

LY4286533 (formerly 4ET1103) is an orally bioavailable, peripherally acting small molecule inhibitor of mitogen-activated protein kinase-interacting kinase (MNK) developed for the treatment of chronic neuropathic pain. Originally developed by 4E Therapeutics, the asset was acquired by Eli Lilly in June 2026. LY4286533 targets the MNK-eIF4E signaling pathway in peripheral sensory neurons, blocking the phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) to modulate the translation of pain-sensitizing proteins at the site of nociception. By acting peripherally rather than centrally, the drug is designed to deliver effective analgesia without the central nervous system-mediated side effects—such as sedation, cognitive impairment, and addiction risk—associated with opioids and gabapentinoids.