Met-Enkephalin

Pain / Immune / Cancer

Also known as: Methionine-Enkephalin, MENK, Tyr-Gly-Gly-Phe-Met, Opioid Growth Factor, OGF

Endogenous Opioid PeptidesResearch phase: Endogenous peptide (cancer research ongoing)Regulatory: Endogenous peptide. Not approved as a drug. Low-dose naltrexone (LDN) indirectly upregulates met-enkephalin/OGF signaling.

Mechanism

Met-enkephalin (methionine-enkephalin) is a 5-amino-acid endogenous opioid peptide — one of the first natural painkillers discovered in the brain. It primarily activates delta-opioid receptors to modulate pain. Interestingly, met-enkephalin also acts as the "Opioid Growth Factor" (OGF), regulating cell growth through the OGFr receptor, which has led to cancer research investigating its anti-proliferative effects.

Technical detail

Met-enkephalin (Tyr-Gly-Gly-Phe-Met) is a pentapeptide derived from proenkephalin (PENK) processing. It is a preferential delta-opioid receptor (DOR) agonist with moderate mu-opioid receptor (MOR) affinity. DOR activation couples through Gi/Go proteins to inhibit adenylyl cyclase, activate GIRK channels, and inhibit N-type Ca2+ channels in pain circuits. As the Opioid Growth Factor (OGF), it binds the OGF receptor (OGFr), a nuclear-associated receptor that upregulates p16INK4a and p21WAF1/CIP1 cyclin-dependent kinase inhibitors, arresting cell cycle at G1/S. This anti-proliferative axis has been studied in pancreatic cancer, head/neck cancer, and multiple sclerosis.

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