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Melanotan II (MT-II): structure and mechanism Melanotan II is a synthetic cyclic heptapeptide with sequence Ac-Nle 4 -Asp 5 -His 6 -D-Phe 7 -Arg 8 -Trp 9 -Lys 10 -NH 2 with a lactam bridge between Asp 5 and Lys 10 that cyclizes the molecule and stabilizes the active conformation

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Activated PKA and EPAC2 can close ATP-dependent K + channels and voltage-dependent K + channels, leading to membrane depolarization and the activation of voltage-dependent calcium channels (VDCC), resulting in Ca 2+ influx