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With nominations open for the BVA Young Vet of the Year 2024, last year's winner Henry Lamb describes his experience of securing the prestigious award. [ABSTRACT FROM AUTHOR]

ABSTRACT Targeted melanoma therapies, including treatment with the small molecule drug dabrafenib, can become ineffective due to acquired drug resistance. Dabrafenib targets BRAF‐V600E, a mutation that is present in more than half of melanoma cancers. Therefore, drug discovery efforts need to explore alternative candidate molecules that selectively target and kill melanoma cells via mechanisms different to those of current drugs. Marine fungi are an underexplored resource for bioactive molecules. Mortiamide‐D, a seven amino acid cyclic peptide from Mortierella sp, is an example molecule with desirable features for drug development. We synthesized mortiamide‐D and three rationally designed analogs and observed modest micromolar activity against HT144 melanoma cells that are sensitive or resistant to dabrafenib. By contrast, mortiamide‐D and analogs did not kill noncancer HaCaT cells at these concentrations. Substitution of D‐Ile at position 7 with D‐Arg improved membrane permeability and enhanced potency against HT144 cells via a mode‐of‐action that includes perturbation of mitochondrial membrane potential. These studies suggest the potential of mortiamides as modifiable scaffolds for developing a new class of molecule for targeting melanoma cells. [ABSTRACT FROM AUTHOR]