Pharmacological activity of Plitidepsin

Plitidepsin (also known as dehydrodidemnin B, marketed by PharmaMar, S.A. under the trade name Aplidin) is a chemical compound extracted from the ascidian Aplidium albicans.It is currently undergoing clinical trial testing. It is a member of the class of compounds known as didemnins.

Structure

Plitidepsin is a cyclic depsipeptide, meaning it is a cyclic peptide in which there is one or more ester bond in place of one or more of a peptide bond. Its chemical structure is very close to that of didemnin B, the only difference being that the lactate residue in didemnin B is present in the oxidized pyruvate version.

Pharmacological activity

Like all didemnin compounds, plitidepsin exhibits antitumor, antiviral and immunosuppressive activities. It shows promise in shrinking tumors in pancreatic, stomach, bladder, and prostate cancers.

Plitidepsin inhibits the human protein eEF1A which has potential interactions with multiple coronavirus proteins. Plitidepsin possesses antiviral activity against SARS-CoV-2 in vitro and in an in vivo mouse model.

Research

Plitidepsin has undergone an extensive clinical development program for the treatment of cancer. Pharmacokinetic and safety properties of plitidepsin have been gathered from several Phase I and II clinical trials which have also explored different i.v. dosing schedules and infusion times. Based on the results obtained from a Phase III clinical trial (ADMYRE), the Australian Therapeutic Goods Administration approved the combination of plitidepsin with dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma in 2018.