Plitidepsin

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Plitidepsin
Aplidine.svg
Names
IUPAC name
(S)-N-((R)-1-(((3S,6R,7S,10R,11S,15S,17S,20S,25aS)-10-((S)-sec-butyl)-11-hydroxy-20-isobutyl-15-isopropyl-3-(4-methoxybenzyl)-2,6,17-trimethyl-1,4,8,13,16,18,21-heptaoxodocosahydro-1H-pyrrolo[2,1-f][1,15,4,7,10,20]dioxatetraazacyclotricosin-7-yl)amino)-4-methyl-1-oxopentan-2-yl)-N-methyl-1-(2-oxopropanoyl)pyrrolidine-2-carboxamide
Other names
Aplidine; Dehydrodidemnin B; Aplidin; N-[1-(1,2-Dioxopropyl)-L-prolyl]didemnin A
Identifiers
137219-37-5 YesY
ChEBI CHEBI:90205
ChemSpider 26001665 YesY
Jmol 3D model Interactive image
Properties
C57H87N7O15
Molar mass 1,110.36 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

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.[1] It is currently undergoing clinical trial testing. It is a member of the class of compounds known as didemnins.

Chemical structure[edit]

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[edit]

Like all didemnin compounds, plitidepsin exhibits antitumor, antiviral and immunosuppressive activities. It shows promise in shrinking tumors in pancreatic, stomach, bladder, and prostate cancers.[2][3]

Clinical trials[edit]

In July 2003, plitidepsin was granted orphan drug status by the European Medicines Agency for treating acute lymphoblastic leukemia.[4]

As of 2007, it was undergoing multicenter phase II clinical trials.[3]

In 2016, early results in a small phase I trial for multiple myeloma were announced.[5]

References[edit]

  1. ^ Cragg, G.M. & Newman, D.J. (2004). "Marine natural products and related compounds in clinical and advanced preclinical trials". Journal of Natural Products. 67 (8): 1216–1238. doi:10.1021/np040031y. PMID 15332835. 
  2. ^ Garrison, Tom. Oceanography: An Invitation to Marine Science 4th ed. United States: Brooks/Cole. 2002. 98.
  3. ^ a b Adrio, J.; et al. (2007). "Total Synthesis and Biological Evaluation of Tamandarin B Analogues". Journal of Organic Chemistry. 72 (14): 5129–5138. doi:10.1021/jo070412r. 
  4. ^ Public Summary of Positive Opinion for Orphan Designation of Aplidine for the Treatment of Acute Lymphoblastic Leukaemia
  5. ^ ASCO: Plitidepsin Shows Activity in Multiple Myeloma. June 2016