Plitidepsin

Plitidepsin
Names
Systematic IUPAC name
(2S)-N-[(1R)-1-({(3S,6R,7S,10R,11S,15S,17S,20S,25aS)-10-[(2S)-Butan-2-yl]-11-hydroxy-3-[(4-methoxyphenyl)methyl]-2,6,17-trimethyl-20-(2-methylpropyl)-1,4,8,13,16,18,21-heptaoxo-15-(propan-2-yl)docosahydro-15H-pyrrolo[2,1-d] [10,19,1,4,7,14]dioxatetraazacyclotricosin-7-yl}carbamoyl)-3-methylbutyl]-N-methyl-1-(2-oxopropanoyl)pyrrolidine-2-carboxamide
Other names
Aplidine; Aplidin, dehydrodidemnin B; Aplidin; N-[1-(1,2-Dioxopropyl)-L-prolyl]didemnin A
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
KEGG
UNII
  • InChI=1S/C59H91N7O14/c1-15-35(8)50-47(69)30-49(71)80-53(34(6)7)52(72)37(10)54(73)60-41(26-32(2)3)58(77)65-24-16-18-42(65)48(70)31-63(12)44(29-39-20-22-40(79-14)23-21-39)46(68)28-36(9)51(56(75)61-50)62-55(74)45(27-33(4)5)64(13)59(78)43-19-17-25-66(43)57(76)38(11)67/h20-23,32-37,41-45,47,50-51,53,69H,15-19,24-31H2,1-14H3,(H,60,73)(H,61,75)(H,62,74)/t35-,36-,37-,41-,42-,43-,44-,45+,47-,50+,51-,53-/m0/s1
    Key: RZFJKZZAZSUBCF-VETSTYKFSA-N
  • O=C([C@@H](NC([C@@H](C)C([C@@H](OC(C[C@H](O)[C@H](NC([C@@H](NC([C@H](N(C([C@H]1N(C(C(C)=O)=O)CCC1)=O)C)CC(C)C)=O)[C@@H](C)OC([C@H](CC2=CC=C(OC)C=C2)N3C)=O)=O)[C@@H](C)CC)=O)C(C)C)=O)=O)CC(C)C)N4[C@H](C3=O)CCC4
Properties
C57H87N7O15
Molar mass 1110.357 g·mol−1
Pharmacology
L01XX57 (WHO)
Legal status
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 and sold under the brand name Aplidin, is a chemical compound extracted from the ascidian Aplidium albicans.[3]

Medical uses

In Australia, plitidepsin, in combination with dexamethasone, is indicated for the treatment of people with relapsed and refractory multiple myeloma.[1][2][4]

Pharmacological activity

Plitidepsin exhibits antitumor, antiviral and immunosuppressive activities. It shows promise in shrinking tumors in pancreatic, stomach, bladder, and prostate cancers.[5][6]

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.[7]

Society and culture

In July 2003, plitidepsin was granted orphan drug status by the European Medicines Agency (EMA) for treating acute lymphoblastic leukemia.[8] In December 2017, the EMA's Committee for Medicinal Products for Human Use (CHMP) adopted a negative opinion, recommending the refusal of the marketing authorization for the treatment of multiple myeloma.[9] After a re-examination of the opinion, the refusal of the marketing authorization was confirmed in March 2018.[9] The CHMP is of the opinion that the benefits of Aplidin do not outweigh its risks.[9] In October 2020, the General Court upheld PharmaMar's appeal and annulled the decision refusing marketing authorization for Aplidin, and the European Commission then returned the application for Aplidin to the EMA.[9][10] In July 2025, PharmaMar withdrew its application for a marketing authorization of Aplidin for the treatment of multiple myeloma.[9]

Plitidepsin was approved for medical used in Australia in December 2018.[2]

References

  1. ^ a b c https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2018-PI-02713-1
  2. ^ a b c d "AusPAR: Plitidepsin". Therapeutic Goods Administration (TGA). 8 July 2019.
  3. ^ Newman DJ, Cragg GM (August 2004). "Marine natural products and related compounds in clinical and advanced preclinical trials". Journal of Natural Products. 67 (8): 1216–38. doi:10.1021/np040031y. PMID 15332835.
  4. ^ "Aplidin (Specialised Therapeutics Pharma Pty Ltd)". Therapeutic Goods Administration (TGA). 24 July 2025. Retrieved 27 July 2025.
  5. ^ Garrison T (2002). Oceanography: An Invitation to Marine Science (4th ed.). United States: Brooks/Cole. p. 98.
  6. ^ Adrio J, Cuevas C, Manzanares I, Joullié MM (July 2007). "Total synthesis and biological evaluation of tamandarin B analogues". The Journal of Organic Chemistry. 72 (14): 5129–38. doi:10.1021/jo070412r. PMID 17555353.
  7. ^ White KM, Rosales R, Yildiz S, Kehrer T, Miorin L, Moreno E, et al. (January 2021). "Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A". Science. 371 (6532): 926–931. Bibcode:2021Sci...371..926W. doi:10.1126/science.abf4058. PMC 7963220. PMID 33495306.
  8. ^ "Public Summary of Positive Opinion for Orphan Designation of Aplidine for the Treatment of Acute Lymphoblastic Leukaemia" (PDF). European Medicines Agency (EMA). 1 September 2011.
  9. ^ a b c d e "Aplidin EPAR". European Medicines Agency (EMA).
  10. ^ "Aplidin". European Medicines Agency. 28 October 2020. Retrieved 11 July 2024.

Further reading

Delgado-Calle J, Kurihara N, Atkinson EG, Nelson J, Miyagawa K, Galmarini CM, et al. (April 2019). "Aplidin (plitidepsin) is a novel anti-myeloma agent with potent anti-resorptive activity mediated by direct effects on osteoclasts". Oncotarget. 10 (28): 2709–2721. doi:10.18632/oncotarget.26831. PMC 6505631. PMID 31105871.

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