Plitidepsin
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MedKoo CAT#: 200150

CAS#: 137219-37-5

Description: Plitidepsin is a cyclic depsipeptide isolated from the marine tunicate Aplidium albicans. Plitidepsin displays a broad spectrum of antitumor activities, inducing apoptosis by triggering mitochondrial cytochrome c release, initiating the Fas/DC95, JNK pathway and activating caspase 3 activation. This agent also inhibits elongation factor 1-a, thereby interfering with protein synthesis, and induces G1 arrest and G2 blockade, thereby inhibiting tumor cell growth.


Chemical Structure

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Plitidepsin
CAS# 137219-37-5

Theoretical Analysis

MedKoo Cat#: 200150
Name: Plitidepsin
CAS#: 137219-37-5
Chemical Formula: C57H87N7O15
Exact Mass: 1109.62602
Molecular Weight: 1110.34
Elemental Analysis: C, 61.66; H, 7.90; N, 8.83; O, 21.61

Price and Availability

Size Price Availability Quantity
5.0mg USD 950.0 2 Weeks
10.0mg USD 1450.0 2 Weeks
25.0mg USD 2850.0 2 Weeks
50.0mg USD 4650.0 2 Weeks
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Synonym: aplidine; dehydrodemnin B. US brand name: Aplidin.

IUPAC/Chemical 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-15H-pyrrolo[2,1-f][1,15]dioxa[4,7,10,20]tetraazacyclotricosin-7-yl)amino)-4-methyl-1-oxopentan-2-yl)-N-methyl-1-(2-oxopropanoyl)pyrrolidine-2-carboxamide

InChi Key: UUSZLLQJYRSZIS-LXNNNBEUSA-N

InChi Code: InChI=1S/C57H87N7O15/c1-15-33(8)46-44(66)29-45(67)79-49(32(6)7)48(68)34(9)50(69)58-39(26-30(2)3)54(73)64-25-17-19-41(64)56(75)62(13)43(28-37-20-22-38(77-14)23-21-37)57(76)78-36(11)47(52(71)59-46)60-51(70)42(27-31(4)5)61(12)55(74)40-18-16-24-63(40)53(72)35(10)65/h20-23,30-34,36,39-44,46-47,49,66H,15-19,24-29H2,1-14H3,(H,58,69)(H,59,71)(H,60,70)/t33-,34-,36+,39-,40-,41-,42+,43-,44-,46+,47-,49-/m0/s1

SMILES Code: CC[C@@H]([C@@H]1[C@@H](O)CC(O[C@@H](C(C)C)C([C@H](C)C(N[C@@H](CC(C)C)C(N2CCC[C@H]2C(N(C)[C@@H](CC3=CC=C(OC)C=C3)C(O[C@H](C)[C@H](NC([C@H](N(C([C@@H]4CCCN4C(C(C)=O)=O)=O)C)CC(C)C)=O)C(N1)=O)=O)=O)=O)=O)=O)=O)C

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not soluble in water.

Shelf Life: >5 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Preparing Stock Solutions

The following data is based on the product molecular weight 1110.34 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL

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 1: Pardanani A, Tefferi A, Guglielmelli P, Bogani C, Bartalucci N, Rodríguez J, Extremera S, Pérez I, Alfaro V, Vannucchi AM. Evaluation of plitidepsin in patients with primary myelofibrosis and post polycythemia vera/essential thrombocythemia myelofibrosis: results of preclinical studies and a phase II clinical trial. Blood Cancer J. 2015 Mar 13;5:e286. doi: 10.1038/bcj.2015.5. PubMed PMID: 25768401; PubMed Central PMCID: PMC4382667.

2: Lollo G, Hervella P, Calvo P, Avilés P, Guillén MJ, Garcia-Fuentes M, Alonso MJ, Torres D. Enhanced in vivo therapeutic efficacy of plitidepsin-loaded nanocapsules decorated with a new poly-aminoacid-PEG derivative. Int J Pharm. 2015 Apr 10;483(1-2):212-9. doi: 10.1016/j.ijpharm.2015.02.028. Epub 2015 Feb 11. PubMed PMID: 25681727.

3: Galmarini CM, D'Incalci M, Allavena P. Trabectedin and plitidepsin: drugs from the sea that strike the tumor microenvironment. Mar Drugs. 2014 Jan 27;12(2):719-33. doi: 10.3390/md12020719. Review. PubMed PMID: 24473171; PubMed Central PMCID: PMC3944511.

4: Oliveira H, Thevenot J, Garanger E, Ibarboure E, Calvo P, Aviles P, Guillen MJ, Lecommandoux S. Nano-encapsulation of plitidepsin: in vivo pharmacokinetics, biodistribution, and efficacy in a renal xenograft tumor model. Pharm Res. 2014 Apr;31(4):983-91. doi: 10.1007/s11095-013-1220-3. Epub 2013 Nov 28. PubMed PMID: 24287622.

5: Plummer R, Lorigan P, Brown E, Zaucha R, Moiseyenko V, Demidov L, Soriano V, Chmielowska E, Andrés R, Kudryavtseva G, Kahatt C, Szyldergemajn S, Extremera S, de Miguel B, Cullell-Young M, Calvert H. Phase I-II study of plitidepsin and dacarbazine as first-line therapy for advanced melanoma. Br J Cancer. 2013 Sep 17;109(6):1451-9. doi: 10.1038/bjc.2013.477. Epub 2013 Aug 29. PubMed PMID: 23989947; PubMed Central PMCID: PMC3776988.

6: Muñoz-Alonso MJ, Álvarez E, Guillén-Navarro MJ, Pollán M, Avilés P, Galmarini CM, Muñoz A. c-Jun N-terminal kinase phosphorylation is a biomarker of plitidepsin activity. Mar Drugs. 2013 May 21;11(5):1677-92. doi: 10.3390/md11051677. PubMed PMID: 23697951; PubMed Central PMCID: PMC3707168.

7: Ribrag V, Caballero D, Fermé C, Zucca E, Arranz R, Briones J, Gisselbrecht C, Salles G, Gianni AM, Gomez H, Kahatt C, Corrado C, Szyldergemajn S, Extremera S, de Miguel B, Cullell-Young M, Cavalli F. Multicenter phase II study of plitidepsin in patients with relapsed/refractory non-Hodgkin's lymphoma. Haematologica. 2013 Mar;98(3):357-63. doi: 10.3324/haematol.2012.069757. Epub 2012 Oct 12. PubMed PMID: 23065525; PubMed Central PMCID: PMC3659946.

8: Barboza NM, Medina DJ, Budak-Alpdogan T, Aracil M, Jimeno JM, Bertino JR, Banerjee D. Plitidepsin (Aplidin) is a potent inhibitor of diffuse large cell and Burkitt lymphoma and is synergistic with rituximab. Cancer Biol Ther. 2012 Jan 15;13(2):114-22. doi: cbt.13.2.18876. PubMed PMID: 22336911; PubMed Central PMCID: PMC3336068.

9: Geoerger B, Estlin EJ, Aerts I, Kearns P, Gibson B, Corradini N, Doz F, Lardelli P, Miguel BD, Soto A, Prados R, Vassal G. A phase I and pharmacokinetic study of plitidepsin in children with advanced solid tumours: an Innovative Therapies for Children with Cancer (ITCC) study. Eur J Cancer. 2012 Feb;48(3):289-96. doi: 10.1016/j.ejca.2011.10.036. Epub 2011 Nov 24. PubMed PMID: 22119199.

10: Soto-Matos A, Szyldergemajn S, Extremera S, Miguel-Lillo B, Alfaro V, Coronado C, Lardelli P, Roy E, Corrado CS, Kahatt C. Plitidepsin has a safe cardiac profile: a comprehensive analysis. Mar Drugs. 2011;9(6):1007-23. doi: 10.3390/md9061007. Epub 2011 Jun 9. PubMed PMID: 21747745; PubMed Central PMCID: PMC3131558.

11: Salazar R, Plummer R, Oaknin A, Robinson A, Pardo B, Soto-Matos A, Yovine A, Szyldergemajn S, Calvert AH. Phase I study of weekly plitidepsin as 1-hour infusion combined with carboplatin in patients with advanced solid tumors or lymphomas. Invest New Drugs. 2011 Dec;29(6):1406-13. doi: 10.1007/s10637-010-9488-1. Epub 2010 Jul 10. PubMed PMID: 20623160.

12: Mateos MV, Cibeira MT, Richardson PG, Prosper F, Oriol A, de la Rubia J, Lahuerta JJ, García-Sanz R, Extremera S, Szyldergemajn S, Corrado C, Singer H, Mitsiades CS, Anderson KC, Bladé J, San Miguel J. Phase II clinical and pharmacokinetic study of plitidepsin 3-hour infusion every two weeks alone or with dexamethasone in relapsed and refractory multiple myeloma. Clin Cancer Res. 2010 Jun 15;16(12):3260-9. doi: 10.1158/1078-0432.CCR-10-0469. Epub 2010 Jun 8. PubMed PMID: 20530693.

13: Longo-Sorbello GS, Gao H, Mishra PJ, Kamen B, Soto A, Jimeno J, Aracil M, Paz de Paz MF, Bertino JR, Banerjee D. Heparin and suramin alter plitidepsin uptake via inhibition of GPCR coupled signaling. J Chemother. 2009 Nov;21(5):550-7. PubMed PMID: 19933047.

14: Dumez H, Gallardo E, Culine S, Galceran JC, Schöffski P, Droz JP, Extremera S, Szyldergemajn S, Fléchon A. Phase II study of biweekly plitidepsin as second-line therapy for advanced or metastatic transitional cell carcinoma of the urothelium. Mar Drugs. 2009 Sep 16;7(3):451-63. doi: 10.3390/md7030451. PubMed PMID: 19841725; PubMed Central PMCID: PMC2763111.

15: Baudin E, Droz JP, Paz-Ares L, van Oosterom AT, Cullell-Young M, Schlumberger M. Phase II study of plitidepsin 3-hour infusion every 2 weeks in patients with unresectable advanced medullary thyroid carcinoma. Am J Clin Oncol. 2010 Feb;33(1):83-8. doi: 10.1097/COC.0b013e31819fdf5e. PubMed PMID: 19704366.

16: Le Tourneau C, Faivre S, Ciruelos E, Domínguez MJ, López-Martín JA, Izquierdo MA, Jimeno J, Raymond E. Reports of clinical benefit of plitidepsin (Aplidine), a new marine-derived anticancer agent, in patients with advanced medullary thyroid carcinoma. Am J Clin Oncol. 2010 Apr;33(2):132-6. doi: 10.1097/COC.0b013e318199fb6e. PubMed PMID: 19687728.

17: Muñoz-Alonso MJ, González-Santiago L, Martínez T, Losada A, Galmarini CM, Muñoz A. The mechanism of action of plitidepsin. Curr Opin Investig Drugs. 2009 Jun;10(6):536-42. Review. PubMed PMID: 19513942.

18: Eisen T, Thomas J, Miller WH Jr, Gore M, Wolter P, Kavan P, Martín JA, Lardelli P. Phase II study of biweekly plitidepsin as second-line therapy in patients with advanced malignant melanoma. Melanoma Res. 2009 Jun;19(3):185-92. doi: 10.1097/CMR.0b013e32832bbde6. PubMed PMID: 19436178.

19: Schöffski P, Guillem V, Garcia M, Rivera F, Tabernero J, Cullell M, Lopez-Martin JA, Pollard P, Dumez H, del Muro XG, Paz-Ares L. Phase II randomized study of Plitidepsin (Aplidin), alone or in association with L-carnitine, in patients with unresectable advanced renal cell carcinoma. Mar Drugs. 2009;7(1):57-70. doi: 10.3390/md7010057. Epub 2009 Mar 5. PubMed PMID: 19370171; PubMed Central PMCID: PMC2666889.

20: Nalda-Molina R, Valenzuela B, Ramon-Lopez A, Miguel-Lillo B, Soto-Matos A, Perez-Ruixo JJ. Population pharmacokinetics meta-analysis of plitidepsin (Aplidin) in cancer subjects. Cancer Chemother Pharmacol. 2009 Jun;64(1):97-108. doi: 10.1007/s00280-008-0841-4. Epub 2008 Oct 22. PubMed PMID: 18941750.



Additional Information

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.

plitidepsin exhibits antitumor, antiviral and immunosuppressive activities. It shows promise in shrinking tumors in pancreatic, stomach, bladder, and prostate cancers. As of 2007, it was undergoing multicenter phase II clinical trials, In July 2003, plitidepsin was granted orphan drug status by the European Medicines Agency for treating acute lymphoblastic leukemia.