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MedKoo Cat#: 200150 | Name: Plitidepsin
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

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

Plitidepsin
Plitidepsin
CAS#137219-37-5

Theoretical Analysis

MedKoo Cat#: 200150

Name: Plitidepsin

CAS#: 137219-37-5

Chemical Formula: C57H87N7O15

Exact Mass: 1109.6260

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
1mg USD 250.00 Ready to ship
5mg USD 750.00 Ready to ship
10mg USD 1,350.00 Ready to ship
25mg USD 2,650.00 Ready to Ship
50mg USD 3,950.00 2 Weeks
100mg USD 6,250.00 2 Weeks
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Related CAS #
No Data
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
More Info
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.
Biological target:
Plitidepsin is a cyclic depsipeptide that inhibits elongation factor 1-a and induces G1 arrest and G2 blockade.
In vitro activity:
It was investigated, in vitro, whether aplidine could affect endothelial cell functions relevant to angiogenesis. Aplidine inhibited the proliferation of endothelial cells (Figure 4). The antiproliferative effect of aplidine was observed when proliferation was stimulated by both VEGF and FGF-2. Some inhibitory effect was observed after 1 h exposure to the compound, with IC50 of 8.1 and 5.7 nm for VEGF and FGF-2, respectively. Exposure to aplidine for longer times (24–72 h) increased the cytotoxic effect of the compound (Figure 4). Aplidine also affected endothelial cell motility and invasiveness, assayed in the Boyden chamber, using supernatant of NIH-3T3 cells as the attractant. Pretreatment with aplidine for 1 h resulted in a dose-dependent inhibition of cell migration, with an IC50 of 5.5 nm for chemotaxis and 0.9 nm for invasiveness (Figure 5). The same results were obtained when aplidine was added to the lower compartment of the chemotaxis chamber (not shown). Aplidine also inhibited the motility and invasive response of endothelial cells to VEGF and FGF-2 (for chemotaxis, IC50 was 9.5 and 11.6 nm; for chemoinvasion, IC50 was 1.8 and 0.5 nm for VEGF and FGF-2, respectively). These findings that aplidine blocked endothelial cell proliferation, migration, invasion and cord formation in vitro suggest that the compound acts at multiple levels of the angiogenic cascade. Reference: Br J Cancer. 2004 Jun 14; 90(12): 2418–2424. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409535/
In vivo activity:
The antiangiogenic activity of aplidine was investigated in the chick CAM assay, in vivo, a useful model to investigate the effect of compounds on both basal angiogenesis and angiogenesis induced by an exogenous stimulus (Ribatti et al, 2001). Aplidine, added to the CAM, affected the basal growth of vessels, inhibiting the number of blood vessels in 80% of the treated embryos (Figure 1). Aplidine also affected angiogenesis induced by exogenous angiogenic factors added to the CAMs. Vascular endothelial growth factor or FGF-2 induced the growth of numerous allantoic vessels converging like spokes toward the sponge (Figure 2A). Aplidine (10 nm) significantly reduced the angiogenic response induced by VEGF and, at a lower extent, by FGF-2 (Figures 1 and 2B). It was next investigated whether aplidine also inhibited tumour angiogenesis induced in the CAM by tumours. The human ovarian carcinoma 1A9 and its VEGF overexpressing clone 1A9-VS4 were injected subcutaneously in nude mice. The addition of aplidine caused a significant (P⩽0.001) reduction in the angiogenic response induced by the tumour specimens (number of vessels was 20±4 and 11±3 for 1A9-VS4 and 1A9, respectively, Figure 3B). These findings indicate that aplidine prevented angiogenesis in vivo, affecting both physiologic, spontaneous angiogenesis of the embryo, angiogenesis induced by exogenous stimuli (VEGF and FGF-2) and tumour angiogenesis Reference: Br J Cancer. 2004 Jun 14; 90(12): 2418–2424. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409535/
Solvent mg/mL mM comments
Solubility
H2O 0.0 0.02
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 1,110.34 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
Formulation protocol:
1. Gajate C, An F, Mollinedo F. Rapid and selective apoptosis in human leukemic cells induced by Aplidine through a Fas/CD95- and mitochondrial-mediated mechanism. Clin Cancer Res. 2003 Apr;9(4):1535-45. PMID: 12684430. 2. Taraboletti G, Poli M, Dossi R, Manenti L, Borsotti P, Faircloth GT, Broggini M, D'Incalci M, Ribatti D, Giavazzi R. Antiangiogenic activity of aplidine, a new agent of marine origin. Br J Cancer. 2004 Jun 14;90(12):2418-24. doi: 10.1038/sj.bjc.6601864. PMID: 15173857; PMCID: PMC2409535. 3. Verrucci M, Pancrazzi A, Aracil M, Martelli F, Guglielmelli P, Zingariello M, Ghinassi B, D'Amore E, Jimeno J, Vannucchi AM, Migliaccio AR. CXCR4-independent rescue of the myeloproliferative defect of the Gata1low myelofibrosis mouse model by Aplidin. J Cell Physiol. 2010 Nov;225(2):490-9. doi: 10.1002/jcp.22228. PMID: 20458749; PMCID: PMC3780594.
In vitro protocol:
1. Gajate C, An F, Mollinedo F. Rapid and selective apoptosis in human leukemic cells induced by Aplidine through a Fas/CD95- and mitochondrial-mediated mechanism. Clin Cancer Res. 2003 Apr;9(4):1535-45. PMID: 12684430. 2. Taraboletti G, Poli M, Dossi R, Manenti L, Borsotti P, Faircloth GT, Broggini M, D'Incalci M, Ribatti D, Giavazzi R. Antiangiogenic activity of aplidine, a new agent of marine origin. Br J Cancer. 2004 Jun 14;90(12):2418-24. doi: 10.1038/sj.bjc.6601864. PMID: 15173857; PMCID: PMC2409535.
In vivo protocol:
1. Taraboletti G, Poli M, Dossi R, Manenti L, Borsotti P, Faircloth GT, Broggini M, D'Incalci M, Ribatti D, Giavazzi R. Antiangiogenic activity of aplidine, a new agent of marine origin. Br J Cancer. 2004 Jun 14;90(12):2418-24. doi: 10.1038/sj.bjc.6601864. PMID: 15173857; PMCID: PMC2409535. 1. Verrucci M, Pancrazzi A, Aracil M, Martelli F, Guglielmelli P, Zingariello M, Ghinassi B, D'Amore E, Jimeno J, Vannucchi AM, Migliaccio AR. CXCR4-independent rescue of the myeloproliferative defect of the Gata1low myelofibrosis mouse model by Aplidin. J Cell Physiol. 2010 Nov;225(2):490-9. doi: 10.1002/jcp.22228. PMID: 20458749; PMCID: PMC3780594.
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Outcomes and clinical characteristics of the compassionate use of plitidepsin in COVID-19 patients with solid tumours, haematological malignancies or anti-CD20 antibody treatment. Infect Dis (Lond). 2024 Jul;56(7):575-580. doi: 10.1080/23744235.2024.2351043. Epub 2024 May 14. PMID: 38743059. 3: Zhang W, Wang J, Shan C. The eEF1A protein in cancer: Clinical significance, oncogenic mechanisms, and targeted therapeutic strategies. Pharmacol Res. 2024 Jun;204:107195. doi: 10.1016/j.phrs.2024.107195. Epub 2024 Apr 25. PMID: 38677532. 4: Garcia MR, Andrade PB, Lefranc F, Gomes NGM. Marine-Derived Leads as Anticancer Candidates by Disrupting Hypoxic Signaling through Hypoxia-Inducible Factors Inhibition. Mar Drugs. 2024 Mar 23;22(4):143. doi: 10.3390/md22040143. 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PMID: 37481109. 11: Lorente-González M, Terán-Tinedo JR, Zevallos-Villegas A, Laorden D, Mariscal-Aguilar P, Suárez-Ortiz M, Cano-Sanz E, Ortega-Fraile MÁ, Hernández- Núñez J, Falcone A, Saiz-Lou EM, Plaza-Moreno MC, García-Fadul C, Valle-Falcones M, Sánchez-Azofra A, Funes-Moreno C, De-La-Calle-Gil I, Navarro-Casado R, Carballo-López D, Gholamian-Ovejero S, Gallego-Rodríguez B, Villén-Villegas T, Landete P. Severe SARS-CoV-2 Pneumonia and Pneumomediastinum/Pneumothorax: A Prospective Observational Study in an Intermediate Respiratory Care Unit. J Intensive Care Med. 2023 Nov;38(11):1023-1041. doi: 10.1177/08850666231180165. Epub 2023 Jun 12. PMID: 37306158; PMCID: PMC10261956. 12: Yarza R, Bover M, Herrera-Juarez M, Rey-Cardenas M, Paz-Ares L, Lopez-Martin JA, Haanen J. Efficacy of T-Cell Receptor-Based Adoptive Cell Therapy in Cutaneous Melanoma: A Meta-Analysis. Oncologist. 2023 Jun 2;28(6):e406-e415. doi: 10.1093/oncolo/oyad078. 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PMID: 35736200; PMCID: PMC9230156. 19: Teran-Tinedo JR, Gonzalez-Rubio J, Najera A, Castany-Faro A, Contreras MLN, Garcia IM, Lopez-Mellado L, Lorente-Gonzalez M, Perez-Garvin P, Sacristan-Crespo G, Suarez-Ortiz M, Navarro-Lopez JD, Jimenez-Diaz L, Landete P. Clinical characteristics and respiratory care in hospitalized vaccinated SARS-CoV-2 patients. EClinicalMedicine. 2022 Jun;48:101453. doi: 10.1016/j.eclinm.2022.101453. Epub 2022 May 20. PMID: 35611064; PMCID: PMC9121909. 20: Ledford H. Hundreds of COVID trials could provide a deluge of new drugs. Nature. 2022 Mar;603(7899):25-27. doi: 10.1038/d41586-022-00562-0. PMID: 35233098.