| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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Plitidepsin (dehydrodemnin B; aplidine; Aplidin) is a naturally occurring cyclic depsipeptide extracted from the marine tunicate Aplidium albicans with a broad spectrum of anticancer activities.
| ln Vitro |
In MOLT-4 cells, plitidepsin (20 nM; 1 h) causes VEGF dependency [1]. In normal endothelial cells, which express VEGFR-1 but do not support VEGF, plitidepsin (20 nM; 1 h) does not significantly decrease VEGF-R1 mRNA [1]. SARS-CoV-2 is inhibited by plitidepsin, with an IC90 of 1.76 nM. Plitidepsin exhibits anti-SARS-CoV-2 action in hACE2-293T cells, with an IC90 of 0.88 nM. Plitidepsin suppresses SARS-CoV-2 replication in the established cell model of human lung cell samples, with an IC90 of 3.14 nM and a selectivity index of 40.4 [1].
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| ln Vivo |
In BALB/c samples expressing human ACE2, plitidepsin (ip; 0.3 mg/kg or 1 mg/kg; 2 hours prior to SARS-CoV-2 infection) dramatically lowers SARS-CoV-2 infection. In comparison to the vector desert, the SARS-CoV-2 viral decrease in the lungs was almost two log units lower in the 0.3 mg/kg plitidepsin group and 1.5 log units lower in the 1 mg/kg group [2].
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| Animal Protocol |
Animal/Disease Models: balb/c (Bagg ALBino) mouse[2]. 1]
Doses: 0.3 mg/kg; 1 mg/kg Dosing: 1 mg/kg QD for 1 day; 0.3 mg/kg daily for 3 days Experimental Results: Shown in vivo in SARS-CoV-2 infection mouse model Antiviral effect. |
| ADME/Pharmacokinetics |
Metabolism / Metabolites
Hepatic |
| References | |
| Additional Infomation |
Plitidepsin is a didemnin that is didemin B in which the hydroxy group of the 1-(2-hydroxypropanoyl)-L-prolinamide moiety has been oxidised to the corresponding ketone. It was originally isolated from the Mediterranean tunicate Aplidium albicans. It has a role as a marine metabolite, an antineoplastic agent and an anticoronaviral agent.
Aplidine is a peptide found in tunicates which shows promise in shrinking tumors in pancreatic, stomach, bladder, and prostate cancers. The specific marine organism is Aplidium albicans. Aplidine is also of interest as a potential treatment for some leukemias. 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. Drug Indication Intended for the treatment of various forms of cancer. Treatment of Coronavirus disease 2019 (COVID-19) Mechanism of Action Plitidepsin has antineoplastic activity which stems from plitidepsin's ability to inhibit cell growth and induce apoptosis. Plitidepsin's primary intracellular target is the eukaryotic elongation factor 1A2 (eEF1A2). It also inhibits the growth and induces apoptosis in MOLT-4 cells by inhibiting VEGF secretion, which blocks the VEGF/VEGFR-1 autocrine loop that is required for the growth of the MOLT-4 cells. Through inhibition of eEF1A, plitidepsin also demonstrated antiviral activity against SARS-CoV-2. The exact mechanism of action is not fully understood and plitidepsin may have multiple modes of action. |
| Molecular Formula |
C57H87N7O15
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|---|---|
| Molecular Weight |
1110.34
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| Exact Mass |
1109.63
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| Elemental Analysis |
C, 61.66; H, 7.90; N, 8.83; O, 21.61
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| CAS # |
137219-37-5
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| PubChem CID |
9812534
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| Appearance |
White to off-white solid powder
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| Density |
1.24g/cm3
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| Index of Refraction |
1.567
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| LogP |
-0.59
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
15
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| Rotatable Bond Count |
15
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| Heavy Atom Count |
79
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| Complexity |
2200
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| Defined Atom Stereocenter Count |
12
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| SMILES |
O=C1[C@]([H])(C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C([C@@]([H])(C([H])([H])[H])C([C@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])OC(C([H])([H])[C@@]([H])([C@@]([H])([C@@]([H])(C([H])([H])[H])C([H])([H])C([H])([H])[H])N([H])C([C@]([H])([C@@]([H])(C([H])([H])[H])OC([C@]([H])(C([H])([H])C2C([H])=C([H])C(=C([H])C=2[H])OC([H])([H])[H])N(C([H])([H])[H])C([C@]2([H])C([H])([H])C([H])([H])C([H])([H])N21)=O)=O)N([H])C([C@@]([H])(C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H])N(C([H])([H])[H])C([C@]1([H])C([H])([H])C([H])([H])C([H])([H])N1C(C(C([H])([H])[H])=O)=O)=O)=O)=O)O[H])=O)=O)=O
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| InChi Key |
UUSZLLQJYRSZIS-LXNNNBEUSA-N
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| 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
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| Chemical Name |
(2S)-N-[(2R)-1-[[(3S,6S,8S,12S,13R,16S,17R,20S,23S)-13-[(2S)-butan-2-yl]-12-hydroxy-20-[(4-methoxyphenyl)methyl]-6,17,21-trimethyl-3-(2-methylpropyl)-2,5,7,10,15,19,22-heptaoxo-8-propan-2-yl-9,18-dioxa-1,4,14,21-tetrazabicyclo[21.3.0]hexacosan-16-yl]amino]-4-methyl-1-oxopentan-2-yl]-N-methyl-1-(2-oxopropanoyl)pyrrolidine-2-carboxamide
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| Synonyms |
dehydrodemnin B; aplidine. US brand name: Aplidin.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~100 mg/mL (~90.1 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (2.25 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (2.25 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9006 mL | 4.5031 mL | 9.0063 mL | |
| 5 mM | 0.1801 mL | 0.9006 mL | 1.8013 mL | |
| 10 mM | 0.0901 mL | 0.4503 mL | 0.9006 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Trial of Plitidepsin (Aplidin®) in Combination With Bortezomib and Dexamethasone in Multiple Myeloma Patients Double Refractory to Bortezomib and Lenalidomide
CTID: NCT03117361
Phase: Phase 2 Status: Terminated
Date: 2020-12-02
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