Plitidepsin (Synonyms: Aplidin, Dehydrodidemnin B) |
رقم الكتالوجGC49148
One-Click Copy Product Info
|
Plitidepsin (Aplidine) هو عامل فعال مضاد للسرطان من خلال استهداف eEF1A2 (KD = 80 نانومتر)
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 137219-37-5
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
Plitidepsin is a cyclic depsipeptide that targets eEF1A2, with a KD value of 80nM [1]. Plitidepsin inhibits the replication of SARS-CoV-2 by suppressing the activity of eEF1A, with an IC50 value of 0.73nM[2]. Plitidepsin can induce a dose-dependent cell cycle arrest process, accompanied by the induction of early oxidative stress, the rapid activation of Rac1 GTPase, and the continuous activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38/MAPK), ultimately leading to caspase-dependent apoptosis[3]. Plitidepsin has been widely used to inhibit the growth of various cancer cells and xenograft tumors[4].
In vitro, Plitidepsin treatment for 48 hours significantly inhibited the proliferation of KOC-7C cells, RMG-I cells, and TOV-21G cells, with IC50 values of 3.61nM, 4.97nM, and 2.51nM, respectively[5]. Treatment with 450nM Plitidepsin for 6 hours induced endoplasmic reticulum stress and autophagy in HeLa cells and promoted the degradation of the CHOP protein[6].
In vivo, Plitidepsin treatment via intraperitoneal injection at a dose of 90μg/kg five times a week for 1 week significantly inhibited the serum paraprotein concentration and myeloma-related angiogenesis in the 5T33MMvv myeloma mouse model [7]. For three consecutive days, a daily intraperitoneal injection of 1mg/kg dose of Plitidepsin was administered, which significantly inhibited tumor growth in the ARO-81 cell-xenograft mouse model, and suppressed the expression of multiple angiogenesis genes[8].
References:
[1] Losada A, Muñoz-Alonso M J, García C, et al. Translation elongation factor eEF1A2 is a novel anticancer target for the marine natural product plitidepsin[J]. Scientific reports, 2016, 6(1): 35100.
[2] White K M, Rosales R, Yildiz S, et al. Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A[J]. Science, 2021, 371(6532): 926-931.
[3] Alonso-Álvarez S, Pardal E, Sánchez-Nieto D, et al. Plitidepsin: design, development, and potential place in therapy[J]. Drug Design, Development and Therapy, 2017: 253-264.
[4] Barboza N M, Medina D J, Budak-Alpdogan T, et al. Plitidepsin (Aplidin) is a potent inhibitor of diffuse large cell and Burkitt lymphoma and is synergistic with rituximab[J]. Cancer biology & therapy, 2012, 13(2): 114-122.
[5] Miyake R, Yamanaka S, Matsubara S, et al. Preclinical activity of plitidepsin against clear cell carcinoma of the ovary[J]. Anticancer Research, 2021, 41(9): 4277-4285.
[6] Losada A, Berlanga J J, Molina-Guijarro J M, et al. Generation of endoplasmic reticulum stress and inhibition of autophagy by plitidepsin induces proteotoxic apoptosis in cancer cells[J]. Biochemical pharmacology, 2020, 172: 113744.
[7] Caers J, Menu E, De Raeve H, et al. Antitumour and antiangiogenic effects of Aplidin® in the 5TMM syngeneic models of multiple myeloma[J]. British journal of cancer, 2008, 98(12): 1966-1974.
[8] Straight A M, Oakley K, Moores R, et al. Aplidin reduces growth of anaplastic thyroid cancer xenografts and the expression of several angiogenic genes[J]. Cancer chemotherapy and pharmacology, 2006, 57(1): 7-14.
| Cell experiment [1]: | |
Cell lines | KOC-7C cells |
Preparation Method | KOC-7C cells were cultured in DMEM medium containing 10% fetal bovine serum (FBS) in 5% CO2 at 37°C. Cells were placed in 96-well plates at a concentration of 1×104 cells per well. The cells were treated with different concentrations of Plitidepsin (0, 0.1, 0.5, 1, 5, 10, and 50nM) for 48 hours, and then the cell viability was analyzed. |
Reaction Conditions | 0, 0.1, 0.5, 1, 5, 10, and 50nM; 48h |
Applications | Plitidepsin treatment significantly reduced cell proliferation in KOC-7C cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | BALB/c nu/nu mice |
Preparation Method | BALB/c nu/nu mice (20-24g) were housed in a specialized animal care facility, in a room with constant temperature (25°C), humidity control, and a 12/12h light/dark cycle with free access to food and water. Mice were injected subcutaneously with 1×106 ARO-81 cells. Cells were allowed to implant for 3 weeks. Mice were then randomized (n=10 for each treatment) to receive one of the following treatments for 3 days. Negative control—vehicle only (PBS); Plitidepsin group: 1mg/kg/day. All vehicle and Plitidepsin treatments were administered intraperitoneally. Tumor size was measured daily with skin calipers. |
Dosage form | 1mg/kg/day for 3 days; i.p. |
Applications | Plitidepsin treatment significantly inhibited tumor growth in the ARO-81 cell-xenograft mouse model. |
References: | |
| Cas No. | 137219-37-5 | SDF | |
| المرادفات | Aplidin, Dehydrodidemnin B | ||
| Canonical SMILES | O=C1N2[C@](CCC2)([H])C(N([C@H](C(O[C@@H]([C@@H](C(N[C@]([C@H](CC(O[C@H](C([C@@H](C(N[C@H]1CC(C)C)=O)C)=O)C(C)C)=O)O)([H])[C@@H](C)CC)=O)NC([C@@H](CC(C)C)N(C)C([C@H]3N(C(C(C)=O)=O)CCC3)=O)=O)C)=O)CC4=CC=C(C=C4)OC)C)=O | ||
| Formula | C57H87N7O15 | M.Wt | 1110.3 |
| الذوبان | DMSO : 100 mg/mL (90.06 mM; Need ultrasonic) | Storage | -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 900.7 μL | 4.5033 mL | 9.0066 mL |
| 5 mM | 180.1 μL | 900.7 μL | 1.8013 mL |
| 10 mM | 90.1 μL | 450.3 μL | 900.7 μL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 39 reference(s) in Google Scholar.)