Plitidepsin是一种环状缩肽，靶向eEF1A2，KD值为80nM。
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.
Plitidepsin是一种环状缩肽，靶向eEF1A2，KD值为80nM[1]。Plitidepsin通过抑制eEF1A的活性来抑制 SARS-CoV-2的复制，IC50值为0.73nM[2]。Plitidepsin可诱导剂量依赖性的细胞周期阻滞过程，同时伴有早期氧化应激的诱导、Rac1 GTPase的快速激活以及c-Jun N-terminal kinase (JNK)和p38丝裂原活化蛋白激酶的持续激活，最终导致caspase依赖性凋亡[3]。Plitidepsin已被广泛用于抑制多种癌细胞和异种移植肿瘤的生长[4]。
在体外，Plitidepsin处理48小时显著抑制了KOC-7C细胞、RMG-I细胞和TOV-21G细胞的增殖，IC50值分别为3.61nM、4.97nM和2.51nM[5]。使用450nM的Plitidepsin处理HeLa细胞6小时，诱导了内质网应激和自噬，并促进了CHOP蛋白的降解[6]。
在体内，每周五次腹腔注射90µg/kg剂量的Plitidepsin，持续1周，显著抑制了5T33MMvv骨髓瘤小鼠模型中的血清paraprotein浓度和骨髓瘤相关的血管生成[7]。连续三天每日腹腔注射1mg/kg剂量的Plitidepsin，显著抑制了ARO-81细胞异种移植小鼠模型中的肿瘤生长，并抑制了多种血管生成基因的表达[8]。
| 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 | |
| 别名 | 普拉泰,Aplidine | ||
| 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 | ||
| 分子式 | C57H87N7O15 | 分子量 | 1110.3 |
| 溶解度 | DMSO : 100 mg/mL (90.06 mM; Need ultrasonic) | 储存条件 | -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet