What Is Plitidepsin?
Plitidepsin, also known as Aplidin, is a cyclic depsipeptide originally isolated from the Mediterranean tunicate Aplidium albicans. Its dual antitumor and antiviral capabilities position it as a potential treatment option for cancer and infectious diseases. Structurally, plitidepsin belongs to the class of cyclic depsipeptides, characterized by sequences of amino and hydroxy carboxylic acids arranged in a ring structure.
| Catalog | Product Name | |
| ACM137219375 | Plitidepsin | Inquiry |
How Does Plitidepsin Work?
Plitidepsin exerts its biological activity primarily through inhibition of the eukaryotic elongation factor 1A2 (eEF1A2). This disruption interferes with protein synthesis and induces apoptosis in malignant cells. Additionally, plitidepsin targets the VEGF/VEGFR-1 autocrine loop, which is crucial for the survival and proliferation of certain cancer cells, such as MOLT-4 leukemia cells.
Fig.1 (A) Chemical structure. (B) Besides inducing apoptosis of Chronic Lymphocytic Leukemia (CLL) cells, Plitidepsin also acts on monocytes and NLCs[1].
Beyond its antitumor effects, plitidepsin has demonstrated antiviral properties, particularly against SARS-CoV-2. By inhibiting eEF1A - a host factor required for viral replication - plitidepsin effectively suppresses viral propagation in infected cells. Its dual functionality makes Plitidepsin a versatile therapeutic agent.
What Are the Clinical Applications of Plitidepsin?
Cancer Therapy
Plitidepsin demonstrates substantial anticancer effectiveness in multiple studies that include both preclinical and clinical research. Studies have examined plitidepsin as a treatment option for multiple types of cancer.
- Multiple Myeloma (MM): The Therapeutic Goods Administration (TGA) granted approval in Australia for the use of plitidepsin together with dexamethasone to treat multiple myeloma that has relapsed or become refractory.
- Non-Hodgkin's Lymphoma (NHL): Clinical trials are assessing plitidepsin for treatment of refractory or relapsed cases alongside gemcitabine.
- Solid Tumors: The compound shows cytotoxic effects on multiple cancer types, including non-small cell lung cancer along with breast cancer, melanoma, sarcoma, gastric cancer, ovarian cancer, bladder cancer, and colorectal cancer.
Antiviral Potential Against SARS-CoV-2
Plitidepsin has been tested for its efficacy against COVID-19. Research using in vitro and animal models reveals significant reductions in viral load and pulmonary inflammation when using this agent, suggesting its suitability for antiviral purposes.
Fig.2 Plitidepsin's host-directed anti-SARS-CoV-2 action mechanisms[2].
What Are the Side Effects of Plitidepsin?
Plitidepsin is well-tolerated by most patients but presents significant side effects, which can be detailed in the following categories.
| Category | Common Adverse Effects | Incidence Rate |
| Gastrointestinal | Nausea, vomiting, diarrhea | 37%, 16.8%, 14.4% |
| Systemic | Fatigue, peripheral edema, appetite loss | 36.5%, 12%, 6% |
| Hematological | Thrombocytopenia, neutropenia, anemia | 3%, 2%, 3% |
| Musculoskeletal | Myalgia, muscle weakness | 14.4%, 9.6% |
| Injection Site | Pain, erythema | Rare |
| Other | Fever, liver enzyme elevation, arrhythmias | 7%-11% |
| Severe Adverse Events | Pneumonia, sepsis, dehydration | 24%, 12%, 5% |
| Elderly Patients | High incidence of hyperglycemia | 80% |
*The above data is for reference only.
The majority of negative reactions to Plitidepsin treatment can be addressed through dose modifications or supportive medical interventions.
How Does Plitidepsin Interact with Other Drugs?
Plitidepsin's metabolism is influenced by co-administered drugs, which can enhance or reduce its therapeutic effects.
- Increased Metabolism: Abatacept
- Decreased Metabolism: Acetaminophen, Amiodarone
- Increased Risk of Toxicity: Ambroxol (methemoglobinemia risk), Dexamethasone (enhanced gastrointestinal and muscular toxicity)
| Catalog | Product Name | |
| ACM18683915 | Ambroxol | Inquiry |
What Is the Regulatory Status of Plitidepsin?
Plitidepsin has received regulatory approvals and designations worldwide:
- Australia: Plitidepsin received approval in December 2018 for multiple myeloma treatment under the trade name Aplidin.
- United States & European Union: The FDA and EMA have both recognized Plitidepsin with orphan drug designation.
- Other Markets: Plitidepsin has obtained regulatory approvals across South America and Mexico, as well as Canada, the Asia-Pacific region, the Middle East, and North Africa.
FAQs
1) What makes plitidepsin different from other cancer drugs?
Plitidepsin functions by targeting eEF1A2, which represents a distinctive approach unlike that of traditional chemotherapy treatments. The compound demonstrates extensive anticancer capabilities through its dual actions of triggering apoptosis and disrupting VEGF signaling.
2) Can plitidepsin be used for COVID-19 treatment?
Plitidepsin has demonstrated significant antiviral properties in preclinical studies but continues to undergo clinical testing to determine its safety and effectiveness for COVID-19 treatment.
3) Is plitidepsin used as a first-line treatment for cancer?
Currently, plitidepsin is mainly indicated for relapsed or refractory multiple myeloma in combination with dexamethasone. Its potential as a first-line therapy is still under investigation.
4) What precautions should be taken when using plitidepsin?
Patients should be monitored for hematologic toxicity, liver enzyme elevation, and muscle-related side effects. Dose modifications may be necessary for those with severe adverse reactions.
5) Which supplier provides plitidepsin for research applications?
Alfa Chemistry supplies pharmaceutical researchers with high-purity plitidepsin for antitumor and antiviral study applications.
References
- Galmarini C. M., et al. Trabectedin and Plitidepsin: Drugs from the Sea that Strike the Tumor Microenvironment. Mar. Drugs (2014).
- Papapanou M., et al. Plitidepsin: Mechanisms and Clinical Profile of a Promising Antiviral Agent against COVID-19. J. Pers. Med. (2021).
