Miriplatin
[CAS# 141977-79-9]

Identification

• Classification: API >> Antineoplastic agents
• Name: Miriplatin
• Synonyms: [(1R,2R)-1,2-Cyclohexanediamine]bis(myristato)platinum
• Molecular Formula: C₃₄H₆₈N₂O₄Pt
• Molecular Weight: 764.02
• CAS Registry Number: 141977-79-9
• SMILES: CCCCCCCCCCCCCC(=O)[O-].CCCCCCCCCCCCCC(=O)[O-].C1CC[C@H]([C@@H](C1)N)N.[Pt+2]

Properties

• Solubility: DMSO: 2 mg/mL (Expl.)

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P280-P305+P351+P338

Discovery and Applications

Miriplatin is an anticancer agent that belongs to the class of platinum-based chemotherapy drugs, specifically a platinum(II) complex. It is primarily used in the treatment of liver cancer, particularly hepatocellular carcinoma (HCC), which is a common type of liver cancer. Unlike other platinum-based drugs such as cisplatin and carboplatin, miriplatin is designed to be less nephrotoxic and to have more localized effects, making it particularly useful for treating cancers that are difficult to access through systemic chemotherapy.

The discovery and development of miriplatin originated from the need for effective treatments for liver cancer, a malignancy with poor prognosis due to its late diagnosis and resistance to conventional therapies. Researchers sought to create a platinum compound that could be directly injected into the tumor to deliver high local concentrations of the drug while minimizing the systemic side effects typically seen with traditional platinum-based chemotherapy.

Miriplatin is used in a form that is suitable for regional chemotherapy, where it is injected directly into the tumor or the blood vessels supplying the tumor. This localized treatment strategy aims to deliver higher concentrations of the drug to the cancerous tissue while limiting exposure to healthy tissues. The drug is typically administered through transcatheter arterial chemoembolization (TACE), a procedure commonly used in liver cancer treatment. TACE involves injecting chemotherapy directly into the artery that supplies blood to the liver tumor, followed by the embolization (blocking) of the artery to restrict blood flow, thereby trapping the chemotherapy drug within the tumor.

Miriplatin exerts its anticancer effects through the same mechanism as other platinum-based drugs: it binds to DNA in cancer cells, forming platinum-DNA adducts that interfere with DNA replication and transcription. This leads to DNA damage and activates cell death pathways, particularly apoptosis, in the targeted cancer cells. The platinum center in miriplatin coordinates with DNA bases, causing crosslinking and preventing the DNA from unwinding, which is crucial for cell division.

One of the advantages of miriplatin over traditional platinum-based drugs is its reduced toxicity profile, especially regarding nephrotoxicity. Platinum compounds like cisplatin are known to cause significant kidney damage, which limits their use in some patients. Miriplatin, by comparison, has been shown to have a lower incidence of nephrotoxic effects, making it a safer alternative for certain patients, particularly those with preexisting kidney problems.

Miriplatin has been studied and used primarily in Japan, where it has been approved for clinical use for the treatment of hepatocellular carcinoma, especially in patients who are not candidates for surgery or who have advanced disease. It has also been explored in other types of cancer, including those that involve the liver and bile ducts, although its use remains less widespread in other parts of the world.

The clinical application of miriplatin has demonstrated promising results, particularly when used as part of regional chemotherapy regimens in liver cancer. It is often utilized in cases where surgery is not an option, and it has been shown to improve tumor response rates, providing patients with a viable treatment option for managing advanced liver cancer.

Like other chemotherapy drugs, miriplatin can cause side effects, although its localized administration helps to minimize the systemic toxicities. Common side effects include liver function abnormalities, nausea, vomiting, and local reactions at the site of injection. The drug’s more specific action on liver tumors also means that it has fewer systemic side effects compared to intravenous platinum therapies, although close monitoring is still required during treatment.

Ongoing studies are focused on optimizing the use of miriplatin, including exploring combination therapies and assessing its long-term efficacy and safety. In addition, research into expanding its use beyond liver cancer, such as for other solid tumors, continues to be a subject of investigation. Despite its current niche application, miriplatin represents a promising treatment option in the growing field of targeted and localized cancer therapies.

References

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