Nedaplatin
[CAS# 95734-82-0]

Identification

• Classification: Biochemical >> Inhibitor >> DNA damage >> DNA/RNA synthesis inhibitor
• Name: Nedaplatin
• Synonyms: (Glycolato-O,O')diammineplatinum(II); cis-Diammine(glycolato)platinum(II)
• Molecular Formula: C₂H₈N₂O₃Pt
• Molecular Weight: 303.18
• CAS Registry Number: 95734-82-0
• SMILES: C(C(=O)O)O.[NH2-].[NH2-].[Pt+2]

Safety Data

• Hazard Symbols: GHS06;GHS08 Danger
• Hazard Statements: H300-H315-H317-H319-H334-H335-H350
• Precautionary Statements: P203-P233-P260-P261-P264-P264+P265-P270-P271-P272-P280-P284-P301+P316-P302+P352-P304+P340-P305+P351+P338-P318-P319-P321-P330-P332+P317-P333+P317-P337+P317-P342+P316-P362+P364-P403-P403+P233-P405-P501

Discovory and Applicatios

Nedaplatin is a platinum-based anticancer drug that is used primarily for the treatment of various types of cancers, including non-small cell lung cancer, ovarian cancer, and head and neck cancers. It is structurally related to cisplatin, one of the most widely used chemotherapy agents, but has been modified to improve its safety profile and reduce side effects.

Nedaplatin was developed in Japan as an alternative to cisplatin, which, while effective in treating a range of cancers, is often associated with severe side effects, particularly nephrotoxicity (kidney damage) and gastrointestinal toxicity. These side effects limit its use, especially in patients with pre-existing kidney conditions or those who require long-term treatment. The goal of creating nedaplatin was to maintain the anticancer efficacy of cisplatin while minimizing these adverse effects.

The chemical structure of nedaplatin features a platinum core similar to cisplatin, but with the substitution of two ethylenediamine ligands (amine groups) by a more stable dicarboxylate group. This modification enhances its solubility in water and may reduce its tendency to bind with cellular proteins that lead to toxic side effects, particularly those affecting the kidneys.

Nedaplatin works by forming highly reactive platinum-DNA adducts in cancer cells. This interaction interferes with DNA replication and transcription, leading to cell cycle arrest and ultimately, cell death. The drug's cytotoxicity is attributed to its ability to crosslink DNA strands, thereby disrupting the integrity of the genetic material. As with other platinum-based drugs, the ultimate goal of nedaplatin therapy is to inhibit the growth and proliferation of tumor cells, leading to the shrinkage or elimination of the tumor.

One of the key benefits of nedaplatin over cisplatin is its reduced nephrotoxicity. Clinical studies have shown that nedaplatin has a lower incidence of kidney-related side effects compared to cisplatin, making it a more suitable option for patients who are at risk of renal complications. However, like all platinum-based chemotherapy drugs, nedaplatin can still cause other side effects, including nausea, vomiting, bone marrow suppression (leading to decreased white blood cell and platelet counts), and peripheral neuropathy.

Nedaplatin has been primarily used in Japan and other Asian countries and is considered an effective treatment option for various solid tumors. It is often used in combination with other chemotherapy agents to enhance its therapeutic effect. For instance, nedaplatin has been combined with other drugs such as paclitaxel or 5-fluorouracil in treatment regimens for certain types of cancers. Clinical trials continue to explore its effectiveness in different cancer types and treatment settings.

Overall, nedaplatin is an important development in the field of chemotherapy, offering a platinum-based treatment option with a more favorable side effect profile compared to cisplatin. Its reduced nephrotoxicity makes it a valuable alternative, particularly for patients who may not be able to tolerate cisplatin. As research continues, nedaplatin may see expanded use in various cancer treatment protocols.

References

1991. Phase I study and pharmacological analysis of cis-diammine(glycolato)platinum (254-S; NSC 375101D) administered by 5-day continuous intravenous infusion. Cancer Research, 51(5).
DOI: Not available
URL: https://pubmed.ncbi.nlm.nih.gov/1997185

2005. Chemosensitivity testing of a novel platinum analog, nedaplatin (254-S), in human gynecological carcinomas: a comparison with cisplatin. Anticancer Research, 25(6B).
URL: https://pubmed.ncbi.nlm.nih.gov/16334133

2014. Nedaplatin or Oxaliplatin Combined with Paclitaxel and Docetaxel as First-Line Treatment for Patients with Advanced Non-Small Cell Lung Cancer. Medical Science Monitor, 20.
DOI: 10.12659/msm.891318