Satraplatin
[CAS# 129580-63-8]

Identification

• Classification: API >> Antineoplastic agents
• Name: Satraplatin
• Synonyms: Bis(acetato-O)amminedichloro(cyclohexanamine)-pt; Platinum (lV) cis-dichloro-trans-bis(acetato-O)ammine(cyclohexanamine)
• Molecular Formula: C₁₀H₂₂Cl₂N₂O₄Pt
• Molecular Weight: 500.29
• CAS Registry Number: 129580-63-8
• SMILES: CC(=O)[O-].CC(=O)[O-].C1CCC(CC1)N.N.[Cl-].[Cl-].[Pt]

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302
• Precautionary Statements: P264-P301+P312-P330

Discovory and Applicatios

Satraplatin, also known by its development code JM 216, is an orally administered platinum-based chemotherapeutic agent. It was developed in the 1990s during efforts to design platinum compounds with improved pharmacological properties over first-generation agents such as cisplatin and carboplatin. Researchers sought compounds that could be administered orally rather than intravenously and that would possess a more favorable toxicity profile, particularly with respect to nephrotoxicity and neurotoxicity.

Satraplatin is a platinum(IV) complex containing two ammine ligands, two acetate ligands, and two chlorides arranged in an octahedral coordination geometry around the central platinum ion. The platinum(IV) oxidation state grants the molecule greater chemical stability compared to the platinum(II) complexes like cisplatin. Once administered and absorbed, Satraplatin is reduced in vivo to a platinum(II) species, which can then form DNA adducts similar to other platinum drugs, leading to inhibition of DNA replication and transcription and ultimately triggering apoptosis in rapidly dividing cancer cells.

The compound was developed primarily for the treatment of solid tumors, including prostate, lung, and ovarian cancers. Clinical development focused most heavily on hormone-refractory prostate cancer. Satraplatin demonstrated promising results in preclinical models and early-phase clinical trials, showing antitumor activity and a manageable side effect profile. Unlike cisplatin, Satraplatin was found to have minimal nephrotoxicity and neurotoxicity, though myelosuppression, particularly thrombocytopenia and neutropenia, was observed as a dose-limiting toxicity.

Satraplatin reached phase III clinical evaluation under the auspices of Spectrum Pharmaceuticals and GPC Biotech. The pivotal SPARC (Satraplatin and Prednisone Against Refractory Cancer) trial investigated the efficacy of Satraplatin in patients with metastatic, castration-resistant prostate cancer who had failed previous chemotherapy. Although the trial showed improvement in progression-free survival, the overall survival benefit did not meet the thresholds required by regulatory agencies, leading to the United States Food and Drug Administration (FDA) declining approval.

Despite not achieving approval, Satraplatin's development contributed significantly to the understanding of platinum-based chemotherapy. It demonstrated that platinum(IV) complexes could be viable oral agents and opened avenues for the development of other platinum(IV) prodrugs with potentially improved therapeutic indices. Research into platinum(IV) coordination chemistry, pharmacokinetics, and mechanisms of reduction and activation has been heavily informed by the experience gained from Satraplatin’s preclinical and clinical journey.

References

1995. A phase I and pharmacology study of an oral platinum complex, JM216: dose-dependent pharmacokinetics with single-dose administration. Cancer Chemotherapy and Pharmacology, 36(6).
DOI: 10.1007/bf00685793

2012. Phase I study of the effects of renal impairment on the pharmacokinetics and safety of satraplatin in patients with refractory solid tumors. Annals of Oncology, 23(4).
DOI: 10.1093/annonc/mdr358

2022. Satraplatin Demonstrates High Cytotoxic Activity Against Genetically Defined Lymphoid Malignancies. Anticancer Research, 42(4).
DOI: 10.21873/anticanres.15658