0 Members and 1 Guest are viewing this topic.
Cisplatin and their analoguesOther analogues in current clinical use include:CHIP * Iproplatin (CHIP) or more formally (cis-dichloro-trans-dihydroxy-cis-bis(isopropylamine)platinum(IV)), € is also less toxic than cisplatin with respect to alopecia, the degree and duration of nausea and vomiting, renal toxicity, neurotoxicity and anaemia. However, it caused the same cumulative toxicity on haemoglobin, leukocyte count and platelet count, and more thrombocytopenia, diarrhoea and leukopenia. Iproplatin has similar response rates, duration of response and survival to that of cisplatin. * Tetraplatin (ormaplatin). Forms intrastrand cross-links but is less cytotoxic than cisplatin. * JM118 (cis-amminedichloro(cyclohexylamine)platinum(II)). This has been shown to form intrastrand cross-links and have a greater cytotoxicity than cisplatin with respect to human ovarian carcinoma cells. * JM149 (cis-amminedichloro(cyclohexylamine)-trans-dihydroxoplatinum(IV)). Forms intrastrand cross-links but is less cytotoxic than cisplatin. * JM216 (bis-acetato-cis-amminedichloro(cyclohexylamine)platinum(IV)). Forms intrastrand cross-links but is less cytotoxic than cisplatin. * JM335 (trans-amminedichloro(cyclohexylamine)dihydroxoplatinum(IV)). This has been shown to have comparable cytotoxicity to cisplatin, because not only is it able to form some intrastrand cross-links, it is also has the unique ability to form single strand breaks. * Transplatin. This complex is very much lower in cytotoxicity than its cis counterpart, however, it has been shown to be more kinetically reactive. € The low cytotoxicity was proposed to be due to fast repairing of its interstrand cross-links, because the adducts do not resemble HMG-box binding sites. Some analogues in current development and clinical testing include: * cis, trans, cis-Pt(NH3)(C6H11NH2)(OOCC3H7)2Cl2. This platinum complex has been designed specifically for oral administration. It is water-soluble, lipophilic and robust enough to survive the gastric environment. However, as it is a platinum(IV) complex, it will undergo relatively slow ligand substitution reactions compared with their platinum(II) analogues, therefore, they may have to be reduced to the kinetically more labile and reactive Pt(II) derivatives in vivo. Many studies have shown this to be possible, where platinum(IV) metal centers are readily reduced by cellular components such as glutathione and ascorbic acid to form the platinum(II) analogues that bind more rapidly to DNA. * Nedaplatin (254S). This cytotoxic drug from Japan has been shown to be active in several solid tumors without renal toxicity. The reported dose limiting toxicity is myelosuppression, especially thrombocytopenia. * Malanato-1,2-diaminocyclohexaneplatinum(II). * 5-Sulfosalicylato-trans-(1,2 diaminocyclohexane)Platinum(II) (SSP). * Poly-[(trans-1,2-diaminocyclohexane)platinum]-carboxyamylose (POLY-PLAT). * 4-Hydroxy-sulfonylphenylacetato(trans-1,2-diaminocyclohexane)platinum(II) (SAP). It seems that for a platinum complex to pass the clinical trials, it must also be significantly more active than cisplatin or structurally different to merit the investment in resources and time for clinical development.