Platinum antitumor agents

These discoveries led to a concerted effort to determine how cisplatin works against these tumors. Such information, it was hoped, would be useful in leading to modifications that would be more effective and/or have fewer and less severe side effects. The result has been a second generation of antitumor agents based on Rosenberg s initial discovery. Cisplatin and two of the more recent antitumor compounds are shown in 

Cisplatin and some related antitumor compounds (o) cis-diamminedichloroplatinum(II), cisplatin (b) diammine(l,l-cyclobutanedicarboxylato) platinum(II), carboplatin  

A deoxyribonucleic acid (DNA) unit and two types of cross-links formed between DNA and platinum anticancer compounds. 

Satraplatin. Trans-bis(a cetato )a m mi ne-cis-dicholoro(cydohexylamine) platinum(IV), satraplatin, also known as JM-216. 

Triplatin. Trans-diamminechloroplatinum(II)-p-(l,6-hexanediamine)-trans-diammineplatinum(II)-p-(l,6-hexanediamine)-trans-diamminechloroplatinum(II) cation, triplatin, also known as BBR3464. 

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Dedon PC, Borch RF. Characterization of the reactions of platinum antitumor agents with biologic and nonbiologic sulfur-containing nucleophiles. Biochem Pharmacol 1987 36 1955-1964. 

Table 4 Platinum antitumor agents in Phase I or II clinical trials...

With just a few exceptions, active platinum antitumor agents contain Pt(II) in a square-planar configuration with two cis primaiy or secondary amines, together with two other more weakly bound ligands such as chlorides or carboxylates 13—17) (Table V). Related Pt(IV) complexes with additional chloro or hydroxo axial ligands are often also active and are believed to be reduced to Pt(II) in vivo with removal of the axial ligands. 

Farrell, N. Non classical platinum antitumor agents perspectives for design and development of new drugs complementary to cisplatin. Cancer Invest. 1993, 77, 578-589. 

The chemistry of platinum antitumor agents has been reviewed. ... 

Figure 11 Clinically used platinum antitumor agents (a) cisplatin (b) carboplatin (c) nedaplatin (d) oxaliplatin (e) lobaplatin...

Table 3 Platinum antitumor agents approved for clinical use...

Extensive updates to section on platinum antitumor agents to include cisplatin, carboplatin, oxaliplatin, satraplatin, and triplatin... 

The third generation of platinum antitumor agents connects the platinum complex with an adequate molecular carrier. Such a carrier can increase the antitumor activity synergically, and also increase the selectivity toward tumor tissue. ... 

Discovery and Development of Third-Generation Platinum Antitumor Agents with Oral Activity... 

AnorMED and its predecessor, the Johnson Matthey Biomedical group undertook a project to discover and develop new platinum antitumor agents, in collaboration with the Institute of Cancer Research. This program prepared and evaluated a large number of platinum compounds and ultimately identified three distinct classes of platinum compound having development potential. The final preclmical lead from each of these classes is depicted in Figure L The orally... 

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