7405. Picoplatin

Nomenclature

CAS number: 181630-15-9
(SP-4-3)-Amminedichloro(2-methylpyridine)platinum; cis-amminedichloro(2-methylpyridine)platinum(II); AMD-473; JM-473; NX-473; ZD-473.
C6H10Cl2N2Pt; mol wt 376.15.
C 19.16%, H 2.68%, Cl 18.85%, N 7.45%, Pt 51.86%.

Description and references

Third generation, sterically hindered Pt-complex that exhibits reduced reactivity with sulfur ligands such as glutathione, q.v.; designed to overcome acquired Pt-chemotherapy resistance. Prepn: B. A. Murrer, EP 727430 (1996 to AnorMED; Inst. of Cancer Research); idem, US 5665771 (1997 to Johnson Matthey). Pharmacology and pharmacokinetics: F. I. Raynaud et al., Clin. Cancer Res. 3, 2063 (1997). Cytotoxicity and DNA binding activity: J. Holford et al., Anti-Cancer Drug Des. 13, 1 (1998). In vitro circumvention of cisplatin resistance: idem, et al,. Br. J. Cancer 77, 366 (1998); of radiosensitizing activity: G. P. Raaphorst et al., Anticancer Res. 24, 613 (2004). LC/MS determn in plasma: T. Oe et al., Anal. Chem. 74, 591 (2002); in urine: eidem, J. Chromatogr. B 792, 217 (2003). Series of articles on clinical evaluations: Eur. J. Cancer 38, Suppl. S1-S31 (2002). Review of early development: L. R. Kelland et al., J. Inorg. Biochem. 77, 111-115 (1999); and therapeutic potential: M. P. Hay, Curr. Opin. Investig. Drugs 1, 263-266 (2000).

Chemical structure

Properties

Pale yellow solid. Sensitive to light. uv max (0.15M sodium chloride): 268 nm. A250/A268 = 0.62. LD50 in mice (mg/kg): 43 i.p., 560 orally (Murrer).

Therapeutic Category

Antineoplastic.

Keywords

Antineoplastic; Platinum Complexes