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Pharmaceuticals

Pedagogy On Platinum Drugs

by Ann M. Thayer
June 28, 2010 | A version of this story appeared in Volume 88, Issue 26

1965

Barnett Rosenberg at Michigan State University reports the effect of platinum on bacteria.

1967

Identification of cis-[PtCl4(NH3)2] as the causative agent.

1968

Pt compounds shown to have antitumor activity. Cisplatin is found to be active in a mouse model of cancer. (1)

1970

S. C. Dhara publishes a method for the rapid synthesis of cisplatin.

1971

Cisplatin tested in humans.

1973

Structure-activity relationships established for Pt compounds by Michael J. Cleare and James D. Hoeschele at Michigan State University.

1976

Oxaliplatin discovered by Yoshinori Kidani and coworkers at Nagoya University (2)

1978

U.S. Food & Drug Administration approves cisplatin. Sold by Bristol-Myers Squibb as Platinol.

1982

First patient tested with carboplatin, discovered by Johnson Matthey, the U.K. Institute for Cancer Research (ICR), and Bristol-Myers Squibb. (3)

1986

Carboplatin approved in Europe and sold by Bristol-Myers Squibb as Paraplatin.

1989

FDA approves carboplatin. Debiopharm licenses oxaliplatin from Nagoya University.

1993

First patient tested with satraplatin, discovered by Johnson Matthey, ICR, and Bristol-Myers Squibb. It is the first oral platinum drug candidate. (4)

1994

Sanofi-Aventis licenses oxaliplatin from Debiopharm.

1996

Oxaliplatin approved in Europe and sold by Sanofi-Aventis as Eloxatin. Patent on cisplatin expires.

1997

First patient treated with picoplatin, developed by Johnson Matthey, ICR, and Bristol-Myers Squibb and licensed to AnorMED. (5)

1999

Novuspharma, a 1998 Roche/Boehringer Mannheim spin-off, starts clinical trials of triplatin tetranitrate (BBR3464), discovered earlier by Nicholas Farrell at Virginia Commonwealth University. (6)

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2000

Patent on carboplatin expires in Europe.

2001

Spectrum Pharmaceuticals licenses satraplatin from Johnson Matthey. AstraZeneca decides to stop picoplatin development with AnorMED.

2002

FDA approves Eloxatin. Spectrum Pharmaceuticals licenses satraplatin to GPC Biotech for development.

2004

Patent on carboplatin expires in U.S. AnorMED licenses picoplatin to NeoRx. Cell Therapeutics (merged with Novuspharma in 2003) halts BBR3464 after Phase II.

2006

Oxaliplatin loses patent protection in Europe.

2007

Phase III clinical trial of picoplatin initiated by Poniard Pharmaceuticals (formerly NeoRx). GPC Biotech says that satraplatin failed to meet endpoint in Phase III trial and withdraws filing for FDA approval. Yakult Honsha agrees to develop satraplatin in Japan.

2008

GPC Biotech's partner Celgene withdraws European regulatory filing and terminates development agreement for satraplatin.

2009

GPC Biotech merges with Agennix, which says it will not develop satraplatin further without the help of a partner.

2010

Poniard reports that picoplatin failed to meet Phase III clinical trial endpoint and is evaluating options for further development. Cell Therapeutics reports antitumor activity in new class of bisplatinates.

2012

Generic versions oxaliplatin to be authorized for sale in U.S.

2013

Oxaliplatin to lose patent protection in the U.S.

Sources: Company information; Nature Reviews 2007, 7, 573; J. Chem. Ed. 2006, 83, 728; Dalton Trans. 2009, 10651. and references within.

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