Document Detail

Synthesis and characterization of AP5346, a novel polymer-linked diaminocyclohexyl platinum chemotherapeutic agent.
MedLine Citation:
PMID:  16984138     Owner:  NLM     Status:  MEDLINE    
Syntheses of the novel polymer-bound platinum-based chemotherapeutic agent poly(HPMA)-GGG-Ama=Pt=(1R,2R)-DACH, AP5346, and its precursors are reported. The method utilized in preclinical development of AP5346 is described herein. Additionally, an improved synthesis, which has shown that ion exchange resins can be removed, significantly less platinum can be used when the reaction mixture is pH-stated, and the synthesis can be performed at a higher concentration, is reported. These combined improvements result in a more cost-effective, scaleable procedure. Various methods of analysis of the drug substance are also discussed. Specifically, (1)H NMR spectroscopy is used for identity and can also distinguish small molecule impurities to below 0.1%. (195)Pt NMR determines the coordination environment of the platinum and also identity and purity in relation to platinum chelation of the construct. Size exclusion chromatography is used to establish the molecular weight of AP5346 while ICP-AES determines platinum content and platinum release rates in phosphate-buffered saline. The cumulative results of this work have yielded an efficient syntheses of a polymer-based chemotherapeutic agent with subsequent detailed characterization methods.
Paul Sood; K Bruce Thurmond; Jeremy E Jacob; Lynda K Waller; George O Silva; Donald R Stewart; David P Nowotnik
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Bioconjugate chemistry     Volume:  17     ISSN:  1043-1802     ISO Abbreviation:  Bioconjug. Chem.     Publication Date:    2006 Sep-Oct
Date Detail:
Created Date:  2006-09-20     Completed Date:  2007-05-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9010319     Medline TA:  Bioconjug Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1270-9     Citation Subset:  IM    
Access Pharmaceuticals, Inc., 2600 Stemmons Freeway, Suite 176, Dallas, Texas 75207, USA.
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MeSH Terms
Antineoplastic Agents* / chemical synthesis,  chemistry,  metabolism
Molecular Structure
Nuclear Magnetic Resonance, Biomolecular
Organoplatinum Compounds* / chemical synthesis,  chemistry,  metabolism
Polymers / chemistry*
Reg. No./Substance:
0/AP5346; 0/Antineoplastic Agents; 0/Organoplatinum Compounds; 0/Polymers

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