PMID- 23506183
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20130320
LR  - 20140731
IS  - 1746-0441 (Print)
IS  - 1746-0441 (Linking)
VI  - 3
IP  - 9
DP  - 2008 Sep
TI  - Structural studies of taxol analogues for drug discovery.
PG  - 1109-22
LID - 10.1517/17460441.3.9.1109 [doi]
AB  - BACKGROUND: The major mechanism of action of antitumor taxanes, including two 
      clinically useful antitumor agents, paclitaxel and docetaxel, lies in their 
      interactions with beta-tubulin in microtubule polymers, leading to cell cycle arrest 
      and apoptosis. However, owing to the technical limitations, the molecular 
      interactions of ligands with the residues in taxane binding sites of tubulin as 
      well as the conformations adopted by taxanes on binding are still not fully 
      understood. OBJECTIVE: This review focuses on the exploration of paclitaxel's 
      interactions with tubulin, and the impact of such efforts on the drug discovery 
      for new taxanes and microtubule stabilizing agents (MSAs). METHODS: Data were 
      identified through the search of Chemical Abstracts and PubMed databases for 
      research articles and reviews up to April 2008. CONCLUSION: Based on a collection 
      of information gathered from crystallography, 1D and 2D NMR spectroscopy (NOESY, 
      ROESY, REDOR), and structural-activity relationship (SAR) by chemical synthesis 
      and pharmacological assays, 'opened' or T-shape conformations have been predicted 
      to be the biologically active ones in recent years, and confirmed by further SAR 
      studies. Some more potent analogues than paclitaxel or simplified compounds with 
      similar potencies to that of paclitaxel have been discovered. Structural studies 
      of taxol analogues will continue to make great contributions to the rational 
      design of taxanes and novel prototype MSAs for drug discovery.
FAU - Fang, Wei-Shuo
AU  - Fang WS
AD  - Key Laboratory of Bioactive Substances and Resources Utilization of Chinese 
      Herbal Medicine (PUMC), Ministry of Education, Beijing 100050, China +86 10 
      63165229 ; +86 10 63017757 ; wfang@imm.ac.cn.
FAU - Wang, Shao-Rong
AU  - Wang SR
LA  - eng
PT  - Journal Article
PL  - England
TA  - Expert Opin Drug Discov
JT  - Expert opinion on drug discovery
JID - 101295755
EDAT- 2008/09/01 00:00
MHDA- 2008/09/01 00:01
CRDT- 2013/03/20 06:00
PHST- 2013/03/20 06:00 [entrez]
PHST- 2008/09/01 00:00 [pubmed]
PHST- 2008/09/01 00:01 [medline]
AID - 10.1517/17460441.3.9.1109 [doi]
PST - ppublish
SO  - Expert Opin Drug Discov. 2008 Sep;3(9):1109-22. doi: 10.1517/17460441.3.9.1109.