PMID- 19470238
OWN - NLM
STAT- MEDLINE
DCOM- 20090629
LR  - 20190608
IS  - 1976-6696 (Print)
IS  - 1976-6696 (Linking)
VI  - 42
IP  - 5
DP  - 2009 May 31
TI  - Development of human tumor necrosis factor-alpha muteins with improved 
      therapeutic potential.
PG  - 260-4
AB  - Tumor necrosis factor-alpha (TNF-alpha) exhibits cytotoxicity towards various 
      tumor cells in vitro and induces apoptotic necrosis in transplanted tumors in 
      vivo. It also shows severe toxicity when used systemically for the treatment of 
      cancer patients, hampering the development of TNF-alpha as a potential anticancer 
      drug. In order to understand the structure-function relation of TNF-alpha with 
      respect to receptor binding, we selected four regions on the bottom of the 
      TNF-alpha trimer that are in close contact with the receptor and carried out 
      mutagenesis studies and computational modeling. From the study, various TNF-alpha 
      muteins with a high therapeutic index were identified. These results will provide 
      a structural basis for the design of highly potent TNF-alpha for therapeutic 
      purposes. By conjugating TNF-alpha muteins with a high therapeutic index to a 
      fusion partner, which targets a marker of angiogenesis, it could be possible to 
      develop TNF-alpha based anticancer drugs.
FAU - Jang, Seung-Hwan
AU  - Jang SH
AD  - Department of Bioinformatics and Life Science and Computer Aided Molecular Design 
      Research Center, Soongsil University, Seoul 156-743, Korea.
FAU - Kim, Hyojin
AU  - Kim H
FAU - Cho, Kwang-Hwi
AU  - Cho KH
FAU - Shin, Hang-Cheol
AU  - Shin HC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Korea (South)
TA  - BMB Rep
JT  - BMB reports
JID - 101465334
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Female
MH  - Humans
MH  - Mice
MH  - Mutagenesis, Site-Directed
MH  - Neoplasms/*drug therapy
MH  - Receptors, Tumor Necrosis Factor/genetics/metabolism
MH  - Recombinant Proteins/*chemistry/genetics/metabolism/*therapeutic use
MH  - Tumor Necrosis Factor-alpha/*chemistry/genetics/metabolism/*therapeutic use
EDAT- 2009/05/28 09:00
MHDA- 2009/06/30 09:00
CRDT- 2009/05/28 09:00
PHST- 2009/05/28 09:00 [entrez]
PHST- 2009/05/28 09:00 [pubmed]
PHST- 2009/06/30 09:00 [medline]
AID - 10.5483/bmbrep.2009.42.5.260 [doi]
PST - ppublish
SO  - BMB Rep. 2009 May 31;42(5):260-4. doi: 10.5483/bmbrep.2009.42.5.260.