Therapeutic Targets Database
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TTD Target ID: TTDC00168

Target Information
NameAntiapoptotic protein BCL-XL    
Type of targetClinical trial target    
SynonymsBcl-XL    
DiseaseAnaplastic Large Cell Lymphomas
[ICD9: 202.8   ICD10: C81-C96]
[1]
Colorectal cancer
[ICD9: 153, 154   ICD10: C18-C21]
[2]
Mesothelioma
[ICD9: 163   ICD10: C45]
[3]
Drug(s)ABT-263Phase IIAdvanced small cell lung cancer; Relapsed or refractory chronic lymphocytic leukemia; Relapsed or refractory lymphoid malignancies[4][5][6]
AT-101Phase IILymphoid Leukemia, Non-Hodgkin's Lymphoma, Prostate Cancer[7]
BioChemical ClassTransmembrane protein    
PathwayAmyotrophic lateral sclerosis (ALS)
Apoptosis
Chronic myeloid leukemia
Jak-STAT signaling pathway
Pancreatic cancer
Pathways in cancer
Small cell lung cancer
UniProt IDQ07817
PDB Structure1BXL; 1G5J; 1LXL; 1MAZ; 1R2D; 1R2E; 1R2G; 1R2H; 1R2I; 1YSG; 1YSI; 1YSN; 2B48; 2LP8; 2LPC; 2M03; 2M04; 2O1Y; 2O2M; 2O2N; 2P1L; 2PON; 2YJ1; 2YQ6; 2YQ7; 2YXJ; 3CVA; 3FDL; 3FDM; 3INQ; 3IO8; 3PL7; 3QKD; 3R85; 3SP7; 3SPF; 3ZK6; 3ZLN; 3ZLO; 3ZLR; 4A1U; 4A1W; 4AQ3; 4EHR; 4HNJ.    
FunctionPotent inhibitor of cell death. Isoform bcl-x(l) anti- apoptotic activity is inhibited by association with siva isoform 1. Inhibits activation of caspases (by similarity). Appears to regulate cell death by blocking the voltage-dependent anion channnel.    
SequenceMSQSNRELVVDFLSYKLSQKGYSWSQFSDVEENRTEAPEGTESEMETPSAINGNPSWHLA DSPAVNGATGHSSSLDAREVIPMAAVKQALREAGDEFELRYRRAFSDLTSQLHITPGTAY QSFEQVVNELFRDGVNWGRIVAFFSFGGALCVESVDKEMQVLVSRIAAWMATYLNDHLEP WIQENGGWDTFVELYGNNAAAESRKGQERFNRWFLTGMTVAGVVLLGSLFSRK
Target ValidationClick to Find Target Validation Information.    
Inhibitor4'-FLUORO-1,1'-BIPHENYL-4-CARBOXYLIC ACID[8]
ABT-263[4][5][6]
AT-101[7]
MultitargetABT-263[4][5][6]
AT-101[7]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Bcl-XL down-regulation suppresses the tumorigenic potential of NPM/ALK in vitro and in vivo. Blood. 2004 Apr 1;103(7):2787-94. Epub 2003 Dec 4. To Reference
Ref 2Enhanced oxaliplatin-induced apoptosis following antisense Bcl-xl down-regulation is p53 and Bax dependent: Genetic evidence for specificity of the antisense effect. Mol Cancer Ther. 2004 Feb;3(2):169-78. To Reference
Ref 3Histone deacetylase inhibitor downregulation of bcl-xl gene expression leads to apoptotic cell death in mesothelioma. Am J Respir Cell Mol Biol. 2001 Nov;25(5):562-8. To Reference
Ref 4Roche. Product Development Pipeline. July 29 2009. To Reference
Ref 5ABT-263 and rapamycin act cooperatively to kill lymphoma cells in vitro and in vivo. Mol Cancer Ther. 2008 Oct;7(10):3265-74. To Reference
Ref 6Cancer Res. 2008 May 1;68(9):3421-8.ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. To Reference
Ref 7Mcl1 downregulation sensitizes neuroblastoma to cytotoxic chemotherapy and small molecule Bcl2-family antagonists. Cancer Biol Ther. 2009 Aug 8;8(16). [Epub ahead of print] To Reference
Ref 8Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. To Reference



 

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