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Bcl-2-like 1

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2845

Nomenclature: Bcl-2-like 1

Abbreviated Name: Bcl-xL

Family: B-cell lymphoma 2 (Bcl-2) protein family

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 233 20q11.21 BCL2L1 BCL2 like 1
Mouse 1 233 2 H1 Bcl2l1 BCL2-like 1
Rat 1 233 3q41 Bcl2l1 Bcl2-like 1
Gene and Protein Information Comments
A shorter human isoform, Bcl-xS, is produced from transcript variant NM_001191 (170 aa). A longer mouse isoform Bcl-x gamma, is produced from transcript variant NM_001289739 (235 aa). For the rat gene we represent the isoform analoghous to the human and mouse in the table above. Note that both a longer rat isoform (284 aa) and a shorter isoform (170 aa) have been reported.
Previous and Unofficial Names Click here for help
BCL2-like 1 | Bcl-X | BCLX
Database Links Click here for help
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of Bcl-xL in complex with ABT-737.
PDB Id:  2YXJ
Ligand:  ABT-737
Resolution:  2.2Å
Species:  Human
References:  3

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
A-1331852 Small molecule or natural product Hs Inhibition 8.2 pEC50 2
pEC50 8.2 (EC50 6.3x10-9 M) [2]
Description: MOLT-4 cell viability assay.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
ABT-737 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Antagonist >9.3 pKi 1
pKi >9.3 (Ki <5x10-10 M) [1]
navitoclax Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist >9.0 pKi 4
pKi >9.0 (Ki <1x10-9 M) [4]
venetoclax Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Antagonist 7.3 pKi 5
pKi 7.3 (Ki 4.8x10-8 M) [5]
obatoclax Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 5.3 pKi 6
pKi 5.3 (Ki 4.69x10-6 M) [6]
Description: In vitro antagonism determined in a fluorescence polarisation assay.
Immunopharmacology Comments
The role of Bcl-2 family members in immunity and disease is reviewed in [5]. Pharmacological inhibition of Bcl-2 family proteins reduces disease severity in several animal models of autoimmunity; see ligand ABT-737 [1].
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 6 GO processes
GO:0019221 cytokine-mediated signaling pathway TAS
GO:0034097 response to cytokine IDA
GO:0036017 response to erythropoietin IEP
GO:0036018 cellular response to erythropoietin IEP
GO:0071347 cellular response to interleukin-1 IEP
GO:0071356 cellular response to tumor necrosis factor IEP
Immuno Process:  Antigen presentation
GO Annotations:  Associated to 2 GO processes, IEA only
GO:1900244 positive regulation of synaptic vesicle endocytosis ISO
click arrow to show/hide IEA associations
GO:0006897 endocytosis IEA

References

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1. Bruncko M, Oost TK, Belli BA, Ding H, Joseph MK, Kunzer A, Martineau D, McClellan WJ, Mitten M, Ng SC et al.. (2007) Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-xL. J. Med. Chem., 50 (4): 641-62. [PMID:17256834]

2. Le Wang, George A. Doherty, Andrew S. Judd*, Zhi-Fu Tao, T. Matthew Hansen, Robin R. Frey, Xiaohong Song, Milan Bruncko, Aaron R. Kunzer, Xilu Wang, Michael D. Wendt, John A. Flygare, Nathaniel D. Catron, Russell A. Judge, Chang H. Park, Shashank Shekhar, Darren C. Phillips, Paul Nimmer, Morey L. Smith, Stephen K. Tahir, Yu Xiao, John Xue John Xue AbbVie Inc., 1 North Waukegan Road, North Chicago, Illinois 60064, United States More by John Xue , Haichao Zhang, Phuong N. Le, Michael J. Mitten, Erwin R. Boghaert, Wenqing Gao, Peter Kovar, Edna F. Choo, Dolores Diaz, Wayne J. Fairbrother, Steven W. Elmore, Deepak Sampath, Joel D. Leverson, and Andrew James Souers. (2020) Discovery of A-1331852, a First-in-Class, Potent, and Orally-Bioavailable BCL-XL Inhibitor. ACS Med. Chem. Lett., [Epub ahead of print]. DOI: 10.1021/acsmedchemlett.9b00568

3. Lee EF, Czabotar PE, Smith BJ, Deshayes K, Zobel K, Colman PM, Fairlie WD. (2007) Crystal structure of ABT-737 complexed with Bcl-xL: implications for selectivity of antagonists of the Bcl-2 family. Cell Death Differ., 14 (9): 1711-3. [PMID:17572662]

4. Park CM, Bruncko M, Adickes J, Bauch J, Ding H, Kunzer A, Marsh KC, Nimmer P, Shoemaker AR, Song X et al.. (2008) Discovery of an orally bioavailable small molecule inhibitor of prosurvival B-cell lymphoma 2 proteins. J. Med. Chem., 51 (21): 6902-15. [PMID:18841882]

5. Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J, Dayton BD, Ding H, Enschede SH, Fairbrother WJ et al.. (2013) ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat. Med., 19 (2): 202-8. [PMID:23291630]

6. Wan Y, Dai N, Tang Z, Fang H. (2018) Small-molecule Mcl-1 inhibitors: Emerging anti-tumor agents. Eur J Med Chem, 146: 471-482. [PMID:29407973]

How to cite this page

B-cell lymphoma 2 (Bcl-2) protein family: Bcl-2-like 1. Last modified on 09/07/2020. Accessed on 26/02/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2845.