BUB1 mitotic checkpoint serine/threonine kinase | Bub family | IUPHAR/BPS Guide to PHARMACOLOGY

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BUB1 mitotic checkpoint serine/threonine kinase

Target not currently curated in GtoImmuPdb

Target id: 1949

Nomenclature: BUB1 mitotic checkpoint serine/threonine kinase

Abbreviated Name: Bub1

Family: Bub family

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1085 2q14 BUB1 BUB1 mitotic checkpoint serine/threonine kinase
Mouse - 1059 2 F1 Bub1 BUB1
Rat - 1059 3q36 Bub1 BUB1 mitotic checkpoint serine/threonine kinase
Previous and Unofficial Names
BUB1A | BUB1L | BUB1, mitotic checkpoint serine/threonine kinase | BUB1
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Structure and Substrate Recruitment of the Human Spindle Checkpoint Kinase Bub
PDB Id:  3E7E
Resolution:  2.31Å
Species:  Human
References:  5
Enzyme Reaction
EC Number: 2.7.11.1

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 2-1-1 [PMID: 24900824] Hs Inhibition 8.3 pIC50 2
pIC50 8.3 (IC50 5x10-9 M) [2]
compound 2-3-2 [PMID: 24900824] Hs Inhibition 8.2 pIC50 2
pIC50 8.2 (IC50 6x10-9 M) [2]
compound 2-3-1 [PMID: 24900824] Hs Inhibition 8.1 pIC50 2
pIC50 8.1 (IC50 9x10-9 M) [2]
compound 2-13-1 [PMID: 24900824] Hs Inhibition 7.5 pIC50 2
pIC50 7.5 (IC50 3x10-8 M) [2]
BAY-524 Hs Inhibition 6.3 pIC50 1
pIC50 6.3 (IC50 4.5x10-7 M) [1]
Description: Measuring inhibition of the recombinant catalytic domain of human Bub1 (amino acids 704–1085).
BAY-320 Hs Inhibition 6.2 pIC50 1
pIC50 6.2 (IC50 6.8x10-7 M) [1]
Description: Measuring inhibition of the recombinant catalytic domain of human Bub1 (amino acids 704–1085).
Clinically-Relevant Mutations and Pathophysiology
Disease:  Mosaic variegated aneuploidy syndrome
Orphanet: ORPHA1052
General Comments
Bub1 as a mitotic checkpoint protein playing multiple roles during mitosis [3,6]. Mitotic checkpoint abrogation through pharmacological inhibition of components of the mitotic checkpoint, such as Bub1 kinase, is being investigated by drug development companies as a novel mechanism for the treatment of proliferative disorders, as evidenced by patent submissions claiming Bub1 inhibitory compounds. For example, BAY-320 and BAY-524 are two of the compounds claimed in patent WO2013092512 [4].

References

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1. Baron AP, von Schubert C, Cubizolles F, Siemeister G, Hitchcock M, Mengel A, Schröder J, Fernández-Montalván A, von Nussbaum F, Mumberg D et al.. (2016) Probing the catalytic functions of Bub1 kinase using the small molecule inhibitors BAY-320 and BAY-524. Elife, 5. [PMID:26885717]

2. Brazeau JF, Rosse G. (2014) Novel cycloalkenepyrazoles as inhibitors of bub1 kinase. ACS Med Chem Lett, 5 (4): 280-1. [PMID:24900824]

3. Elowe S. (2011) Bub1 and BubR1: at the interface between chromosome attachment and the spindle checkpoint. Mol. Cell. Biol., 31 (15): 3085-93. [PMID:21628528]

4. Hitchcock M et al.. (2013) Substituted benzylpyrazoles. Patent number: WO2013092512 A1. Assignee: Bayer Intellectual Property Gmbh, Bayer Pharma Aktiengesellschaft. Priority date: 21/12/2011. Publication date: 27/06/2013.

5. Kang J, Yang M, Li B, Qi W, Zhang C, Shokat KM, Tomchick DR, Machius M, Yu H. (2008) Structure and substrate recruitment of the human spindle checkpoint kinase Bub1. Mol. Cell, 32 (3): 394-405. [PMID:18995837]

6. Roberts BT, Farr KA, Hoyt MA. (1994) The Saccharomyces cerevisiae checkpoint gene BUB1 encodes a novel protein kinase. Mol. Cell. Biol., 14 (12): 8282-91. [PMID:7969164]

How to cite this page

Bub family: BUB1 mitotic checkpoint serine/threonine kinase. Last modified on 20/04/2016. Accessed on 28/09/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1949.