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WD repeat domain 5

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Target not currently curated in GtoImmuPdb

Target id: 2831

Nomenclature: WD repeat domain 5

Family: WD repeat-containing proteins

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 334 9q34.2 WDR5 WD repeat domain 5
Mouse - 334 2 A3 Wdr5 WD repeat domain 5
Rat - 334 3p12 Wdr5 WD repeat domain 5
Previous and Unofficial Names Click here for help
CFAP89 | cilia and flagella associated protein 89 | SWD3, Set1c WD40 repeat protein
Database Links Click here for help
Alphafold P61964 (Hs), P61965 (Mm), Q498M4 (Rn)
ChEMBL Target CHEMBL1075317 (Hs)
Ensembl Gene ENSG00000196363 (Hs), ENSMUSG00000026917 (Mm), ENSRNOG00000008212 (Rn)
Entrez Gene 11091 (Hs), 140858 (Mm), 362093 (Rn)
Human Protein Atlas ENSG00000196363 (Hs)
KEGG Gene hsa:11091 (Hs), mmu:140858 (Mm), rno:362093 (Rn)
OMIM 609012 (Hs)
Pharos P61964 (Hs)
RefSeq Nucleotide NM_017588 (Hs), NM_080848 (Mm), NM_001039034 (Rn)
RefSeq Protein NP_060058 (Hs), NP_543124 (Mm), NP_001034123 (Rn)
SynPHARM 81844 (in complex with OICR-9429)
UniProtKB P61964 (Hs), P61965 (Mm), Q498M4 (Rn)
Wikipedia WDR5 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human WDR5 in complex with compound OICR-9429.
PDB Id:  4QL1
Ligand:  OICR-9429
Resolution:  1.5Å
Species:  Human
References: 

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
OICR-9429 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Binding 7.6 pKd 1,3
⤷ pKd 7.6 (Kd 2.4x10-8 M) [1,3]
Description: Binding affinity determined by BIACore analysis.
MS40 Small molecule or natural product Click here for species-specific activity table Hs Binding 6.9 pKd 2
⤷ pKd 6.9 (Kd 1.25x10-7 M) [2]
compound 41 [PMID: 35436124] Small molecule or natural product Hs Binding >10.7 pKi 4
⤷ pKi >10.7 (Ki <2x10-11 M) [4]
compound 22 [PMID: 38085679] Small molecule or natural product Hs Inhibition >10.7 pKi 5
⤷ pKi >10.7 (Ki <2x10-11 M) [5]
Description: Determined by TR-FRET
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
MS132 Small molecule or natural product Hs Binding 6.9 pKd 8
⤷ pKd 6.9 (Kd 1.22x10-7 M) [8]
Description: Binding affinity determined by isothermal titration calorimetry (ITC)
Immuno Process Associations
Immuno Process:  Immune regulation
Immuno Process:  Immune system development
General Comments
WDR5 is involved in the formation of heterotrimeric or multiprotein complexes eg the histone acetyltransferase complex and the histone methyltransferase complex [6-7]. It is a chromatin-associated protein that is an essential recruiting factor for the MYC oncoprotein (transcription factor) to MYC-regulated genes. WDR5 is a validated molecular target for oncology drug discovery, whose inhibition is predicted to offer therapeutic benefit in solid and haematological malignancies that are driven by oncogenic MYC activity.

References

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1. Grebien F, Vedadi M, Getlik M, Giambruno R, Grover A, Avellino R, Skucha A, Vittori S, Kuznetsova E, Smil D et al.. (2015) Erratum: Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia. Nat Chem Biol, 11 (10): 815. [PMID:26379026]

2. Li D, Yu X, Kottur J, Gong W, Zhang Z, Storey AJ, Tsai YH, Uryu H, Shen Y, Byrum SD et al.. (2022) Discovery of a dual WDR5 and Ikaros PROTAC degrader as an anti-cancer therapeutic. Oncogene, 41 (24): 3328-3340. [PMID:35525905]

3. SGC. OICR-9429 - a chemical probe for WDR5. Accessed on 03/03/2015. Modified on 04/08/2023. thesgc.org, https://www.thesgc.org/chemical-probes/OICR-9429

4. Teuscher KB, Meyers KM, Wei Q, Mills JJ, Tian J, Alvarado J, Sai J, Van Meveren M, South TM, Rietz TA et al.. (2022) Discovery of Potent Orally Bioavailable WD Repeat Domain 5 (WDR5) Inhibitors Using a Pharmacophore-Based Optimization. J Med Chem, 65 (8): 6287-6312. [PMID:35436124]

5. Teuscher KB, Mills JJ, Tian J, Han C, Meyers KM, Sai J, South TM, Crow MM, Van Meveren M, Sensintaffar JL et al.. (2023) Structure-Based Discovery of Potent, Orally Bioavailable Benzoxazepinone-Based WD Repeat Domain 5 Inhibitors. J Med Chem, 66 (24): 16783-16806. [PMID:38085679]

6. Wysocka J, Myers MP, Laherty CD, Eisenman RN, Herr W. (2003) Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1. Genes Dev, 17 (7): 896-911. [PMID:12670868]

7. Yokoyama A, Wang Z, Wysocka J, Sanyal M, Aufiero DJ, Kitabayashi I, Herr W, Cleary ML. (2004) Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression. Mol Cell Biol, 24 (13): 5639-49. [PMID:15199122]

8. Yu X, Li D, Kottur J, Kim HS, Herring LE, Yu Y, Xie L, Hu X, Chen X, Cai L et al.. (2023) Discovery of Potent and Selective WDR5 Proteolysis Targeting Chimeras as Potential Therapeutics for Pancreatic Cancer. J Med Chem, 66 (23): 16168-16186. [PMID:38019706]

How to cite this page

WD repeat-containing proteins: WD repeat domain 5. Last modified on 13/12/2023. Accessed on 23/01/2025. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2831.