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polybromo 1

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Target id: 2738

Nomenclature: polybromo 1

Family: Non-enzymatic BRD containing proteins

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1689 3p21.1 PBRM1 polybromo 1
Mouse - 1704 14 B Pbrm1 polybromo 1
Rat - - 16p16 Pbrm1 polybromo 1
Previous and Unofficial Names Click here for help
BAF180 | PB1
Database Links Click here for help
Alphafold Q86U86 (Hs)
CATH/Gene3D 1.10.30.10, 1.20.920.10
ChEMBL Target CHEMBL1795184 (Hs)
Ensembl Gene ENSG00000163939 (Hs), ENSMUSG00000042323 (Mm), ENSRNOG00000028227 (Rn)
Entrez Gene 55193 (Hs), 66923 (Mm), 306254 (Rn)
Human Protein Atlas ENSG00000163939 (Hs)
KEGG Gene hsa:55193 (Hs), mmu:66923 (Mm), rno:306254 (Rn)
OMIM 606083 (Hs)
Pharos Q86U86 (Hs)
RefSeq Nucleotide NM_018313 (Hs), NM_001081251 (Mm)
RefSeq Protein NP_060783 (Hs), NP_001074720 (Mm)
UniProtKB Q86U86 (Hs)
Wikipedia PBRM1 (Hs)

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
PFI-3 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Binding 7.3 pKd 6
⤷ pKd 7.3 (Kd 4.8x10-8 M) [6]
GNE-235 Small molecule or natural product Click here for species-specific activity table Hs Binding 4.8 – 6.6 pKd 2
⤷ pKd 6.6 (Kd 2.8x10-7 M) [2]
Description: Binding affinity for BD2 of hPBRM1
pKd 4.8 (Kd 1.5x10-5 M) [2]
Description: Binding affinity for BD5 of hPBRM1
GNE-064 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.7 pIC50 8
⤷ pIC50 7.7 (IC50 1.8x10-8 M) [8]
Description: Inhibitory potency at the 5th bromodomain of PBRM1, determined by BromoScan assay
Immunopharmacology Comments
We have included PBRM1 in GtoImmuPdb as its repression has been reported to re-sensitise tumour cells with acquired resistance to immunotherapy (e.g. checkpoint blockade by anti-PD-1 or anti-CTLA-4 mAbs) to T cell-mediated attack [4].
General Comments
PBRM1 is a component of the SWI/SNF chromatin remodeling PBAF complex. More than one fifth of human cancers carry mutations in PBAF subunit genes. The PBAF complex is reported to confer tumour cell resistance to T cell-mediated killing [3], suggesting molecular targets for the development of novel interventions to treat cancers driven by perturbed mSWI/SNF activity [7]. PBRM1 has specifically been identified as a potential target for renal cell carcinoma [1,5].

References

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1. Brugarolas J. (2013) PBRM1 and BAP1 as novel targets for renal cell carcinoma. Cancer J, 19 (4): 324-32. [PMID:23867514]

2. Cochran AG, Flynn M. (2023) GNE-235: A Lead Compound Selective for the Second Bromodomain of PBRM1. J Med Chem, 66 (18): 13116-13134. [PMID:37702400]

3. Kadoch C, Crabtree GR. (2015) Mammalian SWI/SNF chromatin remodeling complexes and cancer: Mechanistic insights gained from human genomics. Sci Adv, 1 (5): e1500447. [PMID:26601204]

4. Pan D, Kobayashi A, Jiang P, Ferrari de Andrade L, Tay RE, Luoma AM, Tsoucas D, Qiu X, Lim K, Rao P et al.. (2018) A major chromatin regulator determines resistance of tumor cells to T cell-mediated killing. Science, 359 (6377): 770-775. [PMID:29301958]

5. Piva F, Santoni M, Matrana MR, Satti S, Giulietti M, Occhipinti G, Massari F, Cheng L, Lopez-Beltran A, Scarpelli M et al.. (2015) BAP1, PBRM1 and SETD2 in clear-cell renal cell carcinoma: molecular diagnostics and possible targets for personalized therapies. Expert Rev Mol Diagn, 15 (9): 1201-10. [PMID:26166446]

6. SGC. PFI-3 A Selective chemical probe for SMARCA bromodomains. Accessed on 10/11/2014. Modified on 04/08/2023. thesgc.org, https://www.thesgc.org/chemical-probes/PFI-3

7. St Pierre R, Kadoch C. (2017) Mammalian SWI/SNF complexes in cancer: emerging therapeutic opportunities. Curr Opin Genet Dev, 42: 56-67. [PMID:28391084]

8. Taylor AM, Bailey C, Belmont LD, Campbell R, Cantone N, Côté A, Crawford TD, Cummings R, DeMent K, Duplessis M et al.. (2022) GNE-064: A Potent, Selective, and Orally Bioavailable Chemical Probe for the Bromodomains of SMARCA2 and SMARCA4 and the Fifth Bromodomain of PBRM1. J Med Chem, 65 (16): 11177-11186. [PMID:35930799]

How to cite this page

Non-enzymatic BRD containing proteins: polybromo 1. Last modified on 18/01/2024. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2738.