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E1A binding protein p300

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Target id: 2735

Nomenclature: E1A binding protein p300

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 - 2414 22q13.2 EP300 E1A binding protein p300
Mouse - 2412 15 E1 Ep300 E1A binding protein p300
Rat - - 7q34 Ep300 E1A binding protein p300
Previous and Unofficial Names Click here for help
histone acetyltransferase p300 | KAT3B
Database Links Click here for help
Alphafold Q09472 (Hs)
CATH/Gene3D 1.10.1630.10, 1.20.1020.10, 1.20.920.10
ChEMBL Target CHEMBL3784 (Hs)
Ensembl Gene ENSG00000100393 (Hs), ENSMUSG00000055024 (Mm), ENSRNOG00000065659 (Rn), ENSRNOG00000000190 (Rn)
Entrez Gene 2033 (Hs), 328572 (Mm), 170915 (Rn)
Human Protein Atlas ENSG00000100393 (Hs)
KEGG Gene hsa:2033 (Hs), mmu:328572 (Mm), rno:170915 (Rn)
OMIM 602700 (Hs)
Pharos Q09472 (Hs)
RefSeq Nucleotide NM_001429 (Hs), NM_177821 (Mm)
RefSeq Protein NP_001420 (Hs), NP_808489 (Mm)
SynPHARM 79942 (in complex with SGC-CBP30)
UniProtKB Q09472 (Hs)
Wikipedia EP300 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the bromodomain of human EP300
PDB Id:  3I3J
Resolution:  2.33Å
Species:  Human
References:  9

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

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
TTK21 Small molecule or natural product Click here for species-specific activity table Hs Activation - - 5
⤷ [5]
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
inobrodib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.8 pKd 14
⤷ pKd 8.8 (Kd 1.7x10-9 M) [14]
Description: Binding affinity for human p300 bromodomain determined by surface plasmon resonance (SPR)
I-CBP112 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.2 pKd 13
⤷ pKd 6.2 (Kd 6.25x10-7 M) [13]
Description: Isothermal titration calorimetry (ITC) assay.
C646 Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 6.4 pKi 4
⤷ pKi 6.4 (Ki 4x10-7 M) [4]
inobrodib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.7 pIC50 14
⤷ pIC50 7.7 (IC50 1.9x10-8 M) [14]
Description: Inhibition of histone binding determined in a cell-based BRET assay.
SGC-CBP30 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Guide to Malaria Pharmacology Ligand Hs Inhibition 7.4 pIC50 10
⤷ pIC50 7.4 (IC50 3.8x10-8 M) [10]
Lys-CoA Peptide Click here for species-specific activity table Hs Inhibition 6.3 pIC50 11
⤷ pIC50 6.3 (IC50 5x10-7 M) [11]
anacardic acid Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.3 pIC50 2
⤷ pIC50 5.3 (IC50 5x10-6 M) [2]
garcinol Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.2 pIC50 1
⤷ pIC50 5.2 (IC50 7x10-6 M) [1]
curcumin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 4.6 pIC50 3
⤷ pIC50 4.6 (IC50 2.5x10-5 M) [3]
plumbagin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 4.6 pIC50 12
⤷ pIC50 4.6 (IC50 2.5x10-5 M) [12]
epigallocatechin-3-gallate Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 4.5 pIC50 8
⤷ pIC50 4.5 (IC50 3x10-5 M) [8]
H3-CoA-20 Peptide Click here for species-specific activity table Hs Inhibition 3.7 pIC50 11
⤷ pIC50 3.7 (IC50 2x10-4 M) [11]
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
CBPD-268 Small molecule or natural product Click here for species-specific activity table Hs Binding 8.0 pIC50 6
⤷ pIC50 8.0 (IC50 9.5x10-9 M) PROTAC [6]
CBPD-409 Small molecule or natural product Click here for species-specific activity table Hs Binding - - 7
⤷ PROTAC [7]
Immunopharmacology Comments
CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses. PMID: 26261308
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune regulation
Immuno Process:  Cytokine production & signalling
Immuno Process:  Cellular signalling
Immuno Process:  B cell (activation)
Immuno Process:  Immune system development
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Colorectal cancer
Disease Ontology: DOID:9256
OMIM: 114500
Disease:  Rubinstein-Taybi syndrome 2; RSTS2
Synonyms: Rubinstein-Taybi syndrome [Disease Ontology: DOID:1933]
Rubinstein-Taybi syndrome due to EP300 haploinsufficiency [Orphanet: ORPHA353284]
Disease Ontology: DOID:1933
OMIM: 613684
Orphanet: ORPHA353284

References

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1. Balasubramanyam K, Altaf M, Varier RA, Swaminathan V, Ravindran A, Sadhale PP, Kundu TK. (2004) Polyisoprenylated benzophenone, garcinol, a natural histone acetyltransferase inhibitor, represses chromatin transcription and alters global gene expression. J Biol Chem, 279 (32): 33716-26. [PMID:15155757]

2. Balasubramanyam K, Swaminathan V, Ranganathan A, Kundu TK. (2003) Small molecule modulators of histone acetyltransferase p300. J Biol Chem, 278 (21): 19134-40. [PMID:12624111]

3. Balasubramanyam K, Varier RA, Altaf M, Swaminathan V, Siddappa NB, Ranga U, Kundu TK. (2004) Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription. J Biol Chem, 279 (49): 51163-71. [PMID:15383533]

4. Bowers EM, Yan G, Mukherjee C, Orry A, Wang L, Holbert MA, Crump NT, Hazzalin CA, Liszczak G, Yuan H et al.. (2010) Virtual ligand screening of the p300/CBP histone acetyltransferase: identification of a selective small molecule inhibitor. Chem Biol, 17 (5): 471-82. [PMID:20534345]

5. Chatterjee S, Mizar P, Cassel R, Neidl R, Selvi BR, Mohankrishna DV, Vedamurthy BM, Schneider A, Bousiges O, Mathis C et al.. (2013) A novel activator of CBP/p300 acetyltransferases promotes neurogenesis and extends memory duration in adult mice. J Neurosci, 33 (26): 10698-712. [PMID:23804093]

6. Chen Z, Wang M, Wu D, Bai L, Xu T, Metwally H, Wang Y, McEachern D, Zhao L, Li R et al.. (2024) Discovery of CBPD-268 as an Exceptionally Potent and Orally Efficacious CBP/p300 PROTAC Degrader Capable of Achieving Tumor Regression. J Med Chem, 67 (7): 5275-5304. [PMID:38477974]

7. Chen Z, Wang M, Wu D, Zhao L, Metwally H, Jiang W, Wang Y, Bai L, McEachern D, Luo J et al.. (2024) Discovery of CBPD-409 as a Highly Potent, Selective, and Orally Efficacious CBP/p300 PROTAC Degrader for the Treatment of Advanced Prostate Cancer. J Med Chem, 67 (7): 5351-5372. [PMID:38530938]

8. Choi KC, Jung MG, Lee YH, Yoon JC, Kwon SH, Kang HB, Kim MJ, Cha JH, Kim YJ, Jun WJ et al.. (2009) Epigallocatechin-3-gallate, a histone acetyltransferase inhibitor, inhibits EBV-induced B lymphocyte transformation via suppression of RelA acetylation. Cancer Res, 69 (2): 583-92. [PMID:19147572]

9. Filippakopoulos P, Picaud S, Mangos M, Keates T, Lambert JP, Barsyte-Lovejoy D, Felletar I, Volkmer R, Müller S, Pawson T et al.. (2012) Histone recognition and large-scale structural analysis of the human bromodomain family. Cell, 149 (1): 214-31. [PMID:22464331]

10. Gallenkamp D, Gelato KA, Haendler B, Weinmann H. (2014) Bromodomains and their pharmacological inhibitors. ChemMedChem, 9 (3): 438-64. [PMID:24497428]

11. Lau OD, Kundu TK, Soccio RE, Ait-Si-Ali S, Khalil EM, Vassilev A, Wolffe AP, Nakatani Y, Roeder RG, Cole PA. (2000) HATs off: selective synthetic inhibitors of the histone acetyltransferases p300 and PCAF. Mol Cell, 5 (3): 589-95. [PMID:10882143]

12. Ravindra KC, Selvi BR, Arif M, Reddy BA, Thanuja GR, Agrawal S, Pradhan SK, Nagashayana N, Dasgupta D, Kundu TK. (2009) Inhibition of lysine acetyltransferase KAT3B/p300 activity by a naturally occurring hydroxynaphthoquinone, plumbagin. J Biol Chem, 284 (36): 24453-64. [PMID:19570987]

13. SGC. I-CBP112 A CREBBP/EP300-selective chemical probe. Accessed on 04/08/2023. Modified on 04/08/2023. thesgc.org, https://www.thesgc.org/chemical-probes/I-CBP112

14. Welti J, Sharp A, Brooks N, Yuan W, McNair C, Chand SN, Pal A, Figueiredo I, Riisnaes R, Gurel B et al.. (2021) Targeting the p300/CBP Axis in Lethal Prostate Cancer. Cancer Discov, 11 (5): 1118-1137. [PMID:33431496]

How to cite this page

Non-enzymatic BRD containing proteins: E1A binding protein p300. Last modified on 02/04/2024. Accessed on 11/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2735.