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CREB binding protein

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Target id: 2734

Nomenclature: CREB binding protein

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 - 2442 16p13.3 CREBBP CREB binding protein
Mouse - 2441 16 A1 Crebbp CREB binding protein
Rat - 2444 10q12 Crebbp CREB binding protein
Previous and Unofficial Names Click here for help
RSTS | Rubinstein-Taybi syndrome
Database Links Click here for help
Alphafold Q92793 (Hs)
CATH/Gene3D 1.10.1630.10, 1.20.1020.10, 1.20.920.10
ChEMBL Target CHEMBL5747 (Hs)
Ensembl Gene ENSG00000005339 (Hs), ENSMUSG00000022521 (Mm), ENSRNOG00000005330 (Rn)
Entrez Gene 1387 (Hs), 12914 (Mm), 54244 (Rn)
Human Protein Atlas ENSG00000005339 (Hs)
KEGG Gene hsa:1387 (Hs), mmu:12914 (Mm), rno:54244 (Rn)
OMIM 600140 (Hs)
Pharos Q92793 (Hs)
RefSeq Nucleotide NM_004380 (Hs), NM_001025432 (Mm), NM_133381 (Rn)
RefSeq Protein NP_004371 (Hs), NP_001020603 (Mm), NP_596872 (Rn)
SynPHARM 79896 (in complex with ischemin)
79941 (in complex with SGC-CBP30)
UniProtKB Q92793 (Hs)
Wikipedia CREBBP (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Solution NMR structure of ischemin bound to the bromodomain of CBP.
PDB Id:  2L84
Ligand:  ischemin
Resolution:  0.0Å
Species:  Human
References:  1
Image of receptor 3D structure from RCSB PDB
Description:  Solution NMR structure showing the association of MS7072 with the bromodomain of CBP.
PDB Id:  2D82
Ligand:  MS7972
Resolution:  0.0Å
Species:  Human
References:  8
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the bromodomain of human CREBBP in complex with SGC-CBP30
PDB Id:  4NR7
Ligand:  SGC-CBP30
Resolution:  1.2Å
Species:  Human
References: 

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 - - 2
⤷ [2]
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 7.8 – 8.8 pKd 10-11
⤷ pKd 8.8 (Kd 1.7x10-9 M) [10]
Description: Binding affinity for hCBP bromodomain determined by surface plasmon resonance (SPR).
pKd 7.8 (Kd 1.4x10-8 M) [11]
Description: Binding affinity for recombinant hCBP bromodomain determined by isothermal titration calorimetry (ITC).
I-CBP112 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.8 pKd 9
⤷ pKd 6.8 (Kd 1.42x10-7 M) [9]
Description: Isothermal titration calorimetry (ITC) assay.
ischemin Small molecule or natural product Hs Inhibition 4.7 pKd 1
⤷ pKd 4.7 (Kd 1.9x10-5 M) [1]
Description: Binding to CBP's bromodomain (amino acid residues 1081-1197)
GNE-049 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 9.0 pIC50 7
⤷ pIC50 9.0 (IC50 1.1x10-9 M) [7]
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 7.2 pIC50 6
⤷ pIC50 7.2 (IC50 6.9x10-8 M) [6]
compound 50 [PMID: 24313754] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.2 pIC50 5
⤷ pIC50 6.2 (IC50 6.31x10-7 M) [5]
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 3
⤷ pIC50 8.0 (IC50 1.1x10-8 M) PROTAC [3]
CBPD-409 Small molecule or natural product Click here for species-specific activity table Hs Binding - - 4
⤷ PROTAC [4]
Immunopharmacology Comments
CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses. PMID: 26261308
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune system development
Immuno Process:  Immune regulation
Immuno Process:  Cytokine production & signalling
Immuno Process:  Cellular signalling
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Acute myeloid leukemia with t(8;16)(p11;p13) translocation
Orphanet: ORPHA370026
Disease:  Chromosome 16p13.3 deletion syndrome
Synonyms: Rubinstein-Taybi syndrome due to 16p13.3 microdeletion [Orphanet: ORPHA353281]
OMIM: 610543
Orphanet: ORPHA353281
Disease:  Rubinstein-Taybi syndrome 1; RSTS1
Synonyms: Rubinstein-Taybi syndrome [Disease Ontology: DOID:1933]
Rubinstein-Taybi syndrome due to CREBBP mutations [Orphanet: ORPHA353277]
Disease Ontology: DOID:1933
OMIM: 180849
Orphanet: ORPHA353277

References

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1. Borah JC, Mujtaba S, Karakikes I, Zeng L, Muller M, Patel J, Moshkina N, Morohashi K, Zhang W, Gerona-Navarro G et al.. (2011) A small molecule binding to the coactivator CREB-binding protein blocks apoptosis in cardiomyocytes. Chem Biol, 18 (4): 531-41. [PMID:21513889]

2. 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]

3. 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]

4. 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]

5. Fedorov O, Lingard H, Wells C, Monteiro OP, Picaud S, Keates T, Yapp C, Philpott M, Martin SJ, Felletar I et al.. (2014) [1,2,4]triazolo[4,3-a]phthalazines: inhibitors of diverse bromodomains. J Med Chem, 57 (2): 462-76. [PMID:24313754]

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

7. Romero FA, Murray J, Lai KW, Tsui V, Albrecht BK, An L, Beresini MH, de Leon Boenig G, Bronner SM, Chan EW et al.. (2017) GNE-781, A Highly Advanced Potent and Selective Bromodomain Inhibitor of Cyclic Adenosine Monophosphate Response Element Binding Protein, Binding Protein (CBP). J Med Chem, 60 (22): 9162-9183. [PMID:28892380]

8. Sachchidanand, Resnick-Silverman L, Yan S, Mutjaba S, Liu WJ, Zeng L, Manfredi JJ, Zhou MM. (2006) Target structure-based discovery of small molecules that block human p53 and CREB binding protein association. Chem Biol, 13 (1): 81-90. [PMID:16426974]

9. 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

10. 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]

11. Xiang Q, Wang C, Wu T, Zhang C, Hu Q, Luo G, Hu J, Zhuang X, Zou L, Shen H et al.. (2022) Design, Synthesis, and Biological Evaluation of 1-(Indolizin-3-yl)ethan-1-ones as CBP Bromodomain Inhibitors for the Treatment of Prostate Cancer. J Med Chem, 65 (1): 785-810. [PMID:34962793]

How to cite this page

Non-enzymatic BRD containing proteins: CREB binding protein. Last modified on 02/04/2024. Accessed on 11/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2734.