CREBBP

Summary

CREBBP (CREB binding lysine acetyltransferase , HGNC:2348) is a protein-coding gene on chromosome 16p13.3, encoding CREB-binding protein (Q92793). Acetylates histones, giving a specific tag for transcriptional activation. It is a selective cancer dependency (DepMap: 10.8% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This gene is ubiquitously expressed and is involved in the transcriptional coactivation of many different transcription factors. First isolated as a nuclear protein that binds to cAMP-response element binding protein (CREB), this gene is now known to play critical roles in embryonic development, growth control, and homeostasis by coupling chromatin remodeling to transcription factor recognition. The protein encoded by this gene has intrinsic histone acetyltransferase activity and also acts as a scaffold to stabilize additional protein interactions with the transcription complex. This protein acetylates both histone and non-histone proteins. This protein shares regions of very high sequence similarity with protein p300 in its bromodomain, cysteine-histidine-rich regions, and histone acetyltransferase domain. Mutations in this gene cause Rubinstein-Taybi syndrome (RTS). Chromosomal translocations involving this gene have been associated with acute myeloid leukemia. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 1387 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Rubinstein-Taybi syndrome (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 11
• Clinical variants (ClinVar): 3,157 total — 367 pathogenic, 163 likely-pathogenic
• Phenotypes (HPO): 261
• Druggable target: yes — 13 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 25 cancer types
• Cancer dependency (DepMap): dependent in 10.8% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 38 downstream targets (CollecTRI)
• MANE Select transcript: NM_004380

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2348
Approved symbol	CREBBP
Name	CREB binding lysine acetyltransferase
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	RTS, CBP, KAT3A
Ensembl gene	ENSG00000005339
Ensembl biotype	protein_coding
OMIM	600140
Entrez	1387

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 7 protein_coding, 7 retained_intron, 6 protein_coding_CDS_not_defined

ENST00000262367, ENST00000382070, ENST00000570939, ENST00000571763, ENST00000571826, ENST00000572134, ENST00000572569, ENST00000573517, ENST00000573672, ENST00000574740, ENST00000575237, ENST00000576720, ENST00000634839, ENST00000635753, ENST00000635899, ENST00000635919, ENST00000636002, ENST00000636895, ENST00000637492, ENST00000638158

RefSeq mRNA: 2 — MANE Select: NM_004380 NM_001079846, NM_004380

CCDS: CCDS10509, CCDS45399

Canonical transcript exons

ENST00000262367 — 31 exons

Exon	Start	End
ENSE00000865712	3731192	3731473
ENSE00001062588	3731776	3731937
ENSE00001292463	3725054	3729874
ENSE00001592013	3751726	3751806
ENSE00001594624	3770570	3770986
ENSE00001608958	3781204	3781306
ENSE00001615007	3777613	3777657
ENSE00001638447	3773751	3773930
ENSE00001644140	3757809	3758048
ENSE00001656158	3778700	3778817
ENSE00001670717	3745277	3745354
ENSE00001678454	3778011	3778182
ENSE00001692816	3782684	3782926
ENSE00001693899	3791981	3792094
ENSE00001698951	3738559	3738672
ENSE00001699420	3757288	3757376
ENSE00001709420	3758854	3758972
ENSE00001732416	3780732	3780878
ENSE00001733259	3774569	3774693
ENSE00001744566	3793386	3793626
ENSE00001784635	3767720	3767909
ENSE00001788865	3810603	3810779
ENSE00001789080	3850297	3851009
ENSE00001789918	3749627	3749683
ENSE00001871332	3879832	3880713
ENSE00003460818	3769174	3769353
ENSE00003531262	3739578	3739724
ENSE00003538086	3736036	3736203
ENSE00003544267	3740399	3740549
ENSE00003613508	3744894	3744961
ENSE00003665970	3736650	3736815

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 97.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.7044 / max 624.7420, expressed in 1803 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156048	21.1902	1803
156049	0.5143	297

Top tissues by expression

299 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	97.65	gold quality
tibia	UBERON:0000979	96.03	gold quality
amniotic fluid	UBERON:0000173	95.92	gold quality
adrenal tissue	UBERON:0018303	95.55	gold quality
germinal epithelium of ovary	UBERON:0001304	95.37	gold quality
calcaneal tendon	UBERON:0003701	95.32	gold quality
endothelial cell	CL:0000115	94.82	gold quality
bone marrow cell	CL:0002092	94.81	gold quality
skin of hip	UBERON:0001554	94.54	gold quality
adult organism	UBERON:0007023	94.51	gold quality
caput epididymis	UBERON:0004358	94.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.21	gold quality
ventricular zone	UBERON:0003053	94.19	gold quality
colonic epithelium	UBERON:0000397	94.07	gold quality
mammary duct	UBERON:0001765	94.00	gold quality
epithelium of mammary gland	UBERON:0003244	93.97	gold quality
blood	UBERON:0000178	93.94	gold quality
mononuclear cell	CL:0000842	93.90	gold quality
visceral pleura	UBERON:0002401	93.89	gold quality
monocyte	CL:0000576	93.87	gold quality
leukocyte	CL:0000738	93.87	gold quality
pleura	UBERON:0000977	93.65	gold quality
parietal pleura	UBERON:0002400	93.64	gold quality
left ovary	UBERON:0002119	93.56	gold quality
body of uterus	UBERON:0009853	93.56	gold quality
cauda epididymis	UBERON:0004360	93.49	gold quality
ovary	UBERON:0000992	93.45	gold quality
trabecular bone tissue	UBERON:0002483	93.39	gold quality
esophagus squamous epithelium	UBERON:0006920	93.38	gold quality
ganglionic eminence	UBERON:0004023	93.29	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.66

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

38 targets.

Target	Regulation
ADORA2A
ALOX15	Activation
BRCA1	Unknown
CCK	Unknown
CDKN1A	Activation
CREB1	Activation
CSF2	Unknown
EGFR	Unknown
EP300	Unknown
ERCC1
EZH2	Unknown
FDPS	Activation
HINFP	Activation
HMGCR	Activation
HMGCS1	Activation
HOXA10	Activation
HOXA9	Activation
IFNB1	Unknown
IL4	Activation
INSM1	Activation
IRF1	Activation
LDLR	Activation
LHB	Unknown
MST1	Unknown
MYC
PCK1	Activation
PCK2	Unknown
PPARA	Unknown
PSMC5	Activation
PTGS2	Unknown

Upstream regulators (CollecTRI, top): AHR, AIRE, ALX1, AR, ATF1, ATF3, ATF4, ATF5, BMAL1, CARF, CEBPB, CEBPG, CIITA, CLOCK, CREM, DBP, DIDO1, E2F1, EBF1, EGR1, EGR3, EP300, ESR2, ETS2, EWSR1, FLI1, FOXC1, GCM1, HBP1, HIF1A, HNF4A, ID2, ID4, INSM1, IRF1, IRF2, IRF3, IRF8, JDP2, KAT5

miRNA regulators (miRDB)

172 targeting CREBBP, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-570-3P	99.96	72.41	4910

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 10.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• substrate specificity; structure activity relationship (PMID:11691934)
• The PHD type zinc finger is an integral part of the CBP acetyltransferase domain (PMID:11884585)
• Interaction of PIMT with transcriptional coactivators CBP, p300, and PBP differential role in transcriptional regulation. (PMID:11912212)
• IL-6-inducible expression of the hAGT promoter is mediated by physical association of the COOH terminus of STAT3 with p300/CBP, the recruitment of which targets histone acetylation and results in chromatin remodeling. (PMID:11923478)
• overexpression of CBP is detected from the very early stages of laryngeal carcinogenesis, suggesting that CBP may play a role in malignant transformation of precancerous laryngeal lesions (PMID:11935299)
• role in acetylation of beta-catenin (PMID:11973335)
• Regulatory motifs for CREB-binding protein and Nfe2l2 transcription factors in the upstream enhancer of the mitochondrial uncoupling protein 1 gene. (PMID:12084707)
• A missense mutation has been identified in codon 1175 of CREBBP in a mild case of Rubinstein-Taybi syndrome. (PMID:12114483)
• HIV Tat is a general inhibitor of histone acetylation by cellular HATs and for the CREB-binding protein (CBP), it induces a substrate selectivity (PMID:12154097)
• CBP enhances tumor necrosis alpha-induced cell death in rheumatoid synoviocytes (PMID:12165799)
• role in transcriptional control of the inflammatory response (PMID:12168567)
• is co-expressed with CREB and CBP in extravillous cytotrophoblasts, revealing the in vivo relevance of this transactivation pathway (PMID:12183445)
• results suggest that all-trans-retinoic acid and retinoic acid receptors regulate growth arrest of human mammary epithelial cells and modulate CBP/p300 protein expression (PMID:12242694)
• arginine methylation represents an important mechanism for modulating CBP co-activator transcriptional activity (PMID:12374746)
• Oct-1 potentiates CREB-dependent cyclin D1 transcriptional activity by a phospho-CREB and CREB binding protein-independent mechanism (PMID:12391146)
• CBP has a role in regulating 5-aminolevulinate synthase gene expression via the AP-1 complex in human tumor cells (PMID:12433930)
• structurally distinct modes of recognition of the KIX domain of this protein by Jun and CREB (PMID:12437352)
• interaction of CREB-binding protein with EWS selectively activates hepatocyte nuclear factor 4-mediated transcription (PMID:12459554)
• The CBP/p300 acetylase and the CARM1 methyltransferase can positively regulate the expression of estrogen-responsive genes, there is a crosstalk between lysine acetylation and arginine methylation on chromatin (PMID:12498683)
• recruitment to pp90RSK regulates cAMP response element-binding protein activity which is negatively affected by ERK phosphorylation (PMID:12540838)
• The KID-interacting domain of human coactivator CREB-binding protein (CBP) is the CBP domain that is targeted by HIV-1 Tat during HIV-1 propagation. (PMID:12549909)
• PHD finger mutations cause a loss of CBP acetyltransferase activity (PMID:12566391)
• in human mammary epithelial cells, CBP/p300 were both modulated by an all-trans-retinoic acid (ATRA) signaling pathway and were required for a normal response to ATRA (PMID:12646247)
• deletion of the CBP bromo- and C/H3 domains eliminates stimulation of nucleosomal histone deacetylase activity in vitro and transcriptional coactivation by EBV Zta in transfected cells (PMID:12665567)
• Loss of CREBBP was not statistically significant selection in cancer cells stratified by various criteria for the concordant loss of EP300 and CREBBP. (PMID:12696060)
• CBP and p300 function as co-activators of Sox9 for cartilage tissue-specific gene expression and chondrocyte differentiation. (PMID:12732631)
• p34SEI-1 strongly suppressed CREB-mediated transcription, and this suppression was overcome by excess amount of CBP (PMID:12736710)
• Estrogen receptor-alpha represses human GnRH receptor gene transcription via an indirect mechanism involving Creb-binding protein. (PMID:12947046)
• CBP-induced acetylation of AFX is a novel modification mechanism by which AFX keeps the transcriptional activity mitigating in the nucleus (PMID:12964026)
• Loss of heterozygosity and internal tandem duplication mutations of the CBP gene are frequent events in human esophageal squamous cell carcinoma (PMID:14734447)
• The site of the KID-interacting (KIX) domain of CBP that recognizes c-Jun and mixed lineage leukemia MLL proteins is identified as the same site that binds HIV-1 Tat protein. (PMID:14744133)
• the conserved bromo-domain of the transcriptional coactivator CBP (CREB binding protein) binds specifically to p53 at the C-terminal acetylated lysine 382 (PMID:14759370)
• Novel heterozygous deletion in CREBBP in Rubinstein-Taybi syndrome patient results in the loss of exon 30. (PMID:14974086)
• activity of ESE-1 is positively and negatively modulated by other interacting proteins including Ku70, Ku86, p300, and CBP. (PMID:15075319)
• activation of CREB-binding protein and inhibition of MAPK has a role in cAMP-dependent protein kinase type I regulation of ethanol-induced cAMP response element-mediated gene expression (PMID:15299023)
• CBP acetylation controls HNF6 protein stability (PMID:15304484)
• effect of CREB-binding protein on inhibition of Smad-mediated transcriptional activation by K-bZIP was examined (PMID:15467747)
• E2A-PBX1 interacts directly with the KIX domain of CBP/p300 in the induction of proliferation in primary hematopoietic cells (PMID:15507449)
• important functions in coordinated cell cycle progression (PMID:15522869)
• Smad3 induces chondrogenesis through the activation of SOX9 via CREB-binding protein/p300 recruitment (PMID:15623506)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	crebbpa	ENSDARG00000104609
danio_rerio	crebbpb	ENSDARG00000112452
mus_musculus	Crebbp	ENSMUSG00000022521
rattus_norvegicus	Crebbp	ENSRNOG00000005330
drosophila_melanogaster	nej	FBGN0261617
caenorhabditis_elegans		WBGENE00000366
caenorhabditis_elegans		WBGENE00009595
caenorhabditis_elegans		WBGENE00010545
caenorhabditis_elegans		WBGENE00016220
caenorhabditis_elegans		WBGENE00016221

Paralogs (1): EP300 (ENSG00000100393)

Protein

Protein identifiers

CREB-binding protein — Q92793 (reviewed: Q92793)

Alternative names: Histone lysine acetyltransferase CREBBP, Protein lactyltransferas CREBBP, Protein-lysine acetyltransferase CREBBP

All UniProt accessions (6): Q92793, A0A1B0GUU0, I3L0Q1, I3L293, I3L3I5, I3L466

UniProt curated annotations — full annotation on UniProt →

Function. Acetylates histones, giving a specific tag for transcriptional activation. Mediates acetylation of histone H3 at ‘Lys-18’ and ‘Lys-27’ (H3K18ac and H3K27ac, respectively). Also acetylates non-histone proteins, like DDX21, FBL, IRF2, MAFG, NCOA3, POLR1E/PAF53 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1. Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-BMAL1 and CLOCK-BMAL1 heterodimers. Acetylates PCNA; acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER). Acetylates POLR1E/PAF53, leading to decreased association of RNA polymerase I with the rDNA promoter region and coding region. Acetylates DDX21, thereby inhibiting DDX21 helicase activity. Acetylates FBL, preventing methylation of ‘Gln-105’ of histone H2A (H2AQ104me). In addition to protein acetyltransferase, can use different acyl-CoA substrates, such as lactoyl-CoA, and is able to mediate protein lactylation. Catalyzes lactylation of MRE11 in response to DNA damage, thereby promoting DNA double-strand breaks (DSBs) via homologous recombination (HR). Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway.

Subunit / interactions. Found in a complex containing NCOA2; NCOA3; IKKA; IKKB and IKBKG. Probably part of a complex with HIF1A and EP300. Interacts with GATA1; the interaction results in acetylation and enhancement of transcriptional activity of GATA1. Interacts with MAF and ZCCHC12. Interacts with DAXX; the interaction is dependent on CBP sumoylation and results in suppression of the transcriptional activity via recruitment of HDAC2 to DAXX. Interacts with phosphorylated CREB1. Interacts with CITED4 (C-terminal region). Interacts (via the TAZ-type 1 domain) with HIF1A. Interacts with SRCAP, CARM1, ELF3, MLLT7/FOXO4, N4BP2, NCOA1, NCOA3, NCOA6, PCAF, DDX5, DDX17, PELP1, PML, SMAD1, SMAD2, SMAD3, SPIB and TRERF1. Interacts with KLF1; the interaction results in acetylation of KLF1 and enhancement of its transcriptional activity. Interacts with MTDH. Interacts with NFATC4. Interacts with MAFG; the interaction acetylates MAFG in the basic region and stimulates NFE2 transcriptional activity through increasing its DNA-binding activity. Interacts with IRF2; the interaction acetylates IRF2 and regulates its activity on the H4 promoter. Interacts with IRF3 (when phosphorylated); forming the dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I interferon genes. Interacts (via N-terminus) with SS18L1/CREST (via C-terminus). Interacts with MECOM. Interacts with CITED1 (via C-terminus). Interacts with FOXO1; the interaction acetylates FOXO1 and inhibits its transcriptional activity. Interacts with NPAS2, CLOCK and BMAL1. Interacts with ASF1A and ASF1B; this promotes histone acetylation. Interacts with acetylated TP53/p53 and with the acetylated histones H3 and H4. Interacts (via transactivation domain and C-terminus) with PCNA; the interaction occurs on chromatin in UV-irradiated damaged cells. Interacts with DHX9 (via N-terminus); this interaction mediates association with RNA polymerase II holoenzyme and stimulates CREB-dependent transcriptional activation. Interacts with SMAD4; negatively regulated by ZBTB7A. Interacts with DUX4 (via C-terminus). Forms a complex with KMT2A and CREB1. Interacts with DDX3X; this interaction may facilitate HNF4A acetylation. Interacts with MSX1; the interaction may inhibit MSX1 autoinactivation. Interacts with ACSS2. (Microbial infection) Interacts with HTLV-1 Tax, p30II and HBZ. (Microbial infection) Interacts with human herpes virus 8/HHV-8 protein vIRF-1; this interaction inhibits CREBBP binding to IRF3. (Microbial infection) Interacts with HIV-1 Tat.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Methylation of the KIX domain by CARM1 blocks association with CREB. This results in the blockade of CREB signaling, and in activation of apoptotic response. Phosphorylated by CHUK/IKKA at Ser-1382 and Ser-1386; these phosphorylations promote cell growth by switching the binding preference of CREBBP from TP53 to NF-kappa-B. Phosphorylated by _ at Ser-124 in response to DNA damage, promoting interaction with MRE11 and lactylation of MRE11. Sumoylation negatively regulates transcriptional activity via the recruitment of DAAX. Autoacetylation is required for binding to protein substrates, such as acetylated histones and acetylated TP53/p53. Autoacetylation is induced by glucose and fatty acids.

Disease relevance. Chromosomal aberrations involving CREBBP may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with KAT6A; translocation t(11;16)(q23;p13.3) with KMT2A/MLL1; translocation t(10;16)(q22;p13) with KAT6B. KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription. Rubinstein-Taybi syndrome 1 (RSTS1) [MIM:180849] A disorder characterized by craniofacial abnormalities, postnatal growth deficiency, broad thumbs, broad big toes, intellectual disability and a propensity for development of malignancies. The disease is caused by variants affecting the gene represented in this entry. Menke-Hennekam syndrome 1 (MKHK1) [MIM:618332] A form of Menke-Hennekam syndrome, a congenital autosomal dominant disease characterized by developmental delay, growth retardation, and craniofacial dysmorphism. Patients have intellectual disability of variable severity, speech delay, autistic behavior, short stature and microcephaly. Main facial characteristics include short palpebral fissures, telecanthi, depressed nasal ridge, short nose, anteverted nares, short columella and long philtrum. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The KIX domain mediates binding to HIV-1 Tat.

Isoforms (2)

UniProt ID	Names	Canonical?
Q92793-1	1	yes
Q92793-2	2

RefSeq proteins (2): NP_001073315, NP_004371* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000197	Znf_TAZ	Domain
IPR000433	Znf_ZZ	Domain
IPR001487	Bromodomain	Domain
IPR003101	KIX_dom	Domain
IPR009110	Nuc_rcpt_coact	Homologous_superfamily
IPR010303	RING_CBP-p300	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013178	Histone_AcTrfase_Rtt109/CBP	Family
IPR014744	Nuc_rcpt_coact_CREBbp	Domain
IPR018359	Bromodomain_CS	Conserved_site
IPR031162	CBP_P300_HAT	Domain
IPR035898	TAZ_dom_sf	Homologous_superfamily
IPR036427	Bromodomain-like_sf	Homologous_superfamily
IPR036529	KIX_dom_sf	Homologous_superfamily
IPR037073	Nuc_rcpt_coact_CREBbp_sf	Homologous_superfamily
IPR038547	RING_CBP-p300_sf	Homologous_superfamily
IPR043145	Znf_ZZ_sf	Homologous_superfamily
IPR056484	PHD_P300	Domain

Pfam: PF00439, PF00569, PF02135, PF02172, PF06001, PF08214, PF09030, PF23570

Enzyme classification (BRENDA):

• EC 2.3.1.48 — histone acetyltransferase (BRENDA: 41 organisms, 681 substrates, 1134 inhibitors, 140 Km, 96 kcat entries)

Substrate kinetics (BRENDA)

27 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ACETYL-COA	0.0002–0.046	51
HISTONE H3	0.007–2.09	23
HISTONE H4	—	11
HISTONE H4 PEPTIDE	0.0208–0.197	7
HISTONE	0.075–1.4	6
HISTONE H3 TAIL PEPTIDE	0.044–0.112	4
PICCOLONUA4 PEPTIDE	0.135–0.372	4
3-AZIDOPROPIONYL-COA	0.0002–0.0086	3
4-PENTYNOYL-COA	0.0009–0.0859	3
SPERMIDINE	0.18–0.27	3
5-HEXYNOYL-COA	0.0006–0.0117	2
6-HEPTYNOYL-COA	0.0003–0.0237	2
HISTONE H3-PEPTIDE	0.05–0.49	2
PROTEIN P53	1.28–4.63	2
3-AZIDOPROPANOYL-COA	0.0103	1

Catalyzed reactions (Rhea), 3 shown:

• L-lysyl-[histone] + acetyl-CoA = N(6)-acetyl-L-lysyl-[histone] + CoA + H(+) (RHEA:21992)
• L-lysyl-[protein] + acetyl-CoA = N(6)-acetyl-L-lysyl-[protein] + CoA + H(+) (RHEA:45948)
• (S)-lactoyl-CoA + L-lysyl-[protein] = N(6)-[(S)-lactoyl]-L-lysyl-[protein] + CoA + H(+) (RHEA:61996)

UniProt features (209 total): sequence variant 38, compositionally biased region 31, helix 27, modified residue 25, binding site 25, region of interest 14, turn 11, strand 10, mutagenesis site 9, sequence conflict 5, cross-link 3, domain 3, zinc finger region 3, site 2, initiator methionine 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

144 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5I86	X-RAY DIFFRACTION	1.05
5J0D	X-RAY DIFFRACTION	1.05
5I89	X-RAY DIFFRACTION	1.07
5KTW	X-RAY DIFFRACTION	1.09
4NYX	X-RAY DIFFRACTION	1.1
5EP7	X-RAY DIFFRACTION	1.2
4NR7	X-RAY DIFFRACTION	1.2
6YIL	X-RAY DIFFRACTION	1.22
5MMG	X-RAY DIFFRACTION	1.23
5MPN	X-RAY DIFFRACTION	1.23
6YIM	X-RAY DIFFRACTION	1.23
7WX2	X-RAY DIFFRACTION	1.24
5OWK	X-RAY DIFFRACTION	1.25
5KTX	X-RAY DIFFRACTION	1.27
9GET	X-RAY DIFFRACTION	1.29
5ENG	X-RAY DIFFRACTION	1.3
6AXQ	X-RAY DIFFRACTION	1.3
5I83	X-RAY DIFFRACTION	1.35
5MME	X-RAY DIFFRACTION	1.35
5MQG	X-RAY DIFFRACTION	1.35
6FQO	X-RAY DIFFRACTION	1.35
5KTU	X-RAY DIFFRACTION	1.38
6ALC	X-RAY DIFFRACTION	1.39
6AY3	X-RAY DIFFRACTION	1.39
4OUF	X-RAY DIFFRACTION	1.4
5MPZ	X-RAY DIFFRACTION	1.4
5I8G	X-RAY DIFFRACTION	1.41
5W0E	X-RAY DIFFRACTION	1.41
9JUY	X-RAY DIFFRACTION	1.42
4NYW	X-RAY DIFFRACTION	1.43

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92793-F1	54.31	0.20

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 29–30 (breakpoint for translocation to form kat6b-crebbp); 266–267 (breakpoint for translocation to form kat6a-crebbp)

Ligand- & substrate-binding residues (25): 363; 367; 380; 385; 394; 398; 404; 409; 418; 422; 427; 430 …

Post-translational modifications (28): 1763, 2063, 2076, 2079, 2351, 998, 1033, 1056, 2, 121, 124, 220, 601, 625, 657, 1014, 1030, 1076, 1216, 1382 …

Mutagenesis-validated functional residues (9):

Position	Phenotype
124	decreased phosphorylation and lactylation of mre11.
1116	impairs binding to acetylated histones.
1126	impairs binding to acetylated histones.
1162	abolishes interaction with asf1a.
1165	abolishes interaction with asf1a.
1170	impairs binding to acetylated histones.
1179	impairs interaction with asf1a.
1180	abolishes interaction with asf1a.
1183	abolishes interaction with asf1a.

Function

Pathways and Gene Ontology

Reactome pathways

125 pathways

ID	Pathway
R-HSA-1234158	Regulation of gene expression by Hypoxia-inducible Factor
R-HSA-1368108	BMAL1:CLOCK,NPAS2 activates circadian expression
R-HSA-1912408	Pre-NOTCH Transcription and Translation
R-HSA-1989781	PPARA activates gene expression
R-HSA-201722	Formation of the beta-catenin:TCF transactivating complex
R-HSA-210744	Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells
R-HSA-2122947	NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis
R-HSA-2426168	Activation of gene expression by SREBF (SREBP)
R-HSA-2644606	Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2894862	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-3134973	LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production
R-HSA-3214847	HATs acetylate histones
R-HSA-3371568	Attenuation phase
R-HSA-350054	Notch-HLH transcription pathway
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation
R-HSA-3899300	SUMOylation of transcription cofactors
R-HSA-400206	Regulation of lipid metabolism by PPARalpha
R-HSA-5617472	Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-5621575	CD209 (DC-SIGN) signaling
R-HSA-6803204	TP53 Regulates Transcription of Genes Involved in Cytochrome C Release
R-HSA-8866907	Activation of the TFAP2 (AP-2) family of transcription factors
R-HSA-8939246	RUNX1 regulates transcription of genes involved in differentiation of myeloid cells
R-HSA-8941856	RUNX3 regulates NOTCH signaling
R-HSA-9013508	NOTCH3 Intracellular Domain Regulates Transcription
R-HSA-9013695	NOTCH4 Intracellular Domain Regulates Transcription
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-918233	TRAF3-dependent IRF activation pathway
R-HSA-933541	TRAF6 mediated IRF7 activation
R-HSA-9614657	FOXO-mediated transcription of cell death genes

MSigDB gene sets: 1055 (showing top): REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, PID_HDAC_CLASSI_PATHWAY, GOBP_N_TERMINAL_PROTEIN_AMINO_ACID_ACETYLATION, BIOCARTA_RELA_PATHWAY, REACTOME_SIGNALING_BY_NOTCH, GOBP_REGULATION_OF_DNA_RECOMBINATION, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, AAGCAAT_MIR137, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_EMBRYONIC_DIGIT_MORPHOGENESIS

GO Biological Process (30): negative regulation of transcription by RNA polymerase II (GO:0000122), response to hypoxia (GO:0001666), stimulatory C-type lectin receptor signaling pathway (GO:0002223), regulation of DNA-templated transcription (GO:0006355), protein acetylation (GO:0006473), signal transduction (GO:0007165), canonical NF-kappaB signal transduction (GO:0007249), regulation of smoothened signaling pathway (GO:0008589), negative regulation of transcription by RNA polymerase I (GO:0016479), N-terminal peptidyl-lysine acetylation (GO:0018076), positive regulation of transforming growth factor beta receptor signaling pathway (GO:0030511), protein destabilization (GO:0031648), cellular response to nutrient levels (GO:0031669), cellular response to UV (GO:0034644), homeostatic process (GO:0042592), embryonic digit morphogenesis (GO:0042733), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), rhythmic process (GO:0048511), protein-containing complex assembly (GO:0065003), cAMP/PKA signal transduction (GO:0141156), regulation of cellular response to heat (GO:1900034), positive regulation of protein localization to nucleus (GO:1900182), positive regulation of double-strand break repair via homologous recombination (GO:1905168), double-strand break repair via homologous recombination (GO:0000724), chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), protein stabilization (GO:0050821), protein K48-linked deubiquitination (GO:0071108), energy homeostasis (GO:0097009)

GO Molecular Function (23): transcription coactivator binding (GO:0001223), p53 binding (GO:0002039), chromatin binding (GO:0003682), damaged DNA binding (GO:0003684), transcription coactivator activity (GO:0003713), transcription corepressor activity (GO:0003714), histone acetyltransferase activity (GO:0004402), zinc ion binding (GO:0008270), acetyltransferase activity (GO:0016407), chromatin DNA binding (GO:0031490), MRF binding (GO:0043426), histone H3K18 acetyltransferase activity (GO:0043993), histone H3K27 acetyltransferase activity (GO:0044017), tau protein binding (GO:0048156), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), protein-lysine-acetyltransferase activity (GO:0061733), peptide lactyltransferase (CoA-dependent) activity (GO:0120300), DNA-binding transcription factor binding (GO:0140297), transcription coregulator activity (GO:0003712), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), metal ion binding (GO:0046872)

GO Cellular Component (8): histone acetyltransferase complex (GO:0000123), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear body (GO:0016604)

Reactome top-level categories

Rollup of top-20 pathways:

Category	Pathways
Cellular response to hypoxia	1
Circadian clock	1
Pre-NOTCH Expression and Processing	1
Regulation of lipid metabolism by PPARalpha	1
TCF dependent signaling in response to WNT	1
Regulation of beta-cell development	1
Signaling by NOTCH1	1
Mitochondrial biogenesis	1
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1
Signaling by NOTCH1 PEST Domain Mutants in Cancer	1
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	1
Cytosolic sensors of pathogen-associated DNA	1
Chromatin modifying enzymes	1
HSF1-dependent transactivation	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
negative regulation of DNA-templated transcription	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
DNA-templated transcription	2
cellular response to stimulus	2
biological_process	2
positive regulation of DNA-templated transcription	2
binding	2
DNA binding	2
transcription coregulator activity	2
acyltransferase activity, transferring groups other than amino-acyl groups	2
histone H3 acetyltransferase activity	2
response to stress	1
response to decreased oxygen levels	1
innate immune response activating cell surface receptor signaling pathway	1
cellular response to lectin	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
protein acylation	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
intracellular signaling cassette	1
smoothened signaling pathway	1
regulation of signal transduction	1
regulation of transcription by RNA polymerase I	1
transcription by RNA polymerase I	1
N-terminal protein amino acid acetylation	1
peptidyl-lysine acetylation	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
positive regulation of cellular response to transforming growth factor beta stimulus	1
regulation of protein stability	1
response to nutrient levels	1
response to UV	1
cellular response to light stimulus	1
embryonic limb morphogenesis	1

Protein interactions and networks

STRING

5086 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CREBBP	CREB1	P16220	997
CREBBP	TP53	P04637	996
CREBBP	KAT2B	Q92831	993
CREBBP	CTNNB1	P35222	992
CREBBP	NCOA1	Q15788	992
CREBBP	HIF1A	Q16665	991
CREBBP	IRF3	Q14653	989
CREBBP	NCOA3	Q9Y6Q9	989
CREBBP	EP300	Q09472	983
CREBBP	HTT	P42858	982
CREBBP	JUN	P05412	969
CREBBP	BMAL1	O00327	965
CREBBP	CLOCK	O15516	965
CREBBP	STAT1	P42224	964
CREBBP	SMAD3	P84022	964

IntAct

445 interactions, top by confidence:

A	B	Type	Score
TP53	TP53	psi-mi:“MI:0915”(physical association)	0.980
TP53	EP300	psi-mi:“MI:0914”(association)	0.980
TP53	CREBBP	psi-mi:“MI:2364”(proximity)	0.960
CREBBP	TP53	psi-mi:“MI:0915”(physical association)	0.960
CREBBP	TP53	psi-mi:“MI:0407”(direct interaction)	0.960
CREBBP	TP53	psi-mi:“MI:0192”(acetylation reaction)	0.960
IRF3	CREBBP	psi-mi:“MI:0915”(physical association)	0.930
IRF3	CREBBP	psi-mi:“MI:0407”(direct interaction)	0.930
CREBBP	IRF3	psi-mi:“MI:0914”(association)	0.930
RELA	NFKB1	psi-mi:“MI:0914”(association)	0.920
CDK2	CCNB2	psi-mi:“MI:0914”(association)	0.860
MED23	MED19	psi-mi:“MI:2364”(proximity)	0.770
MEIS1	CREB1	psi-mi:“MI:0914”(association)	0.680
C3orf62	EP300	psi-mi:“MI:2364”(proximity)	0.670

BioGRID (1428): CREBBP (Affinity Capture-Western), KLF2 (Co-localization), KLF4 (Co-localization), UBE2D1 (Reconstituted Complex), CREBBP (Biochemical Activity), CREBBP (Affinity Capture-Western), UBE2I (Reconstituted Complex), CREBBP (Biochemical Activity), CREBBP (Affinity Capture-Western), KAT2B (Reconstituted Complex), KAT2B (Affinity Capture-Western), CREBBP (Affinity Capture-Western), CREBBP (Biochemical Activity), CREBBP (Affinity Capture-Western), JUN (Affinity Capture-Western)

ESM2 similar proteins: A0A0R4IBL7, A3RK74, A4L7N3, A5D7F6, B2RWS6, B5DE09, E1BPQ1, G3V7R4, O00512, O43524, P11420, P45481, P78364, Q09472, Q12778, Q13227, Q14686, Q15596, Q17BA4, Q61026, Q64028, Q66JJ0, Q67FY2, Q6AI39, Q6JHU9, Q6T264, Q7ZUK7, Q810W5, Q86UU0, Q8CHH5, Q8CHP6, Q8IXK0, Q8IZL2, Q921N8, Q924H2, Q92585, Q92793, Q961D9, Q96JK9, Q96RN5

Diamond homologs: A0A0R4IXF6, A0A7U2QYM2, A2AUY4, A2BIL7, A8DZJ1, B2KF05, B2RRD7, B2RWS6, B7ZS37, D4A7T3, E9Q2Z1, F1QW93, F1R5H6, F7DRV9, G5E8P1, G5EGM3, O15164, O60885, O74350, O88379, O95696, P13709, P21675, P25440, P35177, P45481, P51123, P55201, Q03330, Q07442, Q08D75, Q09472, Q12830, Q15059, Q1LUC3, Q23590, Q32S26, Q338B9, Q4R8Y1, Q54BA2

SIGNOR signaling

38 interactions.

A	Effect	B	Mechanism
CHUK	up-regulates	CREBBP	binding
CREBBP	“form complex”	CBP/p300	binding
SS18L1	up-regulates	CREBBP	relocalization
CREBBP	up-regulates	RELA	acetylation
CHUK	up-regulates	CREBBP	phosphorylation
RUNX2	up-regulates	CREBBP	binding
PRKCA	down-regulates	CREBBP	phosphorylation
CREBBP	“form complex”	P300/PCAF	binding
CREBBP	“up-regulates activity”	IFNAR2	acetylation
CREBBP	“up-regulates activity”	IRF9	acetylation
CREBBP	“up-regulates activity”	STAT2	acetylation
CREBBP	“up-regulates activity”	KLF1	acetylation
CREBBP	“up-regulates quantity by expression”	ALOX15	“transcriptional regulation”
CREBBP	“up-regulates activity”	TP53	acetylation
KHDRBS1	“down-regulates activity”	CREBBP	binding
CREBBP	“up-regulates activity”	POU1F1	binding
CREBBP	“up-regulates activity”	LHX3	binding
HIPK2	“up-regulates activity”	CREBBP	phosphorylation
NLK	“up-regulates activity”	CREBBP	phosphorylation
CREBBP	up-regulates	CREB1	binding
RELA	up-regulates	CREBBP	binding
CREBBP	up-regulates	CSK	binding
CREBBP	up-regulates	MYOD1	acetylation
CREBBP	up-regulates	MEF2C	binding
CREBBP	“up-regulates quantity by expression”	INSM1	“transcriptional regulation”
CREBBP	“up-regulates activity”	MYBL1	binding
CREBBP	“up-regulates activity”	MYB	binding
PRKCD	unknown	CREBBP	phosphorylation
CAMK4	“up-regulates activity”	CREBBP	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 146 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of HOX genes during differentiation	6	22.7×	1e-05
G0 and Early G1	5	18.9×	2e-04
BMAL1:CLOCK,NPAS2 activates circadian expression	5	18.2×	2e-04
Transcriptional regulation of white adipocyte differentiation	16	17.9×	3e-13
RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression	5	17.6×	2e-04
Deactivation of the beta-catenin transactivating complex	8	16.1×	3e-06
Expression of BMAL (ARNTL), CLOCK, and NPAS2	6	15.2×	1e-04
R-HSA-400253	5	14.9×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
glial cell proliferation	6	39.1×	1e-06
positive regulation of miRNA transcription	17	36.3×	6e-20
response to muscle stretch	5	28.2×	8e-05
negative regulation of miRNA transcription	6	27.5×	8e-06
cell fate specification	5	19.4×	3e-04
positive regulation of erythrocyte differentiation	5	18.8×	3e-04
positive regulation of transcription initiation by RNA polymerase II	8	16.0×	5e-06
skeletal muscle cell differentiation	6	15.2×	2e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 25 cancer types — ALL, BCC, BLADDER, BLCA, BRCA, CCRCC, CLLSLL, DLBCLNOS, ESCA, HCC, HNSC, LUSC…(+13 more).

Clinical variants and AI predictions

ClinVar

3157 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	367
Likely pathogenic	163
Uncertain significance	1173
Likely benign	844
Benign	162

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1029838	NM_004380.3(CREBBP):c.47_48delinsT (p.Lys16fs)	Pathogenic
1047867	GRCh37/hg19 16p13.3(chr16:3784414-3821324)	Pathogenic
1067259	NM_004380.3(CREBBP):c.4561-1G>A	Pathogenic
1068836	NM_004380.3(CREBBP):c.2574dup (p.Pro859fs)	Pathogenic
1069172	NC_000016.9:g.(?3827594)(3832947_?)del	Pathogenic
1070983	NM_004380.3(CREBBP):c.3676del (p.Ala1226fs)	Pathogenic
1071243	NM_004380.3(CREBBP):c.4679_4683del (p.Glu1560fs)	Pathogenic
1071591	NM_004380.3(CREBBP):c.802G>T (p.Gly268Ter)	Pathogenic
1073076	NC_000016.9:g.(?3900278)(3901030_?)del	Pathogenic
1076909	NM_004380.3(CREBBP):c.4944dup (p.Ile1649fs)	Pathogenic
1098286	NM_004380.3(CREBBP):c.3369+1del	Pathogenic
1172536	NM_004380.3(CREBBP):c.3699-1469_3836+1579del	Pathogenic
1176643	NM_004380.3(CREBBP):c.4621del (p.Glu1541fs)	Pathogenic
1299666	NM_004380.3(CREBBP):c.1676+2_1676+5del	Pathogenic
1308633	NM_004380.3(CREBBP):c.6324C>G (p.Tyr2108Ter)	Pathogenic
1321977	NM_004380.3(CREBBP):c.4133G>A (p.Arg1378Gln)	Pathogenic
1322161	NM_004380.3(CREBBP):c.4606_4607del (p.Glu1536fs)	Pathogenic
1339605	NM_004380.3(CREBBP):c.5600G>T (p.Arg1867Leu)	Pathogenic
1362462	NM_004380.3(CREBBP):c.581del (p.Gly194fs)	Pathogenic
1388252	NM_004380.3(CREBBP):c.4480C>T (p.Pro1494Ser)	Pathogenic
1397911	NM_004380.3(CREBBP):c.2881-13G>A	Pathogenic
1417982	NM_004380.3(CREBBP):c.3425T>C (p.Leu1142Pro)	Pathogenic
1451776	NM_004380.3(CREBBP):c.5782C>T (p.Gln1928Ter)	Pathogenic
1452058	NM_004380.3(CREBBP):c.1618C>T (p.Gln540Ter)	Pathogenic
1454532	NM_004380.3(CREBBP):c.5296_5297insCCCAC (p.Glu1766fs)	Pathogenic
145541	GRCh38/hg38 16p13.3(chr16:3726714-3759009)x1	Pathogenic
1455967	NC_000016.9:g.(?3841962)(3843647_?)del	Pathogenic
1458408	NC_000016.9:g.(?3900278)(3929917_?)del	Pathogenic
1459112	NM_004380.3(CREBBP):c.4561-2A>T	Pathogenic
1460099	NC_000016.9:g.(?3817701)(3860800_?)del	Pathogenic

SpliceAI

4751 predictions. Top by Δscore:

Variant	Effect	Δscore
16:3729870:TAGTC:T	acceptor_gain	1.0000
16:3729871:AGTC:A	acceptor_gain	1.0000
16:3729872:GTC:G	acceptor_gain	1.0000
16:3729873:TC:T	acceptor_gain	1.0000
16:3729874:CC:C	acceptor_gain	1.0000
16:3729874:CCTG:C	acceptor_loss	1.0000
16:3729875:C:CA	acceptor_loss	1.0000
16:3729875:C:CC	acceptor_gain	1.0000
16:3729876:T:G	acceptor_loss	1.0000
16:3729882:C:CT	acceptor_gain	1.0000
16:3729883:A:T	acceptor_gain	1.0000
16:3731187:CCTA:C	donor_loss	1.0000
16:3731188:CTA:C	donor_loss	1.0000
16:3731190:ACCT:A	donor_gain	1.0000
16:3731190:ACCTC:A	donor_loss	1.0000
16:3731191:C:CA	donor_loss	1.0000
16:3731191:CCTC:C	donor_gain	1.0000
16:3731471:GACCT:G	acceptor_loss	1.0000
16:3731472:ACC:A	acceptor_loss	1.0000
16:3731473:CCTG:C	acceptor_loss	1.0000
16:3731474:C:CC	acceptor_gain	1.0000
16:3731474:CTGC:C	acceptor_loss	1.0000
16:3731475:T:G	acceptor_loss	1.0000
16:3731772:CTACC:C	donor_loss	1.0000
16:3731773:TACC:T	donor_loss	1.0000
16:3731774:A:T	donor_loss	1.0000
16:3731774:ACCT:A	donor_gain	1.0000
16:3731775:C:CG	donor_loss	1.0000
16:3731775:CCTC:C	donor_gain	1.0000
16:3731777:T:TA	donor_gain	1.0000

AlphaMissense

16090 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:3728736:C:G	R2104P	1.000
16:3728737:G:T	R2104S	1.000
16:3728745:A:C	I2101S	1.000
16:3728745:A:G	I2101T	1.000
16:3728745:A:T	I2101N	1.000
16:3728747:G:C	F2100L	1.000
16:3728747:G:T	F2100L	1.000
16:3728748:A:C	F2100C	1.000
16:3728748:A:G	F2100S	1.000
16:3728749:A:G	F2100L	1.000
16:3728752:C:G	A2099P	1.000
16:3728755:C:G	A2098P	1.000
16:3728757:A:G	M2097T	1.000
16:3728760:A:G	L2096P	1.000
16:3728778:A:C	L2090R	1.000
16:3728778:A:G	L2090P	1.000
16:3728778:A:T	L2090H	1.000
16:3728781:A:C	I2089S	1.000
16:3728787:A:G	L2087P	1.000
16:3728790:A:T	V2086E	1.000
16:3728826:A:G	L2074P	1.000
16:3728826:A:T	L2074Q	1.000
16:3728835:A:G	L2071P	1.000
16:3728838:A:G	L2070P	1.000
16:3728838:A:T	L2070Q	1.000
16:3729498:A:G	L1850P	1.000
16:3729500:C:A	K1849N	1.000
16:3729500:C:G	K1849N	1.000
16:3729502:T:C	K1849E	1.000
16:3729506:T:A	K1847N	1.000

dbSNP variants (sampled 300 via entrez): RS1000059649 (16:3741615 A>G), RS1000064255 (16:3808463 A>G), RS1000067500 (16:3735253 T>C), RS1000071361 (16:3875803 C>T), RS1000072034 (16:3832580 A>C), RS1000089813 (16:3821878 A>C), RS1000127237 (16:3787279 C>G,T), RS1000133879 (16:3754776 T>C), RS1000159074 (16:3779630 C>T), RS1000178517 (16:3780004 G>A), RS1000182321 (16:3847242 A>G), RS1000209492 (16:3779833 G>C), RS1000210193 (16:3813412 C>T), RS1000212361 (16:3754123 G>A), RS1000228269 (16:3813432 C>G)

Disease associations

OMIM: gene MIM:600140 | disease phenotypes: MIM:180849, MIM:618332, MIM:209850, MIM:217990, MIM:612098, MIM:612794, MIM:613424, MIM:142623, MIM:188100, MIM:608644, MIM:163950, MIM:120970, MIM:254500

GenCC curated gene-disease

Disease	Classification	Inheritance
Rubinstein-Taybi syndrome due to CREBBP mutations	Definitive	Autosomal dominant
Rubinstein-Taybi syndrome	Definitive	Autosomal dominant
Menke-Hennekam syndrome 1	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Rubinstein-Taybi syndrome	Definitive	AD

Mondo (27): Rubinstein-Taybi syndrome (MONDO:0019188), Menke-Hennekam syndrome 1 (MONDO:0020763), Rubinstein-Taybi syndrome due to CREBBP mutations (MONDO:0008393), autism (MONDO:0005260), corpus callosum, agenesis of (MONDO:0009022), hypertrichosis (MONDO:0019280), hypertrophic cardiomyopathy 11 (MONDO:0012799), atrial septal defect 5 (MONDO:0013011), dilated cardiomyopathy 1R (MONDO:0013261), left ventricular noncompaction 4 (MONDO:0800350), intellectual disability (MONDO:0001071), neurodevelopmental disorder (MONDO:0700092), hearing loss disorder (MONDO:0005365), Hirschsprung disease, susceptibility to, 1 (MONDO:0007723), teratoma (MONDO:0002601)

Orphanet (18): Rubinstein-Taybi syndrome (Orphanet:783), Rubinstein-Taybi syndrome due to CREBBP mutations (Orphanet:353277), Isolated corpus callosum agenesis (Orphanet:200), Rare disorder with hypertrichosis (Orphanet:79365), Interatrial communication (Orphanet:1478), Familial isolated dilated cardiomyopathy (Orphanet:154), Left ventricular noncompaction (Orphanet:54260), Hirschsprung disease (Orphanet:388), Menke-Hennekam syndrome (Orphanet:592574), Diffuse large B-cell lymphoma (Orphanet:544), Rare genetic intellectual disability (Orphanet:183757), Multiple congenital anomalies/dysmorphic syndrome (Orphanet:68341), Primary ciliary dyskinesia (Orphanet:244), Noonan syndrome (Orphanet:648), Cone rod dystrophy (Orphanet:1872)

HPO phenotypes

261 total (30 of 261 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000034	Hydrocele testis
HP:0000047	Hypospadias
HP:0000049	Shawl scrotum
HP:0000076	Vesicoureteral reflux
HP:0000077	Abnormality of the kidney
HP:0000079	Abnormality of the urinary system
HP:0000119	Abnormality of the genitourinary system
HP:0000126	Hydronephrosis
HP:0000160	Narrow mouth
HP:0000164	Abnormality of the dentition
HP:0000175	Cleft palate
HP:0000189	Narrow palate
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000260	Wide anterior fontanel
HP:0000270	Delayed cranial suture closure
HP:0000273	Facial grimacing
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000288	Abnormality of the philtrum
HP:0000293	Full cheeks
HP:0000294	Low anterior hairline
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000321	Square face

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001762_116	Obesity-related traits	9.000000e-06
GCST001818_6	Metabolite levels (HVA/5-HIAA ratio)	5.000000e-06
GCST001890_1	QT interval (drug interaction)	9.000000e-06
GCST002500_24	QT interval	4.000000e-10
GCST002811_3	Nonsyndromic cleft lip with or without cleft palate	9.000000e-12
GCST004166_27	Nonsyndromic cleft lip with cleft palate	1.000000e-10
GCST006979_241	Heel bone mineral density	4.000000e-11
GCST008758_93	Pre-treatment viral load in HIV-1 infection	3.000000e-18
GCST010396_241	Gut microbiota (bacterial taxa, hurdle binary method)	5.000000e-06
GCST90002398_293	Neutrophil count	1.000000e-13
GCST90002407_553	White blood cell count	6.000000e-13

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004626	IGFBP-3 measurement
EFO:0005131	HVA measurement
EFO:0005132	5-HIAA measurement
EFO:0004682	QT interval
EFO:0003959	cleft lip
EFO:0009270	heel bone mineral density
EFO:0010125	viral load
EFO:0007874	gut microbiome measurement
EFO:0004833	neutrophil count

MeSH disease descriptors (19)

Descriptor	Name	Tree numbers
D061085	Agenesis of Corpus Callosum	C10.500.034; C16.131.666.034; C23.300.008
D001321	Autistic Disorder	F03.625.164.113.500
D002493	Central Nervous System Diseases	C10.228
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
D005901	Glaucoma	C11.525.381
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D006983	Hypertrichosis	C17.800.329.875
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D016403	Lymphoma, Large B-Cell, Diffuse	C04.557.386.480.150.585; C15.604.515.569.480.150.585; C20.683.515.761.480.150.585
D009101	Multiple Myeloma	C04.557.595.500; C14.907.454.460; C15.378.147.780.650; C15.378.463.515.460; C20.683.515.845; C20.683.780.650
D065886	Neurodevelopmental Disorders	F03.625
D009634	Noonan Syndrome	C05.660.207.690; C14.240.400.787; C14.280.400.787; C16.131.240.400.784; C16.131.621.207.690; C17.300.690
D012415	Rubinstein-Taybi Syndrome	C05.116.099.370.797; C05.660.207.850; C10.597.606.360.700; C16.131.077.804; C16.131.260.790; C16.131.621.207.850; C16.320.180.790
D012600	Scoliosis	C05.116.900.800.875
D013724	Teratoma	C04.557.465.910
C567561	Atrial Septal Defect 5 (supp.)
C567419	Cardiomyopathy, Familial Hypertrophic, 11 (supp.)
C535278	Primary ciliary dyskinesia, 3 (supp.)
C536903	Thumb deformity (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (8): CHEMBL3301383 (PROTEIN-PROTEIN INTERACTION), CHEMBL3883300 (PROTEIN FAMILY), CHEMBL4296108 (PROTEIN-PROTEIN INTERACTION), CHEMBL4665593 (PROTEIN-PROTEIN INTERACTION), CHEMBL5465221 (PROTEIN-PROTEIN INTERACTION), CHEMBL5482990 (PROTEIN-PROTEIN INTERACTION), CHEMBL5747 (SINGLE PROTEIN), CHEMBL6066834 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

13 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 378,662 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL107	COLCHICINE	4	93,932
CHEMBL1455	ALTRETAMINE	4	102,000
CHEMBL140	CURCUMIN	3	93,882
CHEMBL19224	PAPAVERINE	3	22,172
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL1232461	MOLIBRESIB	2	1,538
CHEMBL31574	FISETIN	2	7,745
CHEMBL356388	ETAZOLATE	2	1,934
CHEMBL5199076	LUNRESERTIB	2	34
CHEMBL84567	TRACAZOLATE	2	2,685
CHEMBL9514	NOCODAZOLE	2	29,245
CHEMBL4785363	INOBRODIB	1	100
CHEMBL4078100	AZD-5153	1	591

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Non-enzymatic BRD containing proteins

Most potent curated ligand interactions (7 total), top 7:

Ligand	Action	Affinity	Parameter
GNE-049	Inhibition	8.96	pIC50
CBPD-268	Binding	7.96	pIC50
inobrodib	Inhibition	7.85	pKd
SGC-CBP30	Inhibition	7.16	pIC50
I-CBP112	Inhibition	6.85	pKd
compound 50 [PMID: 24313754]	Inhibition	6.2	pIC50
ischemin	Inhibition	4.72	pKd

Binding affinities (BindingDB)

1483 measured of 1926 human assays (1934 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[7-difluoromethyl- 6-(1-methyl-1H- pyrazol-4-yl)-3,4- dihydro-2H-quinolin- 1-yl]-6-(4-methyl- 2-oxo-piperazin- 1-yl)-isoquinoline- 3-carboxylic acid methylamide	IC50	3.3 nM	US-12486251: CBP/EP300 inhibitor and use thereof
1-[7-difluoromethyl- 6-(1-methyl-1H- pyrazol-4-yl)-3,4- dihydro-2H-quinolin- 1-yl]-6-(2-oxo- oxazolidin-3-yl)- isoquinoline-3- carboxylic acid methylamide	IC50	4.2 nM	US-12486251: CBP/EP300 inhibitor and use thereof
1-[3-[2-methyl-6-(1-methylpyrazol-4-yl)-1H-indol-3-yl]-1-[(3S)-oxolan-3-yl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-5-yl]ethanone	IC50	5.14 nM	US-11247989: Therapeutic compounds and uses thereof
1-[7-difluoromethyl- 6-(1-methyl-1H- pyrazol-4-yl)-3,4- dihydro-2H-quinolin- 1-yl]-6-(3-oxo- morpholin-4-yl)- isoquinoline-3- carboxylic acid methylamide	IC50	5.3 nM	US-12486251: CBP/EP300 inhibitor and use thereof
US12486251, Example 46	IC50	5.4 nM	US-12486251: CBP/EP300 inhibitor and use thereof
methyl (S)-3-((1R,3S)-3-(1H-tetrazol-5-yl)cyclohexyl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate and methyl (S)-3-((1S,3R)-3-(1H-tetrazol-5-yl)cyclohexyl)-2-benzyl-7-methyl-3,7,8,9-tetrahydro-6H-imidazo[4,5-f]quinoline-6-carboxylate	IC50	5.5 nM	US-11292791: Tetrahydro-imidazo quinoline compositions as CBP/P300 inhibitors
methyl (7S)-2-benzyl-7-methyl-3-[4-(2H-tetrazol-5-yl)cyclohexyl]-8,9-dihydro-7H-imidazo[4,5-f]quinoline-6-carboxylate	IC50	5.5 nM	US-11292791: Tetrahydro-imidazo quinoline compositions as CBP/P300 inhibitors
(1R)-3-[(7S)-2-[(S)-(5-fluoro-1H-indazol-7-yl)-hydroxymethyl]-6-methoxycarbonyl-7-methyl-8,9-dihydro-7H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylic acid	IC50	5.5 nM	US-11292791: Tetrahydro-imidazo quinoline compositions as CBP/P300 inhibitors
3-[(7S)-2-[(5-fluoro-1H-indol-7-yl)-hydroxymethyl]-6-methoxycarbonyl-7-methyl-8,9-dihydro-7H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylic acid	IC50	5.5 nM	US-11292791: Tetrahydro-imidazo quinoline compositions as CBP/P300 inhibitors
trans-(1R,3R)-3-[(7S)-6-methoxycarbonyl-7-methyl-2-(5H-pyrrolo[2,3-b]pyrazin-2-ylmethyl)-8,9-dihydro-7H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylic acid	IC50	5.5 nM	US-11292791: Tetrahydro-imidazo quinoline compositions as CBP/P300 inhibitors
3-[(7S)-2-[(5-fluoro-1H-indazol-7-yl)-hydroxymethyl]-6-methoxycarbonyl-7-methyl-8,9-dihydro-7H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylic acid	IC50	5.5 nM	US-11292791: Tetrahydro-imidazo quinoline compositions as CBP/P300 inhibitors
3-[(7S)-2-[hydroxy(1H-indazol-5-yl)methyl]-6-methoxycarbonyl-7-methyl-8,9-dihydro-7H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylic acid	IC50	5.5 nM	US-11292791: Tetrahydro-imidazo quinoline compositions as CBP/P300 inhibitors
4-[(7S)-2-(1H-indol-5-ylmethyl)-6-methoxycarbonyl-7-methyl-8,9-dihydro-7H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylic acid	IC50	5.5 nM	US-11292791: Tetrahydro-imidazo quinoline compositions as CBP/P300 inhibitors
trans-(1R,3R)-3-[(7S)-2-(1H-indol-2-ylmethyl)-6-methoxycarbonyl-7-methyl-8,9-dihydro-7H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylic acid	IC50	5.5 nM	US-11292791: Tetrahydro-imidazo quinoline compositions as CBP/P300 inhibitors
trans-(1R,3R)-3-[(7S)-2-(1H-indol-5-ylmethyl)-6-methoxycarbonyl-7-methyl-8,9-dihydro-7H-imidazo[4,5-f]quinolin-3-yl]cyclohexane-1-carboxylic acid	IC50	5.5 nM	US-11292791: Tetrahydro-imidazo quinoline compositions as CBP/P300 inhibitors
US20250188079, Compound 1	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
(trans)-4-[3- [(2S)-1-(3- fluoro-4- methylphenyl) propan-2-yl]-8- (methoxycarbonyl)- 3H,6H,7H,8H,9H- imidazo[4,5- h]isoquinolin-2- yl]cyclohexane- 1-carboxylic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
US20250188079, Compound 3	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
(3S)-4-[2- cyclohexyl-8- (methoxycarbonyl)- 3H,6H,7H,8H, 9H- imidazo[4,5- h]isoquinolin- 3-yl]-3-(3,4- difluorophenyl) butanoic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
methyl 1-[8- (methoxycarbonyl)- 3-[(2S)-1- phenylpropan- 2-yl]- 3H,6H,7H,8H,9H- imidazo[4,5- h]isoquinolin- 2-yl]piperidine- 4-carboxylate	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
US20250188079, Compound 6	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
4-[8-methoxycarbonyl-3-[(2S)-1-(2-methylphenyl)propan-2-yl]-7,9-dihydro-6H-imidazo[4,5-h]isoquinolin-2-yl]cyclohexane-1-carboxylic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
US20250188079, Compound 8	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
US20250188079, Compound 9	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
(3S)-4-[2- cyclohexyl-8- (methoxycarbonyl)- 3H,6H,7H,8H, 9H- imidazo[4,5- h]isoquinolin- 3-yl]-3-(3- fluoro-5- methoxyphenyl) butanoic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
(2S)-3-[2- cyclohexyl-8- (methoxycarbonyl)- 3H,6H,7H,8H, 9H- imidazo[4,5- h]isoquinolin- 3-yl]-2-(5- fluoro-2- methoxyphenyl) propanoic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
(1R,3S)-3-[8- (methoxycarbonyl)- 3-[(2R)-1- phenylpropan- 2-yl]- 3H,6H,7H,8H, 9H- imidazo[4,5- h]isoquinolin- 2- yl]cyclohexane- 1-carboxylic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
(1R,3S)-3-[8- (methoxycarbonyl)- 3-[(2S)-1- phenylpropan- 2-yl]- 3H,6H,7H,8H, 9H- imidazo[4,5- h]isoquinolin- 2- yl]cyclohexane- 1-carboxylic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
1-[3-[(2S)-1- (2- chlorophenyl) propan-2-yl]-8- (methoxycarbonyl)- 3H,6H,7H,8H, 9H- imidazo[4,5- h]isoquinolin- 2-yl]piperidine- 4-carboxylic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
methyl 3-[(2R)- 1- phenylpropan- 2-yl]-2-[(1r,4r)- 4- (methanesulfinyl- carbamoyl) cyclohexyl]- 3H,6H,7H,8H, 9H- imidazo[4,5- h]isoquinoline- 8-carboxylate	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
1-{3-[(2R)-1- (3-fluoro-5- methoxyphenyl) propan-2-yl]-8- (methoxycarbonyl)- 3H,6H,7H,8H,9H- imidazo[4,5- h]isoquinolin- 2-yl}piperidine- 4-carboxylic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
(1R,3R)-3-[8- (methoxycarbonyl)- 3-[(2S)-1-(2- methylphenyl) propan-2-yl]- 3H,6H,7H,8H,9H- imidazo[4,5- h]isoquinolin-2- yl]cyclohexane- 1-carboxylic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
(1S,3S)-3-[8- (methoxycarbonyl)- 3-[(2S)-1-(2- methylphenyl) propan-2-yl]- 3H,6H,7H,8H,9H- imidazo[4,5- h]isoquinolin-2- yl]cyclohexane- 1-carboxylic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
(1S,3S)-3-{3- [(2R)-1-(2- chlorophenyl) propan-2-yl]-8- (methoxycarbonyl)- 3H,6H,7H,8H,9H- imidazo[4,5- h]isoquinolin-2- yl}cyclohexane- 1-carboxylic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
(1R,3R)-3-{3- [(2S)-1-(2- chlorophenyl) propan-2-yl]-8- (methoxycarbonyl)- 3H,6H,7H,8H,9H- imidazo[4,5- h]isoquinolin-2- yl}cyclohexane- 1-carboxylic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
(3S)-4-(2-cyclohexyl-8-methoxycarbonyl-7,9-dihydro-6H-imidazo[4,5-h]isoquinolin-3-yl)-3-(3,4-difluorophenyl)butanoic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
methyl 2- cyclohexyl-3- [(2R)-2- (methanesulfon- ylcarbamoyl)- 2-phenylethyl]- 3H,6H,7H,8H, 9H- imidazo[4,5- h]isoquinoline- 8-carboxylate	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
1-[3-[(2S)-1- (3,4- difluorophenyl) propan-2-yl]-8- (methoxycarbonyl)- 3H,6H,7H,8H, 9H- imidazo[4,5- h]isoquinolin- 2-yl]piperidine- 4-carboxylic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
1-[3-[(2S)-1,1- difluoro-1- phenylpropan- 2-yl]-8- (methoxycarbonyl)- 3H,6H,7H,8H, 9H- imidazo[4,5- h]isoquinolin- 2-yl]piperidine- 4-carboxylic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
(3S)-3-(3,4-difluorophenyl)-4-(8-methoxycarbonyl-2-piperidin-1-yl-7,9-dihydro-6H-imidazo[4,5-h]isoquinolin-3-yl)butanoic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
(2R)-3-[2- cyclohexyl-8- (methoxycarbonyl)- 3H,6H,7H,8H, 9H- imidazo-[4,5- h]isoquinolin- 3-yl]-2-(2,3- difluorophenyl) propanoic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
(2R)-3-[2- cyclohexyl-8- (methoxycarbonyl)- 3H,6H,7H,8H, 9H- imidazo[4,5- h]isoquinolin- 3-yl]-2-(5- fluoro-2- methoxy-4- methylphenyl) propanoic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
(1R,3R)-3-[3- [(2R)-2-(3,4- difluorophenyl) propyl]-8- (methoxycarbonyl)- 3H,6H,7H,8H, 9H- imidazo[4,5- h]isoquinolin- 2- yl]cyclohexane- 1-carboxylic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
(1S,3S)-3-[3- [(2S)-2-(3,4- difluorophenyl) propyl]-8- (methoxycarbonyl)- 3H,6H,7H,8H, 9H-imidazo[4,5- h]isoquinolin- 2- yl]cyclohexane- 1-carboxylic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
(1S,3S)-3[3- [(2R)-2-(3,4- difluorophenyl) propyl]-8- (methoxycarbonyl)- 3H,6H,7H,8H, 9H- imidazo[4,5- h]isoquinolin- 2- yl]cyclohexane- 1-carboxylic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
(1S,3S)-3-[3- [(2R)-1-(3,4- difluorophenyl) propan-2-yl]-8- (methoxycarbonyl)- 3H,6H,7H,8H, 9H- imidazo[4,5- h]isoquinolin- 2- yl]cyclohexane- 1-carboxylic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
(2S)-2-(4- chloro-5- fluoro-2- methoxyphenyl)- 3-[2- cyclohexyl-8- (methoxycarbonyl)- 3H,6H,7H,8H, 9H- imidazo[4,5- h]isoquinolin- 3-yl]propanoic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
3-[(2R)-2-[8- (methoxycarbonyl)-2- (piperidin-1- yl)- 3H,6H,7H,8H,9H- imidazo[4,5- h]isoquinolin-3- yl]propyl]benzoic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
(3S)-4-[2- cyclopentyl-8- (methoxycarbonyl)- 6H,7H,9H- imidazo[4,5- h]isoquinolin- 3-yl]-3- phenylbutanoic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)
(3S)-4-(2-cyclohexyl-8-methoxycarbonyl-7,9-dihydro-6H-imidazo[4,5-h]isoquinolin-3-yl)-3-(3-fluoro-5-methoxyphenyl)butanoic acid	IC50	5.5 nM	US-20250188079: INHIBITING CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)

ChEMBL bioactivities

3483 potent at pChembl≥5 of 3931 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.30	EC50	0.05	nM	CHEMBL5413450
9.70	EC50	0.2	nM	CHEMBL5406029
9.70	EC50	0.2	nM	CHEMBL5426454
9.70	EC50	0.2	nM	CHEMBL5409708
9.70	EC50	0.2	nM	CHEMBL5437022
9.70	EC50	0.2	nM	CHEMBL5405858
9.64	Kd	0.23	nM	CHEMBL4208820
9.52	EC50	0.3	nM	CHEMBL5402691
9.22	EC50	0.6	nM	CHEMBL5439670
9.22	EC50	0.6	nM	CHEMBL5395475
9.12	IC50	0.76	nM	CHEMBL5934856
9.05	IC50	0.9	nM	CHEMBL4217213
9.05	Kd	0.9	nM	CHEMBL4097025
9.04	IC50	0.91	nM	CHEMBL6065520
9.03	IC50	0.94	nM	CHEMBL4097025
9.01	IC50	0.97	nM	CHEMBL5833912
9.00	IC50	1	nM	CHEMBL4069831
9.00	IC50	1	nM	CHEMBL4088793
9.00	IC50	1	nM	CHEMBL5438086
9.00	EC50	1	nM	CHEMBL5438596
9.00	EC50	1	nM	CHEMBL5397398
9.00	IC50	1	nM	CHEMBL5794948
9.00	IC50	1	nM	CHEMBL6044256
9.00	IC50	1	nM	CHEMBL5935353
9.00	IC50	1	nM	CHEMBL5959885
9.00	IC50	1	nM	CHEMBL5776813
9.00	IC50	1	nM	CHEMBL5792372
9.00	IC50	1	nM	CHEMBL5797417
9.00	IC50	1	nM	CHEMBL5757873
9.00	IC50	0.997	nM	CHEMBL4208820
9.00	IC50	1	nM	CHEMBL5935918
8.97	IC50	1.07	nM	CHEMBL5902325
8.96	IC50	1.1	nM	CHEMBL4076748
8.96	EC50	1.1	nM	CHEMBL5419387
8.96	Kd	1.1	nM	CHEMBL4076748
8.96	IC50	1.1	nM	CHEMBL5924385
8.95	IC50	1.13	nM	CHEMBL5901381
8.94	IC50	1.15	nM	CHEMBL5959340
8.94	IC50	1.16	nM	CHEMBL4203082
8.93	IC50	1.17	nM	CHEMBL5827196
8.92	IC50	1.2	nM	CHEMBL4061161
8.92	IC50	1.2	nM	CHEMBL4060566
8.92	IC50	1.2	nM	CHEMBL4203082
8.92	IC50	1.2	nM	CHEMBL4208820
8.92	EC50	1.2	nM	CHEMBL5412027
8.89	EC50	1.3	nM	CHEMBL5405240
8.89	Kd	1.3	nM	INOBRODIB
8.86	IC50	1.39	nM	CHEMBL5934402
8.85	IC50	1.4	nM	CHEMBL4061600
8.85	IC50	1.42	nM	CHEMBL5788216

PubChem BioAssay actives

755 with measured affinity, of 2301 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-[8-[5-acetyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl]isoquinolin-3-yl]-N-[1-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]piperidin-4-yl]pyridine-2-carboxamide	1990959: Induction of CBP degradation in human RS4-11 cells incubated for 4 hrs by Western blot assay	ec50	0.0001	uM
5-[8-[5-acetyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl]isoquinolin-3-yl]-N-[3-[[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]amino]propyl]pyridine-2-carboxamide	1990959: Induction of CBP degradation in human RS4-11 cells incubated for 4 hrs by Western blot assay	ec50	0.0001	uM
5-[8-[5-acetyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl]isoquinolin-3-yl]-N-methylpyridine-2-carboxamide	1372262: Binding affinity to human partial length CREBBP (R1081 to G1197 residues) expressed in bacterial expression system by BROMOscan assay	kd	0.0002	uM
4-[4-[5-[8-[5-acetyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl]isoquinolin-3-yl]pyridine-2-carbonyl]piperazin-1-yl]-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione	1990959: Induction of CBP degradation in human RS4-11 cells incubated for 4 hrs by Western blot assay	ec50	0.0002	uM
5-[8-[5-acetyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl]isoquinolin-3-yl]-N-[8-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]octyl]pyridine-2-carboxamide	1990959: Induction of CBP degradation in human RS4-11 cells incubated for 4 hrs by Western blot assay	ec50	0.0002	uM
5-[8-[5-acetyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl]isoquinolin-3-yl]-N-[5-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-4-yl]pentyl]pyridine-2-carboxamide	1990959: Induction of CBP degradation in human RS4-11 cells incubated for 4 hrs by Western blot assay	ec50	0.0002	uM
5-[8-[5-acetyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl]isoquinolin-3-yl]-N-[4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-4-yl]butyl]pyridine-2-carboxamide	1990959: Induction of CBP degradation in human RS4-11 cells incubated for 4 hrs by Western blot assay	ec50	0.0002	uM
5-[8-[5-acetyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl]isoquinolin-3-yl]-N-[3-[[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-4-yl]amino]propyl]pyridine-2-carboxamide	1990959: Induction of CBP degradation in human RS4-11 cells incubated for 4 hrs by Western blot assay	ec50	0.0002	uM
4-[[2-[5-[8-[5-acetyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl]isoquinolin-3-yl]pyridine-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]amino]-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione	1990959: Induction of CBP degradation in human RS4-11 cells incubated for 4 hrs by Western blot assay	ec50	0.0003	uM
(3R)-N-[3-(7-methoxy-3,4-dihydro-2H-quinolin-1-yl)propyl]-3-methyl-2-oxo-3,4-dihydro-1H-quinoxaline-5-carboxamide	1807214: Binding affinity to CREBBP (unknown origin) assessed as dissociation constant by ITC assay	kd	0.0004	uM
5-[8-[5-acetyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl]isoquinolin-3-yl]-N-[2-[[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-4-yl]amino]ethyl]pyridine-2-carboxamide	1990959: Induction of CBP degradation in human RS4-11 cells incubated for 4 hrs by Western blot assay	ec50	0.0006	uM
5-[8-[5-acetyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl]isoquinolin-3-yl]-N-[6-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]hexyl]pyridine-2-carboxamide	1990959: Induction of CBP degradation in human RS4-11 cells incubated for 4 hrs by Western blot assay	ec50	0.0006	uM
3-[7-(difluoromethyl)-6-(1-methylpyrazol-4-yl)-3,4-dihydro-2H-quinolin-1-yl]-N-methyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carboxamide	1489222: Displacement of biotinylated histone H3K14 peptide ligand from human recombinant His-tagged CBP measured after 10 mins by TR-FRET assay	ic50	0.0009	uM
3-[7-(difluoromethyl)-6-(1-methylpyrazol-4-yl)naphthalen-1-yl]-N-methyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carboxamide	1372218: Inhibition of recombinant His-tagged CBP (unknown origin) by TR-FRET assay	ic50	0.0009	uM
3-[7-(difluoromethyl)-6-(1-methylpyrazol-4-yl)-3,4-dihydro-2H-quinolin-1-yl]-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carboxamide	1489222: Displacement of biotinylated histone H3K14 peptide ligand from human recombinant His-tagged CBP measured after 10 mins by TR-FRET assay	ic50	0.0010	uM
1-[4-[5-acetyl-3-[7-(difluoromethyl)-6-(1-methylpyrazol-4-yl)-3,4-dihydro-2H-quinolin-1-yl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]piperidin-1-yl]ethanone	1489222: Displacement of biotinylated histone H3K14 peptide ligand from human recombinant His-tagged CBP measured after 10 mins by TR-FRET assay	ic50	0.0010	uM
(2R,4R)-1-[4,4-difluoro-1-(4-methoxyphenyl)cyclohexanecarbonyl]-4-fluoro-N-(1H-pyrazolo[4,5-b]pyridin-5-yl)pyrrolidine-2-carboxamide	1965102: Inhibition of CBP (unknown origin) biotinylated H4 (1 to 25)-GSGSK peptide as substrate incubated for 1 hr in presence of acetyl-coA by AlphaLISA assay	ic50	0.0010	uM
5-[8-[5-acetyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl]isoquinolin-3-yl]-N-[1-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]piperidin-4-yl]pyridine-2-carboxamide	1990959: Induction of CBP degradation in human RS4-11 cells incubated for 4 hrs by Western blot assay	ec50	0.0010	uM
5-[8-[5-acetyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl]isoquinolin-3-yl]-N-[5-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]pentyl]pyridine-2-carboxamide	1990959: Induction of CBP degradation in human RS4-11 cells incubated for 4 hrs by Western blot assay	ec50	0.0010	uM
1-[3-[7-(difluoromethyl)-6-(1-methylpyrazol-4-yl)-3,4-dihydro-2H-quinolin-1-yl]-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-5-yl]ethanone	1489222: Displacement of biotinylated histone H3K14 peptide ligand from human recombinant His-tagged CBP measured after 10 mins by TR-FRET assay	ic50	0.0011	uM
5-[8-[5-acetyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl]isoquinolin-3-yl]-N-[2-[[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]amino]ethyl]pyridine-2-carboxamide	1990959: Induction of CBP degradation in human RS4-11 cells incubated for 4 hrs by Western blot assay	ec50	0.0011	uM
1-[3-[7-(difluoromethyl)-6-(1-methylpyrazol-4-yl)-3,4-dihydro-2H-quinolin-1-yl]-1-(1,1-dioxothian-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-5-yl]ethanone	1489222: Displacement of biotinylated histone H3K14 peptide ligand from human recombinant His-tagged CBP measured after 10 mins by TR-FRET assay	ic50	0.0012	uM
1-[3-[7-(difluoromethyl)-6-(1-methylpyrazol-4-yl)-3,4-dihydro-2H-quinolin-1-yl]-1-(1-methylsulfonylpiperidin-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-5-yl]ethanone	1489222: Displacement of biotinylated histone H3K14 peptide ligand from human recombinant His-tagged CBP measured after 10 mins by TR-FRET assay	ic50	0.0012	uM
1-[3-[3-(1-methylpyrazol-4-yl)isoquinolin-8-yl]-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-5-yl]ethanone	1372218: Inhibition of recombinant His-tagged CBP (unknown origin) by TR-FRET assay	ic50	0.0012	uM
5-[8-[5-acetyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl]isoquinolin-3-yl]-N-[3-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]propyl]pyridine-2-carboxamide	1990959: Induction of CBP degradation in human RS4-11 cells incubated for 4 hrs by Western blot assay	ec50	0.0012	uM
(6S)-1-(3,4-difluorophenyl)-6-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-(4-methoxycyclohexyl)benzimidazol-2-yl]piperidin-2-one	2082693: Binding affinity to CBP (unknown origin) by SPR assay	kd	0.0013	uM
5-[8-[5-acetyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl]isoquinolin-3-yl]-N-[4-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]butyl]pyridine-2-carboxamide	1990959: Induction of CBP degradation in human RS4-11 cells incubated for 4 hrs by Western blot assay	ec50	0.0013	uM
1-[3-[7-(difluoromethyl)-6-(1-methylpyrazol-4-yl)-3,4-dihydro-2H-quinolin-1-yl]-1-[(3S)-oxolan-3-yl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-5-yl]ethanone	1489222: Displacement of biotinylated histone H3K14 peptide ligand from human recombinant His-tagged CBP measured after 10 mins by TR-FRET assay	ic50	0.0014	uM
1-[3-[7-(difluoromethyl)-6-(1-methylpyrazol-4-yl)-3,4-dihydro-2H-quinolin-1-yl]-1-piperidin-4-yl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-5-yl]ethanone	1489222: Displacement of biotinylated histone H3K14 peptide ligand from human recombinant His-tagged CBP measured after 10 mins by TR-FRET assay	ic50	0.0015	uM
1-[3-[6-(1-methylpyrazol-4-yl)-7-(trifluoromethyl)-3,4-dihydro-2H-quinolin-1-yl]-1-[(3S)-oxolan-3-yl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-5-yl]ethanone	1489222: Displacement of biotinylated histone H3K14 peptide ligand from human recombinant His-tagged CBP measured after 10 mins by TR-FRET assay	ic50	0.0015	uM
3-acetyl-7-amino-N-[3-(1-cyclopropylpyrazol-4-yl)-2-fluoro-5-(1-hydroxyethyl)phenyl]indolizine-1-carboxamide	1899978: Inhibition of His6-tagged human CBP bromodomain (1081 to 1197 residues) expressed in Escherichia coli BL21 (DE3) incubated for 30 mins by HTRF assay	ic50	0.0015	uM
(6R)-1-(3,4-difluorophenyl)-6-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-(4-methoxycyclohexyl)benzimidazol-2-yl]piperidin-2-one	2027169: Binding affinity to CBP bromodomain (unknown origin) assessed as dissociation constant	kd	0.0017	uM
5-[8-[5-acetyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl]isoquinolin-3-yl]-N-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethyl]pyridine-2-carboxamide	1990959: Induction of CBP degradation in human RS4-11 cells incubated for 4 hrs by Western blot assay	ec50	0.0017	uM
4-[[7-[5-[8-[5-acetyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl]isoquinolin-3-yl]pyridine-2-carbonyl]-7-azaspiro[3.5]nonan-2-yl]amino]-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione	1990959: Induction of CBP degradation in human RS4-11 cells incubated for 4 hrs by Western blot assay	ec50	0.0017	uM
4-[[1-[5-[8-[5-acetyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl]isoquinolin-3-yl]pyridine-2-carbonyl]piperidin-4-yl]amino]-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione	1990959: Induction of CBP degradation in human RS4-11 cells incubated for 4 hrs by Western blot assay	ec50	0.0018	uM
3-acetyl-7-amino-N-[2-fluoro-5-(hydroxymethyl)-3-(1-methylpyrazol-4-yl)phenyl]indolizine-1-carboxamide	1899978: Inhibition of His6-tagged human CBP bromodomain (1081 to 1197 residues) expressed in Escherichia coli BL21 (DE3) incubated for 30 mins by HTRF assay	ic50	0.0019	uM
1-[3-[7-(difluoromethyl)-6-(1-methylpyrazol-4-yl)-3,4-dihydro-2H-quinolin-1-yl]-1-(1-methylpiperidin-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-5-yl]ethanone	1489222: Displacement of biotinylated histone H3K14 peptide ligand from human recombinant His-tagged CBP measured after 10 mins by TR-FRET assay	ic50	0.0020	uM
3-acetyl-N-[2-fluoro-5-(hydroxymethyl)-3-(1-methylpyrazol-4-yl)phenyl]-7-(methylamino)indolizine-1-carboxamide	1899978: Inhibition of His6-tagged human CBP bromodomain (1081 to 1197 residues) expressed in Escherichia coli BL21 (DE3) incubated for 30 mins by HTRF assay	ic50	0.0021	uM
5-[7-(difluoromethyl)-6-(1-methylpyrazol-4-yl)-3,4-dihydro-2H-quinolin-1-yl]-N-methyl-7-propan-2-yl-1H-pyrrolo[2,3-c]pyridine-3-carboxamide	1477685: Inhibition of His tagged recombinant CBP (unknown origin) by TR-FRET assay	ic50	0.0022	uM
4-[8-[5-acetyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl]isoquinolin-3-yl]-1-methylpyrazole-3-carbonitrile	1372218: Inhibition of recombinant His-tagged CBP (unknown origin) by TR-FRET assay	ic50	0.0024	uM
N-[(4-fluorophenyl)methyl]-2-[6-(methylcarbamoylamino)-2’,4’-dioxospiro[1,2-dihydroindene-3,5’-1,3-oxazolidine]-3’-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]acetamide	2139799: Inhibition of CBP BHC domain (unknown origin)	ic50	0.0026	uM
N-[(4-fluorophenyl)methyl]-2-[(3R)-6-(methylcarbamoylamino)-2’,4’-dioxospiro[1,2-dihydroindene-3,5’-1,3-oxazolidine]-3’-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]acetamide	2082696: Inhibition of CBP-BHC domain (unknown origin) assessed as measuring acetylation of biotinylated histone H4 peptide by TR-FRET assay	ic50	0.0026	uM
4-[(4E)-4-[[5-(4,5-dimethyl-2-nitrophenyl)furan-2-yl]methylidene]-3-methyl-5-oxopyrazol-1-yl]benzoic acid	1607763: Inhibition of CBP BHC domain (unknown origin)	ic50	0.0026	uM
1-[3-[3-[5-(difluoromethyl)-1-methylpyrazol-4-yl]isoquinolin-8-yl]-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-5-yl]ethanone	1372218: Inhibition of recombinant His-tagged CBP (unknown origin) by TR-FRET assay	ic50	0.0028	uM
(2R)-2-[[(2S)-2-(4-cyanophenyl)propyl]amino]-N-[5-(1-methylpyrazol-4-yl)-2-pyridinyl]-2-phenylacetamide	1658724: Binding affinity to recombinant full length CBP (unknown origin) incubated for 30 mins followed by H3(1 to 21) addition and measured after 1 hr by scintillation proximity assay	ic50	0.0029	uM
N-(5-acetyl-2-ethoxyphenyl)-3-(2H-tetrazol-5-yl)-5-(1,3-thiazol-4-yl)benzamide	1387627: Displacement of biotinylated acetylated peptide from recombinant human partial length CBP bromodomain (R1081 to G1197 residues) expressed in bacterial expression system measured after 1 hr by bromoscan method	kd	0.0030	uM
3-acetyl-7-amino-N-[3-(1-cyclopropylpyrazol-4-yl)-2-fluoro-5-(hydroxymethyl)phenyl]indolizine-1-carboxamide	1899978: Inhibition of His6-tagged human CBP bromodomain (1081 to 1197 residues) expressed in Escherichia coli BL21 (DE3) incubated for 30 mins by HTRF assay	ic50	0.0030	uM
1-[1-cyclohexyl-3-[7-(difluoromethyl)-6-(1-methylpyrazol-4-yl)-3,4-dihydro-2H-quinolin-1-yl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-5-yl]ethanone	1489222: Displacement of biotinylated histone H3K14 peptide ligand from human recombinant His-tagged CBP measured after 10 mins by TR-FRET assay	ic50	0.0031	uM
4-[2-[[(1R)-2-[6-(1-methylpyrazol-4-yl)-1H-indol-3-yl]-2-oxo-1-phenylethyl]amino]ethyl]benzonitrile	1658724: Binding affinity to recombinant full length CBP (unknown origin) incubated for 30 mins followed by H3(1 to 21) addition and measured after 1 hr by scintillation proximity assay	ic50	0.0032	uM
(2R,4R)-1-[1-(4-chlorophenyl)-3,3-difluorocyclobutanecarbonyl]-4-fluoro-N-(1H-pyrazolo[4,5-b]pyridin-5-yl)pyrrolidine-2-carboxamide	1918474: Inhibition of CBP/p300 in human COLO 320HSR cells assessed as reduction of C-myc levels measured after 24 hrs by HTRF assay	ec50	0.0032	uM

CTD chemical–gene interactions

118 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases reaction, increases expression, affects binding, increases reaction	10
Valproic Acid	decreases expression, affects expression, decreases methylation, increases methylation, affects cotreatment	10
bisphenol A	affects binding, affects folding, decreases reaction, affects cotreatment, increases methylation (+1 more)	7
Tretinoin	decreases reaction, increases reaction, increases expression, affects binding, affects expression	5
Cisplatin	affects cotreatment, decreases expression, increases expression	4
arsenite	decreases expression, increases expression, increases lipidation, affects binding, increases degradation (+5 more)	3
sodium arsenite	decreases expression, increases expression	3
Resveratrol	increases reaction, increases expression, affects cotreatment, affects binding, decreases reaction	3
Fulvestrant	increases methylation, affects binding, decreases reaction, increases reaction, affects cotreatment	3
Diethylstilbestrol	affects binding, increases reaction, decreases reaction	3
Quercetin	affects cotreatment, increases expression, decreases expression	3
Metribolone	affects binding, affects folding, increases reaction, increases activity, decreases expression (+1 more)	3
bisphenol S	affects folding, affects reaction, decreases reaction, affects binding	2
bisphenol AF	increases reaction, decreases reaction, affects binding, affects folding	2
Irinotecan	decreases expression	2
Arsenic	affects methylation, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Dichlorodiphenyl Dichloroethylene	increases activity	2
Bucladesine	affects reaction, affects binding, increases reaction, affects cotreatment	2
Doxorubicin	affects binding, increases reaction, decreases expression	2
Cyproterone Acetate	affects binding, affects folding, increases reaction	2
Okadaic Acid	increases expression, increases phosphorylation	2
aurantio-obtusin	increases phosphorylation	1
CBP30 compound	decreases activity, affects binding	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
2-anisidine	increases expression	1
methylmercuric chloride	affects reaction, affects binding, affects cotreatment	1
triphenyl phosphate	affects expression	1

ChEMBL screening assays

687 unique, capped per target: 644 binding, 43 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2187091	Binding	Inhibition of CREBBP/p53 by p21 luciferase reporter gene assay	Progress in the development and application of small molecule inhibitors of bromodomain-acetyl-lysine interactions. — J Med Chem
CHEMBL5517075	Functional	In vivo PROTAC activity at CRBN/CBP in NOD-SCID mouse xenografted with human MOLM16 cells assessed as reduction in CBP level in tumor at 30 mg/kg, ip administered once daily for 2 weeks and measured 1 day post last dose by Western blot anal	Discovery of a Promising CBP/p300 Degrader XYD129 for the Treatment of Acute Myeloid Leukemia. — J Med Chem

Cellosaurus cell lines

31 cell lines: 19 cancer cell line, 10 induced pluripotent stem cell, 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1112	CAL-62	Cancer cell line	Female
CVCL_1231	GI-1	Cancer cell line	Male
CVCL_1593	NCI-H835	Cancer cell line	Female
CVCL_1676	SBC-1	Cancer cell line	Male
CVCL_2960	IHH-4	Cancer cell line	Male
CVCL_3219	TMH-1	Cancer cell line	Male
CVCL_9W68	JN-DSRCT-1	Cancer cell line	Male
CVCL_A3JS	HPS2876	Induced pluripotent stem cell	Female
CVCL_A3JT	HPS2877	Induced pluripotent stem cell	Female
CVCL_A3JU	HPS2878	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms