KAT2B

Summary

KAT2B (lysine acetyltransferase 2B, HGNC:8638) is a protein-coding gene on chromosome 3p24.3, encoding Histone acetyltransferase KAT2B (Q92831). Functions as a histone acetyltransferase (HAT) to promote transcriptional activation.

CBP and p300 are large nuclear proteins that bind to many sequence-specific factors involved in cell growth and/or differentiation, including c-jun and the adenoviral oncoprotein E1A. The protein encoded by this gene associates with p300/CBP. It has in vitro and in vivo binding activity with CBP and p300, and competes with E1A for binding sites in p300/CBP. It has histone acetyl transferase activity with core histones and nucleosome core particles, indicating that this protein plays a direct role in transcriptional regulation.

Source: NCBI Gene 8850 — RefSeq curated summary.

At a glance

• Gene–disease (curated): steroid-resistant nephrotic syndrome (Limited, GenCC)
• GWAS associations: 19
• Clinical variants (ClinVar): 174 total — 1 pathogenic
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Transcription factor: yes — 15 downstream targets (CollecTRI)
• MANE Select transcript: NM_003884

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8638
Approved symbol	KAT2B
Name	lysine acetyltransferase 2B
Location	3p24.3
Locus type	gene with protein product
Status	Approved
Aliases	P/CAF, GCN5, GCN5L
Ensembl gene	ENSG00000114166
Ensembl biotype	protein_coding
OMIM	602303
Entrez	8850

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000263754, ENST00000426228, ENST00000468111, ENST00000468400, ENST00000469085, ENST00000956098, ENST00000956099, ENST00000956100

RefSeq mRNA: 1 — MANE Select: NM_003884 NM_003884

CCDS: CCDS2634

Canonical transcript exons

ENST00000263754 — 18 exons

Exon	Start	End
ENSE00000755284	20111596	20111787
ENSE00000755443	20114882	20114988
ENSE00000755616	20122668	20122804
ENSE00000755725	20125905	20126113
ENSE00001076221	20146316	20146430
ENSE00001076222	20101287	20101468
ENSE00001076223	20148243	20148306
ENSE00001076233	20148403	20148487
ENSE00001076235	20147963	20147999
ENSE00001189392	20040446	20040780
ENSE00001272618	20152332	20154404
ENSE00001800162	20127423	20127549
ENSE00003494532	20136942	20137052
ENSE00003503981	20099862	20099954
ENSE00003588220	20140221	20140364
ENSE00003607489	20119598	20119723
ENSE00003648324	20072333	20072459
ENSE00003687662	20095263	20095408

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 97.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.8569 / max 132.8561, expressed in 1521 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35663	4.5100	1224
35664	1.8595	710
35658	1.2441	458
35665	0.7935	402
35662	0.2452	108
35659	0.2047	105

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral globus pallidus	UBERON:0002476	97.59	gold quality
trabecular bone tissue	UBERON:0002483	96.49	gold quality
buccal mucosa cell	CL:0002336	96.37	gold quality
corpus callosum	UBERON:0002336	96.26	gold quality
calcaneal tendon	UBERON:0003701	96.23	gold quality
subthalamic nucleus	UBERON:0001906	96.10	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.02	gold quality
amniotic fluid	UBERON:0000173	95.62	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.24	gold quality
substantia nigra pars compacta	UBERON:0001965	95.16	gold quality
biceps brachii	UBERON:0001507	95.04	gold quality
gluteal muscle	UBERON:0002000	94.95	gold quality
heart right ventricle	UBERON:0002080	94.66	gold quality
choroid plexus epithelium	UBERON:0003911	94.56	gold quality
inferior vagus X ganglion	UBERON:0005363	94.49	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.39	gold quality
jejunal mucosa	UBERON:0000399	94.18	gold quality
endothelial cell	CL:0000115	94.17	gold quality
globus pallidus	UBERON:0001875	94.05	gold quality
pigmented layer of retina	UBERON:0001782	94.03	gold quality
retina	UBERON:0000966	94.01	gold quality
superior vestibular nucleus	UBERON:0007227	94.00	gold quality
blood vessel layer	UBERON:0004797	93.96	gold quality
medulla oblongata	UBERON:0001896	93.76	gold quality
bone marrow cell	CL:0002092	93.74	gold quality
oral cavity	UBERON:0000167	93.73	gold quality
trigeminal ganglion	UBERON:0001675	93.64	gold quality
amygdala	UBERON:0001876	93.58	gold quality
bone marrow	UBERON:0002371	93.55	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	93.47	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	62.80
E-HCAD-25	yes	17.31
E-ANND-3	yes	5.04
E-MTAB-6058	no	491.12

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

15 targets.

Target	Regulation
CDK2	Repression
CDKN1A	Activation
CDKN1B	Activation
CLOCK	Unknown
CYP1B1	Unknown
FOXP3
INVS	Activation
IRF7	Repression
LIN28A	Unknown
NPAS2	Unknown
RB1	Activation
SMAD4	Activation
TP73	Unknown
YY1	Unknown
ZEB1	Repression

Upstream regulators (CollecTRI, top): AR, ATF1, ATF4, CEBPB, CTBP2, DDIT3, DNMT1, EGR1, ESR1, FLI1, FOSL1, FOXC1, HOXA10, HOXB2, IRF1, IRF2, IRF4, JDP2, JUNB, KAT7, KAT8, KLF13, KLF1, KLF6, MYC, MYOD1, NCOA1, NCOA2, NCOA3, NFATC1, NFKB, PARP1, PLAGL1, PTF1A, RBPJL, RUNX1, SATB2, SP1, SSRP1, TADA2A

miRNA regulators (miRDB)

213 targeting KAT2B, 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-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821

Literature-anchored findings (GeneRIF, showing 40)

• P/CAF HAT activity and induction of ap97 are involved in calcium-dependent keratinocyte differentiation (PMID:11741939)
• Transcriptional synergy between Tat and PCAF is dependent on the binding of acetylated Tat to the PCAF bromodomain (PMID:12032084)
• acetylated IRF7 displayed impaired DNA binding capability and that over-expression of PCAF led to decreased IRF7 activity (PMID:12374802)
• Data suggest replication stimulation occurs through recruitment of large T antigen to the origin and acetylation by PCAF or GCN5. (PMID:12391158)
• PCAF binding to HIV-1 tat is regulated by the differential acetylation of tat (PMID:12486002)
• HPV 6, 16 and 18 E7 proteins interact with the pCAF acetyltransferase. HPV 16 E7 interacts with the acetyltransferase domain of pCAF, and reduces its acetyltransferase activity in vitro. (PMID:12813456)
• Mechanisms of P/CAF auto-acetylation. (PMID:12888487)
• ER81 is acetylated by two coactivators/acetyltransferases, p300 and p300- and CBP-associated factor (P/CAF) . Whereas p300 acetylates two lysine residues (K33 and K116) within the ER81 N-terminal transactivation domain, P/CAF targets only K116. (PMID:12917345)
• results demonstrate for the first time a novel role for human proliferating cell nuclear antigen(PCNA)in transcriptional repression and in modulating chromatin modification with reciprocal modulation of p300 acetyltransferase and PCNA by each other (PMID:12937166)
• PCAF stimulates p73-mediated transactivation (PMID:14614455)
• acetyltransferase p300 and the receptor tyrosine kinase HER2/Neu activate protein ER81 (PMID:14747462)
• acetylation of AML1 through p300 is a critical manner of posttranslational modification and identify a novel mechanism for regulating the function of AML1 (PMID:14752096)
• the stability of PCAF is regulated by MDM2 by its ubiquitination and degradation (PMID:14769800)
• P/CAF and p300 have roles in acetylation-induced stabilization of E2F1 (PMID:15123636)
• PCAF expression can be induced by wild-type p53 (PMID:15153330)
• stabilization of NF-E4 by acetylation is PCAF-dependent; acetylation of Lys(43) also reduces the interaction between NF-E4 and HDAC1, potentially maximizing the activating ability of the factor (PMID:15273251)
• kinetic occupancy of p300 at mitogen-induced genes in activated T cells reveals promoters that share common patterns of inducible expression, p300 recruitment, dependence on selective p300 domains, and sensitivity to histone deacetylase inhibitors. (PMID:15286281)
• p300 is involved in the transcriptional regulation of IL-12 p40, and IL-12 p40 is one of the target genes of p300 (PMID:15482860)
• GCN5 acetylates c-myc oncoprotein and regulates its function by altering its rate of degradation. (PMID:15572685)
• The HIV Tat protein can be endocytosed by cells and interacts with PCAF, inducing neuronal apoptosis. (PMID:15611041)
• transforming growth factor beta type II receptor promoter activity and acetylation of Sp1 by recruitment of PCAF/p300 to a Sp1.NF-Y complex are induced by Trichostatin A (PMID:15647279)
• CBP and PCAF coactivators mediate ERK1 gene expression at both the transcriptional and post-transcriptional level (PMID:16050810)
• the SREBP-1c.BETA2.E47 complex is in a DNA looping structure which is required for efficient recruitment of CREB-binding protein/p300 (PMID:16055439)
• A genetically engineered PCAF protein exhibits catalytic parameters within 3-fold of those of the wild-type PCAF catalytic domain, suggesting that the loop mutation was not deleterious for HAT activity. (PMID:16060659)
• p300 acetylates of three specific lysines (K264, K266, K273) in the carboxy-terminus of IN, a region that is required for DNA binding. (PMID:16096645)
• DEK interacts with histones and exerts a potent inhibitory effect on both p300 and PCAF-mediated histone acetyltransferase activity and transcription. (PMID:16696975)
• p300 acts in early G1 to prevent RB hyperphosphorylation and delay premature S-phase entry (PMID:16878158)
• Overexpression of p300/Creb binding protein-associated factor increases both the promoter reporter expression and endogenous mRNA level of erythroid-specific 5-aminolevulinate synthase (ALAS2). (PMID:16904069)
• p72 RNA helicase may not only be involved in the p53-Mdm2 regulatory loop, but also profoundly impact on the transcriptome through various CBP/p300 and P/CAF interacting proteins. (PMID:17226766)
• PCAF, in addition to its acetyltransferase activity, possesses an intrinsic ubiquitination activity that is critical for controlling Hdm2 expression levels, and thus p53 functions. (PMID:17293853)
• WRN is a novel cellular cofactor for HIV-1 replication, and the WRN helicase participates in the recruitment of PCAF/P-TEFb-containing transcription complexes (PMID:17317667)
• Both PCAF and BRG1 are also involved in the activation of the myogenin gene in rhabdomyosarcoma (PMID:17468105)
• In vivo co-immunoprecipitation assays showed that p73gamma interacted preferentially with PCAF. (PMID:17611664)
• a large multiprotein complex, which includes Fra-1, p300, P/CAF, junD, junB, and Sp1 acts at the AP1-5 site to produce a synergistic increase in hINV gene expression (PMID:17882273)
• PCAF-dependent acetylation of lysine 380 abrogates repressor function of Fli1 with respect to collagen expression; TGFb-dependent acetylation of Fli1 may represent the principal mechanism for TGFb-induced dissociation of Fli1 from the collagen promoter (PMID:17884818)
• KLF4 might function as an activator or repressor of transcription depending on whether it interacts with co-activators such as p300 and CREB-binding protein or co-repressors such as HDAC3. (PMID:17908689)
• a novel regulatory role of p38 during neuroinflammation where this MAP kinase controls acetylation of NF-kappaB p65 by regulating acetyltransferase activity of coactivator p300. (PMID:17982102)
• histone acetyltransferase P/CAF is a promiscuous histone propionyltransferase (PMID:18247445)
• P/CAF regulates CDK9 function by specifically acetylating the catalytic core of the enzyme especially a Lys needed for ATP coordination & the phosphotransfer reaction. (PMID:18250157)
• Three-dimensional solution structures of the bromodomains of p300/CBP-associated factor (PCAF) bound to peptides derived from histone acetylation sites. (PMID:18400184)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	kat2b	ENSDARG00000062634
mus_musculus	Kat2b	ENSMUSG00000000708
rattus_norvegicus	Kat2b	ENSRNOG00000011871
drosophila_melanogaster	Acf	FBGN0027620
caenorhabditis_elegans		WBGENE00001470

Paralogs (11): BAZ1B (ENSG00000009954), BAZ2A (ENSG00000076108), CECR2 (ENSG00000099954), KAT2A (ENSG00000108773), BAZ2B (ENSG00000123636), BRDT (ENSG00000137948), BRD4 (ENSG00000141867), BRD3 (ENSG00000169925), BPTF (ENSG00000171634), BAZ1A (ENSG00000198604), BRD2 (ENSG00000204256)

Protein

Protein identifiers

Histone acetyltransferase KAT2B — Q92831 (reviewed: Q92831)

Alternative names: Histone acetyltransferase PCAF, Lysine acetyltransferase 2B, P300/CBP-associated factor, Spermidine acetyltransferase KAT2B

All UniProt accessions (1): Q92831

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a histone acetyltransferase (HAT) to promote transcriptional activation. Has significant histone acetyltransferase activity with core histones (H3 and H4), and also with nucleosome core particles. Has a a strong preference for acetylation of H3 at ‘Lys-9’ (H3K9ac). Also acetylates non-histone proteins, such as ACLY, MAPRE1/EB1, PLK4, RRP9/U3-55K and TBX5. Inhibits cell-cycle progression and counteracts the mitogenic activity of the adenoviral oncoprotein E1A. Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-BMAL1 and CLOCK-BMAL1 heterodimers. Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5. Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4. Acetylates RRP9/U3-55K, a core subunit of the U3 snoRNP complex, impairing pre-rRNA processing. Acetylates MAPRE1/EB1, promoting dynamic kinetochore-microtubule interactions in early mitosis. Also acetylates spermidine. (Microbial infection) In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat’s transactivating activity and may help inducing chromatin remodeling of proviral genes.

Subunit / interactions. Interacts with SIRT1. Interacts (unsumoylated form) with NR2C1; the interaction promotes transactivation activity. Interacts with EP300, CREBBP and DDX17. Interacts with NCOA1 and NCOA3. Component of a large chromatin remodeling complex, at least composed of MYSM1, KAT2B/PCAF, RBM10 and KIF11/TRIP5. Interacts with NR2C2 (hypophosphorylated and unsumoylated form); the interaction promotes the transactivation activity of NR2C2. Interacts with KLF1; the interaction does not acetylate KLF1 and there is no enhancement of its transactivational activity. Interacts with NFE4. Interacts with MECOM. Interacts with E2F1; the interaction acetylates E2F1 augmenting its DNA-binding and transcriptional activity. Interacts with NPAS2, BMAL1 and CLOCK. Interacts with BCAS3. Interacts with CEBPB. Interacts with NR4A3. Interacts with NFATC2. Interacts with TBX5. Interacts with PLK4. Interacts with RB1; this interaction leads to RB1 acetylation. Interacts with VRK1. (Microbial infection) Interacts with and acetylates HIV-1 Tat. (Microbial infection) Interacts with HTLV-1 Tax.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome.

Tissue specificity. Ubiquitously expressed but most abundant in heart and skeletal muscle. Also expressed in the skin, in keratinocytes (at protein level).

Disease relevance. Defects in KAT2B has been found in a patient with isolated coloboma, a defect of the eye characterized by the absence of ocular structures due to abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Isolated colobomas may be associated with an abnormally small eye (microphthalmia) or small cornea.

Activity regulation. Activated in vitro by very low concentrations of spermidine, but inhibited at spermidine concentrations higher than 4 uM. The activating effect of low spermidine concentrations may be mediated by N(8)-acetylspermidine produced by KAT2B/P/CAF itself acting as a positive feedback loop.

Domain organisation. (Microbial infection) The bromodomain mediates binding to HIV-1 Tat.

Similarity. Belongs to the acetyltransferase family. GCN5 subfamily.

RefSeq proteins (1): NP_003875* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000182	GNAT_dom	Domain
IPR001487	Bromodomain	Domain
IPR009464	PCAF_N	Domain
IPR016181	Acyl_CoA_acyltransferase	Homologous_superfamily
IPR016376	GCN5/PCAF	Family
IPR018359	Bromodomain_CS	Conserved_site
IPR036427	Bromodomain-like_sf	Homologous_superfamily
IPR037800	GCN5	Family

Pfam: PF00439, PF00583, PF06466

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)
• spermidine + acetyl-CoA = N(8)-acetylspermidine + CoA + H(+) (RHEA:28270)
• L-lysyl-[protein] + acetyl-CoA = N(6)-acetyl-L-lysyl-[protein] + CoA + H(+) (RHEA:45948)

UniProt features (53 total): strand 14, helix 12, compositionally biased region 6, mutagenesis site 4, turn 4, binding site 3, region of interest 3, domain 2, sequence variant 2, chain 1, active site 1, sequence conflict 1

Structure

Experimental structures (PDB)

25 structures.

PDB	Method	Resolution (Å)
5MKX	X-RAY DIFFRACTION	1.68
5FE6	X-RAY DIFFRACTION	1.77
5LVQ	X-RAY DIFFRACTION	2.05
5LVR	X-RAY DIFFRACTION	2.05
5FE7	X-RAY DIFFRACTION	2.08
5FE8	X-RAY DIFFRACTION	2.1
6J3O	X-RAY DIFFRACTION	2.11
5FE3	X-RAY DIFFRACTION	2.12
5FE5	X-RAY DIFFRACTION	2.12
5FE4	X-RAY DIFFRACTION	2.15
5FE1	X-RAY DIFFRACTION	2.22
3GG3	X-RAY DIFFRACTION	2.25
5FE2	X-RAY DIFFRACTION	2.25
1CM0	X-RAY DIFFRACTION	2.3
5FE0	X-RAY DIFFRACTION	2.3
4NSQ	X-RAY DIFFRACTION	2.31
5FE9	X-RAY DIFFRACTION	2.35
5FDZ	X-RAY DIFFRACTION	2.4
1JM4	SOLUTION NMR
1N72	SOLUTION NMR
1WUG	SOLUTION NMR
1WUM	SOLUTION NMR
1ZS5	SOLUTION NMR
2RNW	SOLUTION NMR
2RNX	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92831-F1	78.22	0.44

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 (1): 570 (proton donor/acceptor)

Ligand- & substrate-binding residues (3): 574–576; 581–587; 612–615

Mutagenesis-validated functional residues (4):

Position	Phenotype
752	reduced acetyl-lysine binding.
760	reduced acetyl-lysine binding.
802	reduced acetyl-lysine binding.
809	complete loss of acetyl-lysine binding.

Function

Pathways and Gene Ontology

Reactome pathways

55 pathways

ID	Pathway
R-HSA-1912408	Pre-NOTCH Transcription and Translation
R-HSA-2032785	YAP1- and WWTR1 (TAZ)-stimulated gene expression
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-2644606	Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2894862	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-3214847	HATs acetylate histones
R-HSA-350054	Notch-HLH transcription pathway
R-HSA-5250924	B-WICH complex positively regulates rRNA expression
R-HSA-5578768	Physiological factors
R-HSA-5689901	Metalloprotease DUBs
R-HSA-73762	RNA Polymerase I Transcription Initiation
R-HSA-8936459	RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function
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-9617629	Regulation of FOXO transcriptional activity by acetylation
R-HSA-9772755	Formation of WDR5-containing histone-modifying complexes
R-HSA-9793380	Formation of paraxial mesoderm
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)
R-HSA-1266738	Developmental Biology
R-HSA-157118	Signaling by NOTCH
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-186712	Regulation of beta-cell development
R-HSA-1912422	Pre-NOTCH Expression and Processing
R-HSA-1980143	Signaling by NOTCH1
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 612 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_MEMORY, PID_HDAC_CLASSI_PATHWAY, GOBP_CHROMOSOME_ORGANIZATION, GOBP_N_TERMINAL_PROTEIN_AMINO_ACID_ACETYLATION, REACTOME_SIGNALING_BY_NOTCH, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, GOBP_RIBOSOME_BIOGENESIS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, TAATAAT_MIR126, GOBP_COGNITION, ZHAN_MULTIPLE_MYELOMA_PR_DN, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_BEHAVIOR

GO Biological Process (41): negative regulation of transcription by RNA polymerase II (GO:0000122), positive regulation of transcription from RNA polymerase II promoter by glucose (GO:0000432), gluconeogenesis (GO:0006094), regulation of DNA repair (GO:0006282), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), protein acetylation (GO:0006473), heart development (GO:0007507), memory (GO:0007613), negative regulation of cell population proliferation (GO:0008285), positive regulation of neuron projection development (GO:0010976), N-terminal peptidyl-lysine acetylation (GO:0018076), internal peptidyl-lysine acetylation (GO:0018393), cellular response to insulin stimulus (GO:0032869), cellular response to oxidative stress (GO:0034599), vasodilation (GO:0042311), regulation of RNA splicing (GO:0043484), positive regulation of gluconeogenesis (GO:0045722), positive regulation of fatty acid biosynthetic process (GO:0045723), transcription initiation-coupled chromatin remodeling (GO:0045815), positive regulation of glycolytic process (GO:0045821), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of embryonic development (GO:0045995), negative regulation of centriole replication (GO:0046600), rhythmic process (GO:0048511), regulation of cell division (GO:0051302), regulation of cell cycle (GO:0051726), limb development (GO:0060173), cellular response to parathyroid hormone stimulus (GO:0071374), negative regulation of ferroptosis (GO:0110076), positive regulation of attachment of mitotic spindle microtubules to kinetochore (GO:1902425), negative regulation of rRNA processing (GO:2000233), ubiquitin-dependent protein catabolic process (GO:0006511), fatty acid biosynthetic process (GO:0006633), regulation of gene expression (GO:0010468), negative regulation of fatty acid biosynthetic process (GO:0045717), positive regulation of lipid biosynthetic process (GO:0046889), attachment of mitotic spindle microtubules to kinetochore (GO:0051315)

GO Molecular Function (21): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), chromatin binding (GO:0003682), transcription coregulator activity (GO:0003712), transcription coactivator activity (GO:0003713), diamine N-acetyltransferase activity (GO:0004145), histone acetyltransferase activity (GO:0004402), L-lysine N6-acetyltransferase activity, acting on acetyl phosphate as donor (GO:0004468), cyclin-dependent protein serine/threonine kinase inhibitor activity (GO:0004861), enzyme activator activity (GO:0008047), histone H3 acetyltransferase activity (GO:0010484), acetyltransferase activity (GO:0016407), protein kinase binding (GO:0019901), histone acetyltransferase binding (GO:0035035), histone deacetylase binding (GO:0042826), histone H3K9 acetyltransferase activity (GO:0043992), protein-lysine-acetyltransferase activity (GO:0061733), DNA-binding transcription factor binding (GO:0140297), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), acyltransferase activity, transferring groups other than amino-acyl groups (GO:0016747)

GO Cellular Component (16): SAGA complex (GO:0000124), kinetochore (GO:0000776), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), A band (GO:0031672), I band (GO:0031674), protein-containing complex (GO:0032991), actomyosin (GO:0042641), mitotic spindle (GO:0072686), ATAC complex (GO:0140672), histone acetyltransferase complex (GO:0000123), chromatin (GO:0000785), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-19 pathways:

Category	Pathways
Generic Transcription Pathway	2
Pre-NOTCH Expression and Processing	1
Regulation of beta-cell development	1
Signaling by NOTCH1	1
Signaling by NOTCH1 PEST Domain Mutants in Cancer	1
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	1
Chromatin modifying enzymes	1
Positive epigenetic regulation of rRNA expression	1
Cardiac conduction	1
Deubiquitination	1
RNA Polymerase I Promoter Clearance	1
Transcriptional regulation by RUNX1	1
Transcriptional regulation by RUNX3	1
Signaling by NOTCH3	1
Signaling by NOTCH4	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
transcription by RNA polymerase II	2
regulation of gene expression	2
peptidyl-lysine acetylation	2
binding	2
catalytic activity	2
enzyme binding	2
SAGA-type complex	2
intracellular membraneless organelle	2
sarcomere	2
regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
regulation of transcription from RNA polymerase II promoter by glucose	1
carbon catabolite activation of transcription from RNA polymerase II promoter	1
positive regulation of transcription by glucose	1
glucose metabolic process	1
hexose biosynthetic process	1
DNA repair	1
regulation of DNA metabolic process	1
regulation of cellular response to stress	1
chromatin organization	1
DNA-templated transcription	1
regulation of RNA biosynthetic process	1
regulation of DNA-templated transcription	1
protein acylation	1
animal organ development	1
circulatory system development	1
learning or memory	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
N-terminal protein amino acid acetylation	1
internal protein amino acid acetylation	1
response to insulin	1
cellular response to peptide hormone stimulus	1
response to oxidative stress	1
cellular response to chemical stress	1

Protein interactions and networks

STRING

3598 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KAT2B	EP300	Q09472	998
KAT2B	TADA3	O75528	998
KAT2B	TAF9	Q16594	997
KAT2B	SGF29	Q96ES7	997
KAT2B	TRRAP	Q9Y4A5	996
KAT2B	CREBBP	Q92793	993
KAT2B	KAT5	Q92993	982
KAT2B	AGXT	P21549	981
KAT2B	MYC	P01106	972
KAT2B	TADA2A	O75478	970
KAT2B	HTT	P42858	949
KAT2B	COMMD1	Q8N668	948
KAT2B	HDAC1	Q13547	947
KAT2B	H3C1	P02295	944
KAT2B	NCOA1	Q15788	942

IntAct

159 interactions, top by confidence:

A	B	Type	Score
RB1	E2F1	psi-mi:“MI:0915”(physical association)	0.980
WDR5	KMT2D	psi-mi:“MI:0914”(association)	0.910
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
SGF29	NDC80	psi-mi:“MI:0914”(association)	0.840
TWIST1	TP53	psi-mi:“MI:0914”(association)	0.820
MED23	MED19	psi-mi:“MI:2364”(proximity)	0.770
TAF12	TAF4	psi-mi:“MI:0914”(association)	0.760
TRRAP	ATXN7	psi-mi:“MI:0914”(association)	0.740
TADA3	TADA2A	psi-mi:“MI:0914”(association)	0.740
BUB1B	KAT2B	psi-mi:“MI:0915”(physical association)	0.720
BUB1B	KAT2B	psi-mi:“MI:0403”(colocalization)	0.720
KAT2B	BUB1B	psi-mi:“MI:0915”(physical association)	0.720
KAT2B	BUB1B	psi-mi:“MI:0192”(acetylation reaction)	0.720
BUB1B	KAT2B	psi-mi:“MI:0192”(acetylation reaction)	0.720
KAT2B	E7	psi-mi:“MI:0915”(physical association)	0.700
E7	KAT2B	psi-mi:“MI:0915”(physical association)	0.700
KAT2B	E7	psi-mi:“MI:0407”(direct interaction)	0.700
KAT2B	CREBBP	psi-mi:“MI:0915”(physical association)	0.660

BioGRID (653): KAT2B (Reconstituted Complex), KLF2 (Affinity Capture-Western), KAT2B (Affinity Capture-Western), KAT2B (Co-localization), ACLY (Affinity Capture-Western), CARM1 (Affinity Capture-Western), KAT2B (Affinity Capture-Western), KAT2B (Biochemical Activity), KAT2B (Reconstituted Complex), KAT2B (Biochemical Activity), KAT2B (Reconstituted Complex), tat (Reconstituted Complex), RBM8A (Protein-RNA), KAT2B (Reconstituted Complex), KAT2B (Reconstituted Complex)

ESM2 similar proteins: A0A0R4IXF6, A1A5R8, A9ZLX4, D3YXJ0, E9PUQ8, G3UZ78, O00750, O15164, O54828, P30052, P40818, P48984, P52963, P59997, P97496, Q02225, Q08AX9, Q08BR4, Q08D35, Q16760, Q1LUC3, Q2I6J1, Q3UWM4, Q498F0, Q5JSH3, Q5JTW2, Q5RHD1, Q60665, Q64398, Q68FF0, Q6INA9, Q6NSI8, Q6NVE8, Q6PDG5, Q6ZMT4, Q7ZVP1, Q80U87, Q86XP1, Q8C5W4, Q8N7X0

Diamond homologs: A0A0R4IXF6, A0A7U2QYM2, A2AHJ4, A2AUY4, A2BIL7, B2RRD7, B7ZS37, D4A7T3, E9Q2Z1, F1QW93, F1R5H6, F7DRV9, G5E8P1, O15164, O60885, O74350, O88379, O88665, O95696, P13709, P21675, P25440, P35817, P51123, P53236, P54816, P55201, P87152, Q02206, Q03330, Q07442, Q08D75, Q09948, Q12830, Q15059, Q1LUC3, Q23590, Q32S26, Q338B9, Q4R8Y1

SIGNOR signaling

30 interactions.

A	Effect	B	Mechanism
SIRT2	down-regulates	KAT2B	binding
KAT2B	up-regulates	SMAD2	acetylation
KAT2B	“form complex”	P300/PCAF	binding
KAT2B	up-regulates	NOTCH1	acetylation
KAT2B	up-regulates	NOTCH	acetylation
KAT2B	“form complex”	“SAGA complex”	binding
KAT2B	“down-regulates activity”	“Histone H3”	acetylation
KAT2B	“down-regulates activity”	H3C1	acetylation
KAT2B	“down-regulates activity”	H3-3A	acetylation
KAT2B	“down-regulates activity”	H3-4	acetylation
KAT2B	“down-regulates activity”	H3Y1	acetylation
KAT2B	“down-regulates activity”	H3Y2	acetylation
KAT2B	“down-regulates activity”	H3-2	acetylation
KAT2B	“down-regulates activity”	H3-5	acetylation
KAT2B	“down-regulates activity”	H3C15	acetylation
MDM2	“down-regulates quantity by destabilization”	KAT2B	ubiquitination
PRKDC	“up-regulates activity”	KAT2B	phosphorylation
KAT2B	up-regulates	MYOD1	acetylation
KAT2B	up-regulates	MYOD1	binding
KAT2B	up-regulates	SMAD3	binding
KAT2B	up-regulates	MEF2C	binding
NR3C1	“up-regulates activity”	KAT2B	relocalization
KAT2B	“down-regulates activity”	GLI1	acetylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 97 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
Formation of WDR5-containing histone-modifying complexes	10	37.9×	6e-12
Regulation of TP53 Activity through Acetylation	5	32.6×	1e-05
Epigenetic regulation by WDR5-containing histone modifying complexes	13	28.7×	5e-14
HATs acetylate histones	21	23.8×	3e-21
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	8	22.5×	1e-07
Chromatin organization	19	22.1×	1e-18
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	7	21.6×	1e-06
NOTCH1 Intracellular Domain Regulates Transcription	6	20.4×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
regulation of cell division	8	70.4×	1e-11
regulation of DNA repair	18	57.2×	6e-25
regulation of RNA splicing	17	42.8×	2e-21
regulation of embryonic development	9	34.2×	5e-10
chromosome organization	5	33.4×	2e-05
RNA polymerase II preinitiation complex assembly	8	25.0×	8e-08
positive regulation of transcription initiation by RNA polymerase II	8	25.0×	8e-08
mRNA transcription by RNA polymerase II	6	22.8×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	84
Likely benign	17
Benign	49

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
57768	GRCh38/hg38 3p24.3-24.2(chr3:20054451-23858736)x1	Pathogenic

SpliceAI

3482 predictions. Top by Δscore:

Variant	Effect	Δscore
3:20071664:T:G	donor_gain	1.0000
3:20071669:G:GT	donor_gain	1.0000
3:20095259:T:G	acceptor_gain	1.0000
3:20095260:A:AG	acceptor_gain	1.0000
3:20095260:AAGCT:A	acceptor_gain	1.0000
3:20095261:A:G	acceptor_gain	1.0000
3:20095262:G:GG	acceptor_gain	1.0000
3:20099846:A:AG	acceptor_gain	1.0000
3:20099846:AAT:A	acceptor_gain	1.0000
3:20099847:A:G	acceptor_gain	1.0000
3:20099847:AT:A	acceptor_gain	1.0000
3:20099848:T:G	acceptor_gain	1.0000
3:20099848:T:TA	acceptor_gain	1.0000
3:20099860:A:AG	acceptor_gain	1.0000
3:20099861:G:GG	acceptor_gain	1.0000
3:20101284:AAG:A	acceptor_gain	1.0000
3:20111732:G:GT	donor_gain	1.0000
3:20111733:A:T	donor_gain	1.0000
3:20111739:A:G	donor_gain	1.0000
3:20111788:G:GG	donor_gain	1.0000
3:20119590:C:A	acceptor_gain	1.0000
3:20122652:ATTTT:A	acceptor_gain	1.0000
3:20122656:T:TA	acceptor_gain	1.0000
3:20126109:GACCC:G	donor_gain	1.0000
3:20126110:ACCC:A	donor_gain	1.0000
3:20126111:CCC:C	donor_gain	1.0000
3:20126114:G:GG	donor_gain	1.0000
3:20137048:AACAG:A	donor_loss	1.0000
3:20137049:ACAG:A	donor_loss	1.0000
3:20137050:CAG:C	donor_loss	1.0000

AlphaMissense

5438 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:20040749:T:C	L91P	1.000
3:20040758:T:A	L94H	1.000
3:20040758:T:C	L94P	1.000
3:20040760:G:A	G95R	1.000
3:20040760:G:C	G95R	1.000
3:20040761:G:A	G95E	1.000
3:20040775:T:A	C100S	1.000
3:20040775:T:C	C100R	1.000
3:20040776:G:A	C100Y	1.000
3:20040776:G:C	C100S	1.000
3:20040777:C:G	C100W	1.000
3:20072351:T:A	C108S	1.000
3:20072351:T:C	C108R	1.000
3:20072352:G:A	C108Y	1.000
3:20072352:G:C	C108S	1.000
3:20072352:G:T	C108F	1.000
3:20072353:T:G	C108W	1.000
3:20072358:G:A	G110D	1.000
3:20072360:T:A	W111R	1.000
3:20072360:T:C	W111R	1.000
3:20072361:G:C	W111S	1.000
3:20072362:G:C	W111C	1.000
3:20072362:G:T	W111C	1.000
3:20072435:T:C	C136R	1.000
3:20072436:G:A	C136Y	1.000
3:20072437:T:G	C136W	1.000
3:20072444:T:A	C139S	1.000
3:20072444:T:C	C139R	1.000
3:20072445:G:A	C139Y	1.000
3:20072445:G:C	C139S	1.000

dbSNP variants (sampled 300 via entrez): RS1000017841 (3:20102367 T>A,C), RS1000042938 (3:20124224 A>G), RS1000049214 (3:20081660 A>G), RS1000080982 (3:20101593 G>A,T), RS1000093260 (3:20123818 T>C), RS1000097472 (3:20040950 C>G), RS1000112862 (3:20150755 T>C), RS1000134450 (3:20058948 T>C), RS1000180310 (3:20132407 C>T), RS1000183618 (3:20105968 T>G), RS1000222058 (3:20072058 C>T), RS1000234907 (3:20088625 C>T), RS1000339763 (3:20053204 C>T), RS1000366641 (3:20132758 A>G), RS1000381193 (3:20043799 C>G)

Disease associations

OMIM: gene MIM:602303 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
steroid-resistant nephrotic syndrome	Limited	Autosomal recessive

Mondo (1): steroid-resistant nephrotic syndrome (MONDO:0044765)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST002156_3	Response to mTOR inhibitor (rapamycin)	7.000000e-06
GCST002308_3	Mean arterial pressure (alcohol consumption interaction)	4.000000e-07
GCST002401_2	Post-traumatic stress disorder	8.000000e-06
GCST003181_1	Staphylococcus aureus nasal carriage (intermittent)	9.000000e-09
GCST003601_1	Drug abuse	4.000000e-10
GCST004602_101	Mean corpuscular volume	9.000000e-15
GCST004630_114	Mean corpuscular hemoglobin	3.000000e-12
GCST006011_98	Mean corpuscular volume	1.000000e-10
GCST006624_73	Systolic blood pressure	1.000000e-11
GCST007267_25	Systolic blood pressure	7.000000e-18
GCST009462_43	Optic disc size	1.000000e-08
GCST90002385_421	High light scatter reticulocyte count	2.000000e-15
GCST90002390_476	Mean corpuscular hemoglobin	1.000000e-31
GCST90002392_184	Mean corpuscular volume	8.000000e-46
GCST90002396_191	Mean reticulocyte volume	9.000000e-68
GCST90002397_648	Mean spheric corpuscular volume	2.000000e-70
GCST90002403_136	Red blood cell count	7.000000e-12
GCST90002405_8	Reticulocyte count	4.000000e-18
GCST90002406_75	Reticulocyte fraction of red cells	1.000000e-13

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0005417	response to mTOR inhibitor
EFO:0004329	alcohol drinking
EFO:0006340	mean arterial pressure
EFO:0007758	intermittent Staphylococcus aureus carrier status
EFO:0004527	mean corpuscular hemoglobin
EFO:0006335	systolic blood pressure
EFO:0007986	reticulocyte count
EFO:0010701	mean reticulocyte volume
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3885587 (PROTEIN FAMILY), CHEMBL4523708 (PROTEIN-PROTEIN INTERACTION), CHEMBL5500 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 39,182 (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
CHEMBL1213327	COENZYME_A	3	10,084
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL295316	PLUMBAGIN	1	6,294

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs9829896	Toxicity	3	amphetamine;cannabinoids;cocaine;opioids	Substance-Related Disorders

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9829896	KAT2B, MIR3135A	3	3.50	1	amphetamine;cannabinoids;cocaine;opioids

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 2.3.1.48 Histone acetyltransferases (HATs)

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
compound 1 [PMID: 15724976]	Inhibition	8.29	pIC50
H3-CoA-20	Inhibition	6.52	pIC50
garcinol	Inhibition	5.3	pIC50
LTK-14	Inhibition	5.3	pIC50
anacardic acid	Inhibition	5.07	pIC50
plumbagin	Inhibition	4.3	pIC50
epigallocatechin-3-gallate	Inhibition	4.22	pIC50
MB-3	Inhibition	4.0	pIC50
Lys-CoA	Inhibition	3.7	pIC50

Binding affinities (BindingDB)

161 measured of 169 human assays (169 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-chloro-2-methyl-5-[[(3R,5S)-1-methyl-5-(2-methylpropyl)piperidin-3-yl]amino]pyridazin-3-one	IC50	12.7 nM	US-10239861: Therapeutic compounds and uses thereof
8-[[(1R,2R)-1-(dimethylamino)-1-phenylpropan-2-yl]amino]-6-methylpyrido[2,3-d]pyridazin-5-one	IC50	19 nM	US-10155764: Therapeutic compounds and uses thereof
8-[[(1S,2S)-1-[4-(benzenesulfonyl)phenyl]-1-(dimethylamino)propan-2-yl]amino]-6-methylpyrido[2,3-d]pyridazin-5-one	IC50	20 nM	US-10155764: Therapeutic compounds and uses thereof
4-[[(1R,2S)-1-(dimethylamino)-1-pyridin-2-ylpropan-2-yl]amino]-2-methylphthalazin-1-one	IC50	21 nM	US-10155764: Therapeutic compounds and uses thereof
4-chloro-5-(((3R,5S)-1,5-dimethylpiperidin-3-yl)amino)-2-methylpyridazin-3(2H)-one	IC50	21.5 nM	US-10239861: Therapeutic compounds and uses thereof
4-[[(1S,2S)-1-(dimethylamino)-1-phenylpropan-2-yl]amino]-2-methylphthalazin-1-one	IC50	23 nM	US-10155764: Therapeutic compounds and uses thereof
4-[[(1S,2S)-1-(dimethylamino)-1-(4-phenoxyphenyl)propan-2-yl]amino]-2-methylphthalazin-1-one	IC50	25 nM	US-10155764: Therapeutic compounds and uses thereof
benzyl 4-[(1S,2S)-1-(dimethylamino)-2-[(6-methyl-5-oxopyrido[2,3-d]pyridazin-8-yl)amino]propyl]benzoate	IC50	29 nM	US-10155764: Therapeutic compounds and uses thereof
propan-2-yl 4-[(1S,2S)-1-(dimethylamino)-2-[(6-methyl-5-oxopyrido[2,3-d]pyridazin-8-yl)amino]propyl]benzoate	IC50	30 nM	US-10155764: Therapeutic compounds and uses thereof
(S)-4-chloro-2-methyl-5-((1-methylazepan-3-yl)amino)pyridazin-3(2H)-one	IC50	32.9 nM	US-10239861: Therapeutic compounds and uses thereof
4-[[(1S,2S)-1-(dimethylamino)-1-(4-propan-2-yloxyphenyl)propan-2-yl]amino]-2-methylphthalazin-1-one	IC50	33 nM	US-10155764: Therapeutic compounds and uses thereof
4-chloro-5-[[(3R,6R)-1,6-dimethylpiperidin-3-yl]amino]-2-methylpyridazin-3-one	IC50	34.8 nM	US-10239861: Therapeutic compounds and uses thereof
4-[[(1S,2S)-1-(dimethylamino)-1-phenylpropan-2-yl]amino]-2,5-dimethylphthalazin-1-one	IC50	36 nM	US-10155764: Therapeutic compounds and uses thereof
4-[[(1S,2S)-1-(dimethylamino)-1-(4-phenylmethoxyphenyl)propan-2-yl]amino]-2-methylphthalazin-1-one	IC50	36 nM	US-10155764: Therapeutic compounds and uses thereof
(racemic)-4-chloro-5-(((3RS,5SR)-1,5-dimethylpiperidin-3-yl)amino)-2-methylpyridazin-3(2H)-one	IC50	36.5 nM	US-10239861: Therapeutic compounds and uses thereof
4-[[(3S,4S)-1-(4-chlorophenyl)-3-(dimethylamino)piperidin-4-yl]amino]-2-methylphthalazin-1-one	IC50	40 nM	US-10155764: Therapeutic compounds and uses thereof
8-[[(1S,2S)-1-(dimethylamino)-1-phenylbutan-2-yl]amino]-6-methylpyrido[2,3-d]pyridazin-5-one	IC50	40 nM	US-10155764: Therapeutic compounds and uses thereof
8-[[1-[4-(benzenesulfonyl)phenyl]-1-(dimethylamino)propan-2-yl]amino]-6-methylpyrido[2,3-d]pyridazin-5-one	IC50	40 nM	US-10155764: Therapeutic compounds and uses thereof
4-[[(1S,2S)-1-(dimethylamino)-1-phenylbutan-2-yl]amino]-2-methylphthalazin-1-one	IC50	41 nM	US-10155764: Therapeutic compounds and uses thereof
8-[[(2S)-1-(dimethylamino)propan-2-yl]amino]-6-methylpyrido[2,3-d]pyridazin-5-one	IC50	42 nM	US-10155764: Therapeutic compounds and uses thereof
4-[[(1S,2S)-1-(dimethylamino)-1-(4-hydroxyphenyl)propan-2-yl]amino]-2-methylphthalazin-1-one	IC50	42 nM	US-10155764: Therapeutic compounds and uses thereof
4-[[(1S,2S)-1-[4-(cyclopropylmethoxy)phenyl]-1-(dimethylamino)propan-2-yl]amino]-2-methylphthalazin-1-one	IC50	44 nM	US-10155764: Therapeutic compounds and uses thereof
8-[[(2S)-2-(dimethylamino)-2-phenylethyl]amino]-6-methylpyrido[2,3-d]pyridazin-5-one	IC50	45 nM	US-10155764: Therapeutic compounds and uses thereof
4-[[(1S,2S)-1-(dimethylamino)-1-(4-pyridin-2-yloxyphenyl)propan-2-yl]amino]-2-methylphthalazin-1-one	IC50	46 nM	US-10155764: Therapeutic compounds and uses thereof
4-[[(2S)-2-(dimethylamino)-2-phenylethyl]amino]-2-methylphthalazin-1-one	IC50	47 nM	US-10155764: Therapeutic compounds and uses thereof
4-chloro-5-[[(3R,6S)-1,6-dimethylpiperidin-3-yl]amino]-2-methylpyridazin-3-one	IC50	48.5 nM	US-10239861: Therapeutic compounds and uses thereof
4-[(1S,2S)-1-(dimethylamino)-2-[(6-methyl-5-oxopyrido[2,3-d]pyridazin-8-yl)amino]propyl]-N-methylbenzamide	IC50	50 nM	US-10155764: Therapeutic compounds and uses thereof
4-bromo-2-methyl-5-((1-methylazepan-3-yl)amino)pyridazin-3(2H)-one	IC50	51 nM	US-10239861: Therapeutic compounds and uses thereof
4-chloro-2-methyl-5-[[(3S)-1-methylpiperidin-3-yl]amino]pyridazin-3-one	IC50	51.2 nM	US-10239861: Therapeutic compounds and uses thereof
N-benzyl-4-[(1S,2S)-1-(dimethylamino)-2-[(6-methyl-5-oxopyrido[2,3-d]pyridazin-8-yl)amino]propyl]-N-methylbenzamide	IC50	56 nM	US-10155764: Therapeutic compounds and uses thereof
8-[[(1R,2S)-2-(dimethylamino)cyclopentyl]amino]-6-methylpyrido[2,3-d]pyridazin-5-one	IC50	57 nM	US-10155764: Therapeutic compounds and uses thereof
8-[[(1S,2S)-1-(dimethylamino)-1-[4-(morpholine-4-carbonyl)phenyl]propan-2-yl]amino]-6-methylpyrido[2,3-d]pyridazin-5-one	IC50	59 nM	US-10155764: Therapeutic compounds and uses thereof
4-chloro-5-((1,6-dimethylpiperidin-3-yl)amino)-2-methylpyridazin-3(2H)-one	IC50	60 nM	US-10239861: Therapeutic compounds and uses thereof
4-[[(1S,2S)-1-[4-(benzenesulfonyl)phenyl]-1-(dimethylamino)propan-2-yl]amino]-2-methylphthalazin-1-one	IC50	61 nM	US-10155764: Therapeutic compounds and uses thereof
4-[[(1S,2S)-1-(dimethylamino)-1-(6-methoxy-3-pyridinyl)propan-2-yl]amino]-2-methylphthalazin-1-one	IC50	63 nM	US-10155764: Therapeutic compounds and uses thereof
4-[[2-(dimethylamino)-2-(4-methoxyphenyl)ethyl]amino]-2-methylphthalazin-1-one	IC50	64 nM	US-10155764: Therapeutic compounds and uses thereof
4-[1-(dimethylamino)propan-2-ylamino]-2-methylphthalazin-1-one	IC50	66 nM	US-10155764: Therapeutic compounds and uses thereof
8-[[(1S,2S)-1-(dimethylamino)-1-[4-(pyrrolidine-1-carbonyl)phenyl]propan-2-yl]amino]-6-methylpyrido[2,3-d]pyridazin-5-one	IC50	71 nM	US-10155764: Therapeutic compounds and uses thereof
8-[[(2R)-2-(dimethylamino)propyl]amino]-6-methylpyrido[2,3-d]pyridazin-5-one	IC50	72 nM	US-10155764: Therapeutic compounds and uses thereof
4-[[(1S,2S)-1-(dimethylamino)-1-(4-methoxyphenyl)propan-2-yl]amino]-2-methylphthalazin-1-one	IC50	73 nM	US-10155764: Therapeutic compounds and uses thereof
4-[[(1S,2S)-1-(dimethylamino)-1-(1-phenylpyrazol-4-yl)propan-2-yl]amino]-2-methylphthalazin-1-one	IC50	75 nM	US-10155764: Therapeutic compounds and uses thereof
8-[[(1R,2S)-2-(dimethylamino)cyclohexyl]amino]-6-methylpyrido[2,3-d]pyridazin-5-one	IC50	78 nM	US-10155764: Therapeutic compounds and uses thereof
4-[[(1E,2S)-1-(dimethylamino)-1-(6-oxo-3-pyridinylidene)propan-2-yl]amino]-2-methylphthalazin-1-one	IC50	80 nM	US-10155764: Therapeutic compounds and uses thereof
4-[[(1R,2R)-1-(dimethylamino)-1-phenylpropan-2-yl]amino]-6-methyl-1H-pyrrolo[2,3-d]pyridazin-7-one	IC50	83 nM	US-10155764: Therapeutic compounds and uses thereof
4-chloro-2-methyl-5-[(1-methylpiperidin-3-yl)amino]pyridazin-3-one	IC50	85 nM	US-10239861: Therapeutic compounds and uses thereof
(R)-5-((1-benzylpiperidin-3-yl)amino)-4-chloro-2-methylpyridazin-3(2H)-one	IC50	85.6 nM	US-10239861: Therapeutic compounds and uses thereof
8-[[2-(dimethylamino)-2-phenylethyl]amino]-6-methylpyrido[2,3-d]pyridazin-5-one	IC50	86 nM	US-10155764: Therapeutic compounds and uses thereof
4-[[(1S,2S)-1-(dimethylamino)-1-pyridin-3-ylpropan-2-yl]amino]-2-methylphthalazin-1-one	IC50	86 nM	US-10155764: Therapeutic compounds and uses thereof
4-[2-(dimethylamino)ethylamino]-8-fluoro-2-methylphthalazin-1-one	IC50	87 nM	US-10155764: Therapeutic compounds and uses thereof
4-[[(2R)-2-(dimethylamino)butyl]amino]-2-methylphthalazin-1-one	IC50	89 nM	US-10155764: Therapeutic compounds and uses thereof

ChEMBL bioactivities

358 potent at pChembl≥5 of 442 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.90	Ki	1.259	nM	CHEMBL4069412
8.85	Ki	1.4	nM	CHEMBL4069412
8.15	IC50	7	nM	CHEMBL4574669
8.00	IC50	10	nM	CHEMBL4543497
7.92	Kd	12	nM	CHEMBL4872300
7.90	IC50	12.7	nM	CHEMBL4103402
7.89	IC50	13	nM	CHEMBL4103402
7.85	IC50	14	nM	CHEMBL4449143
7.85	Kd	14	nM	CHEMBL4861491
7.77	IC50	17	nM	CHEMBL4439202
7.72	IC50	19	nM	CHEMBL4067343
7.72	IC50	19	nM	CHEMBL4216214
7.70	IC50	20	nM	CHEMBL6006053
7.68	IC50	21	nM	CHEMBL6034699
7.67	IC50	21.5	nM	CHEMBL5741353
7.66	IC50	22	nM	CHEMBL4545594
7.64	IC50	23	nM	CHEMBL5969144
7.60	IC50	25	nM	CHEMBL4453637
7.60	IC50	25	nM	CHEMBL6058722
7.55	Ki	28	nM	CHEMBL526343
7.54	IC50	29	nM	CHEMBL5955099
7.52	IC50	30	nM	CHEMBL4570924
7.52	IC50	30	nM	CHEMBL4527339
7.52	IC50	30	nM	CHEMBL5751286
7.50	IC50	32	nM	CHEMBL4454700
7.48	IC50	33	nM	CHEMBL5947116
7.48	IC50	32.9	nM	CHEMBL5890431
7.46	IC50	35	nM	CHEMBL4454766
7.46	IC50	34.8	nM	CHEMBL5879193
7.44	IC50	36	nM	CHEMBL4570969
7.44	IC50	36	nM	CHEMBL5743406
7.44	IC50	36	nM	CHEMBL6047198
7.44	IC50	36.5	nM	CHEMBL5968135
7.40	IC50	39.81	nM	CHEMBL4069412
7.40	IC50	40	nM	CHEMBL6014546
7.40	IC50	40	nM	CHEMBL5887959
7.40	IC50	40	nM	CHEMBL6056999
7.39	IC50	41	nM	CHEMBL4471748
7.39	IC50	41	nM	CHEMBL5948810
7.38	IC50	42	nM	CHEMBL6043043
7.38	IC50	42	nM	CHEMBL5876767
7.36	IC50	44	nM	CHEMBL5958341
7.35	IC50	45	nM	CHEMBL6056859
7.35	IC50	45	nM	CHEMBL6029522
7.34	IC50	46	nM	CHEMBL5853521
7.33	IC50	47	nM	CHEMBL4457684
7.33	IC50	47	nM	CHEMBL6050668
7.32	IC50	48	nM	CHEMBL4570969
7.31	IC50	48.5	nM	CHEMBL5811361
7.30	IC50	50	nM	CHEMBL6000774

PubChem BioAssay actives

165 with measured affinity, of 834 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
4-bromo-2-methyl-5-[[(3R,5R)-1-methyl-5-phenylpiperidin-3-yl]amino]pyridazin-3-one	1436226: Binding affinity to human partial length PCAF bromodomain expressed in mammalian expression system by BROMOscan method	ki	0.0013	uM
2-[[(3R,5R)-5-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-methylpiperidin-3-yl]amino]-3-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554033: Inhibition of biotinylated peptide binding to human GST-tagged PCAF bromodomain expressed in Escherichia coli Rosetta (DE3) measured after 15 hrs by HTRF assay	ic50	0.0070	uM
3-methyl-2-[[(3R,5R)-1-methyl-5-(4-phenoxyphenyl)piperidin-3-yl]amino]-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554033: Inhibition of biotinylated peptide binding to human GST-tagged PCAF bromodomain expressed in Escherichia coli Rosetta (DE3) measured after 15 hrs by HTRF assay	ic50	0.0100	uM
5-[4-(2-aminoethyl)anilino]-4-chloro-2-methylpyridazin-3-one	1769024: Binding affinity to PCAF (unknown origin) by BROMOscan method	kd	0.0120	uM
4-chloro-2-methyl-5-[[(3R,5S)-1-methyl-5-(2-methylpropyl)piperidin-3-yl]amino]pyridazin-3-one	1376095: Displacement of biotinylated small molecule ligand from His/FLAG-tagged PCAF bromodomain (719 to 832 residues) (unknown origin) after 15 mins by AlphaLisa method	ic50	0.0130	uM
3-methyl-2-[[(3R,5R)-1-methyl-5-(4-phenylmethoxyphenyl)piperidin-3-yl]amino]-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554033: Inhibition of biotinylated peptide binding to human GST-tagged PCAF bromodomain expressed in Escherichia coli Rosetta (DE3) measured after 15 hrs by HTRF assay	ic50	0.0140	uM
5-[4-(2-aminoethyl)anilino]-4-bromo-2-methylpyridazin-3-one	1769024: Binding affinity to PCAF (unknown origin) by BROMOscan method	kd	0.0140	uM
3-methyl-2-[[(3R,5R)-1-methyl-5-[4-(trifluoromethoxy)phenyl]piperidin-3-yl]amino]-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554033: Inhibition of biotinylated peptide binding to human GST-tagged PCAF bromodomain expressed in Escherichia coli Rosetta (DE3) measured after 15 hrs by HTRF assay	ic50	0.0170	uM
8-[[(1R,2R)-1-(dimethylamino)-1-phenylpropan-2-yl]amino]-6-methylpyrido[2,3-d]pyridazin-5-one	1436227: Displacement of biotinylated small molecule ligand from His/FLAG-tagged PCAF bromodomain (719 to 832 residues) (unknown origin) after 15 mins by AlphaLisa method	ic50	0.0190	uM
8-[[(1S,2S)-1-(dimethylamino)-1-phenylpropan-2-yl]amino]-6-methylpyrido[2,3-d]pyridazin-5-one	1376095: Displacement of biotinylated small molecule ligand from His/FLAG-tagged PCAF bromodomain (719 to 832 residues) (unknown origin) after 15 mins by AlphaLisa method	ic50	0.0190	uM
2-[[(3R,5R)-5-(3-bromophenyl)-1-methylpiperidin-3-yl]amino]-3-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554033: Inhibition of biotinylated peptide binding to human GST-tagged PCAF bromodomain expressed in Escherichia coli Rosetta (DE3) measured after 15 hrs by HTRF assay	ic50	0.0220	uM
3-methyl-2-[[(3R,5R)-1-methyl-5-(3-phenylphenyl)piperidin-3-yl]amino]-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554033: Inhibition of biotinylated peptide binding to human GST-tagged PCAF bromodomain expressed in Escherichia coli Rosetta (DE3) measured after 15 hrs by HTRF assay	ic50	0.0250	uM
2-[[(3R,5R)-5-[4-chloro-3-(trifluoromethyl)phenyl]-1-methylpiperidin-3-yl]amino]-3-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554033: Inhibition of biotinylated peptide binding to human GST-tagged PCAF bromodomain expressed in Escherichia coli Rosetta (DE3) measured after 15 hrs by HTRF assay	ic50	0.0300	uM
2-[[(3R,5R)-5-(4-hydroxyphenyl)-1-methylpiperidin-3-yl]amino]-3-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554033: Inhibition of biotinylated peptide binding to human GST-tagged PCAF bromodomain expressed in Escherichia coli Rosetta (DE3) measured after 15 hrs by HTRF assay	ic50	0.0300	uM
2-[[(3R,5R)-5-(4-methoxyphenyl)-1-methylpiperidin-3-yl]amino]-3-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554033: Inhibition of biotinylated peptide binding to human GST-tagged PCAF bromodomain expressed in Escherichia coli Rosetta (DE3) measured after 15 hrs by HTRF assay	ic50	0.0320	uM
2-[[(3R,5R)-5-(4-butylphenyl)-1-methylpiperidin-3-yl]amino]-3-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554033: Inhibition of biotinylated peptide binding to human GST-tagged PCAF bromodomain expressed in Escherichia coli Rosetta (DE3) measured after 15 hrs by HTRF assay	ic50	0.0350	uM
(1S,2S)-1-N,1-N-dimethyl-2-N-(3-methyl-[1,2,4]triazolo[3,4-a]phthalazin-6-yl)-1-phenylpropane-1,2-diamine	1554033: Inhibition of biotinylated peptide binding to human GST-tagged PCAF bromodomain expressed in Escherichia coli Rosetta (DE3) measured after 15 hrs by HTRF assay	ic50	0.0360	uM
3-methyl-2-[[(3R,5R)-1-methyl-5-phenylpiperidin-3-yl]amino]-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554033: Inhibition of biotinylated peptide binding to human GST-tagged PCAF bromodomain expressed in Escherichia coli Rosetta (DE3) measured after 15 hrs by HTRF assay	ic50	0.0410	uM
3-methyl-2-[[(3R,5R)-1-methyl-5-naphthalen-2-ylpiperidin-3-yl]amino]-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554033: Inhibition of biotinylated peptide binding to human GST-tagged PCAF bromodomain expressed in Escherichia coli Rosetta (DE3) measured after 15 hrs by HTRF assay	ic50	0.0470	uM
6-[[(1S,2S)-1-[4-(benzenesulfonyl)phenyl]-1-(dimethylamino)propan-2-yl]amino]-2,4-dimethyl-1,2,4-triazine-3,5-dione	1376095: Displacement of biotinylated small molecule ligand from His/FLAG-tagged PCAF bromodomain (719 to 832 residues) (unknown origin) after 15 mins by AlphaLisa method	ic50	0.0700	uM
3-methyl-2-[[(1S,5R)-9-methyl-9-azabicyclo[3.3.1]nonan-3-yl]amino]-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554033: Inhibition of biotinylated peptide binding to human GST-tagged PCAF bromodomain expressed in Escherichia coli Rosetta (DE3) measured after 15 hrs by HTRF assay	ic50	0.0730	uM
4-chloro-2-methyl-5-[[(3R,5R)-1-methyl-5-phenylpiperidin-3-yl]amino]pyridazin-3-one	1436228: Displacement of GSK3103956A from FLAG-6 His-Halo tagged human PCAF bromodomain (715 to 831 residues) incubated for 30 mins in dark by TR-FRET assay	ic50	0.0794	uM
2-[[(1S,5R)-9-azabicyclo[3.3.1]nonan-3-yl]amino]-3-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554033: Inhibition of biotinylated peptide binding to human GST-tagged PCAF bromodomain expressed in Escherichia coli Rosetta (DE3) measured after 15 hrs by HTRF assay	ic50	0.1250	uM
3-methyl-2-[[(3R,5R)-5-phenyl-1-prop-2-enylpiperidin-3-yl]amino]-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554031: Binding affinity to human N-terminal His-tagged PCAF by isothermal titration calorimetry	kd	0.2330	uM
4-chloro-2-methyl-5-[(2-methyl-3,4-dihydro-1H-isoquinolin-5-yl)amino]pyridazin-3-one	1436228: Displacement of GSK3103956A from FLAG-6 His-Halo tagged human PCAF bromodomain (715 to 831 residues) incubated for 30 mins in dark by TR-FRET assay	ic50	0.3000	uM
(2S)-2-[[(2R)-5-amino-2-[[(2R)-6-amino-2-[[(2R)-2-[[(2R)-1-[(2S)-2-[[(2R)-2-[[2-[[2-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-5-amino-1-[[(2S)-6-amino-1-[[(2S,3S)-1-[[(2S)-5-carbamimidamido-1-[[(2S)-1-(methylamino)-1-oxopropan-2-yl]amino]-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]carbamoylamino]-6-[[2-[2-[3-[[(2S)-4-[[[(2S,3R,4S,5S)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-2-hydroxy-3,3-dimethylbutanoyl]amino]propanoylamino]ethylsulfanyl]acetyl]amino]hexanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoic acid	1282364: Inhibition of full length recombinant human FLAG-tagged PCAF expressed in baculovirus expression system using histone substrate incubated for 10 mins by radiometric gel assay	ic50	0.3000	uM
2-[4-[4-(aminomethyl)anilino]-5-chloro-6-oxopyridazin-1-yl]acetonitrile	1769024: Binding affinity to PCAF (unknown origin) by BROMOscan method	kd	0.3000	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[2-[[2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-acetamidopropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]amino]-6-aminohexanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-6-aminohexanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]acetyl]amino]-6-[[2-[2-[3-[[(2R)-4-[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-2-hydroxy-3,3-dimethylbutanoyl]amino]propanoylamino]ethylsulfanyl]acetyl]amino]hexanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-6-aminohexanoyl]amino]-5-amino-5-oxopentanoyl]amino]-4-methylpentanoic acid	1422592: Inhibition of recombinant FLAG-tagged human PCAF expressed in Baculovirus expression system using histone peptide as substrate after 10 mins in presence of [14C]-acetyl CoA by phosphorimaging analysis	ic50	0.3000	uM
3-methyl-2-[[(4R,6R)-1-methyl-6-phenylazepan-4-yl]amino]-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554031: Binding affinity to human N-terminal His-tagged PCAF by isothermal titration calorimetry	kd	0.3470	uM
4-chloro-5-[4-[3-(dimethylamino)propyl]anilino]-2-methylpyridazin-3-one	1769024: Binding affinity to PCAF (unknown origin) by BROMOscan method	kd	0.3700	uM
4-chloro-2-methyl-5-[[(3R)-1-methylpiperidin-3-yl]amino]pyridazin-3-one	1436228: Displacement of GSK3103956A from FLAG-6 His-Halo tagged human PCAF bromodomain (715 to 831 residues) incubated for 30 mins in dark by TR-FRET assay	ic50	0.5012	uM
2-[[(3R,5R)-1-(2-hydroxyethyl)-5-phenylpiperidin-3-yl]amino]-3-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554031: Binding affinity to human N-terminal His-tagged PCAF by isothermal titration calorimetry	kd	0.5350	uM
3-ethyl-2-[[(3R,5R)-1-methyl-5-phenylpiperidin-3-yl]amino]-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554031: Binding affinity to human N-terminal His-tagged PCAF by isothermal titration calorimetry	kd	0.6210	uM
2-[[(3R,5R)-1-methyl-5-phenylpiperidin-3-yl]amino]-3-prop-2-enyl-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554031: Binding affinity to human N-terminal His-tagged PCAF by isothermal titration calorimetry	kd	0.6760	uM
2-(4-fluorophenyl)-[1,2]thiazolo[5,4-b]pyridin-3-one	602816: Inhibition of histone acetylase activity of human recombinant PCAF expressed in Escherichia coli using biotinylated oligopeptide sequences from histone H4 (2-24) substrate by In-vitro time-resolved fluorescence immunosorbent acetyltransferase assay	ic50	0.7200	uM
3-methyl-2-[[(3R,5R)-1-methyl-5-phenylpiperidin-3-yl]amino]thieno[3,2-d]pyrimidin-4-one	1554031: Binding affinity to human N-terminal His-tagged PCAF by isothermal titration calorimetry	kd	0.8200	uM
2-(4-bromophenyl)-5-nitro-[1,2]thiazolo[5,4-b]pyridin-3-one	602816: Inhibition of histone acetylase activity of human recombinant PCAF expressed in Escherichia coli using biotinylated oligopeptide sequences from histone H4 (2-24) substrate by In-vitro time-resolved fluorescence immunosorbent acetyltransferase assay	ic50	0.8600	uM
N’-[[6-(3-aminopropylimino)-1-hydroxy-3-pyridinyl]methyl]propane-1,3-diamine	1436227: Displacement of biotinylated small molecule ligand from His/FLAG-tagged PCAF bromodomain (719 to 832 residues) (unknown origin) after 15 mins by AlphaLisa method	ic50	0.9000	uM
2-[[(1R,5S)-9-[(2R)-2-hydroxy-2-phenylethyl]-9-azabicyclo[3.3.1]nonan-3-yl]amino]-3-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554031: Binding affinity to human N-terminal His-tagged PCAF by isothermal titration calorimetry	kd	0.9350	uM
5-[2-(aminomethyl)anilino]-4-chloro-2-methylpyridazin-3-one	1436228: Displacement of GSK3103956A from FLAG-6 His-Halo tagged human PCAF bromodomain (715 to 831 residues) incubated for 30 mins in dark by TR-FRET assay	ic50	1.0000	uM
2-[[(1R,5S)-9-[(2S)-2-hydroxy-2-pyridin-2-ylethyl]-9-azabicyclo[3.3.1]nonan-3-yl]amino]-3-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554031: Binding affinity to human N-terminal His-tagged PCAF by isothermal titration calorimetry	kd	1.1900	uM
3-methyl-2-[[(3R,5R)-5-phenyl-1-(2-phenylethyl)piperidin-3-yl]amino]-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554031: Binding affinity to human N-terminal His-tagged PCAF by isothermal titration calorimetry	kd	1.2000	uM
4-chloro-2-methyl-5-[(1-methylpiperidin-3-yl)amino]pyridazin-3-one	1436228: Displacement of GSK3103956A from FLAG-6 His-Halo tagged human PCAF bromodomain (715 to 831 residues) incubated for 30 mins in dark by TR-FRET assay	ic50	1.2589	uM
2-pyridin-4-yl-1,2-thiazol-3-one	347655: Inhibition of GST-fused recombinant HAT PCAF expressed in Escherichia coli by filter assay	ic50	1.5000	uM
N’-(4-methyl-2-nitrophenyl)propane-1,3-diamine	1436227: Displacement of biotinylated small molecule ligand from His/FLAG-tagged PCAF bromodomain (719 to 832 residues) (unknown origin) after 15 mins by AlphaLisa method	ic50	1.6000	uM
[[(3S)-4-[[3-[2-[[1-[(5S)-5-[[2-[[2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamidopropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-6-aminohexanoyl]amino]-3-phosphonooxypropanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]acetyl]amino]-6-[[(2S)-1-[(2S)-2-[[(2S)-5-(diaminomethylideneamino)-1-[[(2S)-1,6-diamino-1-oxohexan-2-yl]amino]-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-6-oxohexyl]triazol-4-yl]methylsulfanyl]ethylamino]-3-oxopropyl]amino]-3-hydroxy-2,2-dimethyl-4-oxobutoxy]-hydroxyphosphoryl] [(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methyl hydrogen phosphate	1061976: Inhibition of PCAF (unknown origin) using histone H3 derived peptide as substrate after 20 mins by fluorescence assay	ic50	1.7000	uM
methyl 3-(5-chloro-3-oxo-1,2-thiazol-2-yl)propanoate	348157: Inhibition of human recombinant HAT PCAF	ic50	1.8000	uM
2-(4-methoxyphenyl)-5-nitro-[1,2]thiazolo[5,4-b]pyridin-3-one	602816: Inhibition of histone acetylase activity of human recombinant PCAF expressed in Escherichia coli using biotinylated oligopeptide sequences from histone H4 (2-24) substrate by In-vitro time-resolved fluorescence immunosorbent acetyltransferase assay	ic50	1.8300	uM
ethyl 3-(5-chloro-3-oxo-1,2-thiazol-2-yl)propanoate	348157: Inhibition of human recombinant HAT PCAF	ic50	2.0000	uM
ethyl N-[6-[3-(methanesulfonamido)-4-methylphenyl]-3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-yl]carbamate	1777008: Inhibition of PCAF (unknown origin) by fluorometric assay	ic50	2.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects cotreatment, decreases expression	8
trichostatin A	affects cotreatment, decreases expression, affects localization, affects binding, increases reaction (+1 more)	5
Resveratrol	increases expression, affects cotreatment, decreases expression, affects binding, affects reaction (+1 more)	3
Benzo(a)pyrene	decreases expression, increases expression	3
Estradiol	affects binding, affects reaction, increases reaction, affects cotreatment, increases expression (+1 more)	3
Ethinyl Estradiol	affects expression, decreases expression	3
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	3
Cyclosporine	decreases expression, decreases methylation	3
bisphenol A	affects expression, affects cotreatment, increases expression	2
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
perfluorooctane sulfonic acid	decreases expression	2
entinostat	decreases expression, affects cotreatment	2
(+)-JQ1 compound	increases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Doxorubicin	decreases expression, increases expression	2
Methotrexate	affects binding, increases reaction, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Tretinoin	decreases reaction, increases expression, increases reaction, affects binding, affects expression	2
Particulate Matter	increases expression, decreases expression, increases abundance, affects cotreatment	2
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
naringenin	affects cotreatment, increases expression	1
deoxynivalenol	increases expression, affects reaction	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
methylparaben	decreases expression	1
sulforaphane	increases expression	1

ChEMBL screening assays

217 unique, capped per target: 217 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3391510	Binding	Competitive inhibition of recombinant full-length human PCAF catalytic domain/GCN5 expressed in Escherichia coli BL21(DE3) using [14C]-acetyl CoA as substrate after 1 to 10 mins by double reciprocal plot analysis	Development of second generation epigenetic agents — Medchemcomm

Cellosaurus cell lines

9 cell lines: 8 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8J2	Abcam HCT 116 KAT2B KO	Cancer cell line	Male
CVCL_B8XW	Abcam MCF-7 KAT2B KO	Cancer cell line	Female
CVCL_B9LD	Abcam A-549 KAT2B KO	Cancer cell line	Male
CVCL_D7T1	Ubigene A-549 KAT2B KO	Cancer cell line	Male
CVCL_D8NT	Ubigene HCT 116 KAT2B KO	Cancer cell line	Male
CVCL_D9HU	Ubigene HEK293 KAT2B KO	Transformed cell line	Female
CVCL_E0FY	Ubigene HeLa KAT2B KO	Cancer cell line	Female
CVCL_ST89	HAP1 KAT2B (-) 1	Cancer cell line	Male
CVCL_ST90	HAP1 KAT2B (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03408405	PHASE4	WITHDRAWN	ACTHAR Gel for Drug REsistant Nephrotic Syndrome in Children
NCT01716442	PHASE2/PHASE3	UNKNOWN	Rituximab Trial for Pediatric Nephrotic Syndrome
NCT07003438	EARLY_PHASE1	NOT_YET_RECRUITING	Study on the Efficacy and Safety of Fecal Microbiota Transplantation in the Treatment of Steroid - Dependent /Steroid-resistant Nephrotic Syndrome in Children
NCT00883636	Not specified	TERMINATED	Cardiomyopathy in Steroid-resistant Nephrotic Syndrome: Impact of Focal Segmental Glomerulosclerosis
NCT01113385	Not specified	COMPLETED	Oral Galactose in Children With Steroid Resistant Nephrotic Syndrome
NCT03235128	Not specified	UNKNOWN	Clinical Significance of Assesment of Serum miRNA-30a in Childhood Nephrotic Syndrome
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases
NCT06162546	Not specified	RECRUITING	ARREST-NEPHROSIS - Austrian Resistant Nephrotic Syndrome Treatment Response Registry and Biobank
NCT06792448	Not specified	NOT_YET_RECRUITING	Biomarkers and Outcome Predictors of Pediatric Nephrotic Syndrome: A Genetic, Transcriptomic, and Secretome Multiomics Study