NFRKB

Summary

NFRKB (nuclear factor related to kappaB binding protein, HGNC:7802) is a protein-coding gene on chromosome 11q24.3, encoding Nuclear factor related to kappa-B-binding protein (Q6P4R8). Binds to the DNA consensus sequence 5’-GGGGAATCTCC-3’. It is a selective cancer dependency (DepMap: 42.2% of cell lines).

Enables protease binding activity. Involved in several processes, including chromatin remodeling; regulation of chromosome organization; and regulation of nucleobase-containing compound metabolic process. Located in Ino80 complex and nucleoplasm.

Source: NCBI Gene 4798 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 198 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 42.2% of screened cell lines
• MANE Select transcript: NM_001143835

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7802
Approved symbol	NFRKB
Name	nuclear factor related to kappaB binding protein
Location	11q24.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp547B2013, INO80G
Ensembl gene	ENSG00000170322
Ensembl biotype	protein_coding
OMIM	164013
Entrez	4798

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 15 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000446488, ENST00000524746, ENST00000524794, ENST00000526884, ENST00000526940, ENST00000529319, ENST00000530278, ENST00000531318, ENST00000531755, ENST00000532147, ENST00000532225, ENST00000682444, ENST00000875000, ENST00000875001, ENST00000875002, ENST00000936753, ENST00000947152

RefSeq mRNA: 2 — MANE Select: NM_001143835 NM_001143835, NM_006165

CCDS: CCDS44770, CCDS8483

Canonical transcript exons

ENST00000682444 — 27 exons

Exon	Start	End
ENSE00001128659	129864966	129865101
ENSE00001128663	129865877	129865983
ENSE00001128670	129869494	129870261
ENSE00001128678	129872884	129873096
ENSE00001128685	129873745	129874015
ENSE00001128694	129874113	129874333
ENSE00001128703	129874501	129874580
ENSE00001128712	129874793	129874916
ENSE00001128722	129875357	129875463
ENSE00001128729	129876721	129876895
ENSE00001128735	129877325	129877385
ENSE00001128743	129878309	129878355
ENSE00001128750	129878464	129878543
ENSE00001128758	129881443	129881508
ENSE00001128764	129881727	129881853
ENSE00001128769	129882086	129882194
ENSE00001128778	129882451	129882631
ENSE00001128786	129884070	129884143
ENSE00001128815	129888594	129888795
ENSE00001131018	129883122	129883206
ENSE00001653418	129884745	129884846
ENSE00002167977	129894359	129894438
ENSE00002195691	129863636	129864850
ENSE00002200091	129892715	129892870
ENSE00003522010	129886317	129886444
ENSE00003604033	129885435	129885609
ENSE00003917857	129895496	129895578

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 96.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.3250 / max 45.8352, expressed in 1730 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123143	6.3250	1730

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	96.23	gold quality
secondary oocyte	CL:0000655	93.46	gold quality
oocyte	CL:0000023	92.73	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.11	gold quality
endothelial cell	CL:0000115	88.75	gold quality
left lobe of thyroid gland	UBERON:0001120	88.67	gold quality
right uterine tube	UBERON:0001302	88.23	gold quality
thyroid gland	UBERON:0002046	88.23	gold quality
right lobe of thyroid gland	UBERON:0001119	88.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.91	gold quality
skin of leg	UBERON:0001511	87.15	gold quality
left ovary	UBERON:0002119	86.92	gold quality
ovary	UBERON:0000992	86.79	gold quality
testis	UBERON:0000473	86.78	gold quality
ventricular zone	UBERON:0003053	86.70	gold quality
tongue squamous epithelium	UBERON:0006919	86.66	silver quality
skin of abdomen	UBERON:0001416	86.63	gold quality
right testis	UBERON:0004534	86.40	gold quality
left testis	UBERON:0004533	86.36	gold quality
body of uterus	UBERON:0009853	86.35	gold quality
right ovary	UBERON:0002118	86.30	gold quality
vagina	UBERON:0000996	86.16	gold quality
adrenal tissue	UBERON:0018303	85.67	gold quality
gastrocnemius	UBERON:0001388	85.52	gold quality
body of pancreas	UBERON:0001150	85.51	gold quality
zone of skin	UBERON:0000014	85.33	gold quality
granulocyte	CL:0000094	85.30	gold quality
muscle of leg	UBERON:0001383	85.14	gold quality
mucosa of stomach	UBERON:0001199	84.92	gold quality
ectocervix	UBERON:0012249	84.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.48

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
JUN	Activation

miRNA regulators (miRDB)

28 targeting NFRKB, 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-4673	100.00	66.64	1490
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-1911-3P	99.15	66.17	528
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-4539	98.78	67.18	888
HSA-MIR-6882-3P	98.23	67.01	1119
HSA-MIR-4772-3P	98.04	65.60	1203
HSA-MIR-4468	98.01	66.85	1187
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-4638-3P	97.90	65.75	905
HSA-MIR-4308	97.56	67.13	1385
HSA-MIR-2278	97.30	66.19	1130
HSA-MIR-582-3P	96.69	67.38	1019

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 42.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 7)

• NFRKB may be involved in the disorders of transcriptional regulation commonly observed in minimal change nephrotic syndrome relapse. (PMID:22291976)
• The structure of a novel helical domain of NFRKB was determined to 2.18 A resolution. (PMID:22984442)
• Data show that DEUBAD domain in RPN13 (ADRM1) activates ubiquitin thioesterase L5 (UCH-L5), and the related DEUBAD domain in INO80G (NFRKB) inhibits UCH-L5. (PMID:25702870)
• LncRNA DRAIC inhibits proliferation and metastasis of gastric cancer cells through interfering with NFRKB deubiquitination mediated by UCHL5. (PMID:32351584)
• Nuclear Factor Related to KappaB Binding Protein (NFRKB) Is a Telomere-Associated Protein and Involved in Liver Cancer Development. (PMID:34591601)
• The biological function of metazoan-specific subunit nuclear factor related to kappaB binding protein of INO80 complex. (PMID:35093437)
• A large deletion in a non-coding regulatory region leads to NFKB1 haploinsufficiency in two adult siblings. (PMID:38423196)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nfrkb	ENSDARG00000091512
mus_musculus	Nfrkb	ENSMUSG00000042185
rattus_norvegicus	Nfrkb	ENSRNOG00000008278
drosophila_melanogaster	CG11970	FBGN0027503

Protein

Protein identifiers

Nuclear factor related to kappa-B-binding protein — Q6P4R8 (reviewed: Q6P4R8)

Alternative names: DNA-binding protein R kappa-B, INO80 complex subunit G

All UniProt accessions (7): Q6P4R8, E9PJE1, E9PJG2, E9PJU3, E9PM88, E9PQ59, E9PQB0

UniProt curated annotations — full annotation on UniProt →

Function. Binds to the DNA consensus sequence 5’-GGGGAATCTCC-3’. Putative regulatory component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. Modulates the deubiquitinase activity of UCHL5 in the INO80 complex.

Subunit / interactions. Component of the chromatin remodeling INO80 complex; specifically part of a complex module associated with the N-terminus of INO80. Interacts with UCHL5; NFRKB competes with ADRM1 for interaction with UCHL5.

Subcellular location. Nucleus.

Tissue specificity. Expressed in thymus, brain, testes, spleen and liver.

Domain organisation. NFRKB seems to be mostly disordered. The wing-helix like domain doesn’t bind DNA.

Similarity. Belongs to the NFRKB family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6P4R8-1	1	yes
Q6P4R8-2	2
Q6P4R8-3	3

RefSeq proteins (2): NP_001137307, NP_006156 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024867	NFRKB	Family
IPR025220	NFRKB_WH_1	Domain
IPR038106	NFRKB_winged_sf	Homologous_superfamily
IPR044867	DEUBAD_dom	Domain
IPR057748	NFRKB_WH_2	Domain

Pfam: PF14465, PF25793

UniProt features (50 total): helix 14, compositionally biased region 7, modified residue 6, region of interest 6, strand 5, cross-link 4, splice variant 3, sequence conflict 2, chain 1, domain 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
3U21	X-RAY DIFFRACTION	2.18
4WLP	X-RAY DIFFRACTION	3.1
4UF6	X-RAY DIFFRACTION	3.69
4UF5	X-RAY DIFFRACTION	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P4R8-F1	56.56	0.13

Functional residue map

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

Post-translational modifications (10): 228, 298, 351, 1022, 1237, 1291, 327, 469, 488, 488

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5689603	UCH proteinases
R-HSA-5696394	DNA Damage Recognition in GG-NER

MSigDB gene sets: 172 (showing top): MORF_RAGE, GOBP_CHROMOSOME_ORGANIZATION, FREAC2_01, MORF_ATRX, FRASOR_RESPONSE_TO_SERM_OR_FULVESTRANT_DN, GOBP_TELOMERE_ORGANIZATION, MODULE_308, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_REGULATION_OF_TELOMERE_MAINTENANCE, MORF_PPP5C, MORF_FANCG, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_DNA_STRAND_ELONGATION

GO Biological Process (17): telomere maintenance (GO:0000723), regulation of DNA replication (GO:0006275), DNA repair (GO:0006281), regulation of DNA repair (GO:0006282), DNA recombination (GO:0006310), chromatin remodeling (GO:0006338), regulation of chromosome organization (GO:0033044), positive regulation of DNA repair (GO:0045739), positive regulation of DNA-templated transcription (GO:0045893), regulation of embryonic development (GO:0045995), regulation of cell cycle (GO:0051726), regulation of DNA strand elongation (GO:0060382), positive regulation of telomere maintenance in response to DNA damage (GO:1904507), DNA damage response (GO:0006974), positive regulation of macromolecule metabolic process (GO:0010604), obsolete positive regulation of nucleobase-containing compound metabolic process (GO:0045935), regulation of DNA metabolic process (GO:0051052)

GO Molecular Function (3): protease binding (GO:0002020), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), Ino80 complex (GO:0031011)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Deubiquitination	1
Global Genome Nucleotide Excision Repair (GG-NER)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	4
regulation of DNA metabolic process	3
DNA repair	2
positive regulation of response to stimulus	2
regulation of macromolecule metabolic process	2
telomere organization	1
DNA replication	1
DNA damage response	1
regulation of cellular response to stress	1
chromatin organization	1
regulation of organelle organization	1
chromosome organization	1
regulation of DNA repair	1
positive regulation of DNA metabolic process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
embryo development	1
regulation of multicellular organismal development	1
cell cycle	1
regulation of cellular process	1
DNA strand elongation	1
positive regulation of telomere maintenance	1
telomere maintenance in response to DNA damage	1
regulation of telomere maintenance in response to DNA damage	1
cellular response to stress	1
positive regulation of metabolic process	1
macromolecule metabolic process	1
regulation of nucleobase-containing compound metabolic process	1
enzyme binding	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nuclear chromosome	1
INO80-type complex	1

Protein interactions and networks

STRING

1357 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NFRKB	UCHL5	Q9Y5K5	888
NFRKB	ACTR5	Q9H9F9	806
NFRKB	ACTR8	Q9H981	627
NFRKB	TFPT	P0C1Z6	617
NFRKB	RUVBL1	P82276	616
NFRKB	ADRM1	Q16186	603
NFRKB	ETS1	P14921	556
NFRKB	INO80E	Q8NBZ0	554
NFRKB	INO80	Q9ULG1	543
NFRKB	INO80B	Q9C086	507
NFRKB	MCRS1	Q96EZ8	496
NFRKB	CBL	P22681	490
NFRKB	RUVBL2	Q9Y230	477
NFRKB	NFKB2	Q00653	439
NFRKB	NFX1	Q12986	434

IntAct

130 interactions, top by confidence:

A	B	Type	Score
PSMC3	PSMD9	psi-mi:“MI:0914”(association)	0.940
INO80E	YY1	psi-mi:“MI:0914”(association)	0.900
UCHL5	NFRKB	psi-mi:“MI:0915”(physical association)	0.890
NFRKB	UCHL5	psi-mi:“MI:0915”(physical association)	0.890
NFRKB	UCHL5	psi-mi:“MI:0407”(direct interaction)	0.890
UCHL5	NFRKB	psi-mi:“MI:0407”(direct interaction)	0.890
UCHL5	NFRKB	psi-mi:“MI:0914”(association)	0.890
RUVBL1	ZNHIT1	psi-mi:“MI:0914”(association)	0.860
UCHL5	PSMD11	psi-mi:“MI:0914”(association)	0.840
PRPS1	PRPSAP2	psi-mi:“MI:0914”(association)	0.840
UCHL5	PSMD12	psi-mi:“MI:0914”(association)	0.840
YY1	ACTL6A	psi-mi:“MI:0914”(association)	0.830
CCNDBP1	RPLP0	psi-mi:“MI:0914”(association)	0.800
INO80E	TFPT	psi-mi:“MI:0914”(association)	0.790
YY1	TFPT	psi-mi:“MI:0914”(association)	0.740
INO80C	YY1	psi-mi:“MI:0914”(association)	0.740
INO80E	ACTL6A	psi-mi:“MI:0914”(association)	0.640
PSMC3	PSMD12	psi-mi:“MI:0914”(association)	0.640
RUVBL1	POLR3A	psi-mi:“MI:0914”(association)	0.640

BioGRID (210): UCHL5 (Two-hybrid), NFRKB (Affinity Capture-MS), NFRKB (Affinity Capture-MS), NFRKB (Affinity Capture-MS), NFRKB (Affinity Capture-MS), NFRKB (Affinity Capture-MS), NFRKB (Affinity Capture-MS), NFRKB (Affinity Capture-MS), NFRKB (Affinity Capture-MS), NFRKB (Affinity Capture-MS), NFRKB (Co-crystal Structure), NFRKB (Co-purification), UCHL5 (Affinity Capture-Western), INO80 (Affinity Capture-Western), ACTR5 (Co-fractionation)

ESM2 similar proteins: A0JME2, A2AUY4, D3ZKB9, D4A666, E1B7L7, F1QZ88, F6NSX9, F8VPJ6, P59759, P78364, Q08CM4, Q0IHV2, Q15723, Q2IBE6, Q2IBF7, Q2QLB3, Q3TUF7, Q4G0F8, Q5DTH5, Q5U4Q0, Q5ZIE8, Q5ZM88, Q63HK5, Q641Z1, Q6P4L9, Q6P4R8, Q6PIJ4, Q6ZPK0, Q6ZSZ6, Q6ZU65, Q76L83, Q7ZUK7, Q7ZUV7, Q80WC1, Q8AYC1, Q8BZ32, Q8C966, Q8CGV9, Q8CHP6, Q8NDX5

Diamond homologs: Q6P4L9, Q6P4R8, Q6PIJ4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NFRKB	“form complex”	“INO80 complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 136 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
Global Genome Nucleotide Excision Repair (GG-NER)	11	51.3×	1e-14
DNA Damage Recognition in GG-NER	12	35.0×	8e-14
Nucleotide Excision Repair	11	32.0×	3e-12
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	5	23.3×	2e-04
UCH proteinases	17	21.5×	1e-15
Deubiquitination	14	17.7×	4e-12
Degradation of DVL	5	12.1×	3e-03
SPOP-mediated proteasomal degradation of PD-L1(CD274)	5	11.7×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of telomere maintenance in response to DNA damage	13	119.7×	7e-24
regulation of DNA strand elongation	13	112.2×	2e-23
regulation of chromosome organization	13	99.8×	2e-22
positive regulation of DNA repair	14	41.1×	3e-17
regulation of DNA replication	13	39.0×	1e-15
regulation of embryonic development	13	35.2×	3e-15
regulation of DNA repair	14	31.7×	1e-15
DNA recombination	11	30.4×	4e-12

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	161
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4637 predictions. Top by Δscore:

Variant	Effect	Δscore
11:129865100:GG:G	acceptor_gain	1.0000
11:129865102:C:CC	acceptor_gain	1.0000
11:129865868:AGTAC:A	donor_gain	1.0000
11:129865869:GTACT:G	donor_gain	1.0000
11:129865870:TAC:T	donor_gain	1.0000
11:129865871:ACTT:A	donor_gain	1.0000
11:129865872:CTT:C	donor_loss	1.0000
11:129865872:CTTA:C	donor_gain	1.0000
11:129865872:CTTAC:C	donor_gain	1.0000
11:129865873:TT:T	donor_gain	1.0000
11:129865873:TTA:T	donor_loss	1.0000
11:129865874:TACTT:T	donor_gain	1.0000
11:129865875:A:AC	donor_gain	1.0000
11:129865875:A:T	donor_gain	1.0000
11:129865876:C:CA	donor_gain	1.0000
11:129865876:CT:C	donor_gain	1.0000
11:129865876:CTT:C	donor_gain	1.0000
11:129865876:CTTG:C	donor_gain	1.0000
11:129865876:CTTGG:C	donor_gain	1.0000
11:129865979:TTCCC:T	acceptor_gain	1.0000
11:129865980:TCCC:T	acceptor_gain	1.0000
11:129865981:CCC:C	acceptor_gain	1.0000
11:129865981:CCCC:C	acceptor_gain	1.0000
11:129865982:CC:C	acceptor_gain	1.0000
11:129865982:CCC:C	acceptor_gain	1.0000
11:129865982:CCCTA:C	acceptor_loss	1.0000
11:129865983:CC:C	acceptor_gain	1.0000
11:129865984:C:CC	acceptor_gain	1.0000
11:129865984:C:T	acceptor_gain	1.0000
11:129865984:CT:C	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000011855 (11:129875197 G>A), RS1000055902 (11:129893235 T>G), RS1000329764 (11:129867328 T>C), RS1000408087 (11:129885304 T>C), RS1000461984 (11:129885586 C>G), RS1000521748 (11:129886775 T>A), RS1000532338 (11:129897525 C>A,T), RS1000545245 (11:129897169 G>A), RS1000636191 (11:129880012 C>A,T), RS1000747377 (11:129875861 T>G), RS1000881710 (11:129870531 A>G), RS1000979652 (11:129889437 G>A,T), RS1001140220 (11:129876204 A>C), RS1001244413 (11:129881158 T>C), RS1001253662 (11:129894452 T>A,C)

Disease associations

OMIM: gene MIM:164013 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003542_66	Night sleep phenotypes	1.000000e-06
GCST90002385_219	High light scatter reticulocyte count	3.000000e-10
GCST90002405_297	Reticulocyte count	1.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007827	nighttime rest measurement
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725193 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (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
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.18	Kd	66	nM	MOLIBRESIB
7.00	IC50	100	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 7 total; 1 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179221: Binding affinity against NFRKB (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0660	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
entinostat	decreases expression, affects cotreatment	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Valproic Acid	affects expression, decreases methylation	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
quercitrin	increases expression	1
sodium arsenite	increases expression, affects cotreatment, increases abundance	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
4-hydroxy-2-nonenal	decreases expression	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	affects phosphorylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Hydrogen Peroxide	decreases expression	1
Lead	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methapyrilene	increases methylation	1
Ozone	decreases expression, increases abundance	1
Phthalic Acids	decreases methylation	1
Smoke	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697599	Binding	Inhibition of NFRKB (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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