PI4KB

Summary

PI4KB (phosphatidylinositol 4-kinase beta, HGNC:8984) is a protein-coding gene on chromosome 1q21.3, encoding Phosphatidylinositol 4-kinase beta (Q9UBF8). Phosphorylates phosphatidylinositol (PI) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate (PIP). It is a selective cancer dependency (DepMap: 23.3% of cell lines).

Enables 1-phosphatidylinositol 4-kinase activity and 14-3-3 protein binding activity. Involved in inner ear development. Acts upstream of or within lysosome organization. Located in Golgi membrane. Implicated in autosomal dominant nonsyndromic deafness 87.

Source: NCBI Gene 5298 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hearing loss, autosomal dominant 87 (Limited, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 99 total — 4 pathogenic
• Phenotypes (HPO): 5
• Druggable target: yes — 20 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 23.3% of screened cell lines
• MANE Select transcript: NM_001369623

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8984
Approved symbol	PI4KB
Name	phosphatidylinositol 4-kinase beta
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	PI4K-BETA, pi4K92
Ensembl gene	ENSG00000143393
Ensembl biotype	protein_coding
OMIM	602758
Entrez	5298

Gene structure

Transcript identifiers

Ensembl transcripts: 49 — 47 protein_coding, 2 retained_intron

ENST00000368872, ENST00000368873, ENST00000368874, ENST00000368875, ENST00000430800, ENST00000438243, ENST00000446339, ENST00000455060, ENST00000460323, ENST00000469239, ENST00000489223, ENST00000489889, ENST00000529142, ENST00000852743, ENST00000852744, ENST00000852745, ENST00000852746, ENST00000852747, ENST00000852748, ENST00000852749, ENST00000852750, ENST00000852751, ENST00000852752, ENST00000852753, ENST00000852754, ENST00000852755, ENST00000852756, ENST00000852757, ENST00000852758, ENST00000852759, ENST00000852760, ENST00000852761, ENST00000852762, ENST00000852763, ENST00000852764, ENST00000852765, ENST00000933551, ENST00000933552, ENST00000933553, ENST00000933554, ENST00000933555, ENST00000933556, ENST00000933557, ENST00000933558, ENST00000933559, ENST00000943240, ENST00000943241, ENST00000943242, ENST00000943243

RefSeq mRNA: 11 — MANE Select: NM_001369623 NM_001198773, NM_001198774, NM_001198775, NM_001330721, NM_001369623, NM_001369624, NM_001369625, NM_001369626, NM_001369628, NM_001369629, NM_002651

CCDS: CCDS55637, CCDS55638, CCDS81376, CCDS993

Canonical transcript exons

ENST00000368873 — 12 exons

Exon	Start	End
ENSE00000959789	151294409	151294541
ENSE00000959790	151294018	151294138
ENSE00001448172	151291804	151293033
ENSE00001668188	151302194	151302298
ENSE00001687893	151306136	151306363
ENSE00001690709	151327271	151327416
ENSE00001696456	151298808	151299073
ENSE00001705050	151301844	151301967
ENSE00001756379	151310211	151310255
ENSE00001791799	151303541	151303650
ENSE00003463601	151315573	151316509
ENSE00003521777	151307574	151307801

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 97.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.2016 / max 124.1563, expressed in 1815 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14424	19.2131	1806
14427	10.1016	1786
14428	3.5831	1498
14426	0.2419	71
14425	0.0619	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	97.57	gold quality
tibial nerve	UBERON:0001323	97.50	gold quality
left lobe of thyroid gland	UBERON:0001120	97.46	gold quality
right uterine tube	UBERON:0001302	97.46	gold quality
body of uterus	UBERON:0009853	97.13	gold quality
thyroid gland	UBERON:0002046	97.06	gold quality
secondary oocyte	CL:0000655	97.03	gold quality
endocervix	UBERON:0000458	97.01	gold quality
right ovary	UBERON:0002118	96.71	gold quality
left ovary	UBERON:0002119	96.69	gold quality
ectocervix	UBERON:0012249	96.68	gold quality
adenohypophysis	UBERON:0002196	96.63	gold quality
left uterine tube	UBERON:0001303	96.57	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.57	gold quality
stromal cell of endometrium	CL:0002255	96.54	gold quality
pituitary gland	UBERON:0000007	96.37	gold quality
cerebellar hemisphere	UBERON:0002245	96.34	gold quality
cerebellar cortex	UBERON:0002129	96.27	gold quality
skin of leg	UBERON:0001511	96.23	gold quality
skin of abdomen	UBERON:0001416	96.09	gold quality
mucosa of stomach	UBERON:0001199	96.08	gold quality
lower esophagus mucosa	UBERON:0035834	96.07	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.99	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.97	gold quality
spleen	UBERON:0002106	95.94	gold quality
body of stomach	UBERON:0001161	95.88	gold quality
metanephros cortex	UBERON:0010533	95.83	gold quality
minor salivary gland	UBERON:0001830	95.79	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.77	gold quality
right coronary artery	UBERON:0001625	95.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

72 targeting PI4KB, 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-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-4650-5P	99.98	64.69	999
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-6883-5P	99.69	68.05	3785

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 23.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Characterization of type II phosphatidylinositol 4-kinase isoforms reveals association of the enzymes with endosomal vesicular compartments (PMID:11923287)
• determination that the enzyme is primarily cytosolic, and it associates peripherally with plasma membranes, endoplasmic reticulum, and the Golgi (PMID:12324459)
• PI4KIIIbeta (PIK4CB) and PI4KIIalpha (PIK4CA) localize to discrete subcompartments of the Golgi complex in Madin-Darby canine kidney (MDCK) cells. (PMID:15634669)
• PI 4-kinase beta is a key enzyme in the control of spingomyelin synthesis by controlling the flow of ceramide from the ER to the Golgi compartment (PMID:17003043)
• there is a physical and functional relationship between eEF1A2 and PI4KIIIbeta (PMID:17088255)
• PI4KIIalpha or PI4KIIbeta knockdown, but not type III PI4Kbeta knockdown, inhibits Listeria internalization. (PMID:17555516)
• Work suggests an important role for both eEF1A2 and PI4KIIIbeta in the control of PI(4,5)P(2) signaling and actin remodeling. (PMID:18474610)
• genetic or pharmacological modulation of PI4KA and PI4KB inhibits multiple genotypes of HCV (PMID:19605471)
• our library screening completed data on the clathrin-mediated endocytosis-dependant entry route of HCV and identified 2 kinases, PI4KIIIalpha and beta, as relevant potential therapeutic targets. (PMID:19608626)
• Knockdown of PI4KIIalpha does not inhibit EGF-stimulated Akt phosphorylation. (PMID:21218173)
• Study identify the molecular chaperone Hsp90 as a binding partner of PI4KIIbeta, but not of PI4KIIalpha. (PMID:21330372)
• Our data establish PtdIns(4,5)P(2) as a direct activator of TRPV6 and demonstrate that intracellular ATP regulates the channel indirectly as a substrate for type III PI4Ks (PMID:21810903)
• The PI4KIIIbeta likely plays an important role in mammary neoplasia and acinar development. (PMID:21851817)
• results indicate that a viral protein/ACBD3/PI4KB complex is formed to synthesize PI4P at the AiV RNA replication sites and plays an essential role in viral RNA replication (PMID:22124328)
• Phosphatidylinositol 4-kinase IIIbeta is required for severe acute respiratory syndrome coronavirus spike-mediated cell entry. (PMID:22253445)
• The 3A protein of picornaviruses utilizes the golgi adaptor protein ACBD3 to recruit PI4KIIIbeta. (PMID:22258260)
• During authentic HCV infection, PI4P plays an integral role in virus replication; the vesicular transport proteins ARF1 and GBF1 colocalized with PI4KIIIbeta and were both required for HCV replication. (PMID:22359663)
• The lipid kinase PI4KIIIbeta preserves lysosomal identity. (PMID:23258225)
• These results suggest that poliovirus proteins modulate PI4KB activity and provide PI4P for recruitment of OSBP to accumulate unesterified cholesterol on virus-induced membrane structure for formation of a virus replication complex. (PMID:24527995)
• Host ACBD3, PI4KIIIBETA and Aichi virus proteins complexes enhances phosphatidylinositol 4-phosphate synthesis and is critical for viral replication. (PMID:24672044)
• Authors found that NS5A and PI4KB competed for association of acyl-coenzyme A binding domain containing protein 3 (ACBD3), which inhibited hepatitis C virus replication. (PMID:24792752)
• these data provide a mechanism for how PI4KIIIbeta coordinates Rab11 and its effectors on PI4P-enriched membranes and also provide strategies for the design of specific inhibitors that could potentially target plasmodial PI4KIIIbeta to combat malaria. (PMID:24876499)
• PI4KIIIbeta likely plays a role in breast oncogenesis and that cooperation between Rab11a and PI4KIIIbeta represents a novel Akt activation pathway. (PMID:24962317)
• Although human rhinovirus 3A protein was previously shown to interact with ACBD3, these data suggest that PI4KIIIbeta recruitment occurred independently of both GBF1 and ACBD3. (PMID:25410869)
• Analysis reveals novel aspects of the PI4KIIIb-Rab11 complex and determines binding and catalytic sites of the kinase. (PMID:26756197)
• Data show that ACBD3 can recruit PI4KB to model membranes as well as redirect PI4KB to cellular membranes where it is not naturally found. Also, results show that ACBD3 regulates the enzymatic activity of PI4KB kinase through membrane recruitment rather than allostery. (PMID:27009356)
• The results showed that, in contrast to the enteroviruses and the cardioviruses, foot-and-mouth disease virus replication does not require PI4KIII (PI4KIIIalpha and PI4KIIIbeta), and phosphatidylinositol 4-phosphate levels do not increase in foot-and-mouth disease virus-infected cells and phosphatidylinositol 4-phosphate is not seen at replication organelles. (PMID:27093462)
• esults show that Aichi virus 3A protein activates the lipid kinase activity of PI4KIIIb,which activation is sensitized by the protein ACBD3. The interfaces between PI4KIIIbeta-ACBD3 and ACBD3-3A were mapped with hydrogen-deuterium exchange mass spectrometry. (PMID:27989622)
• PI4KIIIbeta interaction with the VHS domain of GGA2 affected PI4KIIIbeta localization. (PMID:28289207)
• several disordered regions of PI4KB become protected from proteolytical degradation upon 14-3-3 binding. (PMID:28864297)
• These results suggest that PtdIns 4-kinase II beta may be a novel regulator of Par-4 through protein-protein interactions. (PMID:30606737)
• In vitro reconstitution revealed that the membrane is necessary for the formation of ACBD3:PI4KB:Rab11 protein complex at physiological (nanomolar) concentrations. (PMID:30679637)
• Altogether, these data provide new insight into the central role of ACBD3 in recruiting PI4KB by enterovirus 3A and reveal the minimal domains of ACBD3 involved in recruiting PI4KB and supporting enterovirus replication. (PMID:30755512)
• Two variant prioritization pipelines based on AR inheritance and runs of homozygosity (ROH), identified two novel homozygous variants in KCNJ10 and PI4KB and five rare homozygous variants in PVRL4, RORC, FLG2, FCRL1, NIT1 and one common homozygous variant in HSPA6 segregating in all four patients (PMID:31640787)
• PI4KB on Inclusion Bodies Formed by ER Membrane Remodeling Facilitates Replication of Human Parainfluenza Virus Type 3. (PMID:31747597)
• Phosphatidylinositol 4-kinase III beta regulates cell shape, migration, and focal adhesion number. (PMID:32583740)
• Phosphatidylinositol 4-kinase IIIbeta mediates contraction-induced GLUT4 translocation and shows its anti-diabetic action in cardiomyocytes. (PMID:33090289)
• Phosphatidylinositol 4-kinase beta mutations cause nonsyndromic sensorineural deafness and inner ear malformation. (PMID:33358777)
• circSLC6A6 Sponges miR-497-5p to Promote Endometrial Cancer Progression via the PI4KB/Hedgehog Axis. (PMID:34258297)
• The C10orf76-PI4KB axis orchestrates CERT-mediated ceramide trafficking to the distal Golgi. (PMID:37195633)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pi4kb	ENSDARG00000040111
mus_musculus	Pi4kb	ENSMUSG00000038861
rattus_norvegicus	Pi4kb	ENSRNOG00000021024
drosophila_melanogaster	fwd	FBGN0004373
caenorhabditis_elegans		WBGENE00018076

Paralogs (9): PIK3C2A (ENSG00000011405), PIK3CB (ENSG00000051382), PIK3C3 (ENSG00000078142), PIK3CG (ENSG00000105851), PIK3CA (ENSG00000121879), PIK3C2B (ENSG00000133056), PIK3C2G (ENSG00000139144), PIK3CD (ENSG00000171608), PI4KA (ENSG00000241973)

Protein

Protein identifiers

Phosphatidylinositol 4-kinase beta — Q9UBF8 (reviewed: Q9UBF8)

Alternative names: NPIK, PI4K92, PI4KIII

All UniProt accessions (8): Q9UBF8, A0A0A0MSL0, A0A0B4J1S8, A6PVV8, E9PL47, F8W860, H0Y4F8, H0YCW3

UniProt curated annotations — full annotation on UniProt →

Function. Phosphorylates phosphatidylinositol (PI) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate (PIP). May regulate Golgi disintegration/reorganization during mitosis, possibly via its phosphorylation. Involved in Golgi-to-plasma membrane trafficking. May play an important role in the inner ear development. (Microbial infection) Plays an essential role in Aichi virus RNA replication. Recruited by ACBD3 at the viral replication sites. (Microbial infection) Required for cellular spike-mediated entry of human coronavirus SARS-CoV.

Subunit / interactions. Interacts with ARF1 and ARF3 in the Golgi complex, but not with ARF4, ARF5 or ARF6. Interacts with NCS1/FREQ in a calcium-independent manner. Interacts with CALN1/CABP8 and CALN2/CABP7; in a calcium-dependent manner; this interaction competes with NCS1/FREQ binding. Interacts with ACBD3. Interacts with ARMH3, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ and SFN. Interacts with GGA2 (via VHS domain); the interaction is important for PI4KB location at the Golgi apparatus membrane. Interacts with ATG9A. (Microbial infection) Interacts with Aichi virus protein 3A. Part of a complex Aichi virus protein 3A/ACBD3/PI4KB that allows the synthesis of PI4P at the viral RNA replication sites.

Subcellular location. Endomembrane system. Mitochondrion outer membrane. Rough endoplasmic reticulum membrane. Golgi apparatus. Golgi apparatus membrane. Cytoplasm. Perinuclear region.

Tissue specificity. Widely expressed with highest levels in heart, skeletal muscle, pancreas, testis and ovary. Weakly expressed in liver. Expressed in the innear ear in the epithelium of the spinal organ of corti.

Disease relevance. Deafness, autosomal dominant, 87 (DFNA87) [MIM:620281] A form of non-syndromic, sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA87 is characterized by prelingual, profound sensorineural hearing loss with inner ear anomalies, including cochlear maldevelopment, absence of the osseous spiral lamina, and/or an enlarged vestibular aqueduct. The disease may be caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by wortmannin and adenosine. Increased kinase activity upon interaction with NCS1/FREQ. (Microbial infection) Activated by Aichi virus protein 3A, this activation is sensitized by ACBD3.

Similarity. Belongs to the PI3/PI4-kinase family. Type III PI4K subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UBF8-1	1, NPIK-B	yes
Q9UBF8-2	2, NPIK-C
Q9UBF8-3	3

RefSeq proteins (11): NP_001185702, NP_001185703, NP_001185704, NP_001317650, NP_001356552, NP_001356553, NP_001356554, NP_001356555, NP_001356557, NP_001356558, NP_002642 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000403	PI3/4_kinase_cat_dom	Domain
IPR001263	PI3K_accessory_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR015433	PI3/4_kinase	Family
IPR018936	PI3/4_kinase_CS	Conserved_site
IPR036940	PI3/4_kinase_cat_sf	Homologous_superfamily
IPR049160	PI4KB-PIK1_PIK	Domain
IPR057754	PI4-kinase_beta/PIK1_cat	Domain

Pfam: PF00454, PF21245

Enzyme classification (BRENDA):

• EC 2.7.1.67 — 1-phosphatidylinositol 4-kinase (BRENDA: 26 organisms, 60 substrates, 371 inhibitors, 71 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.018–1.7	43
PHOSPHATIDYLINOSITOL	0.017–1	18
1-PHOSPHATIDYL-1D-MYO-INOSITOL	0.016–0.1	2
GTP	0.62	1

Catalyzed reactions (Rhea), 1 shown:

• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate) + ADP + H(+) (RHEA:19877)

UniProt features (102 total): helix 29, strand 16, modified residue 14, mutagenesis site 14, region of interest 7, sequence conflict 7, sequence variant 4, turn 3, compositionally biased region 2, domain 2, splice variant 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

20 structures.

PDB	Method	Resolution (Å)
8Q6F	X-RAY DIFFRACTION	1.51
8Q6G	X-RAY DIFFRACTION	1.54
8Q6H	X-RAY DIFFRACTION	1.94
5NAS	X-RAY DIFFRACTION	2.08
5LX2	X-RAY DIFFRACTION	2.58
5C46	X-RAY DIFFRACTION	2.65
6GL3	X-RAY DIFFRACTION	2.77
4D0L	X-RAY DIFFRACTION	2.94
8VOF	X-RAY DIFFRACTION	3
5C4G	X-RAY DIFFRACTION	3.2
5EUQ	X-RAY DIFFRACTION	3.2
5FBR	X-RAY DIFFRACTION	3.28
5FBV	X-RAY DIFFRACTION	3.29
4WAE	X-RAY DIFFRACTION	3.32
5FBL	X-RAY DIFFRACTION	3.37
4WAG	X-RAY DIFFRACTION	3.41
5FBW	X-RAY DIFFRACTION	3.49
5FBQ	X-RAY DIFFRACTION	3.79
4D0M	X-RAY DIFFRACTION	6
2N73	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBF8-F1	72.97	0.48

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 (14): 294, 2, 258, 263, 266, 275, 277, 284, 294, 428, 438, 511, 517, 519

Mutagenesis-validated functional residues (14):

Position	Phenotype
40–42	small decrease in armh3-binding. no effect on acbd3-, nor rab11b-binding.
42	no loss of interaction with acbd3.
43–45	drastically decreased acbd3-binding. no effect on armh3-, nor rab11b-binding.
43	loss of interaction with acbd3.
44	loss of interaction with acbd3.
46–47	no effect on acbd3-, armh3-, nor rab11b-binding.
47	no loss of interaction with acbd3.
49–50	no effect on acbd3-, armh3-, nor rab11b-binding.
52	no effect on acbd3-, armh3-, nor rab11b-binding.
53–54	drastically decreased armh3- and rab11b-binding. 6-fold increase in acbd3-binding.
55–56	drastically decreased acbd3-binding. no effect on armh3-, nor rab11b-binding.
55	loss of interaction with acbd3.
56	loss of interaction with acbd3.
57–59	no effect on acbd3-, armh3-, nor rab11b-binding.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1660514	Synthesis of PIPs at the Golgi membrane

MSigDB gene sets: 200 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, YAGI_AML_WITH_INV_16_TRANSLOCATION, GU_PDEF_TARGETS_DN, GOBP_VACUOLE_ORGANIZATION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, TGCACTT_MIR519C_MIR519B_MIR519A, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT, CAGCTG_AP4_Q5, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, SP1_Q2_01, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS

GO Biological Process (8): phosphatidylinositol biosynthetic process (GO:0006661), receptor-mediated endocytosis (GO:0006898), lysosome organization (GO:0007040), signal transduction (GO:0007165), phosphatidylinositol phosphate biosynthetic process (GO:0046854), phosphatidylinositol-mediated signaling (GO:0048015), inner ear development (GO:0048839), lipid metabolic process (GO:0006629)

GO Molecular Function (7): 1-phosphatidylinositol 4-kinase activity (GO:0004430), ATP binding (GO:0005524), 14-3-3 protein binding (GO:0071889), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (12): Golgi membrane (GO:0000139), cytoplasm (GO:0005737), mitochondrial outer membrane (GO:0005741), endosome (GO:0005768), Golgi apparatus (GO:0005794), cytosol (GO:0005829), membrane (GO:0016020), rough endoplasmic reticulum membrane (GO:0030867), perinuclear region of cytoplasm (GO:0048471), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), endomembrane system (GO:0012505)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
PI Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	5
endomembrane system	3
intracellular membrane-bounded organelle	3
bounding membrane of organelle	2
biosynthetic process	1
phosphatidylinositol metabolic process	1
endocytosis	1
lytic vacuole organization	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
glycerophospholipid biosynthetic process	1
intracellular signal transduction	1
ear development	1
anatomical structure development	1
primary metabolic process	1
phosphatidylinositol kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
Golgi apparatus	1
intracellular anatomical structure	1
mitochondrial membrane	1
organelle outer membrane	1
cytoplasmic vesicle	1
endoplasmic reticulum membrane	1
rough endoplasmic reticulum	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

73 interactions, top by confidence:

A	B	Type	Score
PI4KB	YWHAQ	psi-mi:“MI:0915”(physical association)	0.900
PI4KB	YWHAQ	psi-mi:“MI:0914”(association)	0.900
PI4KB	YWHAB	psi-mi:“MI:0915”(physical association)	0.860
PI4KB	YWHAG	psi-mi:“MI:0915”(physical association)	0.860
YWHAQ	WDR62	psi-mi:“MI:0914”(association)	0.830
YWHAB	WDR62	psi-mi:“MI:0914”(association)	0.770
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
RAB11B	SH3BP5	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
	ACBD3	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
PI4KB	ACBD3	psi-mi:“MI:0915”(physical association)	0.540
ACBD3	PI4KB	psi-mi:“MI:0403”(colocalization)	0.540
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
NS	PI4KB	psi-mi:“MI:0915”(physical association)	0.510
PI4KB	NS	psi-mi:“MI:0915”(physical association)	0.510
	GBF1	psi-mi:“MI:0914”(association)	0.500
PI4KB		psi-mi:“MI:0915”(physical association)	0.500

BioGRID (100): PI4KB (Affinity Capture-MS), PI4KB (Affinity Capture-MS), PI4KB (Affinity Capture-MS), PI4KB (Affinity Capture-MS), UTRN (Affinity Capture-MS), PI4KB (Synthetic Lethality), PI4KB (Affinity Capture-Western), PI4KB (Affinity Capture-MS), PI4KB (Affinity Capture-MS), PI4KB (Affinity Capture-MS), PI4KB (Affinity Capture-MS), PI4KB (Affinity Capture-MS), PI4KB (Affinity Capture-MS), PI4KB (Affinity Capture-MS), PI4KB (Affinity Capture-MS)

ESM2 similar proteins: A2AHJ4, A4IID4, A9JRL3, A9X1A0, B0KWC1, B1MTG7, B2KI64, B2RQE8, B3EX61, B4UT09, G5EBH0, O00418, O00763, O02697, O02810, O08561, O08796, O08874, P25455, P48736, P70531, Q07139, Q28C33, Q49GP3, Q4U2V3, Q5R585, Q641K1, Q6DD21, Q6F6B3, Q6GN16, Q6NRE7, Q6PCL9, Q80X66, Q86X55, Q8BKC8, Q8BPM2, Q8CI95, Q8IVH8, Q924I2, Q99JP0

Diamond homologs: A4IID4, A4QPH2, A9X1A0, B0KWC1, B1MTG7, B2KI64, B3EX61, B4UT09, E9Q3L2, G5EDY0, O02697, O02810, O02811, O08561, O08662, O14356, O70167, O70173, O75747, P0CP60, P0CP61, P37297, P39104, P42338, P42347, P42348, P42356, P48736, P50520, P54677, Q0WPX9, Q10366, Q49GP3, Q6GN16, Q8BKC8, Q8BTI9, Q8SQY7, Q9C680, Q9FMJ0, Q9JHG7

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
PRKD1	up-regulates	PI4KB	phosphorylation
PRKD2	up-regulates	PI4KB	phosphorylation
STK38	“up-regulates activity”	PI4KB	phosphorylation
NCS1	“up-regulates activity”	PI4KB
PI4KB	“up-regulates quantity”	“phosphatidylinositol 4-phosphate”	“chemical modification”
PI4KB	up-regulates	“Receptor_mediated_ endocytosis”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 50 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 BAD and translocation to mitochondria	7	161.5×	8e-13
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	142.5×	1e-12
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	142.5×	1e-12
Activation of BH3-only proteins	7	105.3×	1e-11
RHO GTPases activate PKNs	7	67.3×	3e-10
Intrinsic Pathway for Apoptosis	7	62.1×	4e-10
FOXO-mediated transcription	5	50.9×	6e-07
SARS-CoV-1-host interactions	8	42.6×	3e-10

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	45.8×	1e-05
regulation of protein localization	5	25.7×	2e-04
intracellular protein localization	8	20.9×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	66
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
2443951	NM_001369623.2(PI4KB):c.1346T>G (p.Val449Gly)	Pathogenic
2443952	NM_001369623.2(PI4KB):c.2044G>A (p.Glu682Lys)	Pathogenic
2443953	NM_001369623.2(PI4KB):c.2261T>G (p.Met754Arg)	Pathogenic
2443954	NM_001369623.2(PI4KB):c.362A>G (p.Gln121Arg)	Pathogenic

SpliceAI

2079 predictions. Top by Δscore:

Variant	Effect	Δscore
1:151294013:CCCA:C	donor_loss	1.0000
1:151294015:CA:C	donor_loss	1.0000
1:151294045:C:CT	donor_loss	1.0000
1:151294134:ATCAC:A	acceptor_gain	1.0000
1:151294135:TCAC:T	acceptor_gain	1.0000
1:151294136:CAC:C	acceptor_gain	1.0000
1:151294136:CACC:C	acceptor_gain	1.0000
1:151294137:AC:A	acceptor_gain	1.0000
1:151294138:CC:C	acceptor_gain	1.0000
1:151294139:C:CC	acceptor_gain	1.0000
1:151294139:C:T	acceptor_gain	1.0000
1:151294379:C:CA	donor_gain	1.0000
1:151294394:T:A	donor_gain	1.0000
1:151294402:GACTC:G	donor_loss	1.0000
1:151294404:CTC:C	donor_loss	1.0000
1:151294405:TCAC:T	donor_loss	1.0000
1:151294407:A:AC	donor_gain	1.0000
1:151294407:ACAT:A	donor_gain	1.0000
1:151294407:ACATC:A	donor_gain	1.0000
1:151294408:C:CA	donor_gain	1.0000
1:151294408:CAT:C	donor_gain	1.0000
1:151294408:CATC:C	donor_gain	1.0000
1:151294408:CATCC:C	donor_gain	1.0000
1:151294537:TGTGT:T	acceptor_gain	1.0000
1:151294538:GTGT:G	acceptor_gain	1.0000
1:151294539:TGT:T	acceptor_gain	1.0000
1:151294540:GT:G	acceptor_gain	1.0000
1:151294541:TC:T	acceptor_loss	1.0000
1:151294542:C:CC	acceptor_gain	1.0000
1:151294543:T:C	acceptor_loss	1.0000

AlphaMissense

5361 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:151292876:C:A	Q809H	1.000
1:151292876:C:G	Q809H	1.000
1:151292879:G:C	F808L	1.000
1:151292879:G:T	F808L	1.000
1:151292880:A:G	F808S	1.000
1:151292881:A:G	F808L	1.000
1:151292886:T:A	D806V	1.000
1:151292887:C:G	D806H	1.000
1:151292890:A:G	Y805H	1.000
1:151292915:A:C	S796R	1.000
1:151292915:A:T	S796R	1.000
1:151292917:T:G	S796R	1.000
1:151292949:A:G	L785P	1.000
1:151292976:A:G	F776S	1.000
1:151292978:C:A	R775S	1.000
1:151292978:C:G	R775S	1.000
1:151292979:C:A	R775M	1.000
1:151292979:C:G	R775T	1.000
1:151292988:A:G	L772P	1.000
1:151293017:G:C	C762W	1.000
1:151293018:C:T	C762Y	1.000
1:151293019:A:G	C762R	1.000
1:151294065:C:G	R741P	1.000
1:151294068:G:T	A740D	1.000
1:151294069:C:G	A740P	1.000
1:151294077:A:G	L737P	1.000
1:151294080:C:T	G736E	1.000
1:151294081:C:A	G736W	1.000
1:151294081:C:G	G736R	1.000
1:151294081:C:T	G736R	1.000

dbSNP variants (sampled 300 via entrez): RS1000103816 (1:151316900 G>C), RS1000179997 (1:151291335 TGAA>T), RS1000230908 (1:151291651 C>T), RS1000236002 (1:151312632 T>C), RS1000452105 (1:151326735 A>G), RS1000507321 (1:151305936 C>A), RS1000623136 (1:151320110 T>C,G), RS1000669354 (1:151293722 G>C), RS1000707822 (1:151304400 A>G,T), RS1000734814 (1:151301149 A>C), RS1000934451 (1:151300768 G>A), RS1001001565 (1:151318709 C>G), RS1001117187 (1:151318447 T>G), RS1001251702 (1:151325416 G>A), RS1001296425 (1:151306910 A>G)

Disease associations

OMIM: gene MIM:602758 | disease phenotypes: MIM:620281

GenCC curated gene-disease

Disease	Classification	Inheritance
hearing loss, autosomal dominant 87	Limited	Autosomal dominant

Mondo (1): hearing loss, autosomal dominant 87 (MONDO:0859525)

Orphanet (0):

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000365	Hearing impairment
HP:0000376	Incomplete partition of the cochlea type II
HP:0003577	Congenital onset
HP:0011387	Enlarged vestibular aqueduct

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003854_33	Gut microbiota (functional units)	2.000000e-08
GCST005951_38	Body mass index	4.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2096619 (PROTEIN FAMILY), CHEMBL3268 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

20 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 350,394 (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
CHEMBL477	ADENOSINE	4	222,014
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL2396661	ALPELISIB	4	6,070
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL554	LAPATINIB	4	69,326
CHEMBL2017974	BUPARLISIB	3	6,568
CHEMBL4483575	REMIBRUTINIB	3	569
CHEMBL603469	LESTAURTINIB	3
CHEMBL1090090	VX-702	2	1,045
CHEMBL2041980	MMV-048	2	178
CHEMBL2165191	AZD-6482	2	912
CHEMBL230011	TG100-115	2	1,504
CHEMBL283403	ENVIROXIME	2	1,906
CHEMBL3586404	ONATASERTIB	2	1,091
CHEMBL384304	RG-547	2	93
CHEMBL4084907	BIMIRALISIB	2	1,625
CHEMBL4558527	AZD-8154	2	19
CHEMBL475251	R-406	2	762
CHEMBL521851	PICTILISIB	2	6,071

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 1-phosphatidylinositol 4-kinase family

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
compound 22 [WO2019141694A1]	Inhibition	8.4	pIC50
torin 2	Inhibition	7.74	pIC50
PIK-93	Inhibition	7.72	pIC50
wortmannin	Inhibition	6.8	pIC50

Binding affinities (BindingDB)

52 measured of 240 human assays (240 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-[6-amino-5-(2-methyl-1,3-oxazol-5-yl)-3-pyridinyl]-N-[4-(hydroxymethyl)cyclohexyl]-4-methylbenzenesulfonamide	IC50	300 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-Amino-5-(2-methyl-thiazol-5-yl)-pyridin-3-yl]-N-(3-hydroxy-propyl)-4-methyl-benzenesulfonamide	IC50	890 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-(6-amino-5-(2- methyloxazol-5- yl)pyridin-3-yl)-N-((3- hydroxycyclobutyl) methyl)-4- methylbenzenesulfon- amide	IC50	1100 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-amino-5-(2-methyl-1,3-oxazol-5-yl)-3-pyridinyl]-N-(3-hydroxycyclopentyl)-4-methylbenzenesulfonamide	IC50	1200 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-amino-5-(2-methyl-1,3-oxazol-5-yl)-3-pyridinyl]-N-cyclopropyl-4-methylbenzenesulfonamide	IC50	1200 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-amino-5-(2-methyl-1,3-oxazol-5-yl)-3-pyridinyl]-N-[3-hydroxy-3-(trifluoromethyl)cyclopentyl]-4-methylbenzenesulfonamide	IC50	1200 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-amino-5-(2-methyl-1,3-oxazol-5-yl)-3-pyridinyl]-N-(cyclopropylmethyl)-4-methylbenzenesulfonamide	IC50	1400 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-amino-5-(2-methyl-1,3-oxazol-5-yl)-3-pyridinyl]-N-(2,2-difluoroethyl)-4-methylbenzenesulfonamide	IC50	1500 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-amino-5-(2-methyl-1,3-oxazol-5-yl)-3-pyridinyl]-4-methyl-N-(2,2,2-trifluoroethyl)benzenesulfonamide	IC50	1600 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-amino-5-(2-methyl-1,3-oxazol-5-yl)-3-pyridinyl]-N-(2-hydroxypropyl)-4-methylbenzenesulfonamide	IC50	1600 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-Amino-5-(2-methyl-thiazol-5-yl)-pyridin-3-yl]-N-(2-hydroxy-2-methyl-propyl)-4-methyl-benzenesulfonamide	IC50	1620 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
N-(4-hydroxycyclohexyl)-4-methyl-3-[6-(2-methyl-1,3-thiazol-5-yl)pyrazin-2-yl]benzenesulfonamide	IC50	1810 nM	US-9862711: Pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors
3-(6-amino-5-(2- methyloxazol-5- yl)pyridin-3-yl)-N-(3- hydroxypropyl)-4- methylbenzenesulfon- amide	IC50	1900 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-(6-Amino-5-(2-methylthiazol-5-yl)pyridin-3-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide	IC50	1950 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-(6-Amino-5-(2-methylthiazol-5-yl)pyridin-3-yl)-N-(6-hydroxyspiro[3.3]heptan-2-yl)-4-methylbenzenesulfonamide	IC50	2000 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-(6-amino-5-(2- methyloxazol-5- yl)pyridin-3-yl)-N-(2- hydroxyethyl)-4- methylbenzenesulfon- amide	IC50	2000 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-(6-Amino-5-(2-methylthiazol-5-yl)pyridin-3-yl)-4-methylbenzenesulfonamide	IC50	2200 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-(6-Amino-5-(2-methylthiazol-5-yl)pyridin-3-yl)-N-(3-hydroxy-2,2-dimethylpropyl)-4-methylbenzenesulfonamide	IC50	2200 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-(2,5-dimethylpyrazol-3-yl)pyrazin-2-yl]-N-[(3-hydroxycyclobutyl)methyl]-4-methylbenzenesulfonamide	IC50	2450 nM	US-9862711: Pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-amino-5-(2-methyl-1,3-oxazol-5-yl)-3-pyridinyl]-N-(3-hydroxycyclobutyl)-4-methylbenzenesulfonamide	IC50	2500 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-(6-amino-5-(2-methyloxazol-5-yl)pyridin-3-yl)-N-((1r,4r)-4-hydroxycyclohexyl)-4-methylbenzenesulfonamide hydrochloride	IC50	2500 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-amino-5-(3-methyl-1,2-oxazol-5-yl)-3-pyridinyl]-N-(2-hydroxy-2-methylpropyl)benzenesulfonamide	IC50	2900 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
N-(3-hydroxypropyl)-4-methyl-3-[6-(2-methyl-1,3-thiazol-5-yl)pyrazin-2-yl]benzenesulfonamide	IC50	3070 nM	US-9862711: Pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors
N-(4-hydroxycyclohexyl)-4-methyl-3-(6-pyridin-3-ylpyrazin-2-yl)benzenesulfonamide	IC50	3080 nM	US-9862711: Pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-amino-5-(2-methyl-1,3-oxazol-5-yl)-3-pyridinyl]-N-[(3-hydroxyoxetan-3-yl)methyl]-4-methylbenzenesulfonamide	IC50	3200 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-(6-amino-5-(2- methyloxazol-5- yl)pyridin-3-yl)-N-(3- hydroxy-2,2- dimethylpropyl)-4- methylbenzenesulfon- amide	IC50	3300 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-amino-5-(2-methyl-1,3-oxazol-5-yl)-3-pyridinyl]-N-[(1-hydroxycyclopropyl)methyl]-4-methylbenzenesulfonamide	IC50	3400 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-(1,3-dimethylpyrazol-4-yl)pyrazin-2-yl]-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide	IC50	3450 nM	US-9862711: Pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-amino-5-(2-methyl-1,3-oxazol-5-yl)-3-pyridinyl]-N-[(1S,3S)-3-hydroxycyclohexyl]-4-methylbenzenesulfonamide	IC50	3500 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-(6-amino-5-(2-methylthiazol-5-yl)pyridin-3-yl)-N-((1r,4r)-4-hydroxycyclohexyl)-4-methylbenzenesulfonamide	IC50	3800 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-amino-5-(2-methyl-1,3-oxazol-5-yl)-3-pyridinyl]-N-(3-hydroxycyclobutyl)-4-methylbenzenesulfonamide	IC50	3850 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-(6-Amino-5-(2-methyloxazol-5-yl)pyridin-3-yl)-4-methylbenzenesulfonamide	IC50	3900 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-(1,3-dimethylpyrazol-4-yl)pyrazin-2-yl]-4-methyl-N-[(3-methyloxetan-3-yl)methyl]benzenesulfonamide	IC50	4300 nM	US-9862711: Pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors
3-(6-Amino-5-(2-methyloxazol-5-yl)pyridin-3-yl)-4-methyl-N-((3-methyloxetan-3-yl)methyl)benzenesulfonamide	IC50	4400 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-amino-5-(2-methyl-1,3-oxazol-5-yl)-3-pyridinyl]-4-methyl-N-(1,1,1-trifluoro-3-hydroxypropan-2-yl)benzenesulfonamide	IC50	4400 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-(1,3-dimethylpyrazol-4-yl)pyrazin-2-yl]-N-[(3-hydroxycyclobutyl)methyl]-4-methylbenzenesulfonamide	IC50	4400 nM	US-9862711: Pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-(1,3-dimethylpyrazol-4-yl)pyrazin-2-yl]-N-(3-hydroxy-2,2-dimethylpropyl)-4-methylbenzenesulfonamide	IC50	4400 nM	US-9862711: Pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors
(1-((3-(6-Amino-5-(2-methylthiazol-5-yl)pyridin-3-yl)-4-methylphenyl)sulfonyl)azetidin-3-yl)methanol	IC50	4600 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-(6-amino-5-(2- methyloxazol-5- yl)pyridin-3-yl)-4- methyl-N-(oxetan-3- ylmethyl)benzenesulfon- amide	IC50	4700 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-amino-5-(2-methyl-1,3-oxazol-5-yl)-3-pyridinyl]-4-methyl-N-(oxan-3-ylmethyl)benzenesulfonamide	IC50	4800 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-(6-Amino-5-(2-methylthiazol-5-yl)pyridin-3-yl)-N-(2-hydroxyethyl)-4-methylbenzenesulfonamide	IC50	5200 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-(1,3-dimethylpyrazol-4-yl)pyrazin-2-yl]-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide	IC50	5300 nM	US-9862711: Pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors
3-(6-Amino-5-(2-methylthiazol-5-yl)pyridin-3-yl)-4-methyl-N-(oxetan-3-ylmethyl)benzenesulfonamide	IC50	6200 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
trans 3-(6-Amino-5-(1- methyl-1H-pyrazol-4- yl)pyridin-3-yl)-N-(4- hydroxy cyclohexyl)-4- methylbenzene- sulfonamide	IC50	6600 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-amino-5-(2-cyclopropyl-1,3-oxazol-5-yl)-3-pyridinyl]-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide	IC50	6800 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
STK16-IN-1	IC50	7940 nM
3-[6-Amino-5-(3-methyl-isoxazol-5-yl)-pyridin-3-yl]-4-methyl-N-(3-methyl-oxetan-3-ylmethyl)-benzenesulfonamide hydrochloride	IC50	8100 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
3-(6-Amino-5-(2-methylthiazol-5-yl)pyridin-3-yl)-N-((3-(hydroxymethyl)oxetan-3-yl)methyl)-4-methylbenzenesulfonamide	IC50	8400 nM	US-10112926: Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors
N-(4-hydroxycyclohexyl)-4-methyl-3-[6-[5-(morpholin-4-ylmethyl)thiophen-3-yl]pyrazin-2-yl]benzenesulfonamide	IC50	8600 nM	US-9862711: Pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors
3-[6-(1,3-dimethylpyrazol-4-yl)pyrazin-2-yl]-N-(2-hydroxyspiro[3.3]heptan-6-yl)-4-methylbenzenesulfonamide	IC50	9400 nM	US-9862711: Pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors

ChEMBL bioactivities

500 potent at pChembl≥5 of 626 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.01	IC50	0.98	nM	CHEMBL3923414
8.70	IC50	2	nM	CHEMBL4205416
8.62	IC50	2.4	nM	CHEMBL3930509
8.43	Kd	3.7	nM	CHEMBL3936684
8.40	IC50	4	nM	CHEMBL4215340
8.40	IC50	4	nM	CHEMBL4205416
8.40	IC50	4	nM	CHEMBL4211696
8.40	IC50	4	nM	CHEMBL5619521
8.40	IC50	4	nM	CHEMBL5618321
8.30	IC50	5	nM	CHEMBL4206816
8.30	IC50	5	nM	CHEMBL4211181
8.30	IC50	5	nM	CHEMBL6163838
8.30	IC50	5	nM	CHEMBL6146491
8.28	IC50	5.3	nM	CHEMBL3958915
8.24	IC50	5.7	nM	CHEMBL2407818
8.22	IC50	6	nM	CHEMBL6133146
8.22	IC50	6	nM	CHEMBL6150125
8.21	IC50	6.1	nM	CHEMBL3976651
8.21	IC50	6.2	nM	CHEMBL3920652
8.21	Kd	6.1	nM	CHEMBL3974986
8.21	IC50	6.1	nM	CHEMBL5188324
8.15	IC50	7	nM	CHEMBL4215244
8.15	IC50	7	nM	CHEMBL4203566
8.15	IC50	7	nM	CHEMBL6160285
8.15	IC50	7	nM	CHEMBL6171005
8.15	IC50	7	nM	CHEMBL6149562
8.14	IC50	7.23	nM	CHEMBL3911522
8.10	IC50	8	nM	CHEMBL4203041
8.10	IC50	8	nM	CHEMBL4202450
8.10	IC50	8	nM	CHEMBL4209793
8.10	IC50	8	nM	CHEMBL2397317
8.10	IC50	8	nM	CHEMBL4215340
8.10	IC50	8	nM	CHEMBL6145562
8.10	IC50	8	nM	CHEMBL6161580
8.10	IC50	8	nM	CHEMBL6146998
8.10	IC50	8	nM	CHEMBL1233882
8.07	IC50	8.6	nM	CHEMBL3939697
8.05	IC50	9	nM	CHEMBL3957128
8.05	IC50	9	nM	CHEMBL4207851
8.00	IC50	10	nM	CHEMBL1652677
8.00	IC50	10	nM	AZD-6482
8.00	IC50	10	nM	CHEMBL6144293
8.00	IC50	10	nM	CHEMBL6170967
7.96	IC50	11	nM	CHEMBL4210308
7.96	IC50	11	nM	CHEMBL4211181
7.96	IC50	11	nM	CHEMBL6120583
7.90	IC50	12.5	nM	CHEMBL3959713
7.90	IC50	12.5	nM	CHEMBL1229535
7.89	IC50	13	nM	CHEMBL4215244
7.89	IC50	13	nM	CHEMBL6169715

PubChem BioAssay actives

406 with measured affinity, of 995 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
N-[2-[[6-chloro-3-(4-methoxy-3-morpholin-4-ylsulfonylphenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl]amino]ethyl]acetamide	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0010	uM
4-(5-amino-2-pyridin-3-yl-[1,3]thiazolo[5,4-d]pyrimidin-7-yl)-N-(4-methoxyphenyl)piperazine-1-carboxamide	1381469: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system using PI lipid kinase substrate after 60 mins by ADP-Glo assay	ic50	0.0020	uM
N-[2-[[6-chloro-3-[3-(dimethylsulfamoyl)-4-methoxyphenyl]-2-methylimidazo[1,2-b]pyridazin-8-yl]amino]ethyl]acetamide	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0024	uM
N-[(1-benzyltriazol-4-yl)methyl]-5-[6-chloro-8-[(2-ethyl-4-pyridinyl)methylamino]-2-methylimidazo[1,2-b]pyridazin-3-yl]-2-methoxybenzenesulfonamide	1324687: Binding affinity to 6xHisGB1 tagged PI4KB (unknown origin) expressed in Escherichia coli BL21 Star by fluorescence anisotropy based method	kd	0.0037	uM
2-fluoro-4-[2-methyl-7-[(3-methylsulfonylphenyl)methylamino]pyrazolo[1,5-a]pyrimidin-3-yl]phenol	2128441: Inhibition of Phosphatidylinositol 4-Kinase III beta (unknown origin) preincubated for 10 min followed by incubated with ATP for 1 hr by ADP-Glo kinase assay	ic50	0.0040	uM
4-[2,5-dimethyl-7-[(3-methylsulfonylphenyl)methylamino]pyrazolo[1,5-a]pyrimidin-3-yl]-2-fluorophenol	2128441: Inhibition of Phosphatidylinositol 4-Kinase III beta (unknown origin) preincubated for 10 min followed by incubated with ATP for 1 hr by ADP-Glo kinase assay	ic50	0.0040	uM
(3S)-4-(5-amino-[1,3]thiazolo[5,4-d]pyrimidin-7-yl)-N-(4-methoxy-2-methylphenyl)-3-methylpiperazine-1-carboxamide	1381469: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system using PI lipid kinase substrate after 60 mins by ADP-Glo assay	ic50	0.0040	uM
4-[4-chloro-3-(methylcarbamoyl)phenyl]-N-[(3-pyrazol-1-ylphenyl)methyl]pyridine-2-carboxamide	1381469: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system using PI lipid kinase substrate after 60 mins by ADP-Glo assay	ic50	0.0040	uM
4-(5-amino-2-pyridin-3-yl-[1,3]thiazolo[5,4-d]pyrimidin-7-yl)-N-(4-methylphenyl)piperazine-1-carboxamide	1381468: Inhibition of PI4K3beta in human PBMC assessed as reduction in mitomycin-C treated human RPMI1788 cells-stimulated lymphocyte proliferation by measuring reduction in [3H]thymidine incorporation preincubated for 5 days followed by [3H]thymidine addition measured after 18 hrs by liquid scintillation counting method	ic50	0.0050	uM
(3S)-4-(6-amino-1-methylpyrazolo[5,4-d]pyrimidin-4-yl)-N-(4-methoxy-2-methylphenyl)-3-methylpiperazine-1-carboxamide	1381533: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system	ic50	0.0050	uM
5-[6-chloro-8-[(2-ethyl-4-pyridinyl)methylamino]-2-methylimidazo[1,2-b]pyridazin-3-yl]-N-(1-hydroxybutan-2-yl)-2-methoxybenzenesulfonamide	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0053	uM
2-fluoro-4-[2-methyl-8-[(3-methylsulfonylphenyl)methylamino]imidazo[1,2-a]pyrazin-3-yl]phenol	1876214: Inhibition of PI4KIIIbeta (unknown origin)	ic50	0.0057	uM
5-[6-chloro-8-[(2-ethyl-4-pyridinyl)methylamino]-2-methylimidazo[1,2-b]pyridazin-3-yl]-N-(2-hydroxyethyl)-2-methoxybenzenesulfonamide	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0061	uM
5-[6-chloro-8-[(2-ethyl-4-pyridinyl)methylamino]-2-methylimidazo[1,2-b]pyridazin-3-yl]-2-methoxy-N-prop-2-ynylbenzenesulfonamide	1324687: Binding affinity to 6xHisGB1 tagged PI4KB (unknown origin) expressed in Escherichia coli BL21 Star by fluorescence anisotropy based method	kd	0.0061	uM
5-[6-chloro-8-[(2-ethyl-4-pyridinyl)methylamino]-2-methylimidazo[1,2-b]pyridazin-3-yl]-N-ethyl-2-hydroperoxybenzenesulfonamide	1876214: Inhibition of PI4KIIIbeta (unknown origin)	ic50	0.0061	uM
1-[5-[6-chloro-8-[(2-ethyl-4-pyridinyl)methylamino]-2-methylimidazo[1,2-b]pyridazin-3-yl]-2-methoxyphenyl]sulfonylpiperidin-4-ol	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0062	uM
(3S)-4-(2-aminothieno[2,3-d]pyrimidin-4-yl)-N-(4-methoxy-2-methylphenyl)-3-methylpiperazine-1-carboxamide	1381469: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system using PI lipid kinase substrate after 60 mins by ADP-Glo assay	ic50	0.0070	uM
(3S)-4-(6-amino-[1,2]thiazolo[5,4-d]pyrimidin-4-yl)-N-(4-methoxy-2-methylphenyl)-3-methylpiperazine-1-carboxamide	1381469: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system using PI lipid kinase substrate after 60 mins by ADP-Glo assay	ic50	0.0070	uM
N-[2-[[6-chloro-3-[3-(1-hydroxybutan-2-ylsulfamoyl)-4-methoxyphenyl]-2-methylimidazo[1,2-b]pyridazin-8-yl]amino]ethyl]acetamide	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0072	uM
(3S)-4-(5-amino-[1,3]thiazolo[5,4-d]pyrimidin-7-yl)-N-(4-methoxyphenyl)-3-methylpiperazine-1-carboxamide	1381469: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system using PI lipid kinase substrate after 60 mins by ADP-Glo assay	ic50	0.0080	uM
(3S)-4-(2-amino-9-methylpurin-6-yl)-N-(4-methoxy-2-methylphenyl)-3-methylpiperazine-1-carboxamide	1381469: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system using PI lipid kinase substrate after 60 mins by ADP-Glo assay	ic50	0.0080	uM
1-propan-2-yl-3-quinolin-6-ylpyrazolo[3,4-d]pyrimidin-4-amine	507078: Inhibition of recombinant PI4Kbeta by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0080	uM
3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-(2-morpholin-4-ylethyl)pyrazolo[1,5-a]pyrimidin-7-amine	1381469: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system using PI lipid kinase substrate after 60 mins by ADP-Glo assay	ic50	0.0080	uM
N-[2-chloro-5-[2,5-dimethyl-7-[(2-methyl-4-pyridinyl)methylamino]pyrazolo[1,5-a]pyrimidin-3-yl]phenyl]methanesulfonamide	1381468: Inhibition of PI4K3beta in human PBMC assessed as reduction in mitomycin-C treated human RPMI1788 cells-stimulated lymphocyte proliferation by measuring reduction in [3H]thymidine incorporation preincubated for 5 days followed by [3H]thymidine addition measured after 18 hrs by liquid scintillation counting method	ic50	0.0080	uM
5-[6-chloro-8-[(2-ethyl-4-pyridinyl)methylamino]-2-methylimidazo[1,2-b]pyridazin-3-yl]-2-methoxy-N-prop-2-enylbenzenesulfonamide	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0086	uM
5-[6-chloro-8-[(2-ethyl-4-pyridinyl)methylamino]-2-methylimidazo[1,2-b]pyridazin-3-yl]-N-[2-(dimethylamino)ethyl]-2-methoxybenzenesulfonamide	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0090	uM
4-(5-amino-[1,3]thiazolo[5,4-d]pyrimidin-7-yl)-N-(4-methoxy-2-methylphenyl)piperazine-1-carboxamide	1381469: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system using PI lipid kinase substrate after 60 mins by ADP-Glo assay	ic50	0.0090	uM
1-[4-(5-amino-2-pyridin-3-yl-[1,3]thiazolo[5,4-d]pyrimidin-7-yl)piperazin-1-yl]-2-(4-chlorophenoxy)ethanone	1381469: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system using PI lipid kinase substrate after 60 mins by ADP-Glo assay	ic50	0.0100	uM
4-(5-amino-2-phenyl-[1,3]thiazolo[5,4-d]pyrimidin-7-yl)-N-(4-methoxyphenyl)piperazine-1-carboxamide	1381469: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system using PI lipid kinase substrate after 60 mins by ADP-Glo assay	ic50	0.0110	uM
3-[6-chloro-8-[(2-ethyl-4-pyridinyl)methylamino]-2-methylimidazo[1,2-b]pyridazin-3-yl]-N,N-dimethylbenzenesulfonamide	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0125	uM
N-[5-[4-methoxy-3-(phenylsulfamoyl)phenyl]-4-methyl-1,3-thiazol-2-yl]-2-phenylacetamide	2026520: Inhibition of human recombinant GST tagged P14KIII beta incubated for 10 mins by ADP-Glo kinase method	ic50	0.0140	uM
N-[2-[[6-chloro-3-[3-[4-(hydroxymethyl)piperidin-1-yl]sulfonyl-4-methoxyphenyl]-2-methylimidazo[1,2-b]pyridazin-8-yl]amino]ethyl]acetamide	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0149	uM
N-(4-aminocyclohexyl)-5-[6-chloro-8-[(2-ethyl-4-pyridinyl)methylamino]-2-methylimidazo[1,2-b]pyridazin-3-yl]-2-methoxybenzenesulfonamide	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0157	uM
N-[5-[3-(benzenesulfonamido)-4-methoxyphenyl]-4-methyl-1,3-thiazol-2-yl]-2-(3,5-dimethoxyphenyl)acetamide	2026520: Inhibition of human recombinant GST tagged P14KIII beta incubated for 10 mins by ADP-Glo kinase method	ic50	0.0160	uM
N-[5-[4-methoxy-3-(pyridin-3-ylsulfonylamino)phenyl]-4-methyl-1,3-thiazol-2-yl]-2-phenylacetamide	2026520: Inhibition of human recombinant GST tagged P14KIII beta incubated for 10 mins by ADP-Glo kinase method	ic50	0.0160	uM
N-[5-[3-(diethylsulfamoyl)-4-methoxyphenyl]-4-methyl-1,3-thiazol-2-yl]-2-(3,5-dimethoxyphenyl)acetamide	2026520: Inhibition of human recombinant GST tagged P14KIII beta incubated for 10 mins by ADP-Glo kinase method	ic50	0.0160	uM
5-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-2-bromophenol	507078: Inhibition of recombinant PI4Kbeta by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0170	uM
N-[5-[4-chloro-3-(2-hydroxyethylsulfamoyl)phenyl]-4-methyl-1,3-thiazol-2-yl]acetamide	2198490: Inhibition of PI4KB (unknown origin) by membrane capture assay	ec50	0.0170	uM
5-[6-chloro-8-[(2-ethyl-4-pyridinyl)methylamino]-2-methylimidazo[1,2-b]pyridazin-3-yl]-2-methoxy-N-(2-methoxyethyl)benzenesulfonamide	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0172	uM
6-chloro-N-[(2-ethyl-4-pyridinyl)methyl]-3-(4-methoxy-3-morpholin-4-ylsulfonylphenyl)-2-methylimidazo[1,2-b]pyridazin-8-amine	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0176	uM
4-(5-amino-[1,3]thiazolo[5,4-d]pyrimidin-7-yl)-N-(4-methoxyphenyl)-3-methylpiperazine-1-carboxamide	1381469: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system using PI lipid kinase substrate after 60 mins by ADP-Glo assay	ic50	0.0180	uM
9-(6-amino-3-pyridinyl)-1-[3-(trifluoromethyl)phenyl]benzo[h][1,6]naphthyridin-2-one	2198488: Inhibition of PI4KB (unknown origin) by drug competition for substrate binding based assay	ec50	0.0183	uM
N-[5-[3-(diethylsulfamoyl)-4-methoxyphenyl]-4-methyl-1,3-thiazol-2-yl]-2-phenylacetamide	2026520: Inhibition of human recombinant GST tagged P14KIII beta incubated for 10 mins by ADP-Glo kinase method	ic50	0.0190	uM
6-chloro-N-[(2-ethyl-4-pyridinyl)methyl]-3-(4-methoxy-3-pyrazol-1-ylsulfonylphenyl)-2-methylimidazo[1,2-b]pyridazin-8-amine	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0191	uM
N-[2-[[6-chloro-3-[4-methoxy-3-(prop-2-enylsulfamoyl)phenyl]-2-methylimidazo[1,2-b]pyridazin-8-yl]amino]ethyl]acetamide	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0199	uM
24-[(1S)-1-cyclopropylethyl]-3-methyl-20,20-dioxo-16-oxa-20lambda6,30-dithia-4,6,13,19,24,29-hexazapentacyclo[19.6.1.12,5.17,11.022,26]triaconta-1(27),2,4,7,9,11(29),21(28),22(26)-octaene-12,23-dione	1807067: Inhibition of PI4KB (unknown origin) assessed as reduction in substrate phosphorylation by FRET Adapta assay	ic50	0.0199	uM
(3S)-4-(5-amino-[1,3]thiazolo[5,4-d]pyrimidin-7-yl)-N-(6-methoxy-2-methyl-3-pyridinyl)-3-methylpiperazine-1-carboxamide	1381469: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system using PI lipid kinase substrate after 60 mins by ADP-Glo assay	ic50	0.0200	uM
5-[6-chloro-8-[(2-ethyl-4-pyridinyl)methylamino]-2-methylimidazo[1,2-b]pyridazin-3-yl]-N-[[1-(7-hydroxy-2-oxochromen-3-yl)triazol-4-yl]methyl]-2-methoxybenzenesulfonamide	1324687: Binding affinity to 6xHisGB1 tagged PI4KB (unknown origin) expressed in Escherichia coli BL21 Star by fluorescence anisotropy based method	kd	0.0210	uM
N-[5-[3-(diethylsulfamoyl)-4-methoxyphenyl]-4-methyl-1,3-thiazol-2-yl]-2-(3-methylphenyl)acetamide	2026520: Inhibition of human recombinant GST tagged P14KIII beta incubated for 10 mins by ADP-Glo kinase method	ic50	0.0210	uM
N-[2-[[6-chloro-3-[3-(2-hydroxyethylsulfamoyl)-4-methoxyphenyl]-2-methylimidazo[1,2-b]pyridazin-8-yl]amino]ethyl]acetamide	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0220	uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	decreases expression, affects cotreatment	1
Bortezomib	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Aspirin	decreases expression	1
Caffeine	affects phosphorylation	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Fluorouracil	affects reaction, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Lead	affects splicing	1
Smoke	decreases expression	1
Tretinoin	increases expression	1
Vitamin E	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1

ChEMBL screening assays

258 unique, capped per target: 252 binding, 2 functional, 2 admet, 2 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL758625	Binding	Inhibition of Phosphatidylinositol 4-kinase of human epidermoid carcinoma A431 cells	Synthesis of echiguanine analogs and their ribofuranosyl glycosides that inhibit phosphatidylinositol 4-kinase — Bioorg Med Chem Lett
CHEMBL760329	Functional	Rate of phosphorylation was determined with that of mammalian PI using human erythrocyte PI 4-kinase at 200 uM substrate	Total synthesis of the four stereoisomers of dihexadecanoyl phosphatidylinositol and the substrate stereospecificity of human erythrocyte membrane phosphatidylinositol 4-kinase. — J Med Chem
CHEMBL4622191	ADMET	Binding affinity to PIK4CB (unknown origin)	Stepwise Design of γ-Secretase Modulators with an Advanced Profile by Judicious Coordinated Structural Replacements and an Unconventional Phenyl Ring Bioisostere. — J Med Chem

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_D1PS	Abcam K-562 PI4KB KO	Cancer cell line	Female
CVCL_D2LD	Abcam Raji PI4KB KO	Cancer cell line	Male
CVCL_D7X2	Ubigene A-549 PI4KB KO	Cancer cell line	Male
CVCL_D8SF	Ubigene HCT 116 PI4KB KO	Cancer cell line	Male
CVCL_D9MX	Ubigene HEK293 PI4KB KO	Transformed cell line	Female
CVCL_E0KA	Ubigene HeLa PI4KB KO	Cancer cell line	Female
CVCL_TD40	HAP1 PI4KB (-) 1	Cancer cell line	Male
CVCL_TD41	HAP1 PI4KB (-) 2	Cancer cell line	Male
CVCL_WQ28	Abcam Jurkat PI4KB KO	Cancer cell line	Male

Clinical trials (associated diseases)

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