PIK3CB

Summary

PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta, HGNC:8976) is a protein-coding gene on chromosome 3q22.3, encoding Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (P42338). Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol derivatives at position 3 of the inositol ring to produce 3-phosphoinositides.

This gene encodes an isoform of the catalytic subunit of phosphoinositide 3-kinase (PI3K). These kinases are important in signaling pathways involving receptors on the outer membrane of eukaryotic cells and are named for their catalytic subunit. The encoded protein is the catalytic subunit for PI3Kbeta (PI3KB). PI3KB has been shown to be part of the activation pathway in neutrophils which have bound immune complexes at sites of injury or infection. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 5291 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 140 total — 1 likely-pathogenic
• Druggable target: yes — 53 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types
• MANE Select transcript: NM_006219

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8976
Approved symbol	PIK3CB
Name	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta
Location	3q22.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000051382
Ensembl biotype	protein_coding
OMIM	602925
Entrez	5291

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 31 protein_coding, 3 nonsense_mediated_decay, 3 retained_intron

ENST00000462294, ENST00000462898, ENST00000465581, ENST00000469284, ENST00000473435, ENST00000477593, ENST00000481749, ENST00000483968, ENST00000485060, ENST00000487552, ENST00000493568, ENST00000674063, ENST00000894539, ENST00000894540, ENST00000894541, ENST00000894542, ENST00000894543, ENST00000894544, ENST00000894545, ENST00000894546, ENST00000938758, ENST00000938759, ENST00000938760, ENST00000938761, ENST00000938762, ENST00000938763, ENST00000938764, ENST00000938765, ENST00000938766, ENST00000938767, ENST00000938768, ENST00000938769, ENST00000955024, ENST00000955025, ENST00000955027, ENST00000955028, ENST00000955030

RefSeq mRNA: 2 — MANE Select: NM_006219 NM_001256045, NM_006219

CCDS: CCDS3104

Canonical transcript exons

ENST00000674063 — 24 exons

Exon	Start	End
ENSE00000778970	138755754	138755979
ENSE00001206219	138742558	138742781
ENSE00001823426	138759173	138759359
ENSE00001852016	138834695	138834928
ENSE00001951325	138796463	138796567
ENSE00003466771	138665036	138665203
ENSE00003471257	138712208	138712304
ENSE00003473295	138694786	138694907
ENSE00003473458	138656142	138656274
ENSE00003500113	138707159	138707289
ENSE00003539165	138663906	138664029
ENSE00003542328	138733361	138733438
ENSE00003549174	138714468	138714719
ENSE00003567519	138683678	138683787
ENSE00003574878	138734634	138734804
ENSE00003576354	138684625	138684803
ENSE00003583204	138691000	138691143
ENSE00003593452	138688875	138688974
ENSE00003618652	138704443	138704493
ENSE00003649494	138657690	138657835
ENSE00003652395	138698907	138699095
ENSE00003685634	138681967	138682045
ENSE00003691764	138737707	138737886
ENSE00003896367	138652698	138655526

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 97.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.2311 / max 169.5902, expressed in 1781 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44767	13.8504	1774
44768	0.9632	562
44766	0.3277	181
44765	0.0898	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	97.50	gold quality
medial globus pallidus	UBERON:0002477	96.55	gold quality
endothelial cell	CL:0000115	95.83	gold quality
middle temporal gyrus	UBERON:0002771	95.71	gold quality
choroid plexus epithelium	UBERON:0003911	95.36	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.18	gold quality
globus pallidus	UBERON:0001875	94.97	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.94	gold quality
nephron tubule	UBERON:0001231	93.78	gold quality
cranial nerve II	UBERON:0000941	93.53	gold quality
pons	UBERON:0000988	92.88	gold quality
jejunal mucosa	UBERON:0000399	92.86	gold quality
substantia nigra pars compacta	UBERON:0001965	92.64	gold quality
postcentral gyrus	UBERON:0002581	92.42	gold quality
primary visual cortex	UBERON:0002436	92.10	gold quality
esophagus squamous epithelium	UBERON:0006920	92.09	gold quality
parietal lobe	UBERON:0001872	91.98	gold quality
superior frontal gyrus	UBERON:0002661	91.71	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	91.64	gold quality
lateral globus pallidus	UBERON:0002476	91.47	gold quality
kidney epithelium	UBERON:0004819	91.45	gold quality
buccal mucosa cell	CL:0002336	91.37	gold quality
epithelium of esophagus	UBERON:0001976	91.36	gold quality
occipital lobe	UBERON:0002021	91.35	gold quality
superior vestibular nucleus	UBERON:0007227	91.12	gold quality
bone marrow cell	CL:0002092	91.06	gold quality
trabecular bone tissue	UBERON:0002483	90.94	gold quality
orbitofrontal cortex	UBERON:0004167	90.94	gold quality
upper leg skin	UBERON:0004262	90.77	gold quality
monocyte	CL:0000576	90.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	213.77
E-ANND-3	yes	6.75
E-MTAB-6678	yes	6.14
E-MTAB-6142	no	66.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, STAT1

miRNA regulators (miRDB)

226 targeting PIK3CB, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-9-5P	100.00	72.28	2361
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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-19A-3P	99.98	75.33	2762

Literature-anchored findings (GeneRIF, showing 40)

• These results indicate that in addition to their roles in recruiting the catalytic subunit of PI3K to the insulin receptor substrate proteins, both p85alpha and p85beta play negative roles in insulin signaling (PMID:11752399)
• A function for phosphoinositide 3-kinase beta lipid products in coupling beta gamma to Ras activation in response to lysophosphatidic acid. (PMID:11916960)
• It is unlikely that the promoter polymorphisms -359T/C and -303A/G of the catalytic subunit p110beta gene of human PI 3-kinase have a major impact on insulin secretion, insulin sensitivity, or the risk of type 2 diabetes (PMID:12502677)
• p110 has a role in activation of PI3K gamma along with G beta gamma (PMID:12507995)
• determinination of the involvement of PI3K and MAPK pathways and the importance of cross-talk between these pathways, in glucose-potentiated vascular smooth muscle cell chemotaxis to serum factors (PMID:15242975)
• Data highlight the differential signaling by p110alpha and -beta isoforms. (PMID:15468162)
• Introduction of a pH1 vector producing shRNA (short hairpin RNA) that targets p110beta abolished PIA [N6-(2-phenylisopropyl)adenosine]-induced Akt activation (PMID:16091017)
• although introduction of activating mutations from p110alpha at the corresponding sites in p110beta failed to render the enzyme oncogenic in human cells, the possibility remains that other mutations might activate the beta isoform (PMID:16339315)
• p110beta, -gamma, and -delta isoforms of class I phosphoinositide 3-kinase have roles in oncogenic transformation (PMID:16432180)
• Reduced activation of NF-kappaB via impaired PI3K/Akt activation under increased TNF-alpha levels could result in increased apoptosis of vitiliginous keratinocytes. (PMID:17522703)
• bFGF augments hypoxia induced VEGF release in breast cancer cells mainly through the PI3K pathway and partly depending on HIF-1 activity. (PMID:17676480)
• C allele is a causal variant capable of attenuating insulin resistance in obese children. (PMID:17977952)
• Our data indicate that different signalling pathways are involved in retinoic acid-induced up-regulation of the secretases. (PMID:17986385)
• PI3Kalpha and -beta present distinct activation requirements and kinetics in G(1) phase, with a selective action of PI3Kalpha at the G(0)/G(1) phase transition (PMID:18285463)
• Phosphoinositide 3-kinase p110beta inhibitor TGX-221 inhibited shear-induced platelet activation and protected platelet function during extracorporeal circulation. (PMID:18327411)
• p85alpha and p110beta are essential for androgen-stimulated AR transactivation, and their aberrant expression or activation might play an important role in prostate cancer progression (PMID:18372911)
• required for sphingosine-1-phosphate -induced endothelial cell migration through activation of Rac1 (PMID:18558630)
• Although p110alpha activation is required to sustain the proliferation of established PIK3CA-mutant tumors, PTEN-deficient tumors are dependent instead on p110beta signaling. (PMID:18755892)
• Rs361072 promoter variant of PIK3CB is associated with insulin resistance not with type 2 diabetes. (PMID:19097921)
• PI3K p110beta positively controls lipopolysaccharide-induced interleukin-12 production through the c-jun kinase (JNK)-1-dependent pathway in human macrophages and dendritic cells. (PMID:19380768)
• PI3Kbeta plays an essential role in GPVI-mediated platelet aggregation and Akt activation (PMID:19700402)
• phosphoinositide 3-kinase isoforms alpha and beta have roles in glycoprotein VI-induced platelet signaling and thrombus formation (PMID:19815551)
• Our results support the concept that p110beta appears to be the predominant functional class I PI 3-kinase isoform in prostate cancer cells. (PMID:20058239)
• Data show that similar responses were seen in cancer cells with wild-type or activated mutant PI3K genes treated with p110alpha/delta or p110alpha/beta/delta inhibitors in cell viability assays. (PMID:20103642)
• minor G allele of PIK3CB associates with decreased muscle subunit ratio and lower hepatic glucose production at high plasma insulin levels. (PMID:20107106)
• This study shows that the enhanced transforming potential of p110beta is the result of its decreased inhibition by p85, due to the disruption of an inhibitory C2-iSH2 domain interface. (PMID:21030680)
• In hyperglycemic leptin-deficient Lep(ob/ob) transgenic mice, leptin acutely and potently improves glucose metabolism, before any change of body fat mass, via a mechanism involving the p110alpha and -beta isoforms of phosphatidylinositol-3-kinase. (PMID:21123564)
• Significance of this altered regulation in tumor models of PTEN deletion, as well as the potential implications of the unique p110beta regulation on GPCR-driven tumorigenesis. (PMID:21321382)
• lipid kinase p110beta/p85beta elucidates an unusual SH2-domain-mediated inhibitory mechanism (PMID:21362552)
• study shows that p110beta nuclear localization signal and p85beta nuclear export sequence regulate p85beta/p110beta nuclear localization, supporting the idea that nuclear, but not cytoplasmic, p110beta controls cell survival (PMID:21383062)
• Results define PI3Kbeta as a potential therapeutic target in inflammatory disease. (PMID:21487106)
• This paper reports the first purification of a phosphoinositide 3-kinase and shows that the protein is a heterodimer of an 85 kd regulatory subunit that mediates binding to phosphorylated proteins and a 110 kd catalytic subunit. (PMID:2174051)
• results suggested that down-regulation of p110beta expression by siRNA obviously reduced cell number via accumulation in G(0)-G(1) phase of the cell cycle. (PMID:22528234)
• Combined blockade of P2Y12, P2Y1 and PI3-kinase p110beta fully prevents platelet and leukocyte activation during hypothermic extracorporeal circulation. (PMID:22701645)
• Phosphoinositide 3-kinase C2beta regulates RhoA and the actin cytoskeleton through an interaction with Dbl (PMID:22984590)
• p110beta was activated near metaphase and controlled dynein/dynactin and Aurora B activities in kinetochores, chromosome segregation, and optimal function of the spindle checkpoint (PMID:23051731)
• Disrupting the p110beta-Gbetagamma interaction by mutation or with a cell-permeable peptide inhibitor blocked the transforming capacity of PI3Kbeta in fibroblasts and reduced the proliferation, chemotaxis, and invasiveness (PMID:23211529)
• Data indicate that phosphatidylinositol 3’-kinase (PI3K) alpha and beta p110 isoforms of PI3K are broadly expressed in myeloma. (PMID:23318440)
• In mammalian cells, p110beta acts as a molecular sensor for growth factor availability and induces autophagy by activating a Rab5-mediated signaling cascade. (PMID:23434372)
• p110alpha acts as a negative regulator of beta cell exocytosis and insulin secretion, while p110beta is a positive regulator of insulin secretion through a mechanism separate from its catalytic activity (PMID:23568272)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	pik3cb	ENSDARG00000075253
mus_musculus	Pik3cb	ENSMUSG00000032462
rattus_norvegicus	Pik3cb	ENSRNOG00000016384
drosophila_melanogaster	Pi3K68D	FBGN0015278
drosophila_melanogaster	Pi3K92E	FBGN0015279
caenorhabditis_elegans		WBGENE00000090
caenorhabditis_elegans		WBGENE00009552

Paralogs (9): PIK3C2A (ENSG00000011405), PIK3C3 (ENSG00000078142), PIK3CG (ENSG00000105851), PIK3CA (ENSG00000121879), PIK3C2B (ENSG00000133056), PIK3C2G (ENSG00000139144), PI4KB (ENSG00000143393), PIK3CD (ENSG00000171608), PI4KA (ENSG00000241973)

Protein

Protein identifiers

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform — P42338 (reviewed: P42338)

Alternative names: Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit beta, Serine/threonine protein kinase PIK3CB

All UniProt accessions (8): C9J345, C9JYX0, P42338, F8WDJ8, H0Y871, H7C527, H7C565, H7C5C3

UniProt curated annotations — full annotation on UniProt →

Function. Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol derivatives at position 3 of the inositol ring to produce 3-phosphoinositides. Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Involved in the activation of AKT1 upon stimulation by G-protein coupled receptors (GPCRs) ligands such as CXCL12, sphingosine 1-phosphate, and lysophosphatidic acid. May also act downstream receptor tyrosine kinases. Required in different signaling pathways for stable platelet adhesion and aggregation. Plays a role in platelet activation signaling triggered by GPCRs, alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) and ITAM (immunoreceptor tyrosine-based activation motif)-bearing receptors such as GP6. Regulates the strength of adhesion of ITGA2B/ ITGB3 activated receptors necessary for the cellular transmission of contractile forces. Required for platelet aggregation induced by F2 (thrombin) and thromboxane A2 (TXA2). Has a role in cell survival. May have a role in cell migration. Involved in the early stage of autophagosome formation. Modulates the intracellular level of PtdIns3P (phosphatidylinositol 3-phosphate) and activates PIK3C3 kinase activity. May act as a scaffold, independently of its lipid kinase activity to positively regulate autophagy. May have a role in insulin signaling as scaffolding protein in which the lipid kinase activity is not required. May have a kinase-independent function in regulating cell proliferation and in clathrin-mediated endocytosis. Mediator of oncogenic signal in cell lines lacking PTEN. The lipid kinase activity is necessary for its role in oncogenic transformation. Required for the growth of ERBB2 and RAS driven tumors. Also has a protein kinase activity showing autophosphorylation.

Subunit / interactions. Heterodimer of a catalytic subunit PIK3CB and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3). Interaction with PIK3R2 is required for nuclear localization and nuclear export. Part of a complex with PIK3R1 and PTEN. Binding to PTEN may antagonize the lipid kinase activity under normal growth conditions. Part of a complex involved in autophagosome formation composed of PIK3C3 and PIK3R4. Interacts with BECN1, ATG14 and RAB5A.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed ubiquitously.

Post-translational modifications. Autophosphorylation at Ser-1070 negatively regulates the phosphatidylinositol-4,5-bisphosphate 3-kinase activity.

Domain organisation. The inhibitory interactions with PIK3R1 are mediated by the PI3K-ABD domain and the C2 PI3K-type domain with the iSH2 (inter-SH2) region of PIK3R1; the C2 PI3K-type domain, the PI3K helical domain, and the PI3K/PI4K kinase domain with the nSH2 (N-terminal SH2) region of PIK3R1; and the PI3K/PI4K kinase domain with the cSH2 (C-terminal SH2) region of PIK3R1. The inhibitory interaction between the PI3K-ABD domain and the C2 PI3K-type domain with the iSH2 (inter-SH2) region of PIK3R1 is weak. The nuclear localization signal (NLS) is required for its function in cell survival.

Pathway. Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis.

Similarity. Belongs to the PI3/PI4-kinase family.

RefSeq proteins (2): NP_001242974, NP_006210* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000341	PI3K_Ras-bd_dom	Domain
IPR000403	PI3/4_kinase_cat_dom	Domain
IPR001263	PI3K_accessory_dom	Domain
IPR002420	PI3K-type_C2_dom	Domain
IPR003113	PI3K_ABD	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR015433	PI3/4_kinase	Family
IPR016024	ARM-type_fold	Homologous_superfamily
IPR018936	PI3/4_kinase_CS	Conserved_site
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR035892	C2_domain_sf	Homologous_superfamily
IPR036940	PI3/4_kinase_cat_sf	Homologous_superfamily
IPR037702	PI3-kinase_beta_cat	Domain
IPR042236	PI3K_accessory_sf	Homologous_superfamily

Pfam: PF00454, PF00613, PF00792, PF00794, PF02192

Enzyme classification (BRENDA):

• EC 2.7.1.137 — phosphatidylinositol 3-kinase (BRENDA: 29 organisms, 131 substrates, 146 inhibitors, 16 Km, 0 kcat entries)
• EC 2.7.1.153 — phosphatidylinositol-4,5-bisphosphate 3-kinase (BRENDA: 12 organisms, 48 substrates, 96 inhibitors, 1 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.03–44	7
PHOSPHATIDYLINOSITOL	0.034–64	3
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE	0.004–15	2
PHOSPHATIDYLINOSITOL 4-PHOSPHATE	0.009–10	2
1,2-DIOCTANOYLPHOSPHATIDYLINOSITOL 4,5-DIPHOSPHA	0.05	1
PHOSPHATIDYLINOSITOL-4,5-BISPHOSPHATE	0.011	1

Catalyzed reactions (Rhea), 3 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + ADP + H(+) (RHEA:21292)
• 1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phospho-1D-myo-inositol 4,5-bisphosphate + ATP = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo-inositol 3,4,5-triphosphate) + ADP + H(+) (RHEA:43396)

UniProt features (17 total): domain 5, mutagenesis site 4, region of interest 3, modified residue 2, chain 1, sequence variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P42338-F1	86.62	0.61

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 (2): 324, 1070

Mutagenesis-validated functional residues (4):

Position	Phenotype
342	enhanced inhibition by pik3r1 leading to reduced lipid kinase activity and reduced oncogenicity. does not modify regulat
805	loss of lipid kinase activity. may not affect insulin signaling and cell proliferation. partially affects oncogene-induc
1070	loss of autophosphorylation. no effect on phosphatidylinositol-4,5-bisphosphate 3-kinase activity.
1070	loss of autophosphorylation. decreased basal and stimulated phosphatidylinositol-4,5-bisphosphate 3-kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

32 pathways

ID	Pathway
R-HSA-109704	PI3K Cascade
R-HSA-112399	IRS-mediated signalling
R-HSA-114604	GPVI-mediated activation cascade
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1660499	Synthesis of PIPs at the plasma membrane
R-HSA-186763	Downstream signal transduction
R-HSA-198203	PI3K/AKT activation
R-HSA-201556	Signaling by ALK
R-HSA-202424	Downstream TCR signaling
R-HSA-2029485	Role of phospholipids in phagocytosis
R-HSA-210993	Tie2 Signaling
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-2424491	DAP12 signaling
R-HSA-2730905	Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-373753	Nephrin family interactions
R-HSA-389357	CD28 dependent PI3K/Akt signaling
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-512988	Interleukin-3, Interleukin-5 and GM-CSF signaling
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8853659	RET signaling
R-HSA-9027276	Erythropoietin activates Phosphoinositide-3-kinase (PI3K)
R-HSA-912526	Interleukin receptor SHC signaling
R-HSA-912631	Regulation of signaling by CBL
R-HSA-9673767	Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants
R-HSA-9673770	Signaling by PDGFRA extracellular domain mutants
R-HSA-9680350	Signaling by CSF1 (M-CSF) in myeloid cells
R-HSA-9725370	Signaling by ALK fusions and activated point mutants
R-HSA-9842640	Signaling by LTK in cancer
R-HSA-9842663	Signaling by LTK

MSigDB gene sets: 615 (showing top): REACTOME_INTERLEUKIN_2_FAMILY_SIGNALING, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, MORF_FLT1, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_SIGNALING_PATHWAY, GOBP_MYELOID_CELL_HOMEOSTASIS, GU_PDEF_TARGETS_DN, MORF_MSH3, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM

GO Biological Process (38): endothelial cell proliferation (GO:0001935), regulation of cell-matrix adhesion (GO:0001952), response to ischemia (GO:0002931), sphingosine-1-phosphate receptor signaling pathway (GO:0003376), intracellular calcium ion homeostasis (GO:0006874), endocytosis (GO:0006897), autophagy (GO:0006914), chemotaxis (GO:0006935), homophilic cell-cell adhesion (GO:0007156), signal transduction (GO:0007165), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), G protein-coupled receptor signaling pathway (GO:0007186), positive regulation of autophagy (GO:0010508), positive regulation of endothelial cell migration (GO:0010595), positive regulation of gene expression (GO:0010628), cell migration (GO:0016477), platelet activation (GO:0030168), positive regulation of neutrophil apoptotic process (GO:0033031), positive regulation of Rac protein signal transduction (GO:0035022), phosphatidylinositol-3-phosphate biosynthetic process (GO:0036092), embryonic cleavage (GO:0040016), natural killer cell mediated cytotoxicity (GO:0042267), negative regulation of MAPK cascade (GO:0043409), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), positive regulation of nitric oxide biosynthetic process (GO:0045429), phosphatidylinositol phosphate biosynthetic process (GO:0046854), phosphatidylinositol-mediated signaling (GO:0048015), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), angiogenesis involved in wound healing (GO:0060055), platelet aggregation (GO:0070527), negative regulation of vascular endothelial growth factor signaling pathway (GO:1900747), negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway (GO:1903298), negative regulation of sprouting angiogenesis (GO:1903671), regulation of clathrin-dependent endocytosis (GO:2000369), leukocyte mediated immunity (GO:0002443), lipid metabolic process (GO:0006629), cell adhesion (GO:0007155), innate immune response (GO:0045087)

GO Molecular Function (12): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), 1-phosphatidylinositol-3-kinase activity (GO:0016303), 1-phosphatidylinositol-4-phosphate 3-kinase activity (GO:0035005), insulin receptor substrate binding (GO:0043560), 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity (GO:0046934), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), phosphatidylinositol kinase activity (GO:0052742)

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), phosphatidylinositol 3-kinase complex (GO:0005942), phosphatidylinositol 3-kinase complex, class IA (GO:0005943), midbody (GO:0030496)

Reactome top-level categories

Rollup of top-21 pathways:

Category	Pathways
IRS-mediated signalling	1
IRS-related events triggered by IGF1R	1
Insulin receptor signalling cascade	1
Platelet activation, signaling and aggregation	1
Intracellular signaling by second messengers	1
PI Metabolism	1
Signaling by PDGF	1
Signaling by NTRK1 (TRKA)	1
Signaling by Receptor Tyrosine Kinases	1
TCR signaling	1
Fcgamma receptor (FCGR) dependent phagocytosis	1
Cell surface interactions at the vascular wall	1
PI3K/AKT Signaling in Cancer	1
DAP12 interactions	1
Fc epsilon receptor (FCERI) signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
phosphatidylinositol kinase activity	3
protein kinase activity	2
nuclear lumen	2
epithelial cell proliferation	1
cell-matrix adhesion	1
regulation of cell-substrate adhesion	1
response to stress	1
G protein-coupled receptor signaling pathway	1
sphingolipid mediated signaling pathway	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
response to chemical	1
taxis	1
cell-cell adhesion	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
enzyme-linked receptor protein signaling pathway	1
G protein-coupled receptor activity	1
signal transduction	1
autophagy	1
positive regulation of catabolic process	1
regulation of autophagy	1
regulation of endothelial cell migration	1
positive regulation of cell migration	1
endothelial cell migration	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
cell motility	1

Protein interactions and networks

STRING

2208 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIK3CB	PIK3R2	O00459	997
PIK3CB	PIK3R3	Q92569	997
PIK3CB	PIK3R1	P27986	997
PIK3CB	PIK3R5	Q8WYR1	990
PIK3CB	PIK3CA	P42336	984
PIK3CB	PIK3CD	O00329	983
PIK3CB	PIK3CG	P48736	976
PIK3CB	ARHGEF7	Q14155	962
PIK3CB	RAB5A	P20339	947
PIK3CB	AKT1	P31749	901
PIK3CB	CDC42	P21181	860
PIK3CB	IMMT	Q16891	843
PIK3CB	EGFR	P00533	842
PIK3CB	PTEN	P60484	829
PIK3CB	IRS1	P35568	823

IntAct

146 interactions, top by confidence:

A	B	Type	Score
PIK3R2	PIK3CA	psi-mi:“MI:0914”(association)	0.900
PIK3R3	PIK3CA	psi-mi:“MI:0914”(association)	0.900
PIK3R1	PIK3CD	psi-mi:“MI:0914”(association)	0.890
PIK3CB	PIK3R2	psi-mi:“MI:0914”(association)	0.860
PIK3R2	PIK3CB	psi-mi:“MI:0915”(physical association)	0.860
PIK3R1	PIK3CB	psi-mi:“MI:0915”(physical association)	0.840
PIK3CB	PIK3R1	psi-mi:“MI:0914”(association)	0.840
PIK3R1	PIK3CB	psi-mi:“MI:2364”(proximity)	0.840
PIK3CB	PIK3R3	psi-mi:“MI:0915”(physical association)	0.800
PIK3R3	PIK3CD	psi-mi:“MI:0914”(association)	0.800
NS	PIK3R2	psi-mi:“MI:0914”(association)	0.750
GRB2	WIPF3	psi-mi:“MI:0914”(association)	0.730
PIK3CB	PIK3R1	psi-mi:“MI:0915”(physical association)	0.720
PIK3R1	PIK3CB	psi-mi:“MI:0915”(physical association)	0.720
ERBB3	PIK3R2	psi-mi:“MI:0914”(association)	0.700
PIK3R2	IRS4	psi-mi:“MI:0914”(association)	0.640
PDGFRB	PIK3R2	psi-mi:“MI:0914”(association)	0.610
APP	PIK3CB	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (151): PIK3CB (Affinity Capture-Western), PIK3CB (Affinity Capture-MS), PIK3CB (Affinity Capture-MS), PIK3CB (Affinity Capture-MS), PIK3CB (Affinity Capture-MS), PIK3CB (Affinity Capture-MS), PIK3CB (Affinity Capture-MS), PIK3CB (Co-fractionation), PIK3CB (Co-fractionation), PIK3R1 (Co-fractionation), PIK3CB (Two-hybrid), PIK3CB (Affinity Capture-MS), PIK3CB (Co-localization), PIK3CB (Co-localization), PIK3CB (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K344, D3ZGS3, F1M386, F1MSG6, F1PBJ0, G5EF51, O00329, O02697, O35242, O35904, O70481, O88763, O94830, P32871, P42336, P42337, P42338, P42339, P42347, P42348, P48736, P50520, P54676, P70600, Q01968, Q14289, Q14BI7, Q16JS8, Q3MHU3, Q3UYK3, Q4KWH5, Q4KWH8, Q5D891, Q5ZI89, Q6AZN6, Q6GQ76, Q6NVF0, Q6PF93, Q7Z392, Q80Y98

Diamond homologs: A0A0G2K344, O00329, O00443, O00750, O02697, O35904, O70167, O70173, O75747, P32871, P42336, P42337, P42338, P48736, P50520, P54673, P54674, P54675, P54676, Q0WPX9, Q22258, Q54UC0, Q5RAY1, Q61194, Q8BTI9, Q8WN22, Q9C680, Q9FMJ0, Q9JHG7, Q9VK45, Q9Z1L0, A4IID4, A4QPH2, A9X1A0, B0KWC1, B1MTG7, B2KI64, B3EX61, B4UT09, E9Q3L2

SIGNOR signaling

34 interactions.

A	Effect	B	Mechanism
ERBB3	up-regulates	PIK3CB	binding
ERBB4	up-regulates	PIK3CB	binding
HRAS	“up-regulates activity”	PIK3CB	binding
KRAS	up-regulates	PIK3CB	binding
NRAS	up-regulates	PIK3CB	binding
PIK3CB	“up-regulates quantity”	PIP3	“chemical modification”
dactolisib	down-regulates	PIK3CB	“chemical inhibition”
pictrelisib	down-regulates	PIK3CB	“chemical inhibition”
“2-[[(1R)-1-[7-methyl-2-(4-morpholinyl)-4-oxo-9-pyrido[1,2-a]pyrimidinyl]ethyl]amino]benzoic acid”	down-regulates	PIK3CB	“chemical inhibition”
BKM120	down-regulates	PIK3CB	“chemical inhibition”
CH5132799	down-regulates	PIK3CB	“chemical inhibition”
PIK3AP1	up-regulates	PIK3CB	binding
1-[4-[[2-(2-amino-5-pyrimidinyl)-7-methyl-4-(4-morpholinyl)-6-thieno[3,2-d]pyrimidinyl]methyl]-1-piperazinyl]-2-hydroxy-1-propanone	down-regulates	PIK3CB	“chemical inhibition”
GSK1059615	down-regulates	PIK3CB	“chemical inhibition”
GSK2126458	down-regulates	PIK3CB	“chemical inhibition”
PI-103	down-regulates	PIK3CB	“chemical inhibition”
IC-87114	down-regulates	PIK3CB	“chemical inhibition”
PIK-90	down-regulates	PIK3CB	“chemical inhibition”
PKI-402	down-regulates	PIK3CB	“chemical inhibition”
PP121	down-regulates	PIK3CB	“chemical inhibition”
9-(1-anilinoethyl)-7-methyl-2-(4-morpholinyl)-4-pyrido[1,2-a]pyrimidinone	down-regulates	PIK3CB	“chemical inhibition”
XL765	down-regulates	PIK3CB	“chemical inhibition”
ZSTK-474	down-regulates	PIK3CB	“chemical inhibition”
PTEN	“down-regulates activity”	PIK3CB
CRKL	“up-regulates activity”	PIK3CB	binding
PIK3CB	“down-regulates activity”	GSK3B	phosphorylation
ITGB4	up-regulates	PIK3CB	binding
TNF	up-regulates	PIK3CB
IRS1	“up-regulates activity”	PIK3CB	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 106 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
Regulation of signaling by CBL	10	68.0×	4e-14
Constitutive Signaling by EGFRvIII	6	58.7×	5e-08
PI3K events in ERBB2 signaling	6	55.2×	5e-08
Signaling by ERBB2 ECD mutants	6	55.2×	5e-08
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	6	46.9×	1e-07
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	6	42.7×	2e-07
Signaling by ERBB2 KD Mutants	7	40.6×	4e-08
Downstream signal transduction	7	36.5×	5e-08

GO biological processes:

GO term	Partners	Fold	FDR
phosphatidylinositol 3-kinase/protein kinase B signal transduction	9	20.4×	6e-07
T cell costimulation	5	20.1×	6e-04
insulin receptor signaling pathway	8	19.1×	5e-06
epidermal growth factor receptor signaling pathway	7	18.6×	2e-05
ephrin receptor signaling pathway	5	18.5×	9e-04
cell surface receptor protein tyrosine kinase signaling pathway	8	14.9×	2e-05
vasculogenesis	5	13.7×	2e-03
cellular response to insulin stimulus	7	12.8×	2e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 3 cancer types — BLCA, GBM, PRAD.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	86
Likely benign	15
Benign	7

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
638630	NM_006219.3(PIK3CB):c.2961G>T (p.Glu987Asp)	Likely pathogenic

SpliceAI

3153 predictions. Top by Δscore:

Variant	Effect	Δscore
3:138656136:TTATA:T	donor_loss	1.0000
3:138656137:TATA:T	donor_loss	1.0000
3:138656139:TACC:T	donor_loss	1.0000
3:138656140:A:T	donor_loss	1.0000
3:138656141:C:CG	donor_loss	1.0000
3:138656281:G:GC	acceptor_gain	1.0000
3:138656284:A:AC	acceptor_gain	1.0000
3:138656284:A:C	acceptor_gain	1.0000
3:138656287:C:CT	acceptor_gain	1.0000
3:138656288:A:T	acceptor_gain	1.0000
3:138656310:T:C	acceptor_gain	1.0000
3:138656310:T:TC	acceptor_gain	1.0000
3:138657681:AGTAC:A	donor_loss	1.0000
3:138657682:GTACT:G	donor_loss	1.0000
3:138657683:TAC:T	donor_loss	1.0000
3:138657684:AC:A	donor_loss	1.0000
3:138657685:CTCA:C	donor_loss	1.0000
3:138657686:T:TA	donor_loss	1.0000
3:138657687:CAC:C	donor_loss	1.0000
3:138657688:A:AC	donor_gain	1.0000
3:138657688:ACCG:A	donor_loss	1.0000
3:138657688:ACCGG:A	donor_gain	1.0000
3:138657689:C:CC	donor_gain	1.0000
3:138657689:CCGG:C	donor_gain	1.0000
3:138657689:CCGGC:C	donor_gain	1.0000
3:138663900:GCTCA:G	donor_loss	1.0000
3:138663901:CTCAC:C	donor_loss	1.0000
3:138663902:TCA:T	donor_loss	1.0000
3:138663904:A:C	donor_loss	1.0000
3:138663905:C:CG	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000019979 (3:138722612 T>C), RS1000040377 (3:138689873 T>C), RS1000045307 (3:138741345 G>C), RS1000052335 (3:138784082 T>C), RS1000056818 (3:138835300 T>C), RS1000062701 (3:138777253 T>C), RS1000077623 (3:138827702 G>A,T), RS1000078641 (3:138674718 TC>T), RS1000092574 (3:138681829 A>C,G), RS1000103931 (3:138735696 C>T), RS1000112662 (3:138785032 G>A), RS1000151120 (3:138741632 T>C), RS1000181242 (3:138695899 G>A), RS1000183458 (3:138717311 T>C), RS1000236681 (3:138809869 G>A)

Disease associations

OMIM: gene MIM:602925 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): NK-cell enteropathy (MONDO:0016996)

Orphanet (1): NK-cell enteropathy (Orphanet:263665)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006661_139	Male-pattern baldness	3.000000e-19
GCST90002395_389	Mean platelet volume	8.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL3038510 (PROTEIN COMPLEX), CHEMBL3145 (SINGLE PROTEIN), CHEMBL3559703 (PROTEIN COMPLEX GROUP), CHEMBL3885615 (PROTEIN COMPLEX), CHEMBL6193791 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195502 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

53 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 126,093 (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
CHEMBL2216870	IDELALISIB	4	10,163
CHEMBL2396661	ALPELISIB	4	6,070
CHEMBL3039502	DUVELISIB	4	5,332
CHEMBL3218576	COPANLISIB	4	4,529
CHEMBL3545068	COPANLISIB HYDROCHLORIDE	4	1,306
CHEMBL3643413	LENIOLISIB	4	341
CHEMBL4650215	INAVOLISIB	4	876
CHEMBL1879463	DACTOLISIB	3	7,988
CHEMBL2017974	BUPARLISIB	3	6,568
CHEMBL165	RESVERATROL	3	60,144
CHEMBL2387080	TASELISIB	3	3,473
CHEMBL592445	GEDATOLISIB	3	3,177
CHEMBL603469	LESTAURTINIB	3
CHEMBL1236962	OMIPALISIB	2	3,989
CHEMBL2216863	DEZAPELISIB	2	412
CHEMBL3188551	GSK-2636771	2	1,814
CHEMBL3622533	FIMEPINOSTAT	2	2,487
CHEMBL3984425	EGANELISIB	2	1,200
CHEMBL4800252	RISOVALISIB	2	153
CHEMBL521851	PICTILISIB	2	6,071
CHEMBL1234354	PF-04691502	2
CHEMBL1684984	IZORLISIB	2
CHEMBL1922094	APITOLISIB	2
CHEMBL2105763	QUISINOSTAT	2
CHEMBL2165191	AZD-6482	2
CHEMBL2216859	NEMIRALISIB	2
CHEMBL230011	TG100-115	2
CHEMBL2336325	VISTUSERTIB	2
CHEMBL3218578	BGT-226 FREE BASE	2
CHEMBL3360203	PILARALISIB	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Phosphatidylinositol kinases

Most potent curated ligand interactions (62 total), top 25:

Ligand	Action	Affinity	Parameter
KU-0060648	Inhibition	9.3	pIC50
compound 15a [PMID: 32069401]	Inhibition	9.24	pIC50
compound 5d [PMID: 31335136]	Inhibition	9.15	pIC50
PF-06843195	Inhibition	8.7	pKi
compound 82 [PMID: 21332118]	Inhibition	8.7	pKi
PI-103	Inhibition	8.52	pIC50
copanlisib	Inhibition	8.43	pIC50
AZD8186	Inhibition	8.4	pIC50
TGX-221	Inhibition	8.3	pIC50
neolymphostin A	Inhibition	8.24	pKd
wortmannin	Inhibition	8.12	pKd
NVP-CLR457	Inhibition	8.08	pIC50
AZD6482	Inhibition	8.0	pIC50
bimiralisib	Inhibition	7.96	pKd
ZSTK474	Inhibition	7.77	pIC50
SAR260301	Inhibition	7.64	pIC50
apitolisib	Inhibition	7.57	pIC50
PIK-108	Negative	7.55	pIC50
pictilisib	Inhibition	7.48	pIC50
taselisib	Inhibition	7.28	pKi
fimepinostat	Inhibition	7.27	pIC50
BGT-226	Inhibition	7.2	pIC50
VS-5584	Inhibition	7.17	pIC50
samotolisib	Inhibition	7.11	pIC50
compound 20f [PMID: 28520415]	Inhibition	7.1	pIC50

Binding affinities (BindingDB)

940 measured of 1636 human assays (1637 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2,4-diamino-6-[[(1S)-1-[3-(6-amino-3-pyridinyl)-5-chloro-4-oxoquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile	IC50	0.7 nM	US-9221795: Phosphatidylinositol 3-kinase inhibitors
2,4-diamino-6-[[(1S)-1-[3-(6-amino-3-pyridinyl)-5-chloro-4-oxoquinazolin-2-yl]propyl]amino]pyrimidine-5-carbonitrile	IC50	0.8 nM	US-9221795: Phosphatidylinositol 3-kinase inhibitors
N-[2-(dimethylamino)ethyl]-8-[1-(3-fluoroanilino)ethyl]-2-morpholin-4-yl-4-oxochromene-6-carboxamide	IC50	1 nM	US-8673906: Chromenone derivatives
2,4-diamino-6-[[(1S)-1-[3-(6-amino-3-pyridinyl)-5,8-dichloro-4-oxoquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile	IC50	1 nM	US-9221795: Phosphatidylinositol 3-kinase inhibitors
2,4-diamino-6-[[(1S)-1-[3-(6-amino-4-methyl-3-pyridinyl)-5-chloro-4-oxoquinazolin-2-yl]propyl]amino]pyrimidine-5-carbonitrile	IC50	1 nM	US-9221795: Phosphatidylinositol 3-kinase inhibitors
2,4-diamino-6-[[(1S)-1-[3-(6-amino-4-methyl-3-pyridinyl)-5-chloro-4-oxoquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile	IC50	1 nM	US-9221795: Phosphatidylinositol 3-kinase inhibitors
US8895549, 11	IC50	1.6 nM	US-8895549: Aminoalcohol substituted 2,3-dihydroimidazo[1,2-c]quinazoline derivatives useful for treating hyper-proliferative disorders and diseases associated with angiogenesis
2,4-diamino-6-[[(1S)-1-[3-(5-aminopyrazin-2-yl)-5,8-dichloro-4-oxoquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile	IC50	1.8 nM	US-9499523: Phosphatidylinositol 3-kinase inhibitors
US8895549, 24	IC50	1.99 nM	US-8895549: Aminoalcohol substituted 2,3-dihydroimidazo[1,2-c]quinazoline derivatives useful for treating hyper-proliferative disorders and diseases associated with angiogenesis
N-[2-(dimethylamino)ethyl]-8-[1-(4-fluoroanilino)ethyl]-2-morpholin-4-yl-4-oxochromene-6-carboxamide	IC50	2 nM	US-8673906: Chromenone derivatives
8-(1-anilinoethyl)-N-[2-(dimethylamino)ethyl]-2-morpholin-4-yl-4-oxochromene-6-carboxamide	IC50	2 nM	US-8673906: Chromenone derivatives
N,N-dimethyl-2-morpholin-4-yl-4-oxo-8-[1-(3,4,5-trifluoroanilino)ethyl]chromene-6-carboxamide	IC50	2 nM	US-9718800: Chromenone derivatives
8-[1-(3,5-difluoroanilino)ethyl]-N-ethyl-N-methyl-2-morpholin-4-yl-4-oxochromene-6-carboxamide	IC50	2 nM	US-8673906: Chromenone derivatives
2,4-diamino-6-[[(S)-[3-(6-amino-3-pyridinyl)-5-chloro-4-oxoquinazolin-2-yl]-cyclopropylmethyl]amino]pyrimidine-5-carbonitrile	IC50	2 nM	US-9221795: Phosphatidylinositol 3-kinase inhibitors
2,4-diamino-6-[[(1S)-1-[3-(5-aminopyrazin-2-yl)-5-chloro-4-oxoquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile	IC50	2 nM	US-9499523: Phosphatidylinositol 3-kinase inhibitors
8-[(1R)-1-(3,5-difluoroanilino)ethyl]-N,N-dimethyl-2-morpholin-4-yl-4-oxochromene-6-carboxamide	IC50	2 nM	US-9718800: Chromenone derivatives
US8895549, 9	IC50	2.02 nM	US-8895549: Aminoalcohol substituted 2,3-dihydroimidazo[1,2-c]quinazoline derivatives useful for treating hyper-proliferative disorders and diseases associated with angiogenesis
US8895549, 7	IC50	2.22 nM	US-8895549: Aminoalcohol substituted 2,3-dihydroimidazo[1,2-c]quinazoline derivatives useful for treating hyper-proliferative disorders and diseases associated with angiogenesis
US8895549, 8	IC50	2.62 nM	US-8895549: Aminoalcohol substituted 2,3-dihydroimidazo[1,2-c]quinazoline derivatives useful for treating hyper-proliferative disorders and diseases associated with angiogenesis
US8895549, 19	IC50	2.78 nM	US-8895549: Aminoalcohol substituted 2,3-dihydroimidazo[1,2-c]quinazoline derivatives useful for treating hyper-proliferative disorders and diseases associated with angiogenesis
4-{6-chloroimidazo[1,2-a]pyridin-3-yl}-2-[(2-methyl-5-nitrobenzene)sulfonyl]-1,3-thiazole	IC50	2.8 nM
US8895549, 2	IC50	2.98 nM	US-8895549: Aminoalcohol substituted 2,3-dihydroimidazo[1,2-c]quinazoline derivatives useful for treating hyper-proliferative disorders and diseases associated with angiogenesis
US8895549, 37	IC50	2.98 nM	US-8895549: Aminoalcohol substituted 2,3-dihydroimidazo[1,2-c]quinazoline derivatives useful for treating hyper-proliferative disorders and diseases associated with angiogenesis
8-[1-(3-chloro-5-fluoroanilino)ethyl]-N,N-dimethyl-2-morpholin-4-yl-4-oxochromene-6-carboxamide	IC50	3 nM	US-9718800: Chromenone derivatives
8-[1-(3,5-difluoroanilino)ethyl]-6-(4-hydroxypiperidine-1-carbonyl)-2-morpholin-4-ylchromen-4-one	IC50	3 nM	US-8673906: Chromenone derivatives
N-(cyclopropylmethyl)-8-[1-(3,5-difluoroanilino)ethyl]-2-morpholin-4-yl-4-oxochromene-6-carboxamide	IC50	3 nM	US-8673906: Chromenone derivatives
2-[(1S)-1-[[6-amino-5-(5-methyl-1,3,4-oxadiazol-2-yl)pyrimidin-4-yl]amino]propyl]-5-chloro-3-phenylquinazolin-4-one	IC50	3 nM	US-9670194: Substituted aminopyrimidine compounds and methods of use
2,4-diamino-6-[[(1S)-1-[3-(6-amino-3-pyridinyl)-5-chloro-4-oxoquinazolin-2-yl]butyl]amino]pyrimidine-5-carbonitrile	IC50	3 nM	US-9221795: Phosphatidylinositol 3-kinase inhibitors
2,4-diamino-6-[[(S)-[3-(6-amino-3-pyridinyl)-5-chloro-8-fluoro-4-oxoquinazolin-2-yl]-cyclopropylmethyl]amino]pyrimidine-5-carbonitrile	IC50	3 nM	US-9221795: Phosphatidylinositol 3-kinase inhibitors
8-[(1R)-1-(3,5-difluoroanilino)ethyl]-N,N-dimethyl-2-[(2R)-2-methylmorpholin-4-yl]-4-oxochromene-6-carboxamide	IC50	3 nM	US-9718800: Chromenone derivatives
8-[(1R)-1-(3,4-difluoroanilino)ethyl]-N,N-dimethyl-2-morpholin-4-yl-4-oxochromene-6-carboxamide	IC50	3 nM	US-9718800: Chromenone derivatives
8-[(1R)-1-(3-chloro-2-fluoroanilino)ethyl]-N,N-dimethyl-2-morpholin-4-yl-4-oxochromene-6-carboxamide	IC50	3 nM	US-9718800: Chromenone derivatives
US8895549, 40	IC50	3.09 nM	US-8895549: Aminoalcohol substituted 2,3-dihydroimidazo[1,2-c]quinazoline derivatives useful for treating hyper-proliferative disorders and diseases associated with angiogenesis
US8895549, 14	IC50	3.09 nM	US-8895549: Aminoalcohol substituted 2,3-dihydroimidazo[1,2-c]quinazoline derivatives useful for treating hyper-proliferative disorders and diseases associated with angiogenesis
US8895549, 36	IC50	3.41 nM	US-8895549: Aminoalcohol substituted 2,3-dihydroimidazo[1,2-c]quinazoline derivatives useful for treating hyper-proliferative disorders and diseases associated with angiogenesis
2,4-diamino-6-[[(S)-[3-(5-aminopyrazin-2-yl)-5,8-dichloro-4-oxoquinazolin-2-yl]-cyclopropylmethyl]amino]pyrimidine-5-carbonitrile	IC50	3.6 nM	US-9499523: Phosphatidylinositol 3-kinase inhibitors
US8895549, 5	IC50	3.68 nM	US-8895549: Aminoalcohol substituted 2,3-dihydroimidazo[1,2-c]quinazoline derivatives useful for treating hyper-proliferative disorders and diseases associated with angiogenesis
US8895549, 18	IC50	3.9 nM	US-8895549: Aminoalcohol substituted 2,3-dihydroimidazo[1,2-c]quinazoline derivatives useful for treating hyper-proliferative disorders and diseases associated with angiogenesis
US8895549, 16	IC50	3.94 nM	US-8895549: Aminoalcohol substituted 2,3-dihydroimidazo[1,2-c]quinazoline derivatives useful for treating hyper-proliferative disorders and diseases associated with angiogenesis
8-[1-(3-chloro-4-fluoroanilino)ethyl]-N-(2-hydroxyethyl)-N-methyl-2-morpholin-4-yl-4-oxochromene-6-carboxamide	IC50	4 nM	US-8673906: Chromenone derivatives
8-[1-(3-chloroanilino)ethyl]-N,N-dimethyl-2-morpholin-4-yl-4-oxochromene-6-carboxamide	IC50	4 nM	US-8673906: Chromenone derivatives
8-[1-(2,3-difluoroanilino)ethyl]-N,N-dimethyl-2-morpholin-4-yl-4-oxochromene-6-carboxamide	IC50	4 nM	US-8673906: Chromenone derivatives
8-[1-(5-fluoro-2-methylanilino)ethyl]-N,N-dimethyl-2-morpholin-4-yl-4-oxochromene-6-carboxamide	IC50	4 nM	US-8673906: Chromenone derivatives
8-[1-(2-chloro-5-fluoroanilino)ethyl]-N,N-dimethyl-2-morpholin-4-yl-4-oxochromene-6-carboxamide	IC50	4 nM	US-8673906: Chromenone derivatives
8-[1-(5-chloro-2-methylanilino)ethyl]-N,N-dimethyl-2-morpholin-4-yl-4-oxochromene-6-carboxamide	IC50	4 nM	US-8673906: Chromenone derivatives
8-[1-(3-fluoro-5-methoxyanilino)ethyl]-N,N-dimethyl-2-morpholin-4-yl-4-oxochromene-6-carboxamide	IC50	4 nM	US-8673906: Chromenone derivatives
8-[1-(3-ethynyl-5-fluoroanilino)ethyl]-N,N-dimethyl-2-morpholin-4-yl-4-oxochromene-6-carboxamide	IC50	4 nM	US-8673906: Chromenone derivatives
8-[1-(3,5-difluoroanilino)ethyl]-N,N-diethyl-2-morpholin-4-yl-4-oxochromene-6-carboxamide	IC50	4 nM	US-8673906: Chromenone derivatives
8-[1-(3,5-difluoroanilino)ethyl]-2-morpholin-4-yl-6-(pyrrolidine-1-carbonyl)chromen-4-one	IC50	4 nM	US-8673906: Chromenone derivatives
8-[1-(3,5-difluoroanilino)ethyl]-6-(4-methylpiperazine-1-carbonyl)-2-morpholin-4-ylchromen-4-one	IC50	4 nM	US-8673906: Chromenone derivatives

ChEMBL bioactivities

4640 potent at pChembl≥5 of 4893 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	Ki	0.02	nM	OMIPALISIB
10.30	IC50	0.05	nM	CHEMBL2089119
10.00	IC50	0.1	nM	CHEMBL2089114
10.00	Kd	0.1	nM	CHEMBL4127116
9.89	Ki	0.13	nM	OMIPALISIB
9.89	IC50	0.13	nM	OMIPALISIB
9.72	IC50	0.19	nM	OMIPALISIB
9.70	IC50	0.2	nM	CHEMBL2089120
9.70	IC50	0.2	nM	CHEMBL2089112
9.70	Kd	0.2	nM	CHEMBL4125781
9.70	Kd	0.2	nM	CHEMBL4128507
9.70	Kd	0.2	nM	CHEMBL4127425
9.70	Kd	0.2	nM	CHEMBL4127570
9.70	IC50	0.2	nM	CHEMBL1762790
9.52	IC50	0.3	nM	CHEMBL2018222
9.52	IC50	0.3	nM	CHEMBL2089118
9.52	IC50	0.3	nM	CHEMBL2089116
9.52	Kd	0.3	nM	CHEMBL4130282
9.52	IC50	0.3	nM	CHEMBL5639851
9.52	IC50	0.3	nM	CHEMBL5647196
9.51	Ki	0.31	nM	CHEMBL4878958
9.47	IC50	0.34	nM	CHEMBL4531499
9.43	Ki	0.37	nM	CHEMBL4860369
9.40	IC50	0.4	nM	CHEMBL2018220
9.40	IC50	0.3981	nM	CHEMBL2322340
9.40	IC50	0.3981	nM	CHEMBL2322331
9.40	IC50	0.4	nM	CHEMBL3408270
9.40	Kd	0.4	nM	CHEMBL3956037
9.40	IC50	0.4	nM	CHEMBL4176771
9.39	IC50	0.41	nM	OMIPALISIB
9.30	IC50	0.5	nM	CHEMBL2018222
9.30	IC50	0.5	nM	CHEMBL2089109
9.30	IC50	0.5	nM	CHEMBL2089108
9.30	IC50	0.5	nM	CHEMBL2089107
9.30	IC50	0.5	nM	CHEMBL1086377
9.30	IC50	0.5	nM	CHEMBL5268567
9.28	IC50	0.53	nM	CHEMBL4166144
9.28	Ki	0.53	nM	OMIPALISIB
9.28	IC50	0.52	nM	OMIPALISIB
9.27	IC50	0.54	nM	CHEMBL4527563
9.24	IC50	0.58	nM	CHEMBL4440406
9.22	IC50	0.6	nM	CHEMBL2018219
9.22	IC50	0.6	nM	CHEMBL2089106
9.22	Ki	0.6	nM	CHEMBL2206921
9.22	IC50	0.6	nM	GSK-1059615
9.21	IC50	0.62	nM	CHEMBL5592140
9.20	IC50	0.631	nM	CHEMBL2089106
9.20	IC50	0.631	nM	CHEMBL2322338
9.18	IC50	0.66	nM	CHEMBL5569425
9.17	IC50	0.67	nM	CHEMBL4739883

PubChem BioAssay actives

2984 with measured affinity, of 4468 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
2,4-difluoro-N-[2-methoxy-5-(4-pyridazin-4-ylquinolin-6-yl)-3-pyridinyl]benzenesulfonamide	1994267: Inhibition of P13Kbeta (unknown origin) assessed as inhibition constant	ki	<0.0001	uM
8-[1-(3,5-difluoroanilino)ethyl]-N-[2-(dimethylamino)ethyl]-2-morpholin-4-ylquinoxaline-6-carboxamide	1491554: Binding affinity to wild-type human PIK3Cbeta (P118 to S1070 residues) expressed in mammalian expression system by KINOMEScan assay	kd	0.0001	uM
2-[[4-[(3-chloro-2-methylphenyl)methyl]-2-morpholin-4-yl-7-oxo-[1,3]thiazolo[4,5-d]pyrimidin-5-yl]sulfanyl]acetic acid	682825: Inhibition of PI3K beta by continuous TR-FRET assay	ic50	0.0001	uM
4-[(3-chloro-2-methylphenyl)methyl]-5-(hydroxymethyl)-2-morpholin-4-yl-[1,3]thiazolo[4,5-d]pyrimidin-7-one	682825: Inhibition of PI3K beta by continuous TR-FRET assay	ic50	0.0001	uM
8-[(1R)-1-(3,5-difluoroanilino)ethyl]-N-[2-(dimethylamino)ethyl]-2-morpholin-4-ylquinoxaline-6-carboxamide	1491554: Binding affinity to wild-type human PIK3Cbeta (P118 to S1070 residues) expressed in mammalian expression system by KINOMEScan assay	kd	0.0002	uM
8-[1-(3-fluoroanilino)ethyl]-N-[2-(methylamino)ethyl]-2-morpholin-4-ylquinoxaline-6-carboxamide	1491554: Binding affinity to wild-type human PIK3Cbeta (P118 to S1070 residues) expressed in mammalian expression system by KINOMEScan assay	kd	0.0002	uM
N-[2-(dimethylamino)ethyl]-8-[(3-fluoro-2-methylanilino)methyl]-2-morpholin-4-ylquinoxaline-6-carboxamide	1491554: Binding affinity to wild-type human PIK3Cbeta (P118 to S1070 residues) expressed in mammalian expression system by KINOMEScan assay	kd	0.0002	uM
[8-[1-(3,5-difluorophenyl)pyrrolidin-2-yl]-2-morpholin-4-ylquinoxalin-6-yl]-[(3R,5S)-3,5-dimethylpiperazin-1-yl]methanone	1491554: Binding affinity to wild-type human PIK3Cbeta (P118 to S1070 residues) expressed in mammalian expression system by KINOMEScan assay	kd	0.0002	uM
5-[[1-(4-amino-6-methyl-1,3,5-triazin-2-yl)benzimidazol-2-yl]amino]benzene-1,3-diol	589586: Inhibition of PI3Kbeta	ic50	0.0002	uM
5-amino-4-[(3-chloro-2-methylphenyl)methyl]-2-morpholin-4-yl-[1,3]thiazolo[4,5-d]pyrimidin-7-one	682825: Inhibition of PI3K beta by continuous TR-FRET assay	ic50	0.0002	uM
5-(hydroxymethyl)-4-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-2-morpholin-4-yl-[1,3]thiazolo[4,5-d]pyrimidin-7-one	682825: Inhibition of PI3K beta by continuous TR-FRET assay	ic50	0.0002	uM
8-[(2R)-1-(3,5-difluorophenyl)pyrrolidin-2-yl]-N,N-dimethyl-2-morpholin-4-ylquinoxaline-6-carboxamide	1491554: Binding affinity to wild-type human PIK3Cbeta (P118 to S1070 residues) expressed in mammalian expression system by KINOMEScan assay	kd	0.0003	uM
2,4-difluoro-N-[2-methoxy-5-[4-methyl-8-[(3R)-oxolan-3-yl]oxyquinazolin-6-yl]-3-pyridinyl]benzenesulfonamide	1525585: Inhibition of recombinant human N-terminal FLAG-tagged full-length p110beta/human p85alpha expressed in Sf9 insect cells using PIP2 as substrate by ADP-glo assay	ic50	0.0003	uM
N-[2-chloro-5-[3-(6-morpholin-4-yl-3-pyridinyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-3-pyridinyl]benzenesulfonamide	2140009: Inhibition of PI3Kbeta (unknown origin)	ic50	0.0003	uM
N-[2-chloro-5-[3-[1-(2-morpholin-4-ylethyl)pyrazol-4-yl]-1H-pyrrolo[2,3-b]pyridin-5-yl]-3-pyridinyl]benzenesulfonamide	2140009: Inhibition of PI3Kbeta (unknown origin)	ic50	0.0003	uM
2-methyl-5-(2-methylmorpholin-4-yl)-3-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-[1,2,4]triazolo[1,5-a]pyrimidin-7-one	657204: Inhibition of PI3Kbeta by continuous read time resolved fluorescence resonance energy transfer displacement assay	ic50	0.0003	uM
4-[(3-chloro-2-methylphenyl)methyl]-5-methoxy-2-morpholin-4-yl-[1,3]thiazolo[4,5-d]pyrimidin-7-one	682825: Inhibition of PI3K beta by continuous TR-FRET assay	ic50	0.0003	uM
4-[(3-chloro-2-methylphenyl)methyl]-5-methylsulfanyl-2-morpholin-4-yl-[1,3]thiazolo[4,5-d]pyrimidin-7-one	682825: Inhibition of PI3K beta by continuous TR-FRET assay	ic50	0.0003	uM
18-fluoro-25-methoxy-31-methyl-22,22-dioxo-3,22lambda6,30-trithia-6,8,15,23,26-pentazahexacyclo[22.3.1.12,5.110,13.117,21.04,9]hentriaconta-1(28),2(31),4,6,8,10,12,17,19,21(29),24,26-dodecaen-16-one	1785806: Inhibition of human PI3K p110beta/p85alpha by HTRF assay	ki	0.0003	uM
2-methyl-3-N-[2-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-6-morpholin-4-ylimidazo[1,2-b]pyridazine-3,8-diamine	1325758: Binding affinity to human PI3Kbeta (118 to 1070 residues) expressed in mammalian expression system by KINOMEscan assay	kd	0.0004	uM
N-[5-[2-amino-4-methyl-8-[(3R)-oxolan-3-yl]oxyquinazolin-6-yl]-2-methoxy-3-pyridinyl]-2,4-difluorobenzenesulfonamide	1355491: Inhibition of PI3Kbeta (unknown origin) using PIP2 as substrate by ADP-Glo assay	ic50	0.0004	uM
8-[(1R)-1-(3,5-difluoroanilino)ethyl]-N,N-dimethyl-2-[(2S)-2-methylmorpholin-4-yl]-4-oxochromene-6-carboxamide	1195949: Inhibition of PI3Kbeta in PTEN-null human MDA-MB-468 cells assessed as inhibition of Akt phosphorylation after 2 hrs	ic50	0.0004	uM
2-methylsulfanyl-3-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-5-morpholin-4-yl-[1,2,4]triazolo[1,5-a]pyrimidin-7-one	657204: Inhibition of PI3Kbeta by continuous read time resolved fluorescence resonance energy transfer displacement assay	ic50	0.0004	uM
25-methoxy-31-methyl-22,22-dioxo-3,22lambda6,30-trithia-6,8,15,23,26-pentazahexacyclo[22.3.1.12,5.110,13.117,21.04,9]hentriaconta-1(28),2(31),4,6,8,10,12,17(29),18,20,24,26-dodecaen-16-one	1785806: Inhibition of human PI3K p110beta/p85alpha by HTRF assay	ki	0.0004	uM
2-methyl-3-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-5-morpholin-4-yl-1H-pyrazolo[1,5-a]pyrimidin-7-one	727752: Inhibition of PI3Kbeta (unknown origin)	ic50	0.0004	uM
3-[(2,3-dichlorophenyl)methyl]-5-morpholin-4-yl-2-(trifluoromethyl)-1H-pyrazolo[1,5-a]pyrimidin-7-one	727752: Inhibition of PI3Kbeta (unknown origin)	ic50	0.0004	uM
2-(4-ethylpiperazin-1-yl)-N-[4-(2-morpholin-4-yl-4-oxochromen-8-yl)dibenzothiophen-1-yl]acetamide	768759: Inhibition of PI-3K beta (unknown origin)	ic50	0.0005	uM
3-[(3-fluoro-2-piperidin-4-ylphenyl)methyl]-2-methyl-6-morpholin-4-ylimidazo[1,2-b]pyridazin-8-amine	1934077: Inhibition of PI3Kbeta (unknown origin)	ic50	0.0005	uM
2,4-difluoro-N-[2-methoxy-5-[4-methyl-8-(oxan-4-yloxy)quinazolin-6-yl]-3-pyridinyl]benzenesulfonamide	1525585: Inhibition of recombinant human N-terminal FLAG-tagged full-length p110beta/human p85alpha expressed in Sf9 insect cells using PIP2 as substrate by ADP-glo assay	ic50	0.0005	uM
N-[5-[2-amino-4-methyl-8-(oxan-4-yloxy)quinazolin-6-yl]-2-methoxy-3-pyridinyl]-2,4-difluorobenzenesulfonamide	1355491: Inhibition of PI3Kbeta (unknown origin) using PIP2 as substrate by ADP-Glo assay	ic50	0.0005	uM
4-[(3-chloro-2-methylphenyl)methyl]-5-methyl-2-morpholin-4-yl-[1,3]thiazolo[4,5-d]pyrimidin-7-one	682825: Inhibition of PI3K beta by continuous TR-FRET assay	ic50	0.0005	uM
5-cyclopropyl-4-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-2-morpholin-4-yl-[1,3]thiazolo[4,5-d]pyrimidin-7-one	682825: Inhibition of PI3K beta by continuous TR-FRET assay	ic50	0.0005	uM
5-ethyl-4-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-2-morpholin-4-yl-[1,3]thiazolo[4,5-d]pyrimidin-7-one	682825: Inhibition of PI3K beta by continuous TR-FRET assay	ic50	0.0005	uM
2,4-difluoro-N-[2-methoxy-5-[3-[5-[2-(4-methylpiperazin-1-yl)ethyl]-1,3,4-oxadiazol-2-yl]imidazo[1,2-a]pyridin-6-yl]-3-pyridinyl]benzenesulfonamide	1560709: Inhibition of recombinant human full-length His-tagged p110beta/p85alpha expressed in baculovirus expression system using PIP2 as substrate measured after 1 hr by ADP-glo assay	ic50	0.0006	uM
N-(2-aminophenyl)-4-[3-[6-[5-[(2,4-difluorophenyl)sulfonylamino]-6-methoxy-3-pyridinyl]-4-methylquinazolin-8-yl]oxypropyl]benzamide	2096575: Inhibition of PI3Kbeta (unknown origin) using PIP2 as substrate incubated for 1 hr in presence of ATP by ADP-Glo assay	ic50	0.0006	uM
(5Z)-5-[(4-pyridin-4-ylquinolin-6-yl)methylidene]-1,3-thiazolidine-2,4-dione	1994223: Inhibition of P13Kbeta (unknown origin)	ic50	0.0006	uM
5-methyl-4-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-2-morpholin-4-yl-[1,3]thiazolo[4,5-d]pyrimidin-7-one	682825: Inhibition of PI3K beta by continuous TR-FRET assay	ic50	0.0006	uM
2-amino-4-[5-chloro-2-[[6-chloro-5-(dimethylsulfamoylamino)-3-pyridinyl]amino]-3-pyridinyl]-6-methyl-1,3,5-triazine	714986: Inhibition of human N-terminal polyHis-tagged PI3K p110beta expressed in baculovirus infected Hi5 cells using Phosphatidylinositol-4,5-bisphosphate as substrate after 20 mins by AlphaScreen assay	ki	0.0006	uM
2-methyl-3-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-5-morpholin-4-yl-[1,2,4]triazolo[1,5-a]pyrimidin-7-one	657204: Inhibition of PI3Kbeta by continuous read time resolved fluorescence resonance energy transfer displacement assay	ic50	0.0006	uM
3-[(2,3-dichlorophenyl)methyl]-2-ethyl-5-pyridin-4-yl-1H-pyrazolo[1,5-a]pyrimidin-7-one	727752: Inhibition of PI3Kbeta (unknown origin)	ic50	0.0006	uM
2,4-diamino-6-[[(S)-[8-chloro-6-fluoro-4-oxo-3-(1H-pyrazol-5-yl)quinazolin-2-yl]-cyclopropylmethyl]amino]pyrimidine-5-carbonitrile	1438034: Inhibition of N-terminal His6-tagged recombinant full-length human PI3K p110beta/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2/ATP as substrate after 30 mins by TR-FRET assay	ic50	0.0007	uM
2,4-diamino-6-[[(1S)-1-[5-chloro-4-oxo-3-(1H-pyrazol-5-yl)quinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile	1438034: Inhibition of N-terminal His6-tagged recombinant full-length human PI3K p110beta/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2/ATP as substrate after 30 mins by TR-FRET assay	ic50	0.0007	uM
2,4-difluoro-N-[2-methoxy-5-[4-methyl-8-[(3-methyloxetan-3-yl)methoxy]quinazolin-6-yl]-3-pyridinyl]benzenesulfonamide	1525585: Inhibition of recombinant human N-terminal FLAG-tagged full-length p110beta/human p85alpha expressed in Sf9 insect cells using PIP2 as substrate by ADP-glo assay	ic50	0.0007	uM
4-amino-6-[[(1S)-1-[5-chloro-3-(4-hydroxyphenyl)-4-oxoquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile	1438034: Inhibition of N-terminal His6-tagged recombinant full-length human PI3K p110beta/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2/ATP as substrate after 30 mins by TR-FRET assay	ic50	0.0007	uM
2,4-difluoro-N-[2-methoxy-5-[4-[(E)-4-(4-methylpiperazin-1-yl)-4-oxobut-2-en-2-yl]quinolin-6-yl]-3-pyridinyl]benzenesulfonamide	1731676: Inhibition of PI3Kbeta (unknown origin) using PIP2 as substrate measured after 1 hr by ADP-glo assay	ic50	0.0007	uM
N-(2-aminophenyl)-7-[6-[5-[(2,4-difluorophenyl)sulfonylamino]-6-methoxy-3-pyridinyl]-4-methylquinazolin-8-yl]oxyheptanamide	2096575: Inhibition of PI3Kbeta (unknown origin) using PIP2 as substrate incubated for 1 hr in presence of ATP by ADP-Glo assay	ic50	0.0007	uM
2-(difluoromethyl)-1-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)benzimidazol-4-ol	626777: Inhibition of human recombinant PI3K p110beta expressed in Sf21 insect cells using phosphatidylinositol as substrate after 1 hr by phosphoimaging	ic50	0.0007	uM
N-[2-(dimethylamino)ethyl]-4-[[(2E)-2-[[7-fluoro-5-methoxy-2-(1,3,5-trimethylpyrazol-4-yl)-1H-indol-3-yl]methylidene]-3-oxo-1-benzofuran-5-yl]carbamoylamino]-N-methylbenzamide	484473: Inhibition of PI3Kbeta	ic50	0.0007	uM
methyl (3S)-3-[4-(2-aminopyrimidin-5-yl)-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidine-1-carboxylate	1707452: Inhibition of recombinant human PI3K p110beta/p85alpha using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 15 mins followed by addition of ATP and measured after 30 mins by fluorescence polarisation assay	ki	0.0008	uM
2-(difluoromethyl)-1-(4,6-dimorpholin-4-ylpyrimidin-2-yl)benzimidazol-4-ol	626777: Inhibition of human recombinant PI3K p110beta expressed in Sf21 insect cells using phosphatidylinositol as substrate after 1 hr by phosphoimaging	ic50	0.0008	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cannabidiol	affects cotreatment, decreases expression, increases expression	6
Benzo(a)pyrene	increases expression, decreases expression	4
Tretinoin	increases expression, decreases expression, decreases reaction, increases activity	3
moringin	affects cotreatment, decreases expression	2
bisphenol A	affects cotreatment, affects methylation, decreases expression, decreases methylation	2
entinostat	increases expression, affects cotreatment	2
Resveratrol	decreases expression, affects binding, decreases activity	2
Valproic Acid	increases expression	2
aristolochic acid I	decreases expression	1
alpha phellandrene	increases expression	1
bis(tri-n-butyltin)oxide	increases expression	1
morin	increases expression	1
sinomenine	increases expression, increases phosphorylation, decreases reaction	1
decabromobiphenyl ether	decreases expression	1
tributyltin	increases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
cobaltous chloride	increases expression	1
dioscin	decreases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
ochratoxin A	increases expression	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
methylmercury II	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
fosbretabulin	decreases expression, increases reaction	1
tamibarotene	affects expression	1
di-n-butylphosphoric acid	affects expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases expression, increases reaction	1

ChEMBL screening assays

841 unique, capped per target: 814 binding, 20 admet, 6 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1219775	Binding	Inhibition of PI3K (p110beta/p85-alpha) at 1 uM by radiometric method	Discovery of pyrrole-indoline-2-ones as Aurora kinase inhibitors with a different inhibition profile. — J Med Chem
CHEMBL4124222	ADMET	Inhibition of recombinant human 6His-tagged PI3K p110beta/p85alpha using DiC8-PIP2 as substrate preincubated for 10 mins followed by substrate addition measured after 60 mins by ADP-Glo assay	Discovery of Highly Isoform Selective Orally Bioavailable Phosphoinositide 3-Kinase (PI3K)-γ Inhibitors. — J Med Chem
CHEMBL5123068	Toxicity	Inhibition of human PI3Kbeta by ADP-Glo assay	Discovery of novel 7,8-dihydropteridine-6(5H)-one-based DNA-PK inhibitors as potential anticancer agents via scaffold hopping strategy. — Eur J Med Chem

Cellosaurus cell lines

13 cell lines: 12 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0392	LN-18	Cancer cell line	Male
CVCL_1056	A-498	Cancer cell line	Male
CVCL_A1FL	Evsa-T GDC-0941-resistant clone 1	Cancer cell line	Female
CVCL_A1FN	ZR-75-1 GDC-0941-resistant	Cancer cell line	Female
CVCL_D7X9	Ubigene A-549 PIK3CB KO	Cancer cell line	Male
CVCL_D8SQ	Ubigene HCT 116 PIK3CB KO	Cancer cell line	Male
CVCL_D9N8	Ubigene HEK293 PIK3CB KO	Transformed cell line	Female
CVCL_E0KK	Ubigene HeLa PIK3CB KO	Cancer cell line	Female
CVCL_E1IQ	HyCyte A-498 KO-hCBX7	Cancer cell line	Male
CVCL_E2T3	MTC-22	Cancer cell line	Female

Clinical trials (associated diseases)

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