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): 143 total — 1 likely-pathogenic
• Regional missense constraint (gnomAD): 1 of 4 regions constrained (≈2% of expected missense variation)
• GTEx eGene: eQTL in 19 tissues, sQTL in 2 (q < 0.05)
• Drug target: yes — 5 curated mechanism-of-action drugs, 26 via a complex or family; 53 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types (inferred from mutation patterns)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.32 (highly constrained)
• MANE Select transcript: NM_006219
• Interaction hub: 10,184 STRING partners (top 1% of genes corpus-wide)
• Notable: 143 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 49 — 34 protein_coding, 12 nonsense_mediated_decay, 3 retained_intron

MANE Select: ENST00000674063

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 2: 3, TSL 3: 3, TSL 5: 5

ENST00000674063, ENST00000462294, ENST00000462898, ENST00000465581, ENST00000469284, ENST00000473435, ENST00000477593, ENST00000481749, ENST00000483968, ENST00000485060, ENST00000487552, ENST00000493568, 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, ENST00001048974, ENST00001048975, ENST00001048977, ENST00001048978, ENST00001048979, ENST00001048980, ENST00001048981, ENST00001073592, ENST00001073593, ENST00001109068, ENST00001113073, ENST00001144433

RefSeq mRNA: 10 — MANE Select: NM_006219 NM_001256045, NM_001437286, NM_001437287, NM_001437288, NM_001437289, NM_001437290, NM_001437291, NM_001437292, NM_001437293, 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.

Highest expression (Bgee): tendon of biceps brachii, medial globus pallidus, endothelial cell, middle temporal gyrus, choroid plexus epithelium.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PIK3CB is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 19 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 21 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Esophagus Mucosa	eqtl	3.0e-13	+0.17	3:138860948:G:A
Adipose Subcutaneous	eqtl	1.4e-07	-0.14	3:138843468:A:C
Skin Sun Exposed Lower leg	eqtl	2.5e-07	+0.12	3:138862276:C:G
Cells EBV-transformed lymphocytes	eqtl	2.8e-07	+0.27	3:138465843:G:A
Cells Cultured fibroblasts	eqtl	2.9e-06	+0.13	3:138852741:A:T
Breast Mammary Tissue	eqtl	3.6e-04	-0.15	3:138843468:A:C
Skin Not Sun Exposed Suprapubic	eqtl	4.4e-04	+0.22	3:138915124:A:C
Brain Cerebellar Hemisphere	eqtl	3.3e-03	+0.12	3:138334345:A:G
Stomach	eqtl	1.0e-02	-0.57	3:138312297:C:G
Testis	eqtl	1.0e-02	-0.28	3:138373060:A:G
Adipose Subcutaneous	sqtl	1.2e-02	-1.16	3:138009659:C:T
Brain Caudate basal ganglia	sqtl	2.2e-02	+1.02	3:138577167:G:C
Pancreas	eqtl	2.4e-02	+0.30	3:138875640:C:CTTCTA
Colon Transverse	eqtl	2.5e-02	-0.09	3:137967114:T:C
Minor Salivary Gland	eqtl	2.7e-02	-0.21	3:138891654:C:T
Heart Atrial Appendage	eqtl	3.0e-02	-0.33	3:139720725:G:A
Brain Anterior cingulate cortex BA24	eqtl	3.0e-02	+0.11	3:139310129:G:A
Whole Blood	eqtl	3.5e-02	-0.12	3:138864416:C:T
Brain Cerebellum	eqtl	4.0e-02	+0.30	3:138225755:A:C
Liver	eqtl	4.1e-02	-0.13	3:138895915:AT:A

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

showing 100 of 300 tissues 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
renal glomerulus	UBERON:0000074	90.69	gold quality
inferior olivary complex	UBERON:0002127	90.69	gold quality
placenta	UBERON:0001987	90.65	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.63	gold quality
entorhinal cortex	UBERON:0002728	90.56	gold quality
CA1 field of hippocampus	UBERON:0003881	90.55	gold quality
tendon	UBERON:0000043	90.43	gold quality
parotid gland	UBERON:0001831	90.32	gold quality
substantia nigra pars reticulata	UBERON:0001966	90.31	gold quality
mononuclear cell	CL:0000842	90.30	gold quality
colonic mucosa	UBERON:0000317	90.27	gold quality
medulla oblongata	UBERON:0001896	90.17	gold quality
metanephric glomerulus	UBERON:0004736	90.14	gold quality
skin of hip	UBERON:0001554	90.08	gold quality
leukocyte	CL:0000738	90.05	gold quality
bone marrow	UBERON:0002371	90.01	gold quality
tongue squamous epithelium	UBERON:0006919	89.95	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.94	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.71	gold quality
prefrontal cortex	UBERON:0000451	89.62	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.45	gold quality
heart right ventricle	UBERON:0002080	89.38	gold quality
gastrocnemius	UBERON:0001388	89.32	gold quality
seminal vesicle	UBERON:0000998	89.22	gold quality
pigmented layer of retina	UBERON:0001782	89.21	gold quality
retina	UBERON:0000966	89.18	gold quality
jejunum	UBERON:0002115	89.18	gold quality
visceral pleura	UBERON:0002401	88.94	gold quality
renal medulla	UBERON:0000362	88.88	gold quality
muscle of leg	UBERON:0001383	88.81	gold quality
frontal cortex	UBERON:0001870	88.81	gold quality
frontal lobe	UBERON:0016525	88.79	gold quality
caput epididymis	UBERON:0004358	88.78	gold quality
islet of Langerhans	UBERON:0000006	88.72	gold quality
cerebral cortex	UBERON:0000956	88.59	gold quality
palpebral conjunctiva	UBERON:0001812	88.52	gold quality
oral cavity	UBERON:0000167	88.51	gold quality
gingiva	UBERON:0001828	88.48	gold quality
neocortex	UBERON:0001950	88.30	gold quality
pancreas	UBERON:0001264	88.20	gold quality
hair follicle	UBERON:0002073	88.16	gold quality
rectum	UBERON:0001052	88.13	gold quality
body of pancreas	UBERON:0001150	88.09	gold quality
colonic epithelium	UBERON:0000397	88.02	gold quality
germinal epithelium of ovary	UBERON:0001304	88.01	gold quality
cerebellar cortex	UBERON:0002129	88.01	gold quality
parietal pleura	UBERON:0002400	88.01	gold quality
cerebellar hemisphere	UBERON:0002245	88.00	gold quality
telencephalon	UBERON:0001893	87.99	gold quality
gingival epithelium	UBERON:0001949	87.98	gold quality
mammalian vulva	UBERON:0000997	87.97	gold quality
pleura	UBERON:0000977	87.90	gold quality
tonsil	UBERON:0002372	87.86	gold quality
cerebellum	UBERON:0002037	87.83	gold quality
squamous epithelium	UBERON:0006914	87.65	gold quality
penis	UBERON:0000989	87.64	gold quality
cortex of kidney	UBERON:0001225	87.51	gold quality
Ammon’s horn	UBERON:0001954	87.51	gold quality
duodenum	UBERON:0002114	87.45	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	87.44	gold quality
zone of skin	UBERON:0000014	87.34	gold quality
right frontal lobe	UBERON:0002810	87.29	gold quality
corpus epididymis	UBERON:0004359	87.25	gold quality
thyroid gland	UBERON:0002046	87.18	gold quality
brain	UBERON:0000955	87.16	gold quality
ventral tegmental area	UBERON:0002691	87.15	gold quality
kidney	UBERON:0002113	87.13	gold quality
skin of abdomen	UBERON:0001416	87.09	gold quality
central nervous system	UBERON:0001017	87.07	gold quality
ventricular zone	UBERON:0003053	87.06	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Choroid plexus	tissue	55.6
Thyroid gland	tissue	40.4	medium
Postcentral gyrus	tissue	38.1
Locus coeruleus	tissue	33.8
Nucleus accumbens	tissue	33.5
Hippocampus	tissue	29.2	medium
Kidney	tissue	24.6	medium
Putamen	tissue	23.6
Pons	tissue	23.1
Bone marrow	tissue	22.4	medium
Cerebral cortex	tissue	22.3	medium
Somatosensory cortex	tissue	22.3
Skin 1	tissue	22.2	medium
Thalamus	tissue	21.4
Retina	tissue	21.2
Occipital cortex	tissue	21.2
Pancreas	tissue	20.8	medium
Midbrain	tissue	20.6
Motor cortex	tissue	20.1
Cerebellum	tissue	20.0	medium
Superior colliculi	tissue	19.5
Retrosplenial and cingulate cortex	tissue	18.7
Prefrontal cortex	tissue	18.6
Salivary gland	tissue	18.6	medium
Ventral forebrain	tissue	18.6
Basal ganglia	tissue	18.5	medium
Hippocampal formation	tissue	18.5
Entorhinal cortex	tissue	18.5
Retrosplenial cortex	tissue	18.3
Medulla oblongata	tissue	18.2
Spinal cord	tissue	18.2
Parathyroid gland	tissue	18.1	medium
Septum	tissue	17.8
Skeletal muscle	tissue	17.6	low
Placenta	tissue	17.5	medium
Substantia nigra	tissue	17.3
Temporal cortex	tissue	17.2
Periaqueductal gray	tissue	17.1
Rectum	tissue	17.0	medium
Esophagus	tissue	16.9	medium
Hypothalamus	tissue	16.9
Small intestine	tissue	16.8	medium
Duodenum	tissue	16.7	medium
Colon	tissue	16.6	medium
Insular cortex	tissue	16.4
Thymus	tissue	15.8
Amygdala	tissue	15.4
Heart muscle	tissue	14.7	medium
Prostate	tissue	14.0	medium
Corpus callosum	tissue	12.8
Olfactory bulb	tissue	12.4
Tonsil	tissue	12.3	medium
Stomach 1	tissue	12.2	medium
Tongue	tissue	12.2
Appendix	tissue	11.7	medium
Cervix	tissue	11.6	medium
Lymph node	tissue	11.4	low
Seminal vesicle	tissue	11.3	medium
Fallopian tube	tissue	11.3	medium
Breast	tissue	11.1	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Cerebellar cortex (42.0), Precentral gyrus, middle (41.7), Transversal temporal gyrus, anterior (40.5), Area parastriata, superior (40.3), Vermis (40.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, STAT1

miRNA regulators (miRDB)

Targeting PIK3CB by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 226 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.319, missense Z 3.38 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000674063 splits into 4 regions with different missense tolerance; 1 is missense-constrained (≈2% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
3:138,655,392–138,657,788	88 / 147.8	0.60	no
3:138,657,789–138,663,937	3 / 31.1	0.10	yes (p 4.6e-07)
3:138,663,938–138,691,019	165 / 295.4	0.56	no
3:138,691,020–138,759,343	612 / 801.1	0.76	no

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1922019) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 48 distinct phenotype terms.

Mouse phenotype (MP)	Records
insulin resistance	2
decreased platelet aggregation	2
embryonic lethality, incomplete penetrance	2
decreased fibroblast proliferation	2
small testis	1
abnormal spermatogenesis	1
decreased body weight	1
weight loss	1
decreased embryo size	1
postnatal growth retardation	1
increased circulating follicle stimulating hormone level	1
reduced male fertility	1
abnormal seminiferous tubule morphology	1
decreased circulating triglyceride level	1
abnormal spermatogonia proliferation	1
oligozoospermia	1
decreased heart weight	1
increased insulin secretion	1
decreased lumbar vertebrae number	1
decreased testis weight	1
decreased male germ cell number	1
azoospermia	1
decreased circulating cholesterol level	1
impaired glucose tolerance	1
decreased heart rate	1

+23 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	P32871	99.8%	Diamond
Callithrix jacchus	B0KWC1	99.6%	Diamond
Plecturocebus moloch	B1MTG7	99.6%	Diamond
Papio anubis	A9X1A0	99.4%	Diamond
Pongo abelii	Q5RAY1	98.6%	Diamond
Otolemur garnettii	B4UT09	98.2%	Diamond
Glycine max	P42347	97.9%	Diamond
Rhinolophus ferrumequinum	B2KI64	97.2%	Diamond
Sorex araneus	B3EX61	95.8%	Diamond
Sus scrofa	O02697	94.9%	Diamond
Xenopus tropicalis	A4IID4	94.7%	Diamond
Arabidopsis thaliana	Q0WPX9	85.7%	Diamond
Candida albicans SC5314	Q9UW24	57.5%	Diamond
Dictyostelium discoideum	P54677	54.3%	Diamond
Fusarium graminearum PH-1	Q4IB89	51.8%	Diamond
Neurospora crassa OR74A	Q7RZT9	51.8%	Diamond
Schizosaccharomyces pombe 972h-	Q9USR3	46.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
FAIM	protein-coding	55179
LINC01391	ncRNA	103344930
FOXL2	protein-coding	668
CEP70	protein-coding	80321
ESYT3	protein-coding	83850

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, F8WDJ8, P42338, 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 receptor (GPCR) 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. Interacts (via the catalytic domain) with FOXM1 isoform 5 (FOXM1D); FOXM1D also simultaneously binds to the PI3K regulatory subunit which relieves the inhibitory effect of the regulatory subunit on the kinase activity of the catalytic subunit.

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 (10): NP_001242974, NP_001424215, NP_001424216, NP_001424217, NP_001424218, NP_001424219, NP_001424220, NP_001424221, NP_001424222, 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)

• 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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Atypical kinases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, RAS pathway related proteins, Cancer-related genes, Mutational cancer driver genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoli; nucleoplasm; midbody; vesicles

Antibody reliability (HPA): IH approved · IF supported

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)

Type	Positions
Phosphoserine	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 regulation by gpcrs.
805	loss of lipid kinase activity. may not affect insulin signaling and cell proliferation. partially affects oncogene-induced transformation.
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

26 curated (TAS) of 79; 10 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

showing 60 of 79 pathways:

ID	Pathway	Evidence
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer ⚕	curated
R-HSA-9725370	Signaling by ALK fusions and activated point mutants ⚕	curated
R-HSA-9842640	Signaling by LTK in cancer ⚕	curated
R-HSA-9673770	Signaling by PDGFRA extracellular domain mutants ⚕	curated
R-HSA-9673767	Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants ⚕	curated
R-HSA-389357	CD28 dependent PI3K/Akt signaling	curated
R-HSA-9927354	Co-stimulation by ICOS	curated
R-HSA-2424491	DAP12 signaling	curated
R-HSA-202424	Downstream TCR signaling	curated
R-HSA-186763	Downstream signal transduction	curated
R-HSA-114604	GPVI-mediated activation cascade	curated
R-HSA-112399	IRS-mediated signalling	curated
R-HSA-912526	Interleukin receptor SHC signaling	curated
R-HSA-512988	Interleukin-3, Interleukin-5 and GM-CSF signaling	curated
R-HSA-109704	PI3K Cascade	curated
R-HSA-198203	PI3K/AKT activation	curated
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	curated
R-HSA-1257604	PIP3 activates AKT signaling	curated
R-HSA-5673001	RAF/MAP kinase cascade	curated
R-HSA-8853659	RET signaling	curated
R-HSA-2730905	Role of LAT2/NTAL/LAB on calcium mobilization	curated
R-HSA-2029485	Role of phospholipids in phagocytosis	curated
R-HSA-201556	Signaling by ALK	curated
R-HSA-9842663	Signaling by LTK	curated
R-HSA-1660499	Synthesis of PIPs at the plasma membrane	curated
R-HSA-210993	Tie2 Signaling	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-2219528	PI3K/AKT Signaling in Cancer ⚕	—
R-HSA-9700206	Signaling by ALK in cancer ⚕	—
R-HSA-9671555	Signaling by PDGFR in disease ⚕	—
R-HSA-1280218	Adaptive Immune System	—
R-HSA-422475	Axon guidance	—
R-HSA-202733	Cell surface interactions at the vascular wall	—
R-HSA-1500931	Cell-Cell communication	—
R-HSA-9855142	Cellular responses to mechanical stimuli	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-389356	Co-stimulation by CD28	—
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-2172127	DAP12 interactions	—
R-HSA-1266738	Developmental Biology	—
R-HSA-9027276	Erythropoietin activates Phosphoinositide-3-kinase (PI3K)	electronic
R-HSA-2454202	Fc epsilon receptor (FCERI) signaling	—
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis	—
R-HSA-109582	Hemostasis	—
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	electronic
R-HSA-2428924	IGF1R signaling cascade	—
R-HSA-2428928	IRS-related events triggered by IGF1R	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-74751	Insulin receptor signalling cascade	—
R-HSA-451927	Interleukin-2 family signaling	—
R-HSA-9006925	Intracellular signaling by second messengers	—
R-HSA-5683057	MAPK family signaling cascades	—
R-HSA-5684996	MAPK1/MAPK3 signaling	—
R-HSA-1430728	Metabolism	—
R-HSA-556833	Metabolism of lipids	—
R-HSA-199418	Negative regulation of the PI3K/AKT network	—
R-HSA-373753	Nephrin family interactions	electronic
R-HSA-9675108	Nervous system development	—

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 (34): regulation of cell-matrix adhesion (GO:0001952), response to ischemia (GO:0002931), sphingosine-1-phosphate receptor signaling pathway (GO:0003376), endocytosis (GO:0006897), autophagy (GO:0006914), chemotaxis (GO:0006935), 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), 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), 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), regulation of cell adhesion (GO:0030155), innate immune response (GO:0045087)

GO Molecular Function (11): 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)

GO Cellular Component (8): 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)

Reactome top-level categories

21 top-level categories:

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
Cell-Cell communication	1
Co-stimulation by CD28	1
Signaling by VEGF	1
Signaling by Interleukins	1
MAPK1/MAPK3 signaling	1
Negative regulation of the PI3K/AKT network	1

GO top-level categories

showing 60 of 72 GO namespaces:

Category	Terms
phosphatidylinositol kinase activity	3
cellular anatomical structure	3
protein kinase activity	2
nuclear lumen	2
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
vesicle budding from membrane	1
membrane invagination	1
import into cell	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
response to chemical	1
taxis	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
cell activation	1
blood coagulation	1
neutrophil apoptotic process	1
positive regulation of immune system process	1
regulation of neutrophil apoptotic process	1
positive regulation of myeloid cell apoptotic process	1
positive regulation of leukocyte apoptotic process	1
Rac protein signal transduction	1
regulation of Rac protein signal transduction	1
positive regulation of small GTPase mediated signal transduction	1
phosphatidylinositol phosphate biosynthetic process	1
leukocyte mediated cytotoxicity	1
natural killer cell mediated immunity	1
MAPK cascade	1
regulation of MAPK cascade	1
negative regulation of intracellular signal transduction	1
intracellular signaling cassette	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
phosphatidylinositol-3-phosphate biosynthetic process	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 19 of 53 annotations. The rest are phylogenetic / computational / electronic (IEA).

19 experimentally-supported GO terms:

GO term	NS	Evidence
natural killer cell mediated cytotoxicity	BP	direct assay
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	BP	genetic interaction
negative regulation of sprouting angiogenesis	BP	mutant phenotype
negative regulation of vascular endothelial growth factor signaling pathway	BP	genetic interaction
phosphatidylinositol 3-kinase/protein kinase B signal transduction	BP	mutant phenotype
phosphatidylinositol phosphate biosynthetic process	BP	direct assay
positive regulation of Rac protein signal transduction	BP	genetic interaction
positive regulation of endothelial cell migration	BP	genetic interaction
positive regulation of gene expression	BP	mutant phenotype
positive regulation of neutrophil apoptotic process	BP	mutant phenotype
positive regulation of nitric oxide biosynthetic process	BP	mutant phenotype
regulation of cell-matrix adhesion	BP	mutant phenotype
sphingosine-1-phosphate receptor signaling pathway	BP	mutant phenotype
cytoplasm	CC	direct assay
nucleolus	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity	MF	direct assay
protein serine kinase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 10,184 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIK3CB	AKT1	P31749	979
PIK3CB	PTEN	P60484	946
PIK3CB	EGFR	P00533	924
PIK3CB	STAT3	P40763	915
PIK3CB	RPS6KB1	P23443	911
PIK3CB	SRC	P12931	909
PIK3CB	INS	P01308	894
PIK3CB	MAPK3	P27361	880
PIK3CB	TP53	P04637	880
PIK3CB	BCL2	P10415	880
PIK3CB	TNF	P01375	864
PIK3CB	IRS1	P35568	862
PIK3CB	IL6	P05231	859
PIK3CB	CTNNB1	P35222	859
PIK3CB	GSK3B	P49841	858

IntAct

Human interaction partners of PIK3CB in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

24 partners by confidence:

Partner	Interaction type	MIscore	Records
PIK3R2	association	0.860	2
PIK3R1	physical association	0.840	9
PIK3R3	physical association	0.800	1
APP	physical association	0.560	3
YWHAQ	direct interaction	0.540	2
SMAD4	proximity	0.470	3
AKT1	proximity	0.470	2
LPAR5	physical association	0.400	1
M	physical association	0.400	1
NBN	physical association	0.400	1
SEPTIN9	physical association	0.400	1
TPR	physical association	0.400	1
ALAS1	physical association	0.370	1
DVL3	physical association	0.370	1
HPS6	physical association	0.370	1
SPG11	physical association	0.370	1
PAK1	association	0.350	1
FBXW7	proximity	0.270	4
SMARCA4	proximity	0.270	4
SPOP	proximity	0.270	4
HCK	proximity	0.270	2
BRAF	proximity	0.270	1
EGFR	proximity	0.270	1
TFCP2	physical association	0.000	1

BioGRID (153 interactions; top human partners by supporting records): PIK3R1 (Affinity Capture-Western; 14 records), PIK3R2 (Affinity Capture-MS; 7 records), CBL (Affinity Capture-Western; 4 records), EGFR (Affinity Capture-MS; 4 records), EFNB2 (Affinity Capture-MS; 3 records), GRB2 (Affinity Capture-MS; 3 records), PCBP1 (Affinity Capture-MS; 3 records), PIK3R3 (Two-hybrid; 3 records), PTGER3 (Affinity Capture-MS; 3 records), TGFBR2 (Affinity Capture-MS; 3 records), ADRBK1 (Reconstituted Complex; 2 records), CACNG5 (Affinity Capture-MS; 2 records), CDH5 (Affinity Capture-MS; 2 records), CHRM3 (Affinity Capture-MS; 2 records), CRK (Affinity Capture-MS; 2 records)

SIGNOR signaling

showing 33 of 34 signaling 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
PIK3R1	“up-regulates activity”	PIK3CB	binding
PIK3CB	up-regulates	Survival
PI3K	“up-regulates activity”	PIK3CB	binding
PIK3CB	“down-regulates activity”	PIK3CB	phosphorylation

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
PIK3CB-PIK3R1 complex	2	PIK3CB, PIK3R1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 24 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
Extra-nuclear estrogen signaling	5	44.9×	2e-05
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	5	25.5×	8e-05
PIP3 activates AKT signaling	5	17.6×	4e-04
RAF/MAP kinase cascade	5	16.1×	5e-04
G alpha (q) signalling events	5	15.1×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
phosphatidylinositol 3-kinase/protein kinase B signal transduction	5	45.8×	4e-05
cellular response to insulin stimulus	5	37.0×	6e-05
positive regulation of gene expression	5	8.4×	7e-03
negative regulation of apoptotic process	5	7.5×	9e-03

Disease & clinical

Cancer significance

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

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for PIK3CB: 143 ClinVar records (1 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	89
Likely benign	15
Benign	7

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
638630	NM_006219.3(PIK3CB):c.2961G>T (p.Glu987Asp)	Likely pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore PIK3CB’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 29 predictions of 2,326):

Position(s)	Effect	Δscore	Sites
3:138656140–138656141	donor_loss	1.0000	5
3:138656284	acceptor_gain	1.0000
3:138656288	acceptor_gain	1.0000
3:138656310	acceptor_gain	1.0000
3:138657688–138657689	donor_loss	1.0000	5
3:138663904–138663905	donor_loss	1.0000	5
3:138664030–138664031	acceptor_loss	1.0000	6
3:138664036	acceptor_gain	1.0000
3:138665034	donor_gain	1.0000
3:138665035	donor_loss	1.0000	3

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	4.34e-07
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.000164
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000848

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)

GWAS associations

2 associations:

Study	Trait	p-value
GCST006661_114	Male-pattern baldness	3e-19
GCST90002395_274	Mean platelet volume	8e-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)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the PIK3CB protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

5 curated-mechanism drugs:

Drug	Modality	Max phase
FIMEPINOSTAT	Small molecule	2
GSK-2636771	Small molecule	2
AZD-8186	Small molecule	1
BAY-1082439	Small molecule	1
SAR-260301	Small molecule	1

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes PIK3CB — the drug acts on the assembly or class, not necessarily on this subunit alone.

26 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
BUPARLISIB	PI3-kinase class I	8	3
DACTOLISIB	PI3-kinase class I	8	3
GEDATOLISIB	PI3-kinase class I	8	3
TASELISIB	PI3-kinase class I	8	3
APITOLISIB	PI3-kinase class I	8	2
AZD-6482	PI3-kinase class I	8	2
BGT-226	PI3-kinase class I	8	2
IZORLISIB	PI3-kinase class I	8	2
OMIPALISIB	PI3-kinase class I	8	2
PANULISIB	PI3-kinase class I	8	2
PAXALISIB	PI3-kinase class I	8	2
PF-04691502	PI3-kinase class I	8	2
PICTILISIB	PI3-kinase class I	8	2
PILARALISIB	PI3-kinase class I	8	2
RECILISIB	PI3-kinase class I	8	2
SAMOTOLISIB	PI3-kinase class I	8	2
SF-1126	PI3-kinase class I	8	2
SONOLISIB	PI3-kinase class I	8	2
VOXTALISIB	PI3-kinase class I	8	2
ZSTK-474	PI3-kinase class I	8	2
DS-7423	PI3-kinase class I	8	1
GSK-1059615	PI3-kinase class I	8	1
PUQUITINIB MESYLATE DIHYDRATE	PI3-kinase class I	8	1
PWT-33587	PI3-kinase class I	8	1
VS-5584	PI3-kinase class I	8	1
WX-037	PI3-kinase class I	8	1

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 128,555 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

53 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL2396661	ALPELISIB	4	6,400
CHEMBL3218576	COPANLISIB	4	4,784
CHEMBL3545068	COPANLISIB HYDROCHLORIDE	4	1,392
CHEMBL3039502	DUVELISIB	4	5,625
CHEMBL2216870	IDELALISIB	4	10,756
CHEMBL4650215	INAVOLISIB	4	937
CHEMBL3643413	LENIOLISIB	4	379
CHEMBL2017974	BUPARLISIB	3	6,850
CHEMBL1879463	DACTOLISIB	3	8,349
CHEMBL592445	GEDATOLISIB	3	3,340
CHEMBL603469	LESTAURTINIB	3
CHEMBL165	RESVERATROL	3	61,047
CHEMBL2387080	TASELISIB	3	3,643
CHEMBL3622533	FIMEPINOSTAT	2	2,628
CHEMBL3188551	GSK-2636771	2	1,908
CHEMBL4303596	AMG-319	2	1,579
CHEMBL1922094	APITOLISIB	2	3,224
CHEMBL2165191	AZD-6482	2	974
CHEMBL3218578	BGT-226 FREE BASE	2	3,018
CHEMBL4084907	BIMIRALISIB	2	1,722
CHEMBL2216863	DEZAPELISIB	2
CHEMBL3984425	EGANELISIB	2
CHEMBL1684984	IZORLISIB	2
CHEMBL2216859	NEMIRALISIB	2
CHEMBL1236962	OMIPALISIB	2
CHEMBL3586404	ONATASERTIB	2
CHEMBL3813842	PAXALISIB	2
CHEMBL1234354	PF-04691502	2
CHEMBL521851	PICTILISIB	2
CHEMBL3360203	PILARALISIB	2
CHEMBL2105763	QUISINOSTAT	2
CHEMBL4800252	RISOVALISIB	2
CHEMBL3683575	ROGINOLISIB	2
CHEMBL4297181	SAMOTOLISIB	2
CHEMBL3545097	SAPANISERTIB	2
CHEMBL3935857	SERABELISIB	2
CHEMBL230011	TG100-115	2
CHEMBL2336325	VISTUSERTIB	2
CHEMBL3545366	VOXTALISIB	2
CHEMBL586702	ZSTK-474	2
CHEMBL3408248	AZD-8186	1
CHEMBL3644672	BAY-1082439	1
CHEMBL3112866	SAR-260301	1
CHEMBL4439259	AZD-7648	1
CHEMBL3894518	AZD-8835	1
CHEMBL4647810	ELIMUSERTIB	1
CHEMBL3928407	GS-9901	1
CHEMBL3544966	GSK-1059615	1
CHEMBL1908394	GSK-461364	1
CHEMBL4297629	NEDISERTIB	1
CHEMBL1258517	PKI-179	1
CHEMBL4545915	PUQUITINIB MESYLATE DIHYDRATE	1
CHEMBL3393066	VS-5584	1

PharmGKB: 1 entry (CPIC guideline: no)

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)

3120 measured of 5128 human assays (5195 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Sonolisib	IC50	0.006 nM
CHEMBL3819302	IC50	0.015 nM
methyl (3S)-3-[[6-(2-aminopyrimidin-5-yl)-2-morpholin-4-ylpyrimidin-4-yl]amino]-3-(hydroxymethyl)pyrrolidine-1-carboxylate	KI	0.019 nM	US-9758538: Pyrimidine derivatives
2,2-difluoroethyl (3S)-3-[[6-(2-aminopyrimidin-5-yl)-2-morpholin-4-ylpyrimidin-4-yl]amino]-3-(hydroxymethyl)pyrrolidine-1-carboxylate	KI	0.021 nM	US-9758538: Pyrimidine derivatives
2-amino-1-[(3S)-3-[4-(2-aminopyrimidin-5-yl)-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidin-1-yl]-2-methylpropan-1-one	KI	0.023 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
5-[7-[(3S)-3-methyl-1-methylsulfonylpyrrolidin-3-yl]-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-4-yl]pyrimidin-2-amine	KI	0.027 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
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	KI	0.03 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
1-[(3S)-3-[4-(2-aminopyrimidin-5-yl)-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidin-1-yl]-2-hydroxy-2-methylpropan-1-one	KI	0.03 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
CHEMBL3349370	IC50	0.039 nM
(2S)-2-[[2-[(4S)-4-(fluoromethyl)-2-oxo-1,3-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]propanamide	KI	0.04 nM	US-10112932: Benzoxazepin oxazolidinone compounds and methods of use
(2S)-2-[[2-[(4S)-4-(difluoromethyl)-2-oxo-1,3-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]butanamide	KI	0.048 nM	US-10112932: Benzoxazepin oxazolidinone compounds and methods of use
(2S)-2-cyclopropyl-2-[[2-[(4S)-4-(fluoromethyl)-2-oxo-1,3-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]acetamide	KI	0.051 nM	US-10112932: Benzoxazepin oxazolidinone compounds and methods of use
CHEMBL5395998	IC50	0.06 nM
1-[(3R)-3-[4-(2-aminopyrimidin-5-yl)-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidin-1-yl]ethanone	KI	0.078 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
tert-butyl (3S)-3-[[6-(2-aminopyrimidin-5-yl)-2-morpholin-4-ylpyrimidin-4-yl]amino]-3-methylpyrrolidine-1-carboxylate	KI	0.095 nM	US-9758538: Pyrimidine derivatives
JNJ-26481585	IC50	0.1 nM
BAY 80-6946	IC50	0.11 nM
(3S)-3-[4-(2-aminopyrimidin-5-yl)-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]-N-methylpyrrolidine-1-sulfonamide	KI	0.124 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
(3S)-3-[4-(2-aminopyrimidin-5-yl)-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]-N,3-dimethylpyrrolidine-1-carboxamide	KI	0.124 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
1-[(3S)-3-[[6-(2-aminopyrimidin-5-yl)-2-morpholin-4-ylpyrimidin-4-yl]amino]-3-(hydroxymethyl)pyrrolidin-1-yl]-2-methylpropan-1-one	KI	0.135 nM	US-9758538: Pyrimidine derivatives
5-[7-[(3S)-1-methylsulfonylpyrrolidin-3-yl]-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-4-yl]pyrimidin-2-amine	KI	0.153 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
CHEMBL6144167	IC50	0.183 nM
N-(2-(dimethylamino)ethyl)-4-(3-(2-((7-fluoro-5-methoxy-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-indol-3-yl)methylene)-3-oxo-2,3-dihydrobenzofuran-5-yl)ureido)-N-methylbenzamide	IC50	0.2 nM
CHEMBL4440406	IC50	0.2 nM
CHEMBL3577925	IC50	0.23 nM
2-[(1S)-1-[[6-amino-5-[2-(1H-pyrazol-4-yl)ethynyl]pyrimidin-4-yl]amino]ethyl]-5-chloro-3-phenylquinazolin-4-one	IC50	0.3 nM	US-9266878: Phosphatidylinositol 3-kinase inhibitors
2-[(1S)-1-[[6-amino-5-(2-phenylethynyl)pyrimidin-4-yl]amino]ethyl]-5-chloro-3-phenylquinazolin-4-one	IC50	0.3 nM	US-9266878: Phosphatidylinositol 3-kinase inhibitors
[(3S)-3-[[6-(2-aminopyrimidin-5-yl)-2-morpholin-4-ylpyrimidin-4-yl]amino]-1-methylsulfonylpyrrolidin-3-yl]methanol	KI	0.3 nM	US-9758538: Pyrimidine derivatives
CHEMBL5639851	IC50	0.3 nM
CHEMBL5647196	IC50	0.3 nM
CHEMBL4213353	IC50	0.31 nM
(S)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol	IC50	0.36 nM	US-10172859: Arylquinazolines
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
2-[(1S)-1-[[6-amino-5-(2-pyrazin-2-ylethynyl)pyrimidin-4-yl]amino]ethyl]-5-chloro-3-phenylquinazolin-4-one	IC50	0.4 nM	US-9266878: Phosphatidylinositol 3-kinase inhibitors
Gsk-1059615	IC50	0.4 nM
CHEMBL4293970	KD	0.43 nM
CHEMBL3828518	IC50	0.45 nM
CHEMBL6159961	IC50	0.45 nM
CHEMBL5278435	IC50	0.46 nM
(2S)-2-cyclopropyl-2-[[2-[(4R)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]acetamide	KI	0.464 nM	US-10112932: Benzoxazepin oxazolidinone compounds and methods of use
2-[(1S)-1-[[6-amino-5-(2-pyridin-3-ylethynyl)pyrimidin-4-yl]amino]ethyl]-5-chloro-3-phenylquinazolin-4-one	IC50	0.5 nM	US-9266878: Phosphatidylinositol 3-kinase inhibitors
CHEMBL4088855	IC50	0.5 nM
CHEMBL1928725	IC50	0.5 nM
CHEMBL1928555	IC50	0.5 nM
CHEMBL4449091	IC50	0.5 nM
CHEMBL4868231	IC50	0.51 nM
methyl (3S)-3-[4-(2-aminopyrimidin-5-yl)-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]pyrrolidine-1-carboxylate	KI	0.52 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
CHEMBL1910998	IC50	0.53 nM
CHEMBL3827517	IC50	0.55 nM
(3S)-3-[4-(2-aminopyrimidin-5-yl)-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]-N-methylpyrrolidine-1-carboxamide	KI	0.58 nM	US-9260439: Dihydropyrrolopyrimidine 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

3040 with measured affinity, of 4632 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	decreases reaction, increases activity, increases expression, decreases expression	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	affects binding, decreases activity, decreases expression	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	decreases reaction, increases expression, increases phosphorylation	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	decreases expression, increases abundance, affects cotreatment	1
ochratoxin A	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PIK3CB across ~30M SureChEMBL compounds — explore on Sugi Predict.