PIK3CA

Summary

PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, HGNC:8975) is a protein-coding gene on chromosome 3q26.32, encoding Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (P42336). Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides. In precision oncology, PIK3CA C420R confers sensitivity to Alpelisib + Fulvestrant in Breast Cancer (CIViC Level A); 191 further curated variant–drug associations are listed below. It is a selective cancer dependency (DepMap: 42.7% of cell lines).

Phosphatidylinositol 3-kinase is composed of an 85 kDa regulatory subunit and a 110 kDa catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which uses ATP to phosphorylate PtdIns, PtdIns4P and PtdIns(4,5)P2. This gene has been found to be oncogenic and has been implicated in cervical cancers. A pseudogene of this gene has been defined on chromosome 22.

Source: NCBI Gene 5290 — RefSeq curated summary.

At a glance

• Gene–disease (curated): overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes (Definitive, ClinGen) — +6 more curated relationships
• GWAS associations: 8
• Clinical variants (ClinVar): 1,606 total — 53 pathogenic, 40 likely-pathogenic
• Phenotypes (HPO): 383
• Druggable target: yes — 67 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 192 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 47 cancer types
• Cancer dependency (DepMap): dependent in 42.7% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_006218

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8975
Approved symbol	PIK3CA
Name	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
Location	3q26.32
Locus type	gene with protein product
Status	Approved
Aliases	PI3K
Ensembl gene	ENSG00000121879
Ensembl biotype	protein_coding
OMIM	171834
Entrez	5290

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 9 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000263967, ENST00000462255, ENST00000468036, ENST00000477735, ENST00000643187, ENST00000674534, ENST00000674622, ENST00000675467, ENST00000675786, ENST00000675796, ENST00000876545, ENST00000913499, ENST00000913500, ENST00000955189, ENST00000955190

RefSeq mRNA: 1 — MANE Select: NM_006218 NM_006218

CCDS: CCDS43171

Canonical transcript exons

ENST00000263967 — 21 exons

Exon	Start	End
ENSE00000826291	179219196	179219277
ENSE00000826292	179219571	179219735
ENSE00000826297	179225962	179226040
ENSE00000826298	179229272	179229442
ENSE00000826299	179230004	179230121
ENSE00000826300	179230225	179230376
ENSE00000997375	179199690	179199899
ENSE00001077674	179218210	179218334
ENSE00001077691	179209595	179209700
ENSE00001077692	179203544	179203789
ENSE00001077693	179201290	179201540
ENSE00001077694	179204503	179204588
ENSE00001128465	179210431	179210565
ENSE00001128470	179210186	179210338
ENSE00001139987	179234094	179240093
ENSE00001139995	179198750	179199177
ENSE00001493081	179148357	179148603
ENSE00003485038	179219949	179220052
ENSE00003485539	179224700	179224821
ENSE00003489671	179224081	179224187
ENSE00003568097	179220986	179221157

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 94.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.6167 / max 376.9326, expressed in 1781 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
39918	15.0051	1746
39916	3.1296	1339
39919	0.7173	339
39915	0.2927	110
39920	0.2676	102
39917	0.2043	76

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	94.28	gold quality
adrenal tissue	UBERON:0018303	94.02	gold quality
tendon	UBERON:0000043	92.68	gold quality
cortical plate	UBERON:0005343	89.87	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.34	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.24	gold quality
tendon of biceps brachii	UBERON:0008188	88.11	gold quality
ventricular zone	UBERON:0003053	88.04	gold quality
secondary oocyte	CL:0000655	87.31	gold quality
ganglionic eminence	UBERON:0004023	87.30	gold quality
cartilage tissue	UBERON:0002418	87.16	gold quality
heart right ventricle	UBERON:0002080	86.41	gold quality
skin of hip	UBERON:0001554	86.30	gold quality
bone marrow	UBERON:0002371	86.17	gold quality
biceps brachii	UBERON:0001507	86.16	gold quality
colonic epithelium	UBERON:0000397	86.15	gold quality
stromal cell of endometrium	CL:0002255	85.94	gold quality
popliteal artery	UBERON:0002250	85.78	gold quality
tibial artery	UBERON:0007610	85.77	gold quality
subcutaneous adipose tissue	UBERON:0002190	85.75	gold quality
adipose tissue of abdominal region	UBERON:0007808	85.71	gold quality
connective tissue	UBERON:0002384	85.68	gold quality
adipose tissue	UBERON:0001013	85.67	gold quality
bone marrow cell	CL:0002092	85.64	gold quality
omental fat pad	UBERON:0010414	85.58	gold quality
peritoneum	UBERON:0002358	85.52	gold quality
artery	UBERON:0001637	85.48	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	85.47	gold quality
postcentral gyrus	UBERON:0002581	85.40	gold quality
medial globus pallidus	UBERON:0002477	85.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.33

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO3, HIF1A, NFKB, SOX9, TP53, YBX1

miRNA regulators (miRDB)

411 targeting PIK3CA, 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-5692A	100.00	74.40	6850
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-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-19A-3P	99.98	75.33	2762

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 42.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• In squamous cell carcinomas the negative effect of p53 induction on cell survival involves transcriptional inhibition of PIK3CA that is independent of PTEN activity, as PTEN is not expressed in the primary tumors (PMID:11959846)
• agonist binding to Gq-coupled receptors blocks Akt activation via the release of active Galphaq subunits that inhibit PI3K via an inhibitory interaction between Galphaq and p110alpha PI3K. (PMID:12704201)
• data suggest that mutant PIK3CA is likely to function as an oncogene in human cancers; PIK3CA may prove useful for diagnostic and therapeutic purposes (PMID:15016963)
• Missense Mutation in PIK3CA is associated with breast cancers (PMID:15254419)
• Mutations of PIK3CA is associated with anaplastic oligodendrogliomas, high-grade astrocytomas, and medulloblastomas (PMID:15289301)
• oncogenic mutations in human cancers (PMID:15467468)
• Genetic alterations of class IA PI3K subunit genes can occasionally play a role in human glioblastoma by activating the PI3K-AKT signaling pathway independently of PTEN mutation. (PMID:15605984)
• Data show that glucose is a crucial regulator of V-ATPase in renal epithelial cells and that the effect of glucose is mediated by phosphatidylinositol 3-kinase (PI3K). (PMID:15632060)
• determined the growth-regulatory and signaling properties of the three most frequently observed PIK3CA mutations: E542K, E545K, and H1047R (PMID:15647370)
• PIK3CA mutations in exons 9 & 20 were directly sequenced. A novel silent mutation was found. PIK3CA mutation may be an early event in ovarian carcinogenesis. (PMID:15712344)
• Activation of the PI3K signalling pathway in gastric cancer may be achieved through up-regulation or mutation of PIK3CA, in which the latter may be a consequence of mismatch repair deficiency. (PMID:15784156)
• Mutation of PIK3CA is frequent, occurs early in carcinoma development, and has prognostic and therapeutic implications for breast cancer. (PMID:15805248)
• Data indicate that mutations of PIK3CA play an oncogenic role in substantial fractions of ovarian and breast carcinomas. (PMID:15837735)
• mutation of the PIK3CA gene is not common, but its amplification is relatively common and may be a novel mechanism in activating the PI3K/Akt pathway in some thyroid tumors (PMID:15928251)
• Colon cancer-associated PIK3CA mutations are functionally active so that they are likely to be involved in carcinogenesis. (PMID:15930273)
• Amino acid substitutions in PIK3CA from human colorectal cancer cell lines constitutively activate the AKT pathway, and consequently, promote tumor cell growth and invasion. (PMID:15950905)
• PI-3 kinase p110alpha subunit expression and recombinant heparin-binding epidermal growth factor-like growth factor (HB-EGF) synergistically decrease inducible nitric oxide synthase expression and nitric oxide production in intestinal epithelial cells (PMID:16034135)
• copy number gains, instead of mutation, may be a common mechanism for activation of PIK3CA in tumorigenesis of primary nasopharyngeal carcinoma (PMID:16114017)
• an important role of PIK3CA gene aberrations in the molecular pathogenesis of primary glioblastomas (PMID:16150119)
• this study has shown that the mutations detected in the helical and kinase domains of PIK3CA do not seem to affect the PI3-K pathway characteristics of the eight cell lines studied (PMID:16150444)
• The frequent and clustered mutations within PIK3CA make it an attractive molecular marker for early detection and a promising therapeutic target in breast cancer. (PMID:16168105)
• analysis of PIK3CA mutations in ovarian cancer [letter] (PMID:16203798)
• increased activation state of AKT kinase appears to be present in cervical carcinogenesis, and may be accounted for by PIK3CA amplification, whereas PTEN mutation seems to be of little importance (PMID:16287065)
• Mutant PIK3CA is likely to function as an oncogene in anaplastic thyroid cancer and less frequently well-differentiated thyroid carcinomas. (PMID:16288007)
• PIK3CA mutations are associated with breast cancer (PMID:16317585)
• Data show that alpha6 and alpha3 integrin subunits interact with laminin 5 to increase expression of E-cadherin, and suggest that phosphoinositide 3-kinase (PI 3-kinase) activation plays a key role in this cross-talk. (PMID:16339173)
• 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)
• cancer-specific mutations in PIK3CA have made p110alpha an ideal drug target [Review] (PMID:16341083)
• A mutation status profile of the PIK3Ca gene in the National Cancer Institute (NCI)-60 panel of human cancer cell lines provides insights into the role of mutant PIK3Ca in oncogenic signaling (PMID:16376301)
• study extends previous observations in other tumor types by demonstrating presence of somatic PIK3CA mutations in both SCC and adenocarcinoma of the esophagus, thus implicating the PI3K pathway in the initiation and/or progression of esophageal cancers (PMID:16380997)
• These results indicate that PI3K plays different roles in the activation of Ras/ERK1/2 signaling by insulin and EGF, and that insulin-stimulated, but not EGF-stimulated, ERK1/2 and Akt signalings diverge at PI3K. (PMID:16406609)
• AT(1) receptor-mediated activation of PI 3-K/Akt cascades occurs at least partially via the transactivation of EGF receptor, which is under a negative control by AT(2) receptor in hypertrophic scar fibroblasts. (PMID:16522324)
• PIK3CA mutations are associated with head and neck squamous cell carcinoma (PMID:16533766)
• Although a key factor in TRAF6-dependent activation of PI 3-kinase, ectopic expression of Src was insufficient for NF-kappaB activation and, in contrast to NF-kappaB, was not inhibited by IRAK2. (PMID:16569657)
• Mutation of PIK3CA is associated with breast cancer (PMID:16582596)
• Somatic mutations of PIK3CA, encoding p110alpha catalytic subunit of Class IA PI3Ks, have been found in various cancers. (PMID:16627990)
• inhibition of PI 3-kinase activity reduced hypoxic HIF-1alpha protein levels to a similar extent as serum deprivation (PMID:16682946)
• PI3K-IA activity is necessary for both high NaCl- and ionizing radiation-induced activation of ATM and (ii) high NaCl activates PI3K-IA, which, in turn, contributes to full activation of TonEBP/OREBP via ATM. (PMID:16728507)
• Various mutations in a variety of cancers, including a pseudogene and polymorphisms. (PMID:16764926)
• p110alpha play an important role in tumor growth by inducing angiogenesis and by increasing HIF-1alpha and VEGF expression. This work provides a better understanding of the molecular mechanism of human cancer induced by the activation of PI3K signaling. (PMID:16775835)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pik3ca	ENSDARG00000075456
mus_musculus	Pik3ca	ENSMUSG00000027665
rattus_norvegicus	Pik3ca	ENSRNOG00000056371
drosophila_melanogaster	Pi3K68D	FBGN0015278
caenorhabditis_elegans		WBGENE00009552

Paralogs (9): PIK3C2A (ENSG00000011405), PIK3CB (ENSG00000051382), PIK3C3 (ENSG00000078142), PIK3CG (ENSG00000105851), PIK3C2B (ENSG00000133056), PIK3C2G (ENSG00000139144), PI4KB (ENSG00000143393), PIK3CD (ENSG00000171608), PI4KA (ENSG00000241973)

Protein

Protein identifiers

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform — P42336 (reviewed: P42336)

Alternative names: Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha, Phosphoinositide 3-kinase alpha, Phosphoinositide-3-kinase catalytic alpha polypeptide, Serine/threonine protein kinase PIK3CA

All UniProt accessions (6): A0A2R8Y2F6, A0A6Q8PGN9, A0A6Q8PGV1, C9J951, C9JAM9, P42336

UniProt curated annotations — full annotation on UniProt →

Function. Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated 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. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. In addition to its lipid kinase activity, it displays a serine-protein kinase activity that results in the autophosphorylation of the p85alpha regulatory subunit as well as phosphorylation of other proteins such as 4EBP1, H-Ras, the IL-3 beta c receptor and possibly others. Plays a role in the positive regulation of phagocytosis and pinocytosis.

Subunit / interactions. Heterodimer of a catalytic subunit PIK3CA and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3). Interacts with IRS1 in nuclear extracts. Interacts with RUFY3. Interacts with RASD2. Interacts with APPL1. Interacts with HRAS and KRAS. Interaction with HRAS/KRAS is required for PI3K pathway signaling and cell proliferation stimulated by EGF and FGF2. Interacts with FAM83B; activates the PI3K/AKT signaling cascade.

Disease relevance. PIK3CA mutations are involved in various type of cancer. Most of the cancer-associated mutations are missense mutations and map to one of the three hotspots: Glu-542; Glu-545 and His-1047. Mutated isoforms participate in cellular transformation and tumorigenesis induced by oncogenic receptor tyrosine kinases (RTKs) and HRAS/KRAS. Interaction with HRAS/KRAS is required for Ras-driven tumor formation. Mutations increasing the lipid kinase activity are required for oncogenic signaling. The protein kinase activity may not be required for tumorigenesis. Colorectal cancer (CRC) [MIM:114500] A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. The gene represented in this entry may be involved in disease pathogenesis. Breast cancer (BC) [MIM:114480] A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Disease susceptibility is associated with variants affecting the gene represented in this entry. Ovarian cancer (OC) [MIM:167000] The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. Disease susceptibility is associated with variants affecting the gene represented in this entry. Hepatocellular carcinoma (HCC) [MIM:114550] A primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. The gene represented in this entry may be involved in disease pathogenesis. Keratosis, seborrheic (KERSEB) [MIM:182000] A common benign skin tumor. Seborrheic keratoses usually begin with the appearance of one or more sharply defined, light brown, flat macules. The lesions may be sparse or numerous. As they initially grow, they develop a velvety to finely verrucous surface, followed by an uneven warty surface with multiple plugged follicles and a dull or lackluster appearance. The disease is caused by variants affecting the gene represented in this entry. Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) [MIM:602501] A syndrome characterized by a spectrum of anomalies including primary megalencephaly, prenatal overgrowth, brain and body asymmetry, cutaneous vascular malformations, digital anomalies consisting of syndactyly with or without postaxial polydactyly, connective tissue dysplasia involving the skin, subcutaneous tissue, and joints, and cortical brain malformations, most distinctively polymicrogyria. The disease is caused by variants affecting the gene represented in this entry. Congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE) [MIM:612918] A sporadically occurring, non-hereditary disorder characterized by asymmetric somatic hypertrophy and anomalies in multiple organs. It is defined by four main clinical findings: congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and skeletal/spinal abnormalities. The presence of truncal overgrowth and characteristic patterned macrodactyly at birth differentiates CLOVE from other syndromic forms of overgrowth. The disease is caused by variants affecting the gene represented in this entry. Cowden syndrome 5 (CWS5) [MIM:615108] A form of Cowden syndrome, a hamartomatous polyposis syndrome with age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid. The disease is caused by variants affecting the gene represented in this entry. CLAPO syndrome (CLAPO) [MIM:613089] A syndrome characterized by capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry of face and limbs and partial or generalised overgrowth. The disease may be caused by variants affecting the gene represented in this entry. The tissue distribution of the clinical manifestations in CLAPO seems to follow a pattern of somatic mosaicism. Macrodactyly (MADAC) [MIM:155500] A congenital anomaly characterized by fibrofatty tissue enlargement and bony overgrowth affecting the digits or the entire hand or foot. The disease may be caused by variants affecting the gene represented in this entry. The tissue distribution of the clinical manifestations in MADAC seems to follow a pattern of somatic mosaicism. Cerebral cavernous malformations 4 (CCM4) [MIM:619538] A form of cerebral cavernous malformations, a congenital vascular anomaly of the central nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. The lesions are characterized by grossly enlarged blood vessels consisting of a single layer of endothelium and without any intervening neural tissue, ranging in diameter from a few millimeters to several centimeters. CCM4 cases occur sporadically. The disease is caused by variants affecting the gene represented in this entry. Hemifacial myohyperplasia (HFMH) [MIM:606773] A rare disease characterized by facial asymmetry due to unilateral muscular hypertrophy mimicking spasm and orofacial dystonia. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The PI3K-ABD domain and the PI3K-RBD domain interact with the PI3K/PI4K kinase domain. The C2 PI3K-type domain may facilitate the recruitment to the plasma membrane. 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, and the C2 PI3K-type domain, the PI3K helical domain, and the PI3K/PI4K kinase domain with the nSH2 (N-terminal SH2) region of PIK3R1.

Pathway. Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis.

Miscellaneous. The avian sarcoma virus 16 genome encodes an oncogene derived from PIK3CA.

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

RefSeq proteins (1): NP_006209* (*=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
IPR037704	PI3-kinase_alpha_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)
• EC 2.7.11.1 — non-specific serine/threonine protein kinase (BRENDA: 71 organisms, 682 substrates, 228 inhibitors, 23 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

14 substrates with measured Km, best-characterized 14. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0007–0.64	11
ATP	0.03–44	7
PHOSPHATIDYLINOSITOL	0.034–64	3
KKRAARATSNVFA	0.013–0.045	3
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE	0.004–15	2
PHOSPHATIDYLINOSITOL 4-PHOSPHATE	0.009–10	2
PAH1 PHOSPHATIDATE PHOSPHATASE	0.0002	2
RRRLSSLRA	0.0036–0.0037	2
1,2-DIOCTANOYLPHOSPHATIDYLINOSITOL 4,5-DIPHOSPHA	0.05	1
PHOSPHATIDYLINOSITOL-4,5-BISPHOSPHATE	0.011	1
GTP	0.46	1
KKRAARASSNVFA	0.02	1
LYS-LYS-PHE-ASN-ARG-THR-LEU-SER-VAL-ALA	0.0093	1
MYELIN BASIC PROTEIN	0.145	1

Catalyzed reactions (Rhea), 5 shown:

• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + ADP + H(+) (RHEA:12709)
• 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)
• 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + ATP = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + ADP + H(+) (RHEA:55632)

UniProt features (201 total): strand 61, helix 59, sequence variant 51, turn 13, sequence conflict 7, domain 5, region of interest 3, chain 1, site 1

Structure

Experimental structures (PDB)

135 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9CMK	X-RAY DIFFRACTION	1.75
9ASF	X-RAY DIFFRACTION	1.77
9CX0	X-RAY DIFFRACTION	1.92
7L1C	X-RAY DIFFRACTION	1.96
9CWY	X-RAY DIFFRACTION	1.98
8EXL	X-RAY DIFFRACTION	1.99
9CX1	X-RAY DIFFRACTION	2
9CML	X-RAY DIFFRACTION	2.01
9ASG	X-RAY DIFFRACTION	2.03
7L1B	X-RAY DIFFRACTION	2.04
9CWZ	X-RAY DIFFRACTION	2.05
7JIU	X-RAY DIFFRACTION	2.12
7RRG	X-RAY DIFFRACTION	2.12
6PYS	X-RAY DIFFRACTION	2.19
4JPS	X-RAY DIFFRACTION	2.2
7PG5	X-RAY DIFFRACTION	2.2
9B4U	X-RAY DIFFRACTION	2.21
5DXT	X-RAY DIFFRACTION	2.25
8SBC	X-RAY DIFFRACTION	2.3
9CX2	X-RAY DIFFRACTION	2.3
6VO7	X-RAY DIFFRACTION	2.31
4WAF	X-RAY DIFFRACTION	2.39
5UBR	X-RAY DIFFRACTION	2.4
8VCL	X-RAY DIFFRACTION	2.4
7TZ7	X-RAY DIFFRACTION	2.41
8BFU	X-RAY DIFFRACTION	2.41
8DCP	ELECTRON MICROSCOPY	2.41
7K6M	X-RAY DIFFRACTION	2.41
8EXO	X-RAY DIFFRACTION	2.46
8EXV	X-RAY DIFFRACTION	2.48

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P42336-F1	92.50	0.83

Functional residue map

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

Catalytic / active sites (1): 776 (implicated in the recognition of atp as well as pip2. also crucial for autophosphorylation of the p85alpha subunit)

Function

Pathways and Gene Ontology

Reactome pathways

60 pathways

ID	Pathway
R-HSA-109704	PI3K Cascade
R-HSA-112399	IRS-mediated signalling
R-HSA-114604	GPVI-mediated activation cascade
R-HSA-1236382	Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
R-HSA-1250342	PI3K events in ERBB4 signaling
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1433557	Signaling by SCF-KIT
R-HSA-1660499	Synthesis of PIPs at the plasma membrane
R-HSA-180292	GAB1 signalosome
R-HSA-1839117	Signaling by cytosolic FGFR1 fusion mutants
R-HSA-186763	Downstream signal transduction
R-HSA-1963642	PI3K events in ERBB2 signaling
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-416476	G alpha (q) signalling events
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-512988	Interleukin-3, Interleukin-5 and GM-CSF signaling
R-HSA-5637810	Constitutive Signaling by EGFRvIII
R-HSA-5654689	PI-3K cascade:FGFR1
R-HSA-5654695	PI-3K cascade:FGFR2
R-HSA-5654710	PI-3K cascade:FGFR3
R-HSA-5654720	PI-3K cascade:FGFR4

MSigDB gene sets: 1537 (showing top): PID_BCR_5PATHWAY, PID_SHP2_PATHWAY, BIOCARTA_GCR_PATHWAY, REACTOME_INTERLEUKIN_2_FAMILY_SIGNALING, BIOCARTA_PTEN_PATHWAY, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_SIGNALING_PATHWAY

GO Biological Process (51): angiogenesis (GO:0001525), liver development (GO:0001889), vasculature development (GO:0001944), glucose metabolic process (GO:0006006), phagocytosis (GO:0006909), epidermal growth factor receptor signaling pathway (GO:0007173), insulin receptor signaling pathway (GO:0008286), positive regulation of lamellipodium assembly (GO:0010592), negative regulation of gene expression (GO:0010629), response to activity (GO:0014823), response to muscle inactivity (GO:0014870), negative regulation of macroautophagy (GO:0016242), cell migration (GO:0016477), actin cytoskeleton organization (GO:0030036), platelet activation (GO:0030168), negative regulation of actin filament depolymerization (GO:0030835), positive regulation of TOR signaling (GO:0032008), cellular response to insulin stimulus (GO:0032869), response to muscle stretch (GO:0035994), phosphatidylinositol-3-phosphate biosynthetic process (GO:0036092), vascular endothelial growth factor signaling pathway (GO:0038084), TORC2 signaling (GO:0038203), regulation of multicellular organism growth (GO:0040014), response to L-leucine (GO:0043201), anoikis (GO:0043276), regulation of cellular respiration (GO:0043457), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), negative regulation of neuron apoptotic process (GO:0043524), endothelial cell migration (GO:0043542), phosphatidylinositol phosphate biosynthetic process (GO:0046854), insulin-like growth factor receptor signaling pathway (GO:0048009), phosphatidylinositol-mediated signaling (GO:0048015), positive regulation of smooth muscle cell proliferation (GO:0048661), T cell receptor signaling pathway (GO:0050852), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), relaxation of cardiac muscle (GO:0055119), cardiac muscle contraction (GO:0060048), adipose tissue development (GO:0060612), cellular response to glucose stimulus (GO:0071333), cellular response to hydrostatic pressure (GO:0071464)

GO Molecular Function (12): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), 1-phosphatidylinositol-3-kinase activity (GO:0016303), protein kinase activator activity (GO:0030295), 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 (9): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), phosphatidylinositol 3-kinase complex (GO:0005942), phosphatidylinositol 3-kinase complex, class IA (GO:0005943), phosphatidylinositol 3-kinase complex, class IB (GO:0005944), intercalated disc (GO:0014704), lamellipodium (GO:0030027), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-20 pathways:

Category	Pathways
Signaling by Receptor Tyrosine Kinases	2
IRS-mediated signalling	1
IRS-related events triggered by IGF1R	1
Insulin receptor signalling cascade	1
Platelet activation, signaling and aggregation	1
Signaling by Ligand-Responsive EGFR Variants in Cancer	1
Signaling by ERBB4	1
Intracellular signaling by second messengers	1
PI Metabolism	1
Signaling by EGFR	1
FGFR1 mutant receptor activation	1
Signaling by PDGF	1
Signaling by ERBB2	1
Signaling by NTRK1 (TRKA)	1
TCR signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	3
phosphatidylinositol kinase activity	3
cellular anatomical structure	3
cytoplasm	2
phosphatidylinositol 3-kinase complex, class I	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
gland development	1
hepaticobiliary system development	1
system development	1
circulatory system development	1
hexose metabolic process	1
endocytosis	1
ERBB signaling pathway	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
regulation of lamellipodium assembly	1
lamellipodium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
positive regulation of lamellipodium organization	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
response to stimulus	1
response to inactivity	1
negative regulation of autophagy	1
macroautophagy	1
regulation of macroautophagy	1
cell motility	1
cytoskeleton organization	1
actin filament-based process	1
cell activation	1
blood coagulation	1
actin filament depolymerization	1
regulation of actin filament depolymerization	1
negative regulation of cytoskeleton organization	1
negative regulation of protein depolymerization	1
negative regulation of supramolecular fiber organization	1
TOR signaling	1
regulation of TOR signaling	1

Protein interactions and networks

STRING

4602 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIK3CA	PIK3R1	P27986	998
PIK3CA	PIK3R2	O00459	997
PIK3CA	PIK3R3	Q92569	995
PIK3CA	PIK3R5	Q8WYR1	992
PIK3CA	PIK3CB	P42338	984
PIK3CA	PIK3CD	O00329	983
PIK3CA	EGFR	P00533	977
PIK3CA	PIK3CG	P48736	973
PIK3CA	KRAS	P01116	952
PIK3CA	IRS1	P35568	952
PIK3CA	AKT1	P31749	951
PIK3CA	PTEN	P60484	949
PIK3CA	BRAF	P15056	931
PIK3CA	ERBB2	P04626	927
PIK3CA	NRAS	P01111	921

IntAct

250 interactions, top by confidence:

A	B	Type	Score
PIK3CA	PIK3R1	psi-mi:“MI:0407”(direct interaction)	0.960
PIK3CA	PIK3R1	psi-mi:“MI:0915”(physical association)	0.960
PIK3R1	PIK3CA	psi-mi:“MI:0915”(physical association)	0.960
PIK3CA	PIK3R1	psi-mi:“MI:0914”(association)	0.960
PIK3CA	PIK3R3	psi-mi:“MI:0915”(physical association)	0.900
PIK3CA	PIK3R2	psi-mi:“MI:0914”(association)	0.900
PIK3CA	PIK3R2	psi-mi:“MI:0915”(physical association)	0.900

BioGRID (305): PIK3CA (Affinity Capture-Western), PIK3CA (Affinity Capture-MS), PIK3CA (Affinity Capture-MS), PIK3CA (Two-hybrid), PIK3CA (Affinity Capture-MS), PIK3CA (Two-hybrid), BEX1 (Two-hybrid), BEX2 (Two-hybrid), IL13RA2 (Two-hybrid), IL24 (Two-hybrid), PSMC3IP (Two-hybrid), THRSP (Two-hybrid), TNFSF13 (Two-hybrid), UMPS (Two-hybrid), PIK3CA (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, P0C5E7, P22543, P39104, P42339, P42347, P42348, P54677, Q94125, Q95Q95

SIGNOR signaling

74 interactions.

A	Effect	B	Mechanism
PIK3CA	“down-regulates activity”	IRS1
GNB3	up-regulates	PIK3CA	binding
GNG12	up-regulates	PIK3CA	binding
PIK3CA	up-regulates	AKT2
GNB1	up-regulates	PIK3CA	binding
GNG2	up-regulates	PIK3CA	binding
GNG3	up-regulates	PIK3CA	binding
GNGT1	up-regulates	PIK3CA	binding
ERBB3	up-regulates	PIK3CA	binding
ERBB4	up-regulates	PIK3CA	binding
PIK3CA	“up-regulates quantity”	PIP3	“chemical modification”
IRS1	“up-regulates activity”	PIK3CA	binding
KRAS	up-regulates	PIK3CA	binding
NRAS	“up-regulates activity”	PIK3CA	binding
PIK3CA	up-regulates	RAC1
dactolisib	down-regulates	PIK3CA	“chemical inhibition”
pictrelisib	down-regulates	PIK3CA	“chemical inhibition”
PIK3CA	up-regulates	MTOR
BKM120	down-regulates	PIK3CA	“chemical inhibition”
CH5132799	down-regulates	PIK3CA	“chemical inhibition”
CUDC-907	down-regulates	PIK3CA	“chemical inhibition”
D-106669	down-regulates	PIK3CA	“chemical inhibition”
PIK3AP1	up-regulates	PIK3CA	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	PIK3CA	“chemical inhibition”
GSK1059615	down-regulates	PIK3CA	“chemical inhibition”
GSK2126458	down-regulates	PIK3CA	“chemical inhibition”
(2S)-N1-[5-(2-tert-butyl-4-thiazolyl)-4-methyl-2-thiazolyl]pyrrolidine-1,2-dicarboxamide	down-regulates	PIK3CA	“chemical inhibition”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 97 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Constitutive Signaling by EGFRvIII	5	50.3×	4e-06
Regulation of signaling by CBL	6	42.0×	1e-06
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	5	40.2×	8e-06
Interleukin receptor SHC signaling	6	34.5×	3e-06
Interleukin-3, Interleukin-5 and GM-CSF signaling	7	31.3×	1e-06
Signaling by ERBB2 KD Mutants	5	29.8×	3e-05
CD28 dependent PI3K/Akt signaling	5	27.7×	4e-05
Downstream signal transduction	5	26.8×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
phosphatidylinositol 3-kinase/protein kinase B signal transduction	8	20.1×	7e-06
insulin receptor signaling pathway	6	15.8×	9e-04
epidermal growth factor receptor signaling pathway	5	14.8×	3e-03
positive regulation of cell migration	10	7.3×	6e-04
positive regulation of gene expression	11	5.1×	3e-03

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

PIK3CA is the most recurrently mutated gene in breast cancer, and has been found to important in a number of cancer types. An integral part of the PI3K pathway, PIK3CA has long been described as an oncogene, with two main hotspots for activating mutations, the 542/545 region of the helical domain, and the 1047 region of the kinase domain. PIK3CA, and its interaction with the AKT and mTOR pathways, is the subject of an immense amount of research and development, and PI3K inhibition has seen some limited success in recent clinical trials. While monotherapies seem to be limited in their potential, there is a recent interest in pursuing PI3K inhibition as part of a combination therapy regiment with inhibition partners including TKI’s, MEK inhibitors, PARP inhibitors, and in breast cancer, aromatase inhibitors.

From intOGen — cancer-driver classification: activating (oncogene-like) across 47 cancer types — ACYC, ANGS, ANSC, BCC, BLADDER, BLCA, BRCA, CCRCC, CEAD, CESC, CHOL, COAD…(+35 more).

Clinical variants and AI predictions

ClinVar

1606 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	53
Likely pathogenic	40
Uncertain significance	661
Likely benign	699
Benign	50

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1172583	NM_006218.4(PIK3CA):c.3104C>T (p.Ala1035Val)	Pathogenic
1177432	NM_006218.4(PIK3CA):c.3202_3205delinsCTGATAACTGAGAAAATAACTGATAAAATGAAACTGA (p.Asn1068_Ter1069delinsLeuIleThrGluLysIleThrAspLysMetLysLeuArg)	Pathogenic
13652	NM_006218.4(PIK3CA):c.3140A>G (p.His1047Arg)	Pathogenic
13653	NM_006218.4(PIK3CA):c.3140A>T (p.His1047Leu)	Pathogenic
13656	NM_006218.4(PIK3CA):c.1634A>G (p.Glu545Gly)	Pathogenic
13657	NM_006218.4(PIK3CA):c.1636C>A (p.Gln546Lys)	Pathogenic
13659	NM_006218.4(PIK3CA):c.1634A>C (p.Glu545Ala)	Pathogenic
156446	NM_006218.4(PIK3CA):c.353G>A (p.Gly118Asp)	Pathogenic
156447	NM_006218.4(PIK3CA):c.403G>A (p.Glu135Lys)	Pathogenic
156448	NM_006218.4(PIK3CA):c.652G>A (p.Glu218Lys)	Pathogenic
156449	NM_006218.4(PIK3CA):c.1066G>A (p.Val356Ile)	Pathogenic
156452	NM_006218.4(PIK3CA):c.1895T>G (p.Leu632Ter)	Pathogenic
1691324	NM_006218.4(PIK3CA):c.1342_1354del (p.Pro447_Val448insTer)	Pathogenic
1691392	NM_006218.4(PIK3CA):c.1635_1636delinsTA (p.Glu545_Gln546delinsAspLys)	Pathogenic
217292	NM_006218.4(PIK3CA):c.3129G>T (p.Met1043Ile)	Pathogenic
217293	NM_006218.4(PIK3CA):c.1635G>T (p.Glu545Asp)	Pathogenic
218236	NM_006218.4(PIK3CA):c.335T>A (p.Ile112Asn)	Pathogenic
2580765	NM_006218.4(PIK3CA):c.1034A>G (p.Asn345Ser)	Pathogenic
2582274	NM_006218.4(PIK3CA):c.3120G>A (p.Met1040Ile)	Pathogenic
2662642	NM_006218.4(PIK3CA):c.1798G>A (p.Glu600Lys)	Pathogenic
2672088	NM_006218.4(PIK3CA):c.1632_1633delinsAA (p.Glu545Lys)	Pathogenic
31944	NM_006218.4(PIK3CA):c.1624G>A (p.Glu542Lys)	Pathogenic
31945	NM_006218.4(PIK3CA):c.1258T>C (p.Cys420Arg)	Pathogenic
376049	NM_006218.4(PIK3CA):c.263G>A (p.Arg88Gln)	Pathogenic
376050	NM_006218.4(PIK3CA):c.1035T>A (p.Asn345Lys)	Pathogenic
376244	NM_006218.4(PIK3CA):c.1624G>C (p.Glu542Gln)	Pathogenic
376246	NM_006218.4(PIK3CA):c.3062A>G (p.Tyr1021Cys)	Pathogenic
376247	NM_006218.4(PIK3CA):c.3145G>A (p.Gly1049Ser)	Pathogenic
376470	NM_006218.4(PIK3CA):c.1357G>A (p.Glu453Lys)	Pathogenic
376473	NM_006218.4(PIK3CA):c.1625A>C (p.Glu542Ala)	Pathogenic

SpliceAI

3028 predictions. Top by Δscore:

Variant	Effect	Δscore
3:179148600:GAGC:G	donor_gain	1.0000
3:179148601:AGC:A	donor_gain	1.0000
3:179148602:GC:G	donor_gain	1.0000
3:179148602:GCG:G	donor_gain	1.0000
3:179148604:G:GG	donor_gain	1.0000
3:179198745:TTTA:T	acceptor_loss	1.0000
3:179198746:TTAGG:T	acceptor_loss	1.0000
3:179198747:TA:T	acceptor_loss	1.0000
3:179198749:G:GA	acceptor_loss	1.0000
3:179199824:GCAAT:G	donor_gain	1.0000
3:179199898:AGGTA:A	donor_loss	1.0000
3:179199899:GGTAA:G	donor_loss	1.0000
3:179199900:G:T	donor_loss	1.0000
3:179199901:T:G	donor_loss	1.0000
3:179201405:G:GT	donor_gain	1.0000
3:179201406:A:T	donor_gain	1.0000
3:179201416:G:GT	donor_gain	1.0000
3:179201419:G:GG	donor_gain	1.0000
3:179204501:A:AG	acceptor_gain	1.0000
3:179204502:G:GG	acceptor_gain	1.0000
3:179204502:GATC:G	acceptor_gain	1.0000
3:179204502:GATCT:G	acceptor_gain	1.0000
3:179204585:CCAGG:C	donor_loss	1.0000
3:179204586:CAGG:C	donor_loss	1.0000
3:179204587:AGGTA:A	donor_loss	1.0000
3:179204589:GTA:G	donor_loss	1.0000
3:179204590:T:A	donor_loss	1.0000
3:179204594:G:GT	donor_gain	1.0000
3:179209584:A:G	acceptor_gain	1.0000
3:179209697:AGAGG:A	donor_loss	1.0000

AlphaMissense

7111 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:179199756:G:C	R140P	1.000
3:179201397:G:C	A224P	1.000
3:179201482:T:C	L252S	1.000
3:179201494:G:A	G256E	1.000
3:179203578:C:A	P283H	1.000
3:179203578:C:G	P283R	1.000
3:179203752:C:A	A341E	1.000
3:179204510:T:A	V356D	1.000
3:179209596:T:A	W383R	1.000
3:179209596:T:C	W383R	1.000
3:179209597:G:C	W383S	1.000
3:179209598:G:C	W383C	1.000
3:179209598:G:T	W383C	1.000
3:179209658:C:G	C403W	1.000
3:179210204:T:A	W424R	1.000
3:179210204:T:C	W424R	1.000
3:179219251:T:A	W574R	1.000
3:179219251:T:C	W574R	1.000
3:179220027:G:T	G664W	1.000
3:179220028:G:A	G664E	1.000
3:179220042:T:A	W669R	1.000
3:179220042:T:C	W669R	1.000
3:179221048:G:C	R693P	1.000
3:179221105:T:C	L712P	1.000
3:179224726:C:T	S774F	1.000
3:179224737:C:A	P778T	1.000
3:179224737:C:T	P778S	1.000
3:179224738:C:A	P778Q	1.000
3:179224738:C:G	P778R	1.000
3:179224741:T:C	L779P	1.000

dbSNP variants (sampled 300 via entrez): RS1000011706 (3:179222205 T>G), RS1000044043 (3:179187783 G>A,T), RS1000084495 (3:179185378 C>A,T), RS1000090804 (3:179185721 C>T), RS1000129040 (3:179171093 T>C), RS1000235547 (3:179207612 C>T), RS1000238020 (3:179160686 T>A), RS1000264326 (3:179147952 G>A,T), RS1000358773 (3:179154343 A>C), RS1000395367 (3:179200938 A>T), RS1000414251 (3:179153441 A>G,T), RS1000450165 (3:179166188 G>T), RS1000473747 (3:179146674 G>A), RS1000482256 (3:179193870 T>C), RS1000486579 (3:179153864 G>A)

Disease associations

OMIM: gene MIM:171834 | disease phenotypes: MIM:158350, MIM:613659, MIM:114500, MIM:114550, MIM:155500, MIM:162900, MIM:167000, MIM:182000, MIM:211980, MIM:602501, MIM:606773, MIM:612918, MIM:613089, MIM:615108, MIM:114480, MIM:619538, MIM:149000, MIM:153100, MIM:109800, MIM:608354, MIM:608355, MIM:615355, MIM:155350, MIM:300633, MIM:217990, MIM:173900

GenCC curated gene-disease

Disease	Classification	Inheritance
overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes	Definitive	Autosomal dominant
megalencephaly-capillary malformation-polymicrogyria syndrome	Strong	Autosomal dominant
vascular malformation	Strong	Autosomal dominant
Cowden disease	Supportive	Autosomal dominant
Cowden syndrome 5	Limited	Autosomal dominant
familial ovarian cancer	No Known Disease Relationship	Unknown

ClinGen Gene-Disease Validity (3)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hereditary breast carcinoma	Refuted	AD
overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes	Definitive	AD
familial ovarian cancer	No Known Disease Relationship	AD

Mondo (54): Cowden disease (MONDO:0016063), gastric cancer (MONDO:0001056), colorectal cancer (MONDO:0005575), hepatocellular carcinoma (MONDO:0007256), megalodactyly (MONDO:0007962), nevus, epidermal (MONDO:0008093), ovarian cancer (MONDO:0008170), seborrheic keratosis (MONDO:0008420), lung cancer (MONDO:0008903), megalencephaly-capillary malformation-polymicrogyria syndrome (MONDO:0011240), hemifacial myohyperplasia (MONDO:0011723), CLOVES syndrome (MONDO:0013038), CLAPO syndrome (MONDO:0013125), Cowden syndrome 5 (MONDO:0014047), hereditary breast carcinoma (MONDO:0016419)

Orphanet (32): Cowden syndrome (Orphanet:201), CLOVES syndrome (Orphanet:140944), Hemifacial myohyperplasia (Orphanet:141148), CLAPO syndrome (Orphanet:168984), Rare ovarian cancer (Orphanet:213500), Hereditary breast cancer (Orphanet:227535), Megalencephaly-capillary malformation-polymicrogyria syndrome (Orphanet:60040), Woolly hair nevus (Orphanet:79414), Hepatocellular carcinoma (Orphanet:88673), OBSOLETE: Angioosteohypertrophic syndrome (Orphanet:2346), Capillary-lymphatic-venous malformation with segmental distribution (Orphanet:90308), PIK3CA-related overgrowth syndrome (Orphanet:530313), Slow-flow malformation, venous type (Orphanet:211252), Rosette-forming glioneuronal tumor (Orphanet:251975), Rare combined vascular malformation (Orphanet:458837)

HPO phenotypes

383 total (30 of 383 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000020	Urinary incontinence
HP:0000034	Hydrocele testis
HP:0000036	Abnormal penis morphology
HP:0000044	Hypogonadotropic hypogonadism
HP:0000077	Abnormality of the kidney
HP:0000089	Renal hypoplasia
HP:0000098	Tall stature
HP:0000105	Enlarged kidney
HP:0000107	Renal cyst
HP:0000130	Abnormality of the uterus
HP:0000138	Ovarian cyst
HP:0000140	Abnormality of the menstrual cycle
HP:0000141	Amenorrhea
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000160	Narrow mouth
HP:0000218	High palate
HP:0000221	Furrowed tongue
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000267	Cranial asymmetry
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000324	Facial asymmetry
HP:0000327	Hypoplasia of the maxilla
HP:0000337	Broad forehead

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST005993_71	Mean corpuscular hemoglobin	3.000000e-08
GCST010002_445	Refractive error	2.000000e-09
GCST90002390_300	Mean corpuscular hemoglobin	2.000000e-19
GCST90002392_721	Mean corpuscular volume	4.000000e-23
GCST90002396_260	Mean reticulocyte volume	1.000000e-10
GCST90002397_89	Mean spheric corpuscular volume	1.000000e-11
GCST90002403_557	Red blood cell count	2.000000e-16
GCST90002406_50	Reticulocyte fraction of red cells	5.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0004305	erythrocyte count

MeSH disease descriptors (26)

Descriptor	Name	Tree numbers
D061085	Agenesis of Corpus Callosum	C10.500.034; C16.131.666.034; C23.300.008
D006528	Carcinoma, Hepatocellular	C04.557.470.200.025.255; C04.588.274.623.160; C06.301.623.160; C06.552.697.160
D002289	Carcinoma, Non-Small-Cell Lung	C04.588.894.797.520.109.220.249; C08.381.540.140.500; C08.785.520.100.220.500
D003965	Diaphragmatic Eventration	C06.198.257; C16.131.314.244
D006223	Hamartoma Syndrome, Multiple	C04.445.435; C04.651.435; C04.700.435; C16.320.700.435
D065705	Hemimegalencephaly	C05.660.207.536.500; C10.500.507.400.249.500; C16.131.621.207.532.500; C16.131.666.507.400.249.500
D007021	Hypospadias	C12.050.351.875.466; C12.100.500.494.400; C12.200.294.494.400; C12.200.706.516; C12.800.516; C16.131.939.516
D007636	Keratoacanthoma	C17.800.417
D017492	Keratosis, Seborrheic	C17.800.428.580
D007715	Klippel-Trenaunay-Weber Syndrome	C14.907.077.410
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
D007690	Polycystic Kidney Diseases	C12.050.351.968.419.403.875; C12.200.777.419.403.875; C12.950.419.403.875; C16.131.077.717; C16.320.184.625
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
D012509	Sarcoma	C04.557.450.795
D013274	Stomach Neoplasms	C04.588.274.476.767; C06.301.371.767; C06.405.249.767; C06.405.748.789
D020521	Stroke	C10.228.140.300.775; C14.907.253.855
D054079	Vascular Malformations	C14.240.850; C16.131.240.850
C562840	Breast Cancer, Familial (supp.)
C567763	CLAPO Syndrome (supp.)
C567863	Congenital Lipomatous Overgrowth, Vascular Malformations, and Epidermal Nevi (supp.)
C580062	Epidermal Nevus (supp.)
C535862	Hemifacial myohyperplasia (supp.)
C537719	Macrodactyly of the foot (supp.)
C536142	Megalencephaly cutis marmorata telangiectatica congenita (supp.)
C562546	Megalodactyly (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (7): CHEMBL2111367 (PROTEIN COMPLEX), CHEMBL3559703 (PROTEIN COMPLEX GROUP), CHEMBL3885616 (PROTEIN FAMILY), CHEMBL4005 (SINGLE PROTEIN), CHEMBL6193785 (PROTEIN-PROTEIN INTERACTION), CHEMBL6193791 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195560 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

67 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 257,444 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL343448	ROMIDEPSIN	4	12,963
CHEMBL3545068	COPANLISIB HYDROCHLORIDE	4	1,306
CHEMBL3643413	LENIOLISIB	4	341
CHEMBL408513	BELINOSTAT	4	7,765
CHEMBL4650215	INAVOLISIB	4	876
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL1879463	DACTOLISIB	3	7,988
CHEMBL2017974	BUPARLISIB	3	6,568
CHEMBL165	RESVERATROL	3	60,144
CHEMBL2177390	IPATASERTIB	3	2,231
CHEMBL2387080	TASELISIB	3	3,473
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL592445	GEDATOLISIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL1236962	OMIPALISIB	2
CHEMBL2336325	VISTUSERTIB	2
CHEMBL3622533	FIMEPINOSTAT	2
CHEMBL3984425	EGANELISIB	2
CHEMBL3989870	BERZOSERTIB	2
CHEMBL4084907	BIMIRALISIB	2
CHEMBL521851	PICTILISIB	2
CHEMBL586702	ZSTK-474	2

Clinical evidence (CIViC)

Drug × variant × indication: 192 predictive associations from 202 curated evidence items; also 16 prognostic, 4 functional, 3 diagnostic.

Variant	Therapy	Indication	Effect	Level	CIViC
PIK3CA C420R	Alpelisib + Fulvestrant	Breast Cancer	Sensitivity/Response	CIViC A	EID11275
PIK3CA C420R	Capivasertib + Fulvestrant	Her2-receptor Negative Breast Cancer	Sensitivity/Response	CIViC A	EID12183
PIK3CA E453K OR PIK3CA E453Q OR PIK3CA E453A OR PIK3CA E453D OR PIK3CA E453G OR PIK3CA E453V	Fulvestrant + Inavolisib + Palbociclib	Breast Cancer	Sensitivity/Response	CIViC A	EID12540
PIK3CA E542K	Fulvestrant + Capivasertib	Her2-receptor Negative Breast Cancer	Sensitivity/Response	CIViC A	EID12184
PIK3CA E542K	Fulvestrant + Alpelisib	Breast Cancer	Sensitivity/Response	CIViC A	EID7315
PIK3CA E542K OR PIK3CA E542Q OR PIK3CA E542A OR PIK3CA E542D OR PIK3CA E542G OR PIK3CA E542R OR PIK3CA E542V	Palbociclib + Inavolisib + Fulvestrant	Breast Cancer	Sensitivity/Response	CIViC A	EID12535
PIK3CA E545G	Fulvestrant + Capivasertib	Her2-receptor Negative Breast Cancer	Sensitivity/Response	CIViC A	EID12189
PIK3CA E545K	Fulvestrant + Capivasertib	Her2-receptor Negative Breast Cancer	Sensitivity/Response	CIViC A	EID12188
PIK3CA E545K OR PIK3CA E545A OR PIK3CA E545G OR PIK3CA E545D	Fulvestrant + Alpelisib	Breast Cancer	Sensitivity/Response	CIViC A	EID7468
PIK3CA E545K OR PIK3CA E545Q OR PIK3CA E545A OR PIK3CA E545G OR PIK3CA E545V OR PIK3CA E545D OR PIK3CA E545L OR PIK3CA E545R	Palbociclib + Inavolisib + Fulvestrant	Breast Cancer	Sensitivity/Response	CIViC A	EID12534
PIK3CA E545Q	Fulvestrant + Capivasertib	Her2-receptor Negative Breast Cancer	Sensitivity/Response	CIViC A	EID12187
PIK3CA G1049R	Capivasertib + Fulvestrant	Her2-receptor Negative Breast Cancer	Sensitivity/Response	CIViC A	EID12198
PIK3CA G1049S OR PIK3CA G1049R OR PIK3CA G106V OR PIK3CA G106R OR PIK3CA G1049A OR PIK3CA G106S OR PIK3CA G106A OR PIK3CA G106D OR PIK3CA G118D OR PIK3CA G1049C OR PIK3CA G1049D	Palbociclib + Inavolisib + Fulvestrant	Breast Cancer	Sensitivity/Response	CIViC A	EID12537
PIK3CA H1047L	Capivasertib + Fulvestrant	Her2-receptor Negative Breast Cancer	Sensitivity/Response	CIViC A	EID12197
PIK3CA H1047R	Fulvestrant + Capivasertib	Her2-receptor Negative Breast Cancer	Sensitivity/Response	CIViC A	EID12196
PIK3CA H1047R OR PIK3CA H1047Y OR PIK3CA H1047L	Fulvestrant + Alpelisib	Breast Cancer	Sensitivity/Response	CIViC A	EID7318
PIK3CA H1047R OR PIK3CA H1047Y OR PIK3CA H1047L OR PIK3CA H1047D OR PIK3CA H1047I OR PIK3CA H1047N OR PIK3CA H1047P OR PIK3CA H1047Q OR PIK3CA H1047T	Palbociclib + Inavolisib + Fulvestrant	Breast Cancer	Sensitivity/Response	CIViC A	EID12533
PIK3CA Mutation	Alpelisib + Fulvestrant	Breast Cancer	Sensitivity/Response	CIViC A	EID7313
PIK3CA Mutation OR PTEN Mutation OR AKT1 Mutation	Capivasertib + Fulvestrant	Breast Cancer	Sensitivity/Response	CIViC A	EID12020
PIK3CA N345K	Capivasertib + Fulvestrant	Her2-receptor Negative Breast Cancer	Sensitivity/Response	CIViC A	EID12182
PIK3CA N345K OR PIK3CA N345D OR PIK3CA N345H OR PIK3CA N345I OR PIK3CA N345S OR PIK3CA N345T OR PIK3CA N345Y	Palbociclib + Inavolisib + Fulvestrant	Breast Cancer	Sensitivity/Response	CIViC A	EID12538
PIK3CA Q546E OR PIK3CA Q546R	Fulvestrant + Alpelisib	Breast Cancer	Sensitivity/Response	CIViC A	EID7316
PIK3CA Q546K	Capivasertib + Fulvestrant	Her2-receptor Negative Breast Cancer	Sensitivity/Response	CIViC A	EID12191
PIK3CA Q546K OR PIK3CA Q546E OR PIK3CA Q546P OR PIK3CA Q546R OR PIK3CA Q546L OR PIK3CA K111E OR PIK3CA K111N OR PIK3CA K111R OR PIK3CA Q546H	Inavolisib + Fulvestrant + Palbociclib	Breast Cancer	Sensitivity/Response	CIViC A	EID12536
PIK3CA R88Q	Capivasertib + Fulvestrant	Her2-receptor Negative Breast Cancer	Sensitivity/Response	CIViC A	EID12034
PIK3CA R88Q OR PIK3CA C420R OR PIK3CA M1043V OR PIK3CA M1043I OR PIK3CA M1043T	Fulvestrant + Palbociclib + Inavolisib	Breast Cancer	Sensitivity/Response	CIViC A	EID12539
PIK3CA Mutation	Capivasertib	Cancer	Sensitivity/Response	CIViC B	EID3040 +1
MTOR Mutation OR PIK3CA Mutation OR PTEN Mutation OR AKT1 Mutation OR AKT2 Mutation	Sapanisertib	Solid Tumor	Sensitivity/Response	CIViC B	EID12075
PIK3CA Amplification	Ibuprofen + Aspirin + Sulindac	Head And Neck Squamous Cell Carcinoma	Sensitivity/Response	CIViC B	EID7186
PIK3CA E542K	Aspirin	Colorectal Cancer	Sensitivity/Response	CIViC B	EID2033

+162 more predictive associations (showing top 30 by evidence level).

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2699887	Toxicity	3	carboplatin;cisplatin	Non-Small Cell Lung Carcinoma
rs870995	Dosage	3	docetaxel	Non-Small Cell Lung Carcinoma

PharmGKB variants

8 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs870995	PIK3CA	3	0.25	1	docetaxel
rs2459693	PIK3CA		0.00	0
rs2677760	PIK3CA		0.00	0
rs2699887	PIK3CA	3	2.50	1	carboplatin;cisplatin
rs2699905	PIK3CA		0.00	0
rs6443624	PIK3CA		0.00	0
rs67562832	PIK3CA		0.00	0
rs77576241	PIK3CA		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Phosphatidylinositol kinases

Most potent curated ligand interactions (86 total), top 25:

Ligand	Action	Affinity	Parameter
PF-06843195	Inhibition	10.74	pKi
inavolisib	Inhibition	10.47	pKi
taselisib	Inhibition	10.05	pKi
compound 15a [PMID: 32069401]	Inhibition	9.7	pIC50
vulolisib	Inhibition	9.7	pIC50
gedatolisib	Inhibition	9.4	pIC50
copanlisib	Inhibition	9.3	pIC50
PF-04691502	Inhibition	9.24	pKi
HS-173	Inhibition	9.1	pIC50
neolymphostin A	Inhibition	9.06	pKd
compound 5d [PMID: 31335136]	Inhibition	9.06	pIC50
gilmelisib	Inhibition	9.0	pIC50
compound 17 [PMID: 38477582]	Inhibition	9.0	pIC50
zinilisib	Inhibition	9.0	pIC50
compound 82 [PMID: 21332118]	Inhibition	8.92	pKi
bimiralisib	Inhibition	8.82	pKd
paxalisib	Inhibition	8.7	pIC50
PI-103	Inhibition	8.7	pIC50
GSK1059615	Inhibition	8.7	pIC50
panulisib	Inhibition	8.66	pIC50
pictilisib	Inhibition	8.52	pIC50
dactolisib	Inhibition	8.4	pIC50
BGT-226	Inhibition	8.4	pIC50
KU-0060648	Inhibition	8.4	pIC50
compound 27 [PMID: 35834807]	Inhibition	8.36	pIC50

Binding affinities (BindingDB)

4977 measured of 5521 human assays (5525 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-amino-1-[(3S)-3-[4-(2-aminopyrimidin-5-yl)-2-[(3S)-3-methylmorpholin-4-yl]-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidin-1-yl]-3-hydroxy-2-methylpropan-1-one	KI	0.011 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
5-[7-(3-methyl-1-methylsulfonylpyrrolidin-3-yl)-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-4-yl]pyrimidin-2-amine	KI	0.015 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
(2R)-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-3-methylbutan-1-one	KI	0.016 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
5-[7-[(3S)-1-(5,5-dimethyl-4H-1,3-oxazol-2-yl)-3-methylpyrrolidin-3-yl]-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-4-yl]pyrimidin-2-amine	KI	0.019 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
tert-butyl 3-[4-(2-aminopyrimidin-5-yl)-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]-3-methylazetidine-1-carboxylate	KI	0.019 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
(2R)-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-cyclopropylethanone	KI	0.019 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
3-[(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-methyl-3-oxopropanamide	KI	0.019 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
5-[7-(1-cyclopropylsulfonyl-3-methylazetidin-3-yl)-2-[(3S)-3-methylmorpholin-4-yl]-5,6-dihydropyrrolo[2,3-d]pyrimidin-4-yl]pyrimidin-2-amine	KI	0.021 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]-3-methylpyrrolidin-1-yl]-[(1S,2S)-2-fluorocyclopropyl]methanone	KI	0.021 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]-3-methylpyrrolidin-1-yl]-(3-hydroxyazetidin-1-yl)methanone	KI	0.021 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
(S)-2-((1-(4-(1H-1,2,4- triazol-3-yl)phenyl)- 7,8,9,10-tetrahydro-6- oxa-2,10a- diazacycloocta[cd]inden- 4-yl)oxy)butanamide	KI	0.021 nM	US-10065970: Tricyclic PI3K inhibitor compounds and methods of use
(2R)-2-amino-1-[(3S)-3-[4-(2-aminopyrimidin-5-yl)-2-[(3S)-3-methylmorpholin-4-yl]-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidin-1-yl]-2-cyclopropylethanone	KI	0.022 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
(2S)-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-3-methylbutan-1-one	KI	0.022 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
(2R)-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]-3-methylbutan-1-one	KI	0.022 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]-3-methylpyrrolidin-1-yl]-(1-methylpyrazol-3-yl)methanone	KI	0.022 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
(S)-2-((1-(2-fluoro-4- (1H-1,2,4-triazol-5- yl)phenyl)-7,8,9,10- tetrahydro-6-oxa-2,10a- diazacycloocta[cd]inden-4- yl)oxy)propanamide	KI	0.022 nM	US-10065970: Tricyclic PI3K inhibitor compounds and methods of use
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-[(3S)-3-methylmorpholin-4-yl]-5,6-dihydropyrrolo[2,3-d]pyrimidin-4-yl]pyrimidin-2-amine	KI	0.023 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
2-amino-1-[(3S)-3-[4-(2-aminopyrimidin-5-yl)-2-[(3S)-3-methylmorpholin-4-yl]-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidin-1-yl]-2-methylpropan-1-one	KI	0.024 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
5-[7-(1-ethylsulfonyl-3-methylazetidin-3-yl)-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-4-yl]pyrimidin-2-amine	KI	0.024 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
5-[7-(3-methyl-1-propan-2-ylsulfonylazetidin-3-yl)-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-4-yl]pyrimidin-2-amine	KI	0.024 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
3-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]-3-methylbutan-1-one	KI	0.024 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]-3-methylpyrrolidin-1-yl]-cyclopropylmethanone	KI	0.024 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
tert-butyl 4-[4-(2-aminopyrimidin-5-yl)-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]-4-methylpiperidine-1-carboxylate	KI	0.024 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
(S)-1-(1-(2- aminobenzo[d]oxazol- 5-yl)-3-fluoro-7,8,9,10- tetrahydro-6-oxa-2,10a- diazacycloocta[cd]inden- 4-yl)pyrrolidine-2- carboxamide	KI	0.024 nM	US-10065970: Tricyclic PI3K inhibitor compounds and methods of use
(S)-2-((1-(3- aminobenzo[e][1,2,4]tri- azin-7-yl)-7,8,9,10- tetrahydro-6-oxa-2,10a- diazacycloocta[cd]inden-4- yl)oxy)propanamide	KI	0.024 nM	US-10065970: Tricyclic PI3K inhibitor compounds and methods of use
[(3S)-3-[4-(2-aminopyrimidin-5-yl)-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidin-1-yl]-(1-methylcyclopropyl)methanone	KI	0.025 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-methyl-2-(methylamino)propan-1-one	KI	0.025 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
(2R)-2-amino-1-[(3S)-3-[4-(2-aminopyrimidin-5-yl)-2-[(3S)-3-methylmorpholin-4-yl]-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidin-1-yl]butan-1-one	KI	0.026 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
(2R)-2-amino-1-[(3S)-3-[4-(2-aminopyrimidin-5-yl)-2-[(3S)-3-methylmorpholin-4-yl]-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidin-1-yl]-3-fluoropropan-1-one	KI	0.026 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]-3-methylpyrrolidin-1-yl]-(azetidin-3-yl)methanone	KI	0.026 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]-3-methylpyrrolidin-1-yl]-[(2S)-pyrrolidin-2-yl]methanone	KI	0.026 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
(S)-1-(1-(2- aminobenzo[d]oxazol- 5-yl)-3-fluoro-8,9- dihydro-7H-6-oxa- 2,9a- diazabenzo[cd]azulen- 4-yl)pyrrolidine-2- carboxamide	KI	0.026 nM	US-10065970: Tricyclic PI3K inhibitor compounds and methods of use
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
(3S)-3-[4-(2-aminopyrimidin-5-yl)-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidine-1-sulfonamide	KI	0.027 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-methoxyethanone	KI	0.027 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]-3-methylpyrrolidin-1-yl]-[(3R)-oxolan-3-yl]methanone	KI	0.027 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
(S)-2-((1-(2- aminobenzo[d]thiazol- 6-yl)-7,8,9,10- tetrahydro-6-oxa-2,10a- diazacycloocta[cd]inden- 4-yl)oxy)-2- cyclopropylacetamide	KI	0.027 nM	US-10065970: Tricyclic PI3K inhibitor compounds and methods of use
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]-2-cyclopropyl-2-hydroxyethanone	KI	0.028 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]-3-methylpyrrolidin-1-yl]-(3-hydroxycyclobutyl)methanone	KI	0.028 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]-3-methylpyrrolidin-1-yl]-[(3S)-oxolan-3-yl]methanone	KI	0.028 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
(3R)-3-[4-(2-aminopyrimidin-5-yl)-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]-N,3-dimethylpyrrolidine-1-sulfonamide	KI	0.029 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
5-[7-(1-cyclopropylsulfonylazetidin-3-yl)-2-[(3S)-3-methylmorpholin-4-yl]-5,6-dihydropyrrolo[2,3-d]pyrimidin-4-yl]pyrimidin-2-amine	KI	0.03 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
3-[4-(2-aminopyrimidin-5-yl)-2-[(3S)-3-methylmorpholin-4-yl]-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]-N,N-dimethylazetidine-1-sulfonamide	KI	0.03 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
5-[7-(3-methyl-1-methylsulfonylpyrrolidin-3-yl)-2-[(3S)-3-methylmorpholin-4-yl]-5,6-dihydropyrrolo[2,3-d]pyrimidin-4-yl]pyrimidin-2-amine	KI	0.03 nM	US-9260439: Dihydropyrrolopyrimidine derivatives
5-[7-[(3R)-3-methyl-1-methylsulfonylpyrrolidin-3-yl]-2-[(3S)-3-methylmorpholin-4-yl]-5,6-dihydropyrrolo[2,3-d]pyrimidin-4-yl]pyrimidin-2-amine	KI	0.03 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]propan-1-one	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
(3-aminooxolan-3-yl)-[(3S)-3-[4-(2-aminopyrimidin-5-yl)-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidin-1-yl]methanone	KI	0.03 nM	US-9260439: Dihydropyrrolopyrimidine derivatives

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.96	Ki	0.011	nM	CHEMBL3943270
10.82	Ki	0.015	nM	CHEMBL3984086
10.80	Ki	0.016	nM	CHEMBL3925423
10.80	Ki	0.016	nM	CHEMBL3770993
10.72	Ki	0.019	nM	CHEMBL3924367
10.72	Ki	0.019	nM	CHEMBL3964422
10.72	Ki	0.019	nM	CHEMBL3917427
10.72	Ki	0.019	nM	CHEMBL3934181
10.72	IC50	0.019	nM	OMIPALISIB
10.72	Ki	0.019	nM	CHEMBL4764484
10.72	Ki	0.019	nM	OMIPALISIB
10.70	Ki	0.02	nM	OMIPALISIB
10.70	Ki	0.02	nM	CHEMBL5847613
10.68	Ki	0.021	nM	CHEMBL3933148
10.68	Ki	0.021	nM	CHEMBL3950868
10.68	Ki	0.021	nM	CHEMBL3952408
10.68	Ki	0.021	nM	CHEMBL4778025
10.68	Ki	0.021	nM	CHEMBL5953956
10.66	Ki	0.022	nM	CHEMBL3958509
10.66	Ki	0.022	nM	CHEMBL3967130
10.66	Ki	0.022	nM	CHEMBL3916399
10.66	Ki	0.022	nM	CHEMBL3969015
10.66	Ki	0.022	nM	CHEMBL5778370
10.66	Ki	0.022	nM	CHEMBL5808475
10.64	Ki	0.023	nM	CHEMBL3932221
10.64	Ki	0.023	nM	CHEMBL3902135
10.64	Ki	0.023	nM	CHEMBL6019298
10.62	Ki	0.024	nM	CHEMBL3956275
10.62	Ki	0.024	nM	CHEMBL3907741
10.62	Ki	0.024	nM	CHEMBL3926126
10.62	Ki	0.024	nM	CHEMBL3949378
10.62	Ki	0.024	nM	CHEMBL3966977
10.62	Ki	0.024	nM	CHEMBL3980813
10.62	Ki	0.024	nM	CHEMBL5750027
10.62	Ki	0.024	nM	CHEMBL5867381
10.60	Ki	0.025	nM	CHEMBL3926068
10.60	Ki	0.025	nM	CHEMBL3930628
10.60	Ki	0.025	nM	CHEMBL6022825
10.59	Ki	0.026	nM	CHEMBL3981905
10.59	Ki	0.026	nM	CHEMBL3946605
10.59	Ki	0.026	nM	CHEMBL3935717
10.59	Ki	0.026	nM	CHEMBL3917991
10.59	Ki	0.026	nM	CHEMBL5208487
10.59	Ki	0.026	nM	CHEMBL5855663
10.59	Ki	0.026	nM	CHEMBL5775210
10.59	Ki	0.026	nM	CHEMBL5871963
10.57	Ki	0.027	nM	CHEMBL3908620
10.57	Ki	0.027	nM	CHEMBL3975616
10.57	Ki	0.027	nM	CHEMBL3940617
10.57	Ki	0.027	nM	CHEMBL3983948

PubChem BioAssay actives

3438 with measured affinity, of 6100 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
tert-butyl (3S)-3-[4-(2-aminopyrimidin-5-yl)-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidine-1-carboxylate	1707451: Inhibition of recombinant human full-length PI3K p110alpha/p85alpha (322 to 600) expressed in baculovirus infected Sf21 cells 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	<0.0001	uM
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	1707451: Inhibition of recombinant human full-length PI3K p110alpha/p85alpha (322 to 600) expressed in baculovirus infected Sf21 cells 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	<0.0001	uM
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	1707451: Inhibition of recombinant human full-length PI3K p110alpha/p85alpha (322 to 600) expressed in baculovirus infected Sf21 cells 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	<0.0001	uM
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	1707451: Inhibition of recombinant human full-length PI3K p110alpha/p85alpha (322 to 600) expressed in baculovirus infected Sf21 cells 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	<0.0001	uM
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	1707451: Inhibition of recombinant human full-length PI3K p110alpha/p85alpha (322 to 600) expressed in baculovirus infected Sf21 cells 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	<0.0001	uM
(3S)-3-[4-(2-aminopyrimidin-5-yl)-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]-N,3-dimethylpyrrolidine-1-sulfonamide	1707451: Inhibition of recombinant human full-length PI3K p110alpha/p85alpha (322 to 600) expressed in baculovirus infected Sf21 cells 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	<0.0001	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	1707451: Inhibition of recombinant human full-length PI3K p110alpha/p85alpha (322 to 600) expressed in baculovirus infected Sf21 cells 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	<0.0001	uM
(2S)-1-[2-[(4S)-4-(fluoromethyl)-2-oxo-1,3-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]pyrrolidine-2-carboxamide	1897589: Inhibition of PI3Kalpha (unknown origin) using PIP2:3PS as substrate in presence of ATP measured after 120 mins by ADP-Glo assay	ki	<0.0001	uM
Inavolisib	1897589: Inhibition of PI3Kalpha (unknown origin) using PIP2:3PS as substrate in presence of ATP measured after 120 mins by ADP-Glo assay	ki	<0.0001	uM
2,2-difluoroethyl (3S)-3-[[6-(2-aminopyrimidin-5-yl)-5-fluoro-2-morpholin-4-ylpyrimidin-4-yl]amino]-3-(hydroxymethyl)pyrrolidine-1-carboxylate	1707451: Inhibition of recombinant human full-length PI3K p110alpha/p85alpha (322 to 600) expressed in baculovirus infected Sf21 cells 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	<0.0001	uM
tert-butyl (3S)-3-[[6-(2-aminopyrimidin-5-yl)-2-morpholin-4-ylpyrimidin-4-yl]amino]-3-(hydroxymethyl)pyrrolidine-1-carboxylate	1707451: Inhibition of recombinant human full-length PI3K p110alpha/p85alpha (322 to 600) expressed in baculovirus infected Sf21 cells 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	<0.0001	uM
methyl (3S)-3-[[6-(2-aminopyrimidin-5-yl)-2-morpholin-4-ylpyrimidin-4-yl]amino]-3-(hydroxymethyl)pyrrolidine-1-carboxylate	1707451: Inhibition of recombinant human full-length PI3K p110alpha/p85alpha (322 to 600) expressed in baculovirus infected Sf21 cells 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	<0.0001	uM
methyl (3S)-3-[[6-(2-aminopyrimidin-5-yl)-5-fluoro-2-morpholin-4-ylpyrimidin-4-yl]amino]-3-(hydroxymethyl)pyrrolidine-1-carboxylate	1707451: Inhibition of recombinant human full-length PI3K p110alpha/p85alpha (322 to 600) expressed in baculovirus infected Sf21 cells 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	<0.0001	uM
2,2-difluoroethyl (3S)-3-[[6-(2-aminopyrimidin-5-yl)-2-morpholin-4-ylpyrimidin-4-yl]amino]-3-(hydroxymethyl)pyrrolidine-1-carboxylate	1707451: Inhibition of recombinant human full-length PI3K p110alpha/p85alpha (322 to 600) expressed in baculovirus infected Sf21 cells 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	<0.0001	uM
(2S)-1-[2-[(4R)-2-oxo-4-propan-2-yl-1,3-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]pyrrolidine-2-carboxamide	1897589: Inhibition of PI3Kalpha (unknown origin) using PIP2:3PS as substrate in presence of ATP measured after 120 mins by ADP-Glo assay	ki	<0.0001	uM
(2S)-1-[2-(5-amino-2-propan-2-yl-1,2,4-triazol-3-yl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]pyrrolidine-2-carboxamide	1897589: Inhibition of PI3Kalpha (unknown origin) using PIP2:3PS as substrate in presence of ATP measured after 120 mins by ADP-Glo assay	ki	<0.0001	uM
2,4-difluoro-N-[2-methoxy-5-(4-pyridazin-4-ylquinolin-6-yl)-3-pyridinyl]benzenesulfonamide	1467657: Competitive inhibition of human PI3K p110alpha/p85alpha using PIP2 as substrate preincubated for 10 mins followed by ATP addition measured after 30 mins by HTRF assay	ic50	<0.0001	uM
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	1707451: Inhibition of recombinant human full-length PI3K p110alpha/p85alpha (322 to 600) expressed in baculovirus infected Sf21 cells 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	0.0001	uM
5-[7-[(3S)-1-methylsulfonylpyrrolidin-3-yl]-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-4-yl]pyrimidin-2-amine	1707451: Inhibition of recombinant human full-length PI3K p110alpha/p85alpha (322 to 600) expressed in baculovirus infected Sf21 cells 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	0.0001	uM
(3S)-3-[4-(2-aminopyrimidin-5-yl)-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]-N-methylpyrrolidine-1-sulfonamide	1707451: Inhibition of recombinant human full-length PI3K p110alpha/p85alpha (322 to 600) expressed in baculovirus infected Sf21 cells 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	0.0001	uM
(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	1707451: Inhibition of recombinant human full-length PI3K p110alpha/p85alpha (322 to 600) expressed in baculovirus infected Sf21 cells 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	0.0001	uM
2,4-difluoro-N-[2-methoxy-5-(4-pyridin-4-ylquinazolin-6-yl)-3-pyridinyl]benzenesulfonamide	1226264: Inhibition of PI3Kalpha (unknown origin) using PIP2/PS as substrate after 1 hr by luciferase-based luminescence assay	ic50	0.0001	uM
N-[5-(2-amino-4-pyridin-4-ylquinazolin-6-yl)-2-methoxy-3-pyridinyl]-2,4-difluorobenzenesulfonamide	1226264: Inhibition of PI3Kalpha (unknown origin) using PIP2/PS as substrate after 1 hr by luciferase-based luminescence assay	ic50	0.0001	uM
5-chloro-N-[2-chloro-5-(4-pyridin-4-ylthieno[2,3-d]pyrimidin-6-yl)-3-pyridinyl]thiophene-2-sulfonamide	1226264: Inhibition of PI3Kalpha (unknown origin) using PIP2/PS as substrate after 1 hr by luciferase-based luminescence assay	ic50	0.0001	uM
(2S)-1-[2-[(4S)-4-(difluoromethyl)-2-oxo-1,3-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]pyrrolidine-2-carboxamide	1897589: Inhibition of PI3Kalpha (unknown origin) using PIP2:3PS as substrate in presence of ATP measured after 120 mins by ADP-Glo assay	ki	0.0001	uM
(2S)-1-[2-[(4S)-2-oxo-4-(trifluoromethyl)-1,3-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]pyrrolidine-2-carboxamide	1897589: Inhibition of PI3Kalpha (unknown origin) using PIP2:3PS as substrate in presence of ATP measured after 120 mins by ADP-Glo assay	ki	0.0001	uM
(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	1897589: Inhibition of PI3Kalpha (unknown origin) using PIP2:3PS as substrate in presence of ATP measured after 120 mins by ADP-Glo assay	ki	0.0001	uM
(2S)-2-cyclopropyl-2-[[2-[(4S)-4-(difluoromethyl)-2-oxo-1,3-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]acetamide	1897589: Inhibition of PI3Kalpha (unknown origin) using PIP2:3PS as substrate in presence of ATP measured after 120 mins by ADP-Glo assay	ki	0.0001	uM
1-[(3S)-3-[[6-(2-aminopyrimidin-5-yl)-2-morpholin-4-ylpyrimidin-4-yl]amino]-3-(hydroxymethyl)pyrrolidin-1-yl]-2-methylpropan-1-one	1707451: Inhibition of recombinant human full-length PI3K p110alpha/p85alpha (322 to 600) expressed in baculovirus infected Sf21 cells 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	0.0001	uM
tert-butyl (3S)-3-[[6-(2-aminopyrimidin-5-yl)-2-morpholin-4-ylpyrimidin-4-yl]amino]-3-methylpyrrolidine-1-carboxylate	1707451: Inhibition of recombinant human full-length PI3K p110alpha/p85alpha (322 to 600) expressed in baculovirus infected Sf21 cells 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	0.0001	uM
2-amino-N-[7-methoxy-8-(3-morpholin-4-ylpropoxy)-2,3-dihydro-1H-imidazo[1,2-c]quinazolin-5-ylidene]pyrimidine-5-carboxamide	1560707: Inhibition of recombinant human full-length N-terminal His-tagged p110alpha/p85alpha expressed in baculovirus expression system using PIP2 as substrate measured after 1 hr by kinase-glo assay	ic50	0.0001	uM
(2S)-2-cyclopropyl-2-[[2-[(4S)-2-oxo-4-(trifluoromethyl)-1,3-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]acetamide	1897589: Inhibition of PI3Kalpha (unknown origin) using PIP2:3PS as substrate in presence of ATP measured after 120 mins by ADP-Glo assay	ki	0.0001	uM
2,4-difluoro-N-[2-methoxy-5-[3-[1-(3-morpholin-4-ylpropyl)triazol-4-yl]imidazo[1,2-b]pyridazin-6-yl]-3-pyridinyl]benzenesulfonamide	2002971: Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate incubated for 1 hr in presence of ATP by Kinase-Glo plus luminescent assay	ic50	0.0001	uM
(2S,3R)-3-methoxy-1-[2-[(4S)-2-oxo-4-(trifluoromethyl)-1,3-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]pyrrolidine-2-carboxamide	1897589: Inhibition of PI3Kalpha (unknown origin) using PIP2:3PS as substrate in presence of ATP measured after 120 mins by ADP-Glo assay	ki	0.0001	uM
(2S)-2-[[2-(5-amino-2-propan-2-yl-1,2,4-triazol-3-yl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]oxy]propanamide	1897589: Inhibition of PI3Kalpha (unknown origin) using PIP2:3PS as substrate in presence of ATP measured after 120 mins by ADP-Glo assay	ki	0.0001	uM
(2S)-2-[[2-[(4S)-2-oxo-4-(trifluoromethyl)-1,3-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]propanamide	1897589: Inhibition of PI3Kalpha (unknown origin) using PIP2:3PS as substrate in presence of ATP measured after 120 mins by ADP-Glo assay	ki	0.0001	uM
(2S)-2-[[2-[5-(hydroxymethyl)-2-(2,2,2-trifluoroethyl)-1,2,4-triazol-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]oxy]propanamide	1897589: Inhibition of PI3Kalpha (unknown origin) using PIP2:3PS as substrate in presence of ATP measured after 120 mins by ADP-Glo assay	ki	0.0001	uM
N-[5-[3-[1-[2-(dimethylamino)ethyl]triazol-4-yl]imidazo[1,2-b]pyridazin-6-yl]-2-methoxy-3-pyridinyl]-2,4-difluorobenzenesulfonamide	2002971: Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate incubated for 1 hr in presence of ATP by Kinase-Glo plus luminescent assay	ic50	0.0001	uM
2,4-difluoro-N-[2-methoxy-5-[3-[1-(2-morpholin-4-ylethyl)triazol-4-yl]imidazo[1,2-b]pyridazin-6-yl]-3-pyridinyl]benzenesulfonamide	2002971: Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate incubated for 1 hr in presence of ATP by Kinase-Glo plus luminescent assay	ic50	0.0001	uM
4-[2-(1H-indazol-4-yl)-6-[(4-methylsulfonylpiperazin-1-yl)methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine	1915590: Inhibition of PI3Kalpha (unknown origin)	ic50	0.0001	uM
2-(difluoromethyl)-1-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)benzimidazol-4-ol	626767: Inhibition of human PI3K p110alpha helical domain E545K mutant after 2 hrs by HTRF assay	ic50	0.0001	uM
N-[2-chloro-5-(4-pyridin-4-ylthieno[2,3-d]pyrimidin-6-yl)-3-pyridinyl]-2,4-difluorobenzenesulfonamide	1226264: Inhibition of PI3Kalpha (unknown origin) using PIP2/PS as substrate after 1 hr by luciferase-based luminescence assay	ic50	0.0002	uM
2,4-difluoro-N-[2-methoxy-5-[4-methyl-8-(oxan-4-yloxy)quinazolin-6-yl]-3-pyridinyl]benzenesulfonamide	2011702: Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate in presence of ATP by Kinase-Glo assay	ic50	0.0002	uM
1-[4-(4-morpholin-4-ylpyrido[3,2-d]pyrimidin-2-yl)phenyl]-3-(4-sulfamoylphenyl)urea	1467657: Competitive inhibition of human PI3K p110alpha/p85alpha using PIP2 as substrate preincubated for 10 mins followed by ATP addition measured after 30 mins by HTRF assay	ic50	0.0002	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	1560707: Inhibition of recombinant human full-length N-terminal His-tagged p110alpha/p85alpha expressed in baculovirus expression system using PIP2 as substrate measured after 1 hr by kinase-glo assay	ic50	0.0002	uM
2,4-difluoro-N-[2-methoxy-5-[3-(5-methyl-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-6-yl]-3-pyridinyl]benzenesulfonamide	1560707: Inhibition of recombinant human full-length N-terminal His-tagged p110alpha/p85alpha expressed in baculovirus expression system using PIP2 as substrate measured after 1 hr by kinase-glo assay	ic50	0.0002	uM
4-chloro-2-fluoro-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	1560707: Inhibition of recombinant human full-length N-terminal His-tagged p110alpha/p85alpha expressed in baculovirus expression system using PIP2 as substrate measured after 1 hr by kinase-glo assay	ic50	0.0002	uM
methyl 2-[4-[[[6-[5-[(2,4-difluorophenyl)sulfonylamino]-6-methoxy-3-pyridinyl]imidazo[1,2-a]pyridine-3-carbonyl]amino]methyl]triazol-1-yl]benzoate	1560707: Inhibition of recombinant human full-length N-terminal His-tagged p110alpha/p85alpha expressed in baculovirus expression system using PIP2 as substrate measured after 1 hr by kinase-glo assay	ic50	0.0002	uM
2,4-difluoro-N-[2-methoxy-5-[3-[5-(2-methoxyethyl)-1,3,4-oxadiazol-2-yl]imidazo[1,2-a]pyridin-6-yl]-3-pyridinyl]benzenesulfonamide	1560707: Inhibition of recombinant human full-length N-terminal His-tagged p110alpha/p85alpha expressed in baculovirus expression system using PIP2 as substrate measured after 1 hr by kinase-glo assay	ic50	0.0002	uM
3-[5-[6-[5-[(2,4-difluorophenyl)sulfonylamino]-6-methoxy-3-pyridinyl]imidazo[1,2-a]pyridin-3-yl]-1,3,4-oxadiazol-2-yl]benzoic acid	1560707: Inhibition of recombinant human full-length N-terminal His-tagged p110alpha/p85alpha expressed in baculovirus expression system using PIP2 as substrate measured after 1 hr by kinase-glo assay	ic50	0.0002	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation	7
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases reaction, increases reaction, increases response to substance, decreases expression, increases cleavage (+6 more)	5
sodium arsenite	affects reaction, decreases expression, increases abundance, increases expression	4
Cannabidiol	affects cotreatment, decreases expression, increases expression	4
Benzo(a)pyrene	affects methylation, increases expression, decreases expression	3
Sirolimus	increases expression, decreases response to substance, increases activity, decreases expression, decreases reaction	3
moringin	affects cotreatment, decreases expression	2
tributyltin	decreases expression, increases expression	2
ochratoxin A	increases expression	2
entinostat	decreases expression, affects cotreatment	2
alisol B 23-acetate	decreases expression	2
dactolisib	decreases response to substance, increases response to substance	2
N-(6-(6-chloro-5-(4-fluorophenylsulfonamido)pyridin-3-yl)benzo(d)thiazol-2-yl)acetamide	decreases activity	2
1-(4-((2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholinothieno(3,2-d)pyrimidin-6-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one	decreases activity, increases response to substance, affects cotreatment	2
Resveratrol	increases expression, increases phosphorylation, affects binding, decreases activity, decreases reaction (+1 more)	2
Wortmannin	decreases reaction, increases activity, decreases activity	2
Arsenic Trioxide	decreases expression	2
Adenosine Triphosphate	affects binding, decreases reaction, decreases activity	2
Cadmium	increases reaction, decreases expression, decreases reaction, increases abundance	2
Cisplatin	decreases response to substance, increases expression	2
Doxorubicin	decreases expression	2
Drugs, Chinese Herbal	affects binding, decreases activity, increases expression	2
Estradiol	increases expression	2
Niclosamide	decreases expression, decreases reaction, increases expression	2
Plant Extracts	decreases expression, affects cotreatment, increases expression	2
Quercetin	increases phosphorylation, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cadmium Chloride	decreases expression, decreases reaction, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1

ChEMBL screening assays

2034 unique, capped per target: 2009 binding, 19 admet, 4 toxicity, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1105939	Binding	Inhibition of PIK3CA/PIK3R1 at 5 uM	Structure-activity relationship study of EphB3 receptor tyrosine kinase inhibitors. — Bioorg Med Chem Lett
CHEMBL4005472	ADMET	Inhibition of human full length PI3K p110alpha/p85 alpha using PIP2/ATP as substrate after 30 mins by TR-FRET assay	Discovery of a Phosphoinositide 3-Kinase (PI3K) β/δ Inhibitor for the Treatment of Phosphatase and Tensin Homolog (PTEN) Deficient Tumors: Building PI3Kβ Potency in a PI3Kδ-Selective Template by Targeting Nonconserved Asp856. — J Med Chem
CHEMBL5123067	Toxicity	Inhibition of human PI3Kalpha by Kinase-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

3,577 cell lines: 3,572 cancer cell line, 3 transformed cell line, 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0031	MCF-7	Cancer cell line	Female
CVCL_0088	MCF-7L	Cancer cell line	Female
CVCL_0101	SNU-601	Cancer cell line	Male
CVCL_0114	2008/C13*5.25	Cancer cell line	Female
CVCL_0134	A2780	Cancer cell line	Female
CVCL_0135	A2780/CP70	Cancer cell line	Female
CVCL_0139	AGS	Cancer cell line	Female
CVCL_0144	ARO	Cancer cell line	Female
CVCL_0178	BT-20	Cancer cell line	Female
CVCL_0179	BT-474	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04999618	PHASE4	COMPLETED	A New Approach in Laser Surgery Using the Regenerative Solution in Children Diagnosed With Vascular Pathology
NCT03306446	PHASE4	UNKNOWN	Changing the coUrse of cRohn’s Disease With an Early Use of Adalimumab
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00558155	PHASE4	COMPLETED	The Impact of Immunostimulating Nutrition on the Outcome of Surgery
NCT00576940	PHASE4	COMPLETED	Standard and Immunostimulating Enteral Nutrition in Surgical Patients
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT01038154	PHASE4	UNKNOWN	Study to Evaluate the Efficacy of Pravastatin on Survival and Recurrence of Advanced Gastroesophageal Cancer
NCT01234272	PHASE4	COMPLETED	Comparison of the Analgesic Effect Between Intrathecal Morphine and IV-fentanyl Patient Controlled Analgesia (ITM-IVPCA) and Epidural PCA (PCEA) in Patients Undergoing Gastrectomy -Randomized Allocation Study-
NCT01260194	PHASE4	TERMINATED	A Study of Herceptin (Trastuzumab) in Combination With Standard Chemotherapy in Patients With HER Positive Metastatic Gastric Cancer
NCT01271582	PHASE4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01401075	PHASE4	COMPLETED	RCT With Adjuvant Mistletoe Treatment in Gastric Cancer Patients
NCT01471756	PHASE4	COMPLETED	Improving Complete Endoscopic Mucosal Resection (EMR) of Colorectal Neoplasia
NCT01766765	PHASE4	UNKNOWN	Early Jejunostomy Nutrition Minimizes Time to Chemotherapy
NCT01910948	PHASE4	UNKNOWN	Perioperative Application of Omega-3 Polyunsaturated Fatty Acids in Gastric Cancer Patients
NCT01927328	PHASE4	UNKNOWN	Iron Replacement in Oesophagogastric Neoplasia
NCT01962272	PHASE4	COMPLETED	The Effect of Nutritional Counseling for Cancer Patients
NCT01962376	PHASE4	UNKNOWN	Preoperative Chemotherapy With Bevacizumab For Potentially Resectable Gastric Cancer With Liver Metastasis
NCT02047994	PHASE4	RECRUITING	Multicentric Randomized Study of H. Pylori Eradication and Pepsinogen Testing for Prevention of Gastric Cancer Mortality
NCT02235246	PHASE4	COMPLETED	The Effect of Perioperative Intravenous Magnesium on Pain After Endoscopic Submucosal Dissection for Gastric Neoplasm: Prospective Randomized Double-blind Placebo Controlled Study
NCT02366819	PHASE4	SUSPENDED	Genetic Analysis-Guided Irinotecan Hydrochloride Dosing of mFOLFIRINOX in Treating Patients With Locally Advanced Gastroesophageal or Stomach Cancer
NCT02401971	PHASE4	UNKNOWN	Irinotecan Plus Thalidomide in Second Line Advanced Gastric Cancer
NCT02458573	PHASE4	COMPLETED	Comparison of the Effects of Continuous Epidural Analgesia and Continuous Intravenous Analgesia on Postoperative Bowel Movement in Patients Undergoing Laparoscopic Gastrectomy
NCT02638584	PHASE4	COMPLETED	Effects of Ilaprazole on Ulcer Healing Rate and Prevention of Gastrointestinal Bleeding in the Patients Undergone ESD.
NCT02776527	PHASE4	UNKNOWN	A Clinical Trial of Maintenance Treatment of Apatinib in Advanced Gastric Cancer Patients Have Completed Postoprative Adjuvant Chemotherapy
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03550482	PHASE4	COMPLETED	Oncoxin® and Quality of Life in Cancer Patients
NCT03609892	PHASE4	COMPLETED	Helicobacter Rescue Therapy With Berberine Plus Amoxicillin Quadruple Therapy Versus Tetracycline Plus Furazolidone Quadruple Therapy
NCT03642093	PHASE4	UNKNOWN	HOPE - A Study to Evaluate the Effect of a Prehabilitation Program on GI Cancer Patients Planning to Undergo Surgery
NCT03733639	PHASE4	UNKNOWN	Tisseel® as a Reinforcement of Esophagojejunal Anastomoses
NCT04168346	PHASE4	NOT_YET_RECRUITING	Preoperative Intravenous Iron Therapy in Patients With Gastric Cancer
NCT04209933	PHASE4	COMPLETED	Helicobacter Pylori Eradication With Different Bismuth Quadruple Therapies
NCT04591028	PHASE4	WITHDRAWN	A Study to Evaluate Indocyanine Green Lymphangiography to Improve Lymphadenectomy in Gastric Cancer Patients
NCT04607057	PHASE4	UNKNOWN	Supplemental Parenteral Nutrition During Postgastrectomy in Nutritionally at Risk Patient
NCT04660123	PHASE4	COMPLETED	A Real World Study of Bismuth Colloidal Pectin Granules Quadruple Therapy for H. Pylori Eradication
NCT04678492	PHASE4	COMPLETED	Helicobacter Rescue Therapy With High-dose Esomeprazole and Amoxicillin Dual Therapy Versus Bismuth-containing Quadruple Therapy
NCT04697186	PHASE4	COMPLETED	Helicobacter Pylori Eradication With Berberine Plus Amoxicillin Triple Therapy Versus Bismuth-containing Quadruple Therapy
NCT05029453	PHASE4	UNKNOWN	Apatinib Combined With Chemotherapy Versus Chemotherapy in Second-line Gastric Cancer Receiving Prior Anti-PD-1 Therapy
NCT05183126	PHASE4	RECRUITING	Pharmacokinetic Study of Skeletal Muscle Area-based Paclitaxel Infusion in Patients With Cancer
NCT05354856	PHASE4	TERMINATED	The Effect of Chemoradiotherapy on Gastric Perfusion in Patients With Gastric Cancer.
NCT05410535	PHASE4	COMPLETED	To Evaluate Efficacy of Ursodeoxycholic Acid (UDCA) for the Prevention of Gallstone Formation After Gasterectomy