PIK3C2A

Summary

PIK3C2A (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha, HGNC:8971) is a protein-coding gene on chromosome 11p15.1, encoding Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha (O00443). Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers.

The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. The PI3-kinase activity of this protein is not sensitive to nanomolar levels of the inhibitor wortmanin. This protein was shown to be able to be activated by insulin and may be involved in integrin-dependent signaling.

Source: NCBI Gene 5286 — RefSeq curated summary.

At a glance

• Gene–disease (curated): oculocerebrodental syndrome (Strong, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 621 total — 22 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 57
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002645

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8971
Approved symbol	PIK3C2A
Name	phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha
Location	11p15.1
Locus type	gene with protein product
Status	Approved
Aliases	PI3K-C2alpha
Ensembl gene	ENSG00000011405
Ensembl biotype	protein_coding
OMIM	603601
Entrez	5286

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000265970, ENST00000503729, ENST00000531428, ENST00000532035, ENST00000533645, ENST00000691414, ENST00000891469, ENST00000891470, ENST00000891471, ENST00000928047, ENST00000928048, ENST00000928049, ENST00000963734

RefSeq mRNA: 4 — MANE Select: NM_002645 NM_001321378, NM_001321380, NM_001386870, NM_002645

CCDS: CCDS7824

Canonical transcript exons

ENST00000691414 — 33 exons

Exon	Start	End
ENSE00000704364	17094261	17094385
ENSE00000704509	17101278	17101434
ENSE00000704536	17102662	17102831
ENSE00000988322	17148667	17148787
ENSE00000988323	17147517	17147628
ENSE00000988324	17145863	17145942
ENSE00000988327	17135111	17135159
ENSE00000988328	17134819	17135029
ENSE00000988329	17131916	17132038
ENSE00000988330	17129300	17129467
ENSE00000988331	17122702	17122813
ENSE00000988332	17122188	17122333
ENSE00000988333	17119786	17119974
ENSE00000988334	17119220	17119313
ENSE00000988335	17118645	17118739
ENSE00000988336	17117491	17117671
ENSE00000988337	17114361	17114465
ENSE00001151290	17136482	17136625
ENSE00001248387	17168677	17169806
ENSE00003459796	17145668	17145731
ENSE00003479937	17099860	17099969
ENSE00003514512	17091547	17091656
ENSE00003537868	17105169	17105305
ENSE00003546450	17097057	17097264
ENSE00003602449	17110432	17110561
ENSE00003610448	17091334	17091459
ENSE00003622797	17112574	17112666
ENSE00003630952	17150498	17150655
ENSE00003651149	17155526	17155629
ENSE00003691638	17091996	17092068
ENSE00003693375	17092159	17092276
ENSE00003926231	17207848	17207986
ENSE00003929576	17086575	17089920

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 98.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.8018 / max 519.6702, expressed in 1797 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118854	35.8018	1797

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.13	gold quality
jejunal mucosa	UBERON:0000399	97.42	gold quality
blood vessel layer	UBERON:0004797	97.12	gold quality
superficial temporal artery	UBERON:0001614	97.03	gold quality
pigmented layer of retina	UBERON:0001782	96.96	gold quality
caput epididymis	UBERON:0004358	96.81	gold quality
visceral pleura	UBERON:0002401	96.75	gold quality
corpus epididymis	UBERON:0004359	96.71	gold quality
lower lobe of lung	UBERON:0008949	96.69	gold quality
oocyte	CL:0000023	96.55	gold quality
cauda epididymis	UBERON:0004360	96.55	gold quality
choroid plexus epithelium	UBERON:0003911	96.51	gold quality
seminal vesicle	UBERON:0000998	96.45	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.17	gold quality
lateral globus pallidus	UBERON:0002476	96.14	gold quality
calcaneal tendon	UBERON:0003701	96.03	gold quality
medial globus pallidus	UBERON:0002477	95.92	gold quality
globus pallidus	UBERON:0001875	95.89	gold quality
parietal pleura	UBERON:0002400	95.67	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.66	gold quality
pleura	UBERON:0000977	95.56	gold quality
sural nerve	UBERON:0015488	95.44	gold quality
tibia	UBERON:0000979	95.27	gold quality
cartilage tissue	UBERON:0002418	94.81	gold quality
renal medulla	UBERON:0000362	94.75	gold quality
eye	UBERON:0000970	94.37	gold quality
heart right ventricle	UBERON:0002080	94.30	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.28	gold quality
germinal epithelium of ovary	UBERON:0001304	94.25	gold quality
colonic mucosa	UBERON:0000317	94.19	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	39.06
E-CURD-119	yes	24.04
E-ANND-3	yes	12.19

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

225 targeting PIK3C2A, 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-6867-5P	100.00	82.21	3464
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996

Literature-anchored findings (GeneRIF, showing 35)

• Phosphoinositide 3-kinase C2alpha was found to be differentially regulated by alpha(v)beta(3) and alpha(v)beta(5) integrin, and may represent a new regulatory pathway of cell migration downstream of integrin engagement. (PMID:12237112)
• Nickel compounds induce HIF-1 transactivation and Cap43 protein expression through a PI-3K/Akt-dependent and p70(S6k)- independent pathway. (PMID:14729612)
• VEGFR1 and VEGFR2 initiate a clonogenic response in myeloid leukemia cells that is PI3-kinase dependent. (PMID:15183893)
• demonstrated that the isolated clathrin binding domain of Phosphoinositide 3-kinase C2alpha can drive clathrin lattice assembly and can independently modulate clathrin distribution and function when expressed in cells (PMID:16215232)
• analysis of the PI specificities of PX domains and the mechanism by which the PI3K-C2alpha PX domain interacts with PtdIns(4,5)P(2)-containing membranes (PMID:17038310)
• molecular linkage between PI3K-C2alpha and the microtubule motor machinery, with implications for membrane trafficking in intact cells (PMID:17110375)
• phosphoinositide 3-kinase C2alpha has a role in insulin signaling (PMID:17644513)
• Lowering the levels of PI3K-C2alpha in a number of cancer cell lines reduces their proliferation and cell viability. (PMID:18403640)
• Taken together, these data suggest for the first time that in addition to class I PI3Ks in cancer, class II PIK3C2alpha can modulate hepatocellular carcinoma cell growth. (PMID:19591801)
• These data suggest a general role for PI3KC2alpha in regulating physiologically relevant dynamin-independent internalization pathways. (PMID:21081650)
• PI3K-C2alpha plays the crucial role in S1P(1) internalization into the intracellular vesicular compartment, Rac1 activation on endosomes, and thereby migration through regulating vesicular trafficking in ECs (PMID:23192342)
• Class II enzyme PI3K-C2beta and the class IB isozyme p110gamma mainly regulate the S1P- and high density lipoprotein (HDL)-dependent endothelial cell (EC) migration and PI3K-C2alpha primarily controls EC survival (PMID:23320105)
• Data (including data from knockout mice) suggest that PI3KC2a participates in tumor angiogenesis. [REVIEW] (PMID:25233418)
• These observations indicate that PI3K-C2alpha plays the pivotal role in TGFbeta receptor endocytosis and thereby Smad2/3 signaling, participating in angiogenic actions of TGFbeta. (PMID:25614622)
• a model of S. flexneri dissemination is proposed in which the formation of vacuole-like protrusions is mediated by the PIK3C2A-dependent production of the signaling lipid phosphatidylinositol 3-phosphate in the protrusion membrane (PMID:25667265)
• PI3KC2alpha has a role in regulating shear-dependent platelet adhesion via regulation of membrane structure, rather than acute signalling (PMID:25779105)
• MiR-206 regulates endothelial progenitor cell activities by targeting PIK3C2alpha expression.The role of PIK3C2alpha in endothelial progenitor cell function in coronary artery disease (PMID:26175229)
• PI3KC2a knockdown results in rerouting of insulin signaling and pancreatic beta cell proliferation. (PMID:26387957)
• miR-518a-5p was downregulated in imatinib-resistant gastrointestinal stromal tumors (GISTs), and the expression of miR-518a-5p was confirmed with good concordance between real-time PCR and miRNA microarray results. Luciferase reporter assays indicated that miR-518a-5p bound to the PIK3C2A 3’UTR. (PMID:26950487)
• These results elucidated that PIK3C2A mRNA acts as a miR-124 decoy to regulate CD151 and to affect hepatocellular carcinoma malignant phenotypes. (PMID:27270320)
• Therefore, PI3K-C2A is a factor important for human cytomegalovirus replication and has a role in the production of human cytomegalovirus virions. (PMID:27412598)
• Four gene signature (PTEN, PIK3C2A, ITPA and BCL3) is an independent prognostic factors of both overall survival and disease-free survival in clear-cell renal-cell carcinoma. (PMID:27779101)
• PIK3C2A Polymorphism is associated with recurrence in non-small cell lung cancer. (PMID:28150169)
• PIK3C2A was associated with bipolar disorder. (PMID:28195573)
• Results present evidence that PI3K-C2alpha is critical in the proper maturation of endosomes, and for coordinating the use of endosomes as an additional membrane source during autophagy. (PMID:28910396)
• Study illustrates that the C-terminal PX-C2 module of PI3K-C2a plays an important role in membrane anchoring, with the C2 domain providing the primary site of membrane affinity, and suggests a possible role for Ca2+ in regulating PI3K-C2a activity through perturbation of C2 domain membrane interaction. (PMID:30293811)
• PI3K-C2alpha and PI3K-C2beta play differential, indispensable roles in clathrin-mediated pinocytosis. (PMID:30374841)
• MiR-31 suppressed cell proliferation, migration, and invasion of osteosarcoma by targeting PIK3C2A expression. (PMID:30468462)
• The level of PIK3C2A gene expression in patients with acute myocardial infarction is significantly lower than that of healthy people. (PMID:30946353)
• the identification of the first patients with PIK3C2A deficiency establishes a role for PIK3C2A in neurological and skeletal development, as well as vision, and growth and implicates loss-of-function PIK3C2A mutations as a potentially new cause of a cilia-associated disease. (PMID:31034465)
• TGFbeta receptor endocytosis and Smad signaling require synaptojanin1, PI3K-C2alpha-, and INPP4B-mediated phosphoinositide conversions. (PMID:31913757)
• The molecular mechanisms mediating class II PI 3-kinase function in cell physiology. (PMID:33387369)
• Class II phosphatidylinositol 3-kinase-C2alpha is essential for Notch signaling by regulating the endocytosis of gamma-secretase in endothelial cells. (PMID:33664344)
• PI(3,4)P2-mediated cytokinetic abscission prevents early senescence and cataract formation. (PMID:34882480)
• Various Expressions of PIK3C2A and TXNIP Genes and Their Potential Role as Independent Risk Factors for Chronic Stable Angina and Acute Coronary Syndrome. (PMID:36830671)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	pik3c2a	ENSDARG00000060841
mus_musculus	Pik3c2a	ENSMUSG00000030660
rattus_norvegicus	Pik3c2a	ENSRNOG00000020479
drosophila_melanogaster	Pi3K68D	FBGN0015278
drosophila_melanogaster	Pi3K92E	FBGN0015279
caenorhabditis_elegans		WBGENE00000090
caenorhabditis_elegans		WBGENE00009552

Paralogs (9): PIK3CB (ENSG00000051382), PIK3C3 (ENSG00000078142), PIK3CG (ENSG00000105851), PIK3CA (ENSG00000121879), PIK3C2B (ENSG00000133056), PIK3C2G (ENSG00000139144), PI4KB (ENSG00000143393), PIK3CD (ENSG00000171608), PI4KA (ENSG00000241973)

Protein

Protein identifiers

Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha — O00443 (reviewed: O00443)

Alternative names: Phosphoinositide 3-kinase-C2-alpha

All UniProt accessions (4): O00443, A0A0C4DGF9, E9PPP3, L7RRS0

UniProt curated annotations — full annotation on UniProt →

Function. Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers. Has a role in several intracellular trafficking events. Functions in insulin signaling and secretion. Required for translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane and glucose uptake in response to insulin-mediated RHOQ activation. Regulates insulin secretion through two different mechanisms: involved in glucose-induced insulin secretion downstream of insulin receptor in a pathway that involves AKT1 activation and TBC1D4/AS160 phosphorylation, and participates in the late step of insulin granule exocytosis probably in insulin granule fusion. Synthesizes PtdIns3P in response to insulin signaling. Functions in clathrin-coated endocytic vesicle formation and distribution. Regulates dynamin-independent endocytosis, probably by recruiting EEA1 to internalizing vesicles. In neurosecretory cells synthesizes PtdIns3P on large dense core vesicles. Participates in calcium induced contraction of vascular smooth muscle by regulating myosin light chain (MLC) phosphorylation through a mechanism involving Rho kinase-dependent phosphorylation of the MLCP-regulatory subunit MYPT1. May play a role in the EGF signaling cascade. May be involved in mitosis and UV-induced damage response. Required for maintenance of normal renal structure and function by supporting normal podocyte function. Involved in the regulation of ciliogenesis and trafficking of ciliary components.

Subunit / interactions. Part of a complex with ERBB2 and EGFR. Interacts with clathrin trimers. Interacts with SBF2/MTMR13.

Subcellular location. Cell membrane. Cytoplasmic vesicle. Clathrin-coated vesicle. Nucleus. Cytoplasm. Golgi apparatus. trans-Golgi network.

Tissue specificity. Expressed in columnar and transitional epithelia, mononuclear cells, smooth muscle cells, and endothelial cells lining capillaries and small venules (at protein level). Ubiquitously expressed, with highest levels in heart, placenta and ovary, and lowest levels in the kidney. Detected at low levels in islets of Langerhans from type 2 diabetes mellitus individuals.

Post-translational modifications. Phosphorylated upon insulin stimulation; which may lead to enzyme activation. Phosphorylated on Ser-259 during mitosis and upon UV irradiation; which does not change enzymatic activity but leads to proteasomal degradation. Ser-259 phosphorylation may be mediated by CDK1 or JNK, depending on the physiological state of the cell.

Disease relevance. Oculoskeletodental syndrome (OCSKD) [MIM:618440] An autosomal recessive syndrome characterized by congenital cataracts, short stature, dysmorphic features with coarse facies, dental anomalies, multiple skeletal abnormalities, and neurological manifestations. Other recurrent features include hearing loss, secondary glaucoma, and nephrocalcinosis. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by insulin. Only slightly inhibited by wortmannin and LY294002. Activated by clathrin.

Cofactor. Ca(2+) or Mg(2+). Mn(2+) cannot be used.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O00443-1	1	yes
O00443-2	2

RefSeq proteins (4): NP_001308307, NP_001308309, NP_001373799, NP_002636* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR000341	PI3K_Ras-bd_dom	Domain
IPR000403	PI3/4_kinase_cat_dom	Domain
IPR001263	PI3K_accessory_dom	Domain
IPR001683	PX_dom	Domain
IPR002420	PI3K-type_C2_dom	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
IPR036871	PX_dom_sf	Homologous_superfamily
IPR036940	PI3/4_kinase_cat_sf	Homologous_superfamily
IPR037705	PI3-kinase_C2-alpha_cat	Domain
IPR042133	PX_PI3K_C2_alpha	Domain
IPR042236	PI3K_accessory_sf	Homologous_superfamily

Pfam: PF00168, PF00454, PF00613, PF00787, PF00792, PF00794

Enzyme classification (BRENDA):

• EC 2.7.1.154 — phosphatidylinositol-4-phosphate 3-kinase (BRENDA: 7 organisms, 22 substrates, 53 inhibitors, 8 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.015–0.12	5
PHOSPHATIDYLINOSITOL	0.064–0.122	2
PHOSPHATIDYLINOSITOL 4-PHOSPHATE	0.025	1

Catalyzed reactions (Rhea), 3 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)
• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4-bisphosphate) + ADP + H(+) (RHEA:18373)
• 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)

UniProt features (82 total): strand 15, mutagenesis site 12, modified residue 9, sequence conflict 9, helix 8, region of interest 7, site 6, domain 6, compositionally biased region 3, sequence variant 2, initiator methionine 1, chain 1, short sequence motif 1, splice variant 1, turn 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
6BTY	X-RAY DIFFRACTION	1.68
2AR5	X-RAY DIFFRACTION	1.8
6BTZ	X-RAY DIFFRACTION	1.85
2RED	X-RAY DIFFRACTION	2.1
6BU0	X-RAY DIFFRACTION	2.43
2REA	X-RAY DIFFRACTION	2.5
2IWL	X-RAY DIFFRACTION	2.6
6BUB	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00443-F1	72.47	0.35

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 (6): 244 (not phosphorylated); 249 (not phosphorylated); 251 (not phosphorylated); 254 (not phosphorylated); 262 (not phosphorylated); 266 (not phosphorylated)

Post-translational modifications (9): 2, 60, 108, 259, 327, 338, 630, 1281, 1553

Mutagenesis-validated functional residues (12):

Position	Phenotype
103–107	reduces clathrin binding.
254	no effect on phosphorylation in vitro.
259	abolishes phosphorylation, no change in activity.
259	protects from proteolysis.
262	no effect on phosphorylation in vitro.
266	no effect on phosphorylation in vitro.
1250	abolishes lipid kinase activity. affects clathrin distribution when combined with a truncation encompassing the region o
1488	reduces affinity for ptdins(4,5)p2-containing membranes 7-fold.
1490	reduces affinity for ptdins(4,5)p2-containing membranes 7-fold.
1491	reduces affinity for ptdins(4,5)p2-containing membranes 5-fold.
1493	reduces affinity for ptdins(4,5)p2-containing membranes 23-fold.
1503	abolishes interaction with ptdins(4,5)p2-containing membranes.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-1660499	Synthesis of PIPs at the plasma membrane
R-HSA-1660514	Synthesis of PIPs at the Golgi membrane
R-HSA-1660516	Synthesis of PIPs at the early endosome membrane
R-HSA-1660517	Synthesis of PIPs at the late endosome membrane
R-HSA-432722	Golgi Associated Vesicle Biogenesis
R-HSA-8856828	Clathrin-mediated endocytosis

MSigDB gene sets: 519 (showing top): GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, FREAC2_01, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, HNF3ALPHA_Q6, MORF_MSH3, GOBP_CIRCULATORY_SYSTEM_PROCESS, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, MORF_BRCA1, MORF_ATRX, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_CELL_MIGRATION_INVOLVED_IN_SPROUTING_ANGIOGENESIS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS

GO Biological Process (17): phosphatidylinositol biosynthetic process (GO:0006661), exocytosis (GO:0006887), endocytosis (GO:0006897), epidermal growth factor receptor signaling pathway (GO:0007173), insulin receptor signaling pathway (GO:0008286), positive regulation of autophagy (GO:0010508), vascular associated smooth muscle contraction (GO:0014829), cell migration (GO:0016477), phosphatidylinositol-3-phosphate biosynthetic process (GO:0036092), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), platelet-derived growth factor receptor signaling pathway (GO:0048008), phosphatidylinositol-mediated signaling (GO:0048015), clathrin coat assembly (GO:0048268), membrane organization (GO:0061024), positive regulation of cell migration involved in sprouting angiogenesis (GO:0090050), lipid metabolic process (GO:0006629), phosphatidylinositol phosphate biosynthetic process (GO:0046854)

GO Molecular Function (9): ATP binding (GO:0005524), 1-phosphatidylinositol-3-kinase activity (GO:0016303), clathrin binding (GO:0030276), 1-phosphatidylinositol-4-phosphate 3-kinase activity (GO:0035005), phosphatidylinositol binding (GO:0035091), 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity (GO:0046934), nucleotide binding (GO:0000166), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (12): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), trans-Golgi network (GO:0005802), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), clathrin-coated vesicle (GO:0030136), vesicle (GO:0031982), extracellular exosome (GO:0070062), nucleus (GO:0005634), Golgi apparatus (GO:0005794), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
PI Metabolism	4
trans-Golgi Network Vesicle Budding	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
phosphatidylinositol kinase activity	3
cytoplasm	3
vesicle-mediated transport	2
cell surface receptor protein tyrosine kinase signaling pathway	2
intracellular membrane-bounded organelle	2
biosynthetic process	1
phosphatidylinositol metabolic process	1
secretion by cell	1
vesicle fusion to plasma membrane	1
vesicle budding from membrane	1
membrane invagination	1
import into cell	1
ERBB signaling pathway	1
cellular response to insulin stimulus	1
autophagy	1
positive regulation of catabolic process	1
regulation of autophagy	1
smooth muscle contraction	1
vasoconstriction	1
cell motility	1
phosphatidylinositol phosphate biosynthetic process	1
intracellular signaling cassette	1
intracellular signal transduction	1
protein-containing complex assembly	1
cellular component organization	1
cell migration involved in sprouting angiogenesis	1
positive regulation of blood vessel endothelial cell migration	1
regulation of cell migration involved in sprouting angiogenesis	1
primary metabolic process	1
glycerophospholipid biosynthetic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
phosphatidylinositol-3-phosphate biosynthetic process	1
protein binding	1
anion binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1

Protein interactions and networks

STRING

1986 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIK3C2A	GPT	P24298	800
PIK3C2A	NEK8	Q86SG6	796
PIK3C2A	MB	P02144	789
PIK3C2A	CRP	P02741	766
PIK3C2A	F2	P00734	657
PIK3C2A	DMD	P11532	635
PIK3C2A	ALB	P02768	621
PIK3C2A	GPT2	Q8TD30	621
PIK3C2A	DZIP3	Q86Y13	592
PIK3C2A	F3	P13726	583
PIK3C2A	SNRK	Q9NRH2	574
PIK3C2A	TNNI3	P19429	571
PIK3C2A	PKHD1	P08F94	566
PIK3C2A	UQCRB	P14927	563
PIK3C2A	CYGB	Q8WWM9	549
PIK3C2A	GNE	Q9Y223	549

IntAct

173 interactions, top by confidence:

A	B	Type	Score
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
STAMBP	PIK3C2A	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
FAM136A	RBFOX3	psi-mi:“MI:0914”(association)	0.640
QPRT	PIK3C2A	psi-mi:“MI:0914”(association)	0.640
STAMBPL1	PIK3C2A	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
KLHL22	TMEM223	psi-mi:“MI:0914”(association)	0.640
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAZ	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
HAVCR2	TCAF2	psi-mi:“MI:0914”(association)	0.530
CCNJL	PIK3C2A	psi-mi:“MI:0914”(association)	0.530
CLTB	PIK3C2A	psi-mi:“MI:0914”(association)	0.530
TRIM28	ZNF316	psi-mi:“MI:0914”(association)	0.530

BioGRID (237): PIK3C2A (Affinity Capture-MS), PIK3C2A (Affinity Capture-MS), PIK3C2A (Affinity Capture-MS), PIK3C2A (Affinity Capture-MS), PIK3C2A (Affinity Capture-MS), PIK3C2A (Affinity Capture-MS), PIK3C2A (Affinity Capture-MS), CLTA (Co-fractionation), PIK3C2A (Co-fractionation), PIK3C2A (Proximity Label-MS), PIK3C2A (Affinity Capture-MS), PIK3C2A (Affinity Capture-MS), PIK3C2A (Affinity Capture-MS), PIK3C2A (Affinity Capture-MS), PIK3C2A (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GWK2, A0A571BF63, A0JMA8, A0JNE3, A2BGA0, A4IIG7, O00443, P13056, P24781, P28701, P28705, P43354, P45448, P48443, P51128, P51129, Q04913, Q06219, Q07917, Q08E53, Q09555, Q0GFF6, Q0IHW3, Q0VC20, Q1LVF3, Q26622, Q33E94, Q505F1, Q5BJR8, Q5FWP2, Q5R5Y4, Q5RAY1, Q5RCZ5, Q5REL6, Q5RJH6, Q61194, Q64287, Q68F67, Q6DHP9, Q7TNK1

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, A0A075F932, A0FGR8, A0FGR9, A4IJ05, A6QP06, O00445, O08625, O08835, O35681

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CDK1	“down-regulates activity”	PIK3C2A	phosphorylation
PIK3C2A	up-regulates	PIPP	“chemical modification”
PIK3C2A	up-regulates	PIP3	“chemical modification”
IGF1R	up-regulates	PIK3C2A	phosphorylation
PIK3C2A	up-regulates	PLCG1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 168 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	7	50.3×	6e-09
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	44.4×	1e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	44.4×	1e-08
Activation of BH3-only proteins	7	32.8×	7e-08
RHO GTPases activate PKNs	9	26.9×	6e-09
Signaling by RAS mutants	5	19.9×	1e-04
Intrinsic Pathway for Apoptosis	7	19.3×	3e-06
FOXO-mediated transcription	5	15.8×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
clathrin coat assembly	7	44.0×	1e-07
clathrin-dependent endocytosis	7	28.9×	2e-06
negative regulation of protein localization to plasma membrane	5	22.1×	7e-04
protein targeting	5	13.0×	7e-03
intracellular protein localization	9	6.7×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	22
Likely pathogenic	9
Uncertain significance	290
Likely benign	233
Benign	31

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1930899	NM_002645.4(PIK3C2A):c.1555C>T (p.Arg519Ter)	Pathogenic
1989316	NM_002645.4(PIK3C2A):c.2662_2663insAT (p.Ser888fs)	Pathogenic
2014722	NM_002645.4(PIK3C2A):c.7C>T (p.Gln3Ter)	Pathogenic
2014848	NM_002645.4(PIK3C2A):c.4618del (p.Ala1540fs)	Pathogenic
2022801	NM_002645.4(PIK3C2A):c.256del (p.Arg86fs)	Pathogenic
2763849	NM_002645.4(PIK3C2A):c.3541C>T (p.Arg1181Ter)	Pathogenic
2771799	NM_002645.4(PIK3C2A):c.486C>G (p.Tyr162Ter)	Pathogenic
2788291	NM_002645.4(PIK3C2A):c.786_787del (p.Glu263fs)	Pathogenic
2801790	NM_002645.4(PIK3C2A):c.3226C>T (p.Gln1076Ter)	Pathogenic
2860554	NM_002645.4(PIK3C2A):c.1864G>T (p.Gly622Ter)	Pathogenic
3244747	NC_000011.9:g.(?17190204)(17191288_?)del	Pathogenic
3600988	NM_002645.4(PIK3C2A):c.3695T>C (p.Phe1232Ser)	Pathogenic
3644217	NM_002645.4(PIK3C2A):c.493C>T (p.Gln165Ter)	Pathogenic
3657159	NM_002645.4(PIK3C2A):c.2750del (p.Pro917fs)	Pathogenic
3702029	NM_002645.4(PIK3C2A):c.2196C>A (p.Tyr732Ter)	Pathogenic
4703776	NM_002645.4(PIK3C2A):c.3775C>T (p.Arg1259Ter)	Pathogenic
4718762	NM_002645.4(PIK3C2A):c.2193_2196del (p.Tyr732fs)	Pathogenic
4759668	NM_002645.4(PIK3C2A):c.3699_3702del (p.Tyr1234fs)	Pathogenic
4764875	NM_002645.4(PIK3C2A):c.4531_4534del (p.Leu1511fs)	Pathogenic
4772865	NM_002645.4(PIK3C2A):c.2040G>A (p.Trp680Ter)	Pathogenic
4806420	NM_002645.4(PIK3C2A):c.3214C>T (p.Gln1072Ter)	Pathogenic
631522	NM_002645.3(PIK3C2A):c.(?_1-1)_4007+1_4008-1)del	Pathogenic
3600987	NM_002645.4(PIK3C2A):c.1024C>T (p.Arg342Ter)	Likely pathogenic
3773827	NM_002645.4(PIK3C2A):c.4451+1G>T	Likely pathogenic
4056725	NM_002645.4(PIK3C2A):c.3456_3457del (p.Met1152fs)	Likely pathogenic
4713625	NM_002645.4(PIK3C2A):c.2846+1G>T	Likely pathogenic
4724378	NM_002645.4(PIK3C2A):c.3035+1G>C	Likely pathogenic
4724938	NM_002645.4(PIK3C2A):c.3415-2A>G	Likely pathogenic
4806923	NM_002645.4(PIK3C2A):c.2108+1G>A	Likely pathogenic
599543	NM_002645.4(PIK3C2A):c.1640+1G>T	Likely pathogenic

SpliceAI

4650 predictions. Top by Δscore:

Variant	Effect	Δscore
11:17089917:CAAG:C	acceptor_gain	1.0000
11:17089918:AAG:A	acceptor_gain	1.0000
11:17089918:AAGC:A	acceptor_loss	1.0000
11:17089920:GCTA:G	acceptor_loss	1.0000
11:17089921:C:CC	acceptor_gain	1.0000
11:17089921:CTACA:C	acceptor_loss	1.0000
11:17089922:T:G	acceptor_loss	1.0000
11:17091330:TTAC:T	donor_loss	1.0000
11:17091331:TAC:T	donor_loss	1.0000
11:17091332:A:AC	donor_gain	1.0000
11:17091332:AC:A	donor_gain	1.0000
11:17091333:C:CG	donor_gain	1.0000
11:17091333:CC:C	donor_gain	1.0000
11:17091333:CCA:C	donor_gain	1.0000
11:17091333:CCAT:C	donor_gain	1.0000
11:17091333:CCATT:C	donor_gain	1.0000
11:17091455:GTAAC:G	acceptor_gain	1.0000
11:17091456:TAAC:T	acceptor_gain	1.0000
11:17091457:AAC:A	acceptor_gain	1.0000
11:17091458:AC:A	acceptor_gain	1.0000
11:17091459:CC:C	acceptor_gain	1.0000
11:17091460:C:CC	acceptor_gain	1.0000
11:17091460:C:T	acceptor_gain	1.0000
11:17091460:CTAA:C	acceptor_loss	1.0000
11:17091461:T:A	acceptor_loss	1.0000
11:17091545:A:AC	donor_gain	1.0000
11:17091546:C:CC	donor_gain	1.0000
11:17091991:CTCA:C	donor_loss	1.0000
11:17091994:A:C	donor_loss	1.0000
11:17091995:C:T	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000018543 (11:17183647 C>T), RS1000035288 (11:17097841 G>A), RS1000045384 (11:17162082 T>A), RS1000089177 (11:17136961 T>C), RS1000109712 (11:17181734 C>G,T), RS1000110751 (11:17094819 A>G), RS1000115410 (11:17140123 G>A), RS1000147293 (11:17158386 T>TAC,TATAA), RS1000151922 (11:17106604 A>T), RS1000155162 (11:17149767 G>A,T), RS1000199675 (11:17168884 T>C), RS1000203502 (11:17207562 C>T), RS1000233699 (11:17095190 G>A), RS1000271991 (11:17130571 A>G), RS1000310632 (11:17177776 G>A,C)

Disease associations

OMIM: gene MIM:603601 | disease phenotypes: MIM:618440

GenCC curated gene-disease

Disease	Classification	Inheritance
oculocerebrodental syndrome	Strong	Autosomal recessive

Mondo (1): oculocerebrodental syndrome (MONDO:0034145)

Orphanet (1): Oculoskeletodental syndrome (Orphanet:557003)

HPO phenotypes

57 total (30 of 57 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000104	Renal agenesis
HP:0000121	Nephrocalcinosis
HP:0000158	Macroglossia
HP:0000164	Abnormality of the dentition
HP:0000278	Retrognathia
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000294	Low anterior hairline
HP:0000365	Hearing impairment
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000501	Glaucoma
HP:0000519	Developmental cataract
HP:0000599	Abnormality of the frontal hairline
HP:0000677	Oligodontia
HP:0000691	Microdontia
HP:0000766	Abnormal sternum morphology
HP:0000821	Hypothyroidism
HP:0001263	Global developmental delay
HP:0001297	Stroke
HP:0001328	Specific learning disability
HP:0001518	Small for gestational age
HP:0001744	Splenomegaly
HP:0001999	Abnormal facial shape
HP:0002150	Hypercalciuria
HP:0002162	Low posterior hairline
HP:0002240	Hepatomegaly

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002295_3	Schizophrenia or bipolar disorder	6.000000e-09
GCST005951_67	Body mass index	6.000000e-09
GCST005951_68	Body mass index	3.000000e-09
GCST006434_29	Systolic blood pressure x alcohol consumption interaction (2df test)	1.000000e-08
GCST90002402_343	Platelet count	1.000000e-13

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004329	alcohol drinking
EFO:0006335	systolic blood pressure
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1075102 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 17,148 (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
CHEMBL1879463	DACTOLISIB	3	7,988
CHEMBL1922094	APITOLISIB	2	3,070
CHEMBL4558527	AZD-8154	2	19
CHEMBL521851	PICTILISIB	2	6,071

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Phosphatidylinositol kinases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
torin 2	Inhibition	7.55	pIC50

Binding affinities (BindingDB)

123 measured of 167 human assays (167 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
9-(4-hydroxybicyclo[2.2.1]heptan-1-yl)-7-methyl-2-((7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino)-7,9-dihydro-8H-purin-8-one	IC50	0.07 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
9-(4-hydroxybicyclo[2.2.2]octan-1-yl)-7-methyl-2-((7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino)-7,9-dihydro-8H-purin-8-one	IC50	0.71 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
N-[8-(1H-imidazol-5-yl)-2-methyl-6-morpholin-4-ylimidazo[1,2-b]pyridazin-3-yl]-1,2,3,4-tetrahydroisoquinolin-8-amine	KD	5 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
9-(3-fluorobicyclo[1.1.1]pentan-1-yl)-7-methyl-2-((6-methylbenzo[d][1,3]dioxol-5-yl)amino)-7,9-dihydro-8H-purin-8-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
9-(3-fluorobicyclo[1.1.1]pentan-1-yl)-7-methyl-2-((7-methylquinoxalin-6-yl)amino)-7,9-dihydro-8H-purin-8-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
3-(7-methyl-2-((6-methylbenzo[d][1,3]dioxol-5-yl)amino)-8-oxo-7,8-dihydro-9H-purin-9-yl) bicyclo[1.1.1]pentane-1-carbonitrile	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
7-methyl-2-((7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino)-9-(3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)-7,9-dihydro-8H-purin-8-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
7-methyl-2-((6-methylbenzo[d][1,3]dioxol-5-yl)amino)-9-(3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)-7,9-dihydro-8H-purin-8-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
9-(3-(methoxymethyl)bicyclo[1.1.1]pentan-1-yl)-7-methyl-2-((7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino)-7,9-dihydro-8H-purin-8-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
9-(3-(methoxymethyl)bicyclo[1.1.1]pentan-1-yl)-7-methyl-2-((6-methylbenzo[d][1,3]dioxol-5-yl)amino)-7,9-dihydro-8H-purin-8-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
2-(3-(7-methyl-2-((7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino)-8-oxo-7,8-dihydro-9H-purin-9-yl)bicyclo[1.1.1]pentan-1-yl)acetonitrile	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
2-(3-(7-methyl-2-((6-methylbenzo[d][1,3]dioxol-5-yl)amino)-8-oxo-7,8-dihydro-9H-purin-9-yl)bicyclo[1.1.1]pentan-1-yl)acetonitrile	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
9-(4-methoxybicyclo[2.1.1]hexan-1-yl)-7-methyl-2-((7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino)-7,9-dihydro-8H-purin-8-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
9-(4-hydroxybicyclo[2.2.1]heptan-1-yl)-7-methyl-2-((7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino)-7,9-dihydro-8H-purine-8-thione	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
9-(4-hydroxybicyclo[2.2.1]heptan-1-yl)-7-methyl-2-((6-methylbenzo[d][1,3]dioxol-5-yl)amino)-7,9-dihydro-8H-purine-8-thione	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
9-(4-hydroxybicyclo[2.2.1]heptan-1-yl)-7-methyl-2-((7-methylquinoxalin-6-yl)amino)-7,9-dihydro-8H-purine-8-thione	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
2-fluoro-4-((9-(4-methoxybicyclo[2.1.1]hexan-1-yl)-7-methyl-8-oxo-8,9-dihydro-7H-purin-2-yl)amino)-5-methylbenzamide	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
2-((5-fluoro-2-methyl-4-(oxazol-5-yl)phenyl)amino)-9-(4-methoxybicyclo[2.1.1]hexan-1-yl)-7-methyl-7,9-dihydro-8H-purin-8-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
1-(bicyclo[1.1.1]pentan-1-yl)-3-methyl-N-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
1-(bicyclo[1.1.1]pentan-1-yl)-3-methyl-N-(6-methylbenzo[d][1,3]dioxol-5-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
8-{4-Hydroxybicyclo[2.2.1]heptan-1-yl}-5-methyl-2-({7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}amino)-5,6,7,8-tetrahydropteridin-6-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
8-{3-Fluorobicyclo[1.1.1]pentan-1-yl}-5-methyl-2-({7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}amino)-5,6,7,8-tetrahydropteridin-6-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
8-(3-fluorobicyclo[1.1.1]pentan-1-yl)-5-methyl-2-((7-methylquinolin-6-yl)amino)-7,8-dihydropteridin-6(5H)-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
8-(4-methoxybicyclo[2.2.1]heptan-1-yl)-5-methyl-2-((6-methylbenzo[d][1,3]dioxol-5-yl)amino)-7,8-dihydropteridin-6(5H)-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
7’-(3-fluorobicyclo[1.1.1]pentan-1-yl)-2’-((4-methyl-6-(oxazol-5-yl)pyridin-3-yl)amino)spiro[cyclopropane-1,5’-pyrrolo[2,3-d]pyrimidin]-6’(7’H)-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
7’-(3-fluorobicyclo[1.1.1]pentan-1-yl)-2’-((4-methyl-6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)spiro[cyclopropane-1,5’-pyrrolo[2,3-d]pyrimidin]-6’(7’H)-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
7’-(3-fluorobicyclo[1.1.1]pentan-1-yl)-2’-((6-methylbenzo[d][1,3]dioxol-5-yl)amino)spiro[cyclopropane-1,5’-pyrrolo[2,3-d]pyrimidin]-6’(7’H)-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
8-(1H-imidazol-5-yl)-2-methyl-N-[2-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-6-morpholin-4-ylimidazo[1,2-b]pyridazin-3-amine	KD	9 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-methyl-6-morpholin-4-yl-3-N-[2-piperidin-4-yl-3-(trifluoromethyl)phenyl]imidazo[1,2-b]pyridazine-3,8-diamine	KD	11 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
US10087187, Compound 46	KD	11 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
8-(1H-imidazol-5-yl)-2-methyl-6-morpholin-4-yl-N-[2-(morpholin-4-ylmethyl)-3-(trifluoromethyl)phenyl]imidazo[1,2-b]pyridazin-3-amine	KD	12 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-methyl-6-morpholin-4-yl-3-N-[2-(morpholin-4-ylmethyl)-3-(trifluoromethyl)phenyl]imidazo[1,2-b]pyridazine-3,8-diamine	KD	15 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-[[2-[(8-amino-2-methyl-6-morpholin-4-ylimidazo[1,2-b]pyridazin-3-yl)amino]-6-(trifluoromethyl)phenyl]methylamino]propan-1-ol	KD	16 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-methyl-3-N-(3-methyl-2-piperidin-4-ylphenyl)-6-morpholin-4-ylimidazo[1,2-b]pyridazine-3,8-diamine	KD	16 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
[3-(3-chloro-2-methylanilino)-8-(1H-imidazol-5-yl)-6-morpholin-4-ylimidazo[1,2-b]pyridazin-2-yl]methanol	KD	17 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-methyl-3-N-[2-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-6-morpholin-4-ylimidazo[1,2-b]pyridazine-3,8-diamine	KD	20 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-[4-[2-[(8-amino-2-methyl-6-morpholin-4-ylimidazo[1,2-b]pyridazin-3-yl)amino]-6-(trifluoromethyl)phenyl]piperidin-1-yl]ethanol	KD	28 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
3-N-(2,3-dimethylphenyl)-2-methyl-6-morpholin-4-ylimidazo[1,2-b]pyridazine-3,8-diamine	KD	31 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
1-[[2-[(8-amino-2-methyl-6-morpholin-4-ylimidazo[1,2-b]pyridazin-3-yl)amino]-6-(trifluoromethyl)phenyl]methyl]pyrrolidin-3-ol	KD	31 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
N-(3-fluoro-2-methylphenyl)-8-(1H-imidazol-5-yl)-2-methyl-6-morpholin-4-ylimidazo[1,2-b]pyridazin-3-amine	KD	33 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-methyl-3-N-[2-[(3-methylsulfonylazetidin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-6-morpholin-4-ylimidazo[1,2-b]pyridazine-3,8-diamine	KD	34 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-methyl-6-morpholin-4-yl-3-N-(1,2,3,4-tetrahydroisoquinolin-5-yl)imidazo[1,2-b]pyridazine-3,8-diamine	KD	34 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-methyl-6-morpholin-4-yl-3-N-[2-(pyrrolidin-1-ylmethyl)-3-(trifluoromethyl)phenyl]imidazo[1,2-b]pyridazine-3,8-diamine	KD	35 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
1-[[2-[(8-amino-2-methyl-6-morpholin-4-ylimidazo[1,2-b]pyridazin-3-yl)amino]-6-(trifluoromethyl)phenyl]methyl]azetidin-3-ol	KD	40 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
3-N-[3-fluoro-2-(morpholin-4-ylmethyl)phenyl]-2-methyl-6-morpholin-4-ylimidazo[1,2-b]pyridazine-3,8-diamine	KD	42 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-methyl-6-morpholin-4-yl-N-(2-morpholin-4-ylphenyl)-8-(1H-pyrazol-5-yl)imidazo[1,2-b]pyridazin-3-amine	KD	44 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
3-N-[2-[(1,1-dioxo-1,4-thiazinan-4-yl)methyl]-3-(trifluoromethyl)phenyl]-2-methyl-6-morpholin-4-ylimidazo[1,2-b]pyridazine-3,8-diamine	KD	47 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-methyl-3-N-[2-[(3-methylsulfonylpyrrolidin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-6-morpholin-4-ylimidazo[1,2-b]pyridazine-3,8-diamine	KD	47 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-(hydroxymethyl)-3-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-morpholin-4-ylimidazo[1,2-b]pyridazine-8-carboxylic acid	KD	48 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
8-(1H-imidazol-2-yl)-2-methyl-N-[2-methyl-3-(trifluoromethyl)phenyl]-6-morpholin-4-ylimidazo[1,2-b]pyridazin-3-amine	KD	49 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors

ChEMBL bioactivities

78 potent at pChembl≥5 of 83 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.15	IC50	7	nM	CHEMBL5405102
8.02	IC50	9.57	nM	CHEMBL4869265
7.89	IC50	13	nM	CHEMBL5423317
7.55	EC50	28.1	nM	CHEMBL1765602
7.55	IC50	28.1	nM	CHEMBL1765602
7.47	IC50	34	nM	CHEMBL3354566
7.47	IC50	34	nM	DACTOLISIB
7.33	IC50	47	nM	CHEMBL1241857
7.33	IC50	47	nM	CHEMBL5438439
7.25	IC50	56	nM	CHEMBL5421268
7.17	IC50	67	nM	CHEMBL5400266
7.14	IC50	73	nM	CHEMBL5439621
7.11	IC50	78	nM	CHEMBL1241857
7.06	IC50	87	nM	CHEMBL5435824
7.03	IC50	94	nM	CHEMBL5408600
7.02	IC50	95	nM	CHEMBL5400057
7.00	IC50	100	nM	CHEMBL5400057
7.00	IC50	100	nM	CHEMBL5438942
7.00	IC50	100	nM	CHEMBL5428216
6.96	IC50	109	nM	CHEMBL5421268
6.92	IC50	119	nM	CHEMBL5394962
6.92	IC50	121	nM	CHEMBL5422933
6.90	IC50	126	nM	CHEMBL5438439
6.86	IC50	138	nM	CHEMBL5423664
6.85	IC50	140	nM	CHEMBL3218571
6.85	IC50	140	nM	CHEMBL3922359
6.82	IC50	150	nM	CHEMBL5440247
6.80	IC50	160	nM	CHEMBL5408401
6.77	IC50	170	nM	CHEMBL5416390
6.77	IC50	170	nM	CHEMBL5414608
6.75	IC50	176	nM	TORIN1
6.75	EC50	176	nM	CHEMBL5723005
6.70	IC50	200	nM	CHEMBL5422933
6.68	IC50	210	nM	CHEMBL5413402
6.64	IC50	230	nM	CHEMBL5421613
6.62	IC50	240	nM	CHEMBL5403935
6.60	IC50	250	nM	CHEMBL5408172
6.57	IC50	270	nM	CHEMBL5419458
6.50	IC50	316.2	nM	CHEMBL5091438
6.47	IC50	340	nM	CHEMBL5432301
6.40	IC50	400	nM	CHEMBL5419214
6.38	IC50	420	nM	CHEMBL5434141
6.30	IC50	500	nM	CHEMBL5402925
6.29	IC50	510	nM	CHEMBL1476614
6.25	IC50	560	nM	CHEMBL5414871
6.16	IC50	700	nM	CHEMBL5394340
6.11	IC50	780	nM	CHEMBL5437094
6.10	IC50	790	nM	CHEMBL5419311
6.10	IC50	800	nM	CHEMBL5425779
6.08	IC50	830	nM	CHEMBL5438784

PubChem BioAssay actives

77 with measured affinity, of 208 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
6-amino-N-[7-methoxy-8-[(3-nitrophenyl)methoxy]-2,3-dihydro-1H-imidazo[1,2-c]quinazolin-5-ylidene]pyridine-3-carboxamide	2019659: Inhibition of N-terminal 6His-tagged PI3KC2alpha (299 to 1388 residues) (unknown origin) expressed in Escherichia coli DH10 infected in Sf21 insect cells incubated for 60 mins in the presence of ATP by Kinase-Glo reagent based luminescence plate reader analysis	ic50	0.0070	uM
6-amino-N-(7,8-dimethoxy-2,3-dihydro-1H-imidazo[1,2-c]quinazolin-5-ylidene)pyridine-3-carboxamide	2019659: Inhibition of N-terminal 6His-tagged PI3KC2alpha (299 to 1388 residues) (unknown origin) expressed in Escherichia coli DH10 infected in Sf21 insect cells incubated for 60 mins in the presence of ATP by Kinase-Glo reagent based luminescence plate reader analysis	ic50	0.0130	uM
9-(6-amino-3-pyridinyl)-1-[3-(trifluoromethyl)phenyl]benzo[h][1,6]naphthyridin-2-one	2198478: Inhibition of PIK3C2A (unknown origin) by drug competition for substrate binding based assay	ec50	0.0281	uM
2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-ylimidazo[4,5-c]quinolin-1-yl)phenyl]propanenitrile	1321991: Inhibition of human recombinant PI3KC2alpha using substrate PI incubated for 1 hr by Adapta kinase assay	ic50	0.0340	uM
1-[4-(3-methyl-2-oxo-8-quinolin-3-ylimidazo[4,5-c]quinolin-1-yl)phenyl]cyclopropane-1-carbonitrile	1177094: Inhibition of human PI3KC2alpha by non-radiometric ADP-Glo assay	ic50	0.0340	uM
N-(7,8-dimethoxy-2,3-dihydro-1H-imidazo[1,2-c]quinazolin-5-ylidene)pyridine-3-carboxamide	1177094: Inhibition of human PI3KC2alpha by non-radiometric ADP-Glo assay	ic50	0.0470	uM
N-[4-[3-(methanesulfonamido)phenyl]-1,3-thiazol-2-yl]-2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanylacetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.0470	uM
2-[2-[[2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanylacetyl]amino]-1,3-thiazol-4-yl]-N-(2-phenylpropan-2-yl)acetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.0560	uM
N-[4-[3-[methyl(methylsulfonyl)amino]phenyl]-1,3-thiazol-2-yl]-2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanylacetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.0670	uM
N-benzyl-2-[2-[[2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanylacetyl]amino]-1,3-thiazol-4-yl]acetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.0730	uM
N-[4-[2-(3,4-dihydro-1H-isoquinolin-2-yl)-2-oxoethyl]-1,3-thiazol-2-yl]-2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanylacetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.0870	uM
2-[2-[[2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanylacetyl]amino]-1,3-thiazol-4-yl]-N-(thiophen-2-ylmethyl)acetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.0940	uM
2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanyl-N-(1,3-thiazol-2-yl)acetamide	2019679: Inhibition of recombinant GST-tagged human PI3KC2alpha (142 to 1412 residues) expressed in baculovirus expression system using PI lipid kinase as substrate incubated for 1 hrs in the presence of 10 uM ATP by TR-FRET assay	ic50	0.0950	uM
2-[2-[[2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanylacetyl]amino]-1,3-thiazol-4-yl]-N-(1-phenylcyclopropyl)acetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.1000	uM
2-[2-[[2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanylacetyl]amino]-1,3-thiazol-4-yl]-N-phenylacetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.1000	uM
2-[2-[[2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanylacetyl]amino]-1,3-thiazol-4-yl]-N-(2-phenylethyl)acetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.1190	uM
N-[4-(3-hydroxyphenyl)-1,3-thiazol-2-yl]-2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanylacetamide	2019679: Inhibition of recombinant GST-tagged human PI3KC2alpha (142 to 1412 residues) expressed in baculovirus expression system using PI lipid kinase as substrate incubated for 1 hrs in the presence of 10 uM ATP by TR-FRET assay	ic50	0.1210	uM
2-[2-[[2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanylacetyl]amino]-1,3-thiazol-4-yl]-N-(pyridin-4-ylmethyl)acetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.1380	uM
4-[(3-chloro-4-fluorophenyl)methyl]-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazin-3-one	1321984: Inhibition of PI3KC2alpha (unknown origin) expressed in HEK293 cells using phosphatidylinositol and gamma-32P-ATP incubated for 20 mins by TLC assay or high-throughput membrane capture assay	ic50	0.1400	uM
4-[(3-chloro-4-fluorophenyl)methyl]-6-[(E)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazin-3-one	1177094: Inhibition of human PI3KC2alpha by non-radiometric ADP-Glo assay	ic50	0.1400	uM
N-[4-(3-aminophenyl)-1,3-thiazol-2-yl]-2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanylacetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.1500	uM
2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanyl-N-(4-thiophen-3-yl-1,3-thiazol-2-yl)acetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.1600	uM
2-(1H-benzimidazol-2-ylmethylsulfanyl)-3-(2-phenylethyl)pteridin-4-one	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.1700	uM
2-[3-(2,3-dihydro-1H-inden-2-yl)-4-oxopteridin-2-yl]sulfanyl-N-(1,3-thiazol-2-yl)acetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.1700	uM
1-[4-(4-propanoylpiperazin-1-yl)-3-(trifluoromethyl)phenyl]-9-quinolin-3-yl-3,4-dihydrobenzo[h][1,6]naphthyridin-2-one	2198478: Inhibition of PIK3C2A (unknown origin) by drug competition for substrate binding based assay	ec50	0.1760	uM
1-[4-(4-propanoylpiperazin-1-yl)-3-(trifluoromethyl)phenyl]-9-quinolin-3-ylbenzo[h][1,6]naphthyridin-2-one	517860: Inhibition of PI3K-C2 alpha	ic50	0.1760	uM
2-[3-[2-(4-hydroxyphenyl)ethyl]-4-oxopteridin-2-yl]sulfanyl-N-(1,3-thiazol-2-yl)acetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.2100	uM
N-[4-(3-methoxyphenyl)-1,3-thiazol-2-yl]-2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanylacetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.2300	uM
methyl 2-[2-[[2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanylacetyl]amino]-1,3-thiazol-4-yl]acetate	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.2400	uM
2-[3-[2-(3-fluorophenyl)ethyl]-4-oxopteridin-2-yl]sulfanyl-N-(1,3-thiazol-2-yl)acetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.2500	uM
2-[4-oxo-3-(2-thiophen-2-ylethyl)pteridin-2-yl]sulfanyl-N-(1,3-thiazol-2-yl)acetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.2700	uM
24-[(1S)-1-cyclopropylethyl]-3-methyl-20,20-dioxo-16-oxa-20lambda6,30-dithia-4,6,13,19,24,29-hexazapentacyclo[19.6.1.12,5.17,11.022,26]triaconta-1(27),2,4,7,9,11(29),21(28),22(26)-octaene-12,23-dione	1807062: Inhibition of PIK3C2A (unknown origin) assessed as reduction in substrate phosphorylation by FRET Adapta assay	ic50	0.3162	uM
N-[4-[4-(difluoromethoxy)phenyl]-1,3-thiazol-2-yl]-2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanylacetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.3400	uM
N-(1,3-oxazol-2-yl)-2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanylacetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.4000	uM
N-[4-(5-methylthiophen-2-yl)-1,3-thiazol-2-yl]-2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanylacetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.4200	uM
2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanyl-N-phenylacetamide	2019665: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 50 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.5000	uM
2-[3-[2-(1H-indol-3-yl)ethyl]-4-oxopteridin-2-yl]sulfanyl-N-phenylacetamide	2019665: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 50 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.5100	uM
2-[4-oxo-3-(2-phenylcyclopropyl)pteridin-2-yl]sulfanyl-N-(1,3-thiazol-2-yl)acetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.5600	uM
N-(3-methylphenyl)-2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanylacetamide	2019665: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 50 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.7000	uM
N-[4-(4-cyanophenyl)-1,3-thiazol-2-yl]-2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanylacetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.7800	uM
2-[4-oxo-3-(3-phenylpropyl)pteridin-2-yl]sulfanyl-N-(1,3-thiazol-2-yl)acetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.7900	uM
2-[4-oxo-3-(2-phenylethyl)pyrido[2,3-d]pyrimidin-2-yl]sulfanyl-N-(1,3-thiazol-2-yl)acetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.8000	uM
2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanyl-N-pyrimidin-2-ylacetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.8300	uM
2-[3-(2,3-dihydro-1H-inden-1-yl)-4-oxopteridin-2-yl]sulfanyl-N-(1,3-thiazol-2-yl)acetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	0.8400	uM
3-(6-morpholin-4-yl-8-oxa-5,10-diazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-4-yl)phenol	1321984: Inhibition of PI3KC2alpha (unknown origin) expressed in HEK293 cells using phosphatidylinositol and gamma-32P-ATP incubated for 20 mins by TLC assay or high-throughput membrane capture assay	ic50	1.0000	uM
3-(6-morpholin-4-yl-8-oxa-3,5,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaen-4-yl)phenol	1177094: Inhibition of human PI3KC2alpha by non-radiometric ADP-Glo assay	ic50	1.0000	uM
2-[3-[2-(3,4-dimethoxyphenyl)ethyl]-4-oxopteridin-2-yl]sulfanyl-N-phenylacetamide	2019665: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 50 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	1.1000	uM
N-(1-methylpiperidin-4-yl)-4-[4-(2-oxo-9-quinolin-3-ylbenzo[h][1,6]naphthyridin-1-yl)-2-(trifluoromethyl)phenyl]benzamide	603283: Inhibition of PI3K C2alpha	ic50	1.1100	uM
2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanyl-N-(4-phenyl-1,3-thiazol-2-yl)acetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	1.3000	uM
2-(3-benzyl-4-oxopteridin-2-yl)sulfanyl-N-(1,3-thiazol-2-yl)acetamide	2019676: Inhibition of PI3KC2alpha deltaN domain (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 20 mins in the presence of 10 uM ATP by ADP-Glo reagent based Ultra-Glo luciferase assay	ic50	1.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	increases expression	3
Valproic Acid	decreases expression, increases expression	3
Acetaminophen	increases expression, affects cotreatment	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
ginger extract	decreases expression, increases abundance	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases methylation	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	increases expression, affects cotreatment	1
nonanal	increases methylation	1
n-hexanal	increases methylation	1
quercitrin	affects expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases methylation	1
perfluorooctanoic acid	increases expression	1
caprylic aldehyde	increases methylation	1
1-nitropyrene	increases expression	1
pentanal	increases methylation	1
heptanal	increases methylation	1
avobenzone	increases expression	1
celastrol	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
Sorafenib	decreases expression	1

ChEMBL screening assays

90 unique, capped per target: 90 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1100129	Binding	Inhibition of PIK3C2alpha at 1 uM	Discovery of (thienopyrimidin-2-yl)aminopyrimidines as potent, selective, and orally available pan-PI3-kinase and dual pan-PI3-kinase/mTOR inhibitors for the treatment of cancer. — J Med Chem

Cellosaurus cell lines

7 cell lines: 6 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2AR	Abcam HeLa PIK3C2A KO	Cancer cell line	Female
CVCL_D7X7	Ubigene A-549 PIK3C2A KO	Cancer cell line	Male
CVCL_D8SM	Ubigene HCT 116 PIK3C2A KO	Cancer cell line	Male
CVCL_D9N5	Ubigene HEK293 PIK3C2A KO	Transformed cell line	Female
CVCL_E0KI	Ubigene HeLa PIK3C2A KO	Cancer cell line	Female
CVCL_TD56	HAP1 PIK3C2A (-) 1	Cancer cell line	Male
CVCL_TD57	HAP1 PIK3C2A (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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