General Information of Drug Off-Target (DOT) (ID: OTTOMI8J)

DOT Name Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA)
Synonyms
PI3-kinase subunit alpha; PI3K-alpha; PI3Kalpha; PtdIns-3-kinase subunit alpha; EC 2.7.1.137; EC 2.7.1.153; Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha; PtdIns-3-kinase subunit p110-alpha; p110alpha; Phosphoinositide 3-kinase alpha; Phosphoinositide-3-kinase catalytic alpha polypeptide; Serine/threonine protein kinase PIK3CA; EC 2.7.11.1
Gene Name PIK3CA
Related Disease
CLOVES syndrome ( )
Megalencephaly-capillary malformation-polymicrogyria syndrome ( )
Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes ( )
Vascular malformation ( )
Cowden disease ( )
Cowden syndrome 5 ( )
Hereditary breast carcinoma ( )
Familial ovarian cancer ( )
UniProt ID
PK3CA_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2ENQ ; 2RD0 ; 3HHM ; 3HIZ ; 3ZIM ; 4JPS ; 4L1B ; 4L23 ; 4L2Y ; 4OVU ; 4OVV ; 4TUU ; 4TV3 ; 4WAF ; 4YKN ; 4ZOP ; 5DXH ; 5DXT ; 5FI4 ; 5ITD ; 5SW8 ; 5SWG ; 5SWO ; 5SWP ; 5SWR ; 5SWT ; 5SX8 ; 5SX9 ; 5SXA ; 5SXB ; 5SXC ; 5SXD ; 5SXE ; 5SXF ; 5SXI ; 5SXJ ; 5SXK ; 5UBR ; 5UK8 ; 5UKJ ; 5UL1 ; 5XGH ; 5XGI ; 5XGJ ; 6GVF ; 6GVG ; 6GVH ; 6GVI ; 6NCT ; 6OAC ; 6PYS ; 6VO7 ; 7JIU ; 7K6M ; 7K6N ; 7K6O ; 7K71 ; 7L1B ; 7L1C ; 7L1D ; 7MLK ; 7MYN ; 7MYO ; 7PG5 ; 7PG6 ; 7R9V ; 7R9Y ; 7RRG ; 7TZ7 ; 8BFU ; 8DCP ; 8DCX ; 8DD4 ; 8DD8 ; 8EXL ; 8EXO ; 8EXU ; 8EXV ; 8GUA ; 8GUB ; 8GUD ; 8ILR ; 8ILS ; 8ILV ; 8OW2 ; 8SBC ; 8SBJ ; 8TDU ; 8TGD ; 8TS7 ; 8TS8 ; 8TS9 ; 8TSA ; 8TSB ; 8TSC ; 8TSD ; 8TU6
EC Number
2.7.1.137; 2.7.1.153; 2.7.11.1
Pfam ID
PF00454 ; PF00792 ; PF02192 ; PF00794 ; PF00613
Sequence
MPPRPSSGELWGIHLMPPRILVECLLPNGMIVTLECLREATLITIKHELFKEARKYPLHQ
LLQDESSYIFVSVTQEAEREEFFDETRRLCDLRLFQPFLKVIEPVGNREEKILNREIGFA
IGMPVCEFDMVKDPEVQDFRRNILNVCKEAVDLRDLNSPHSRAMYVYPPNVESSPELPKH
IYNKLDKGQIIVVIWVIVSPNNDKQKYTLKINHDCVPEQVIAEAIRKKTRSMLLSSEQLK
LCVLEYQGKYILKVCGCDEYFLEKYPLSQYKYIRSCIMLGRMPNLMLMAKESLYSQLPMD
CFTMPSYSRRISTATPYMNGETSTKSLWVINSALRIKILCATYVNVNIRDIDKIYVRTGI
YHGGEPLCDNVNTQRVPCSNPRWNEWLNYDIYIPDLPRAARLCLSICSVKGRKGAKEEHC
PLAWGNINLFDYTDTLVSGKMALNLWPVPHGLEDLLNPIGVTGSNPNKETPCLELEFDWF
SSVVKFPDMSVIEEHANWSVSREAGFSYSHAGLSNRLARDNELRENDKEQLKAISTRDPL
SEITEQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPPIKPEQAME
LLDCNYPDPMVRGFAVRCLEKYLTDDKLSQYLIQLVQVLKYEQYLDNLLVRFLLKKALTN
QRIGHFFFWHLKSEMHNKTVSQRFGLLLESYCRACGMYLKHLNRQVEAMEKLINLTDILK
QEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKRPLW
LNWENPDIMSELLFQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLS
IGDCVGLIEVVRNSHTIMQIQCKGGLKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRS
CAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGHFLDHKKKKFGYKRERVPFVLTQDF
LIVISKGAQECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSFDDIA
YIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQHALN
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.
KEGG Pathway
Inositol phosphate metabolism (hsa00562 )
Metabolic pathways (hsa01100 )
EGFR tyrosine ki.se inhibitor resistance (hsa01521 )
Endocrine resistance (hsa01522 )
Platinum drug resistance (hsa01524 )
ErbB sig.ling pathway (hsa04012 )
Ras sig.ling pathway (hsa04014 )
Rap1 sig.ling pathway (hsa04015 )
cAMP sig.ling pathway (hsa04024 )
Chemokine sig.ling pathway (hsa04062 )
HIF-1 sig.ling pathway (hsa04066 )
FoxO sig.ling pathway (hsa04068 )
Phosphatidylinositol sig.ling system (hsa04070 )
Sphingolipid sig.ling pathway (hsa04071 )
Phospholipase D sig.ling pathway (hsa04072 )
Autophagy - animal (hsa04140 )
mTOR sig.ling pathway (hsa04150 )
PI3K-Akt sig.ling pathway (hsa04151 )
AMPK sig.ling pathway (hsa04152 )
Apoptosis (hsa04210 )
Longevity regulating pathway (hsa04211 )
Longevity regulating pathway - multiple species (hsa04213 )
Cellular senescence (hsa04218 )
Axon guidance (hsa04360 )
VEGF sig.ling pathway (hsa04370 )
Osteoclast differentiation (hsa04380 )
Focal adhesion (hsa04510 )
Sig.ling pathways regulating pluripotency of stem cells (hsa04550 )
Platelet activation (hsa04611 )
Neutrophil extracellular trap formation (hsa04613 )
Toll-like receptor sig.ling pathway (hsa04620 )
C-type lectin receptor sig.ling pathway (hsa04625 )
JAK-STAT sig.ling pathway (hsa04630 )
.tural killer cell mediated cytotoxicity (hsa04650 )
T cell receptor sig.ling pathway (hsa04660 )
B cell receptor sig.ling pathway (hsa04662 )
Fc epsilon RI sig.ling pathway (hsa04664 )
Fc gamma R-mediated phagocytosis (hsa04666 )
TNF sig.ling pathway (hsa04668 )
Leukocyte transendothelial migration (hsa04670 )
Neurotrophin sig.ling pathway (hsa04722 )
Cholinergic sy.pse (hsa04725 )
Inflammatory mediator regulation of TRP channels (hsa04750 )
Regulation of actin cytoskeleton (hsa04810 )
Insulin sig.ling pathway (hsa04910 )
Progesterone-mediated oocyte maturation (hsa04914 )
Estrogen sig.ling pathway (hsa04915 )
Prolactin sig.ling pathway (hsa04917 )
Thyroid hormone sig.ling pathway (hsa04919 )
Regulation of lipolysis in adipocytes (hsa04923 )
Relaxin sig.ling pathway (hsa04926 )
GnRH secretion (hsa04929 )
Type II diabetes mellitus (hsa04930 )
Insulin resistance (hsa04931 )
Non-alcoholic fatty liver disease (hsa04932 )
AGE-RAGE sig.ling pathway in diabetic complications (hsa04933 )
Growth hormone synthesis, secretion and action (hsa04935 )
Aldosterone-regulated sodium reabsorption (hsa04960 )
Carbohydrate digestion and absorption (hsa04973 )
Alzheimer disease (hsa05010 )
Spinocerebellar ataxia (hsa05017 )
Prion disease (hsa05020 )
Bacterial invasion of epithelial cells (hsa05100 )
Shigellosis (hsa05131 )
Salmonella infection (hsa05132 )
Yersinia infection (hsa05135 )
Chagas disease (hsa05142 )
Amoebiasis (hsa05146 )
Hepatitis C (hsa05160 )
Hepatitis B (hsa05161 )
Measles (hsa05162 )
Human cytomegalovirus infection (hsa05163 )
Influenza A (hsa05164 )
Human papillomavirus infection (hsa05165 )
Human T-cell leukemia virus 1 infection (hsa05166 )
Kaposi sarcoma-associated herpesvirus infection (hsa05167 )
Herpes simplex virus 1 infection (hsa05168 )
Epstein-Barr virus infection (hsa05169 )
Human immunodeficiency virus 1 infection (hsa05170 )
Coro.virus disease - COVID-19 (hsa05171 )
Pathways in cancer (hsa05200 )
Viral carcinogenesis (hsa05203 )
Proteoglycans in cancer (hsa05205 )
MicroR.s in cancer (hsa05206 )
Chemical carcinogenesis - receptor activation (hsa05207 )
Chemical carcinogenesis - reactive oxygen species (hsa05208 )
Colorectal cancer (hsa05210 )
Re.l cell carcinoma (hsa05211 )
Pancreatic cancer (hsa05212 )
Endometrial cancer (hsa05213 )
Glioma (hsa05214 )
Prostate cancer (hsa05215 )
Melanoma (hsa05218 )
Chronic myeloid leukemia (hsa05220 )
Acute myeloid leukemia (hsa05221 )
Small cell lung cancer (hsa05222 )
Non-small cell lung cancer (hsa05223 )
Breast cancer (hsa05224 )
Hepatocellular carcinoma (hsa05225 )
Gastric cancer (hsa05226 )
Central carbon metabolism in cancer (hsa05230 )
Choline metabolism in cancer (hsa05231 )
PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235 )
Diabetic cardiomyopathy (hsa05415 )
Lipid and atherosclerosis (hsa05417 )
Fluid shear stress and atherosclerosis (hsa05418 )
Reactome Pathway
IRS-mediated signalling (R-HSA-112399 )
GPVI-mediated activation cascade (R-HSA-114604 )
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants (R-HSA-1236382 )
PI3K events in ERBB4 signaling (R-HSA-1250342 )
PIP3 activates AKT signaling (R-HSA-1257604 )
Signaling by SCF-KIT (R-HSA-1433557 )
Synthesis of PIPs at the plasma membrane (R-HSA-1660499 )
GAB1 signalosome (R-HSA-180292 )
Signaling by cytosolic FGFR1 fusion mutants (R-HSA-1839117 )
Downstream signal transduction (R-HSA-186763 )
PI3K events in ERBB2 signaling (R-HSA-1963642 )
PI3K/AKT activation (R-HSA-198203 )
Signaling by ALK (R-HSA-201556 )
Downstream TCR signaling (R-HSA-202424 )
Role of phospholipids in phagocytosis (R-HSA-2029485 )
Tie2 Signaling (R-HSA-210993 )
Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530 )
DAP12 signaling (R-HSA-2424491 )
Role of LAT2/NTAL/LAB on calcium mobilization (R-HSA-2730905 )
Nephrin family interactions (R-HSA-373753 )
Costimulation by the CD28 family (R-HSA-388841 )
CD28 dependent PI3K/Akt signaling (R-HSA-389357 )
G alpha (q) signalling events (R-HSA-416476 )
VEGFA-VEGFR2 Pathway (R-HSA-4420097 )
Interleukin-3, Interleukin-5 and GM-CSF signaling (R-HSA-512988 )
Constitutive Signaling by EGFRvIII (R-HSA-5637810 )
PI-3K cascade (R-HSA-5654689 )
PI-3K cascade (R-HSA-5654695 )
PI-3K cascade (R-HSA-5654710 )
PI-3K cascade (R-HSA-5654720 )
Signaling by FGFR2 in disease (R-HSA-5655253 )
Signaling by FGFR4 in disease (R-HSA-5655291 )
Signaling by FGFR1 in disease (R-HSA-5655302 )
Signaling by FGFR3 in disease (R-HSA-5655332 )
RAF/MAP kinase cascade (R-HSA-5673001 )
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558 )
MET activates PI3K/AKT signaling (R-HSA-8851907 )
RET signaling (R-HSA-8853659 )
Extra-nuclear estrogen signaling (R-HSA-9009391 )
RAC1 GTPase cycle (R-HSA-9013149 )
RAC2 GTPase cycle (R-HSA-9013404 )
Erythropoietin activates Phosphoinositide-3-kinase (PI3K) (R-HSA-9027276 )
Activated NTRK2 signals through PI3K (R-HSA-9028335 )
Interleukin receptor SHC signaling (R-HSA-912526 )
Regulation of signaling by CBL (R-HSA-912631 )
Activated NTRK3 signals through PI3K (R-HSA-9603381 )
FLT3 Signaling (R-HSA-9607240 )
Signaling by ERBB2 KD Mutants (R-HSA-9664565 )
Signaling by ERBB2 ECD mutants (R-HSA-9665348 )
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants (R-HSA-9670439 )
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants (R-HSA-9673767 )
Signaling by PDGFRA extracellular domain mutants (R-HSA-9673770 )
Signaling by CSF1 (M-CSF) in myeloid cells (R-HSA-9680350 )
Signaling by FLT3 fusion proteins (R-HSA-9703465 )
Signaling by FLT3 ITD and TKD mutants (R-HSA-9703648 )
Signaling by ALK fusions and activated point mutants (R-HSA-9725370 )
PI3K Cascade (R-HSA-109704 )
BioCyc Pathway
MetaCyc:HS04527-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
CLOVES syndrome DISHPA3U Definitive Somatic mosaicism [1]
Megalencephaly-capillary malformation-polymicrogyria syndrome DISAHLVO Definitive Somatic mosaicism [2]
Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes DISWECW7 Definitive Autosomal dominant [3]
Vascular malformation DIS2DB7A Strong Autosomal dominant [4]
Cowden disease DISMYKCE Supportive Autosomal dominant [5]
Cowden syndrome 5 DIS8N2DI Limited Autosomal dominant [5]
Hereditary breast carcinoma DISAEZT5 Refuted Autosomal dominant [3]
Familial ovarian cancer DISGLR2C No Known Autosomal dominant [3]
------------------------------------------------------------------------------------
⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 6 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Cisplatin DMRHGI9 Approved Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) decreases the response to substance of Cisplatin. [46]
Rigosertib DMOSTXF Phase 3 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) affects the response to substance of Rigosertib. [47]
GDC0941 DM1YAK6 Phase 2 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) increases the response to substance of GDC0941. [48]
BEZ235 DMKBRDL Phase 2 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) decreases the response to substance of BEZ235. [49]
GDC-0980/RG7422 DMF3MV1 Phase 2 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) increases the response to substance of GDC-0980/RG7422. [50]
Lithium chloride DMHYLQ2 Investigative Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) increases the response to substance of Lithium chloride. [51]
------------------------------------------------------------------------------------
⏷ Show the Full List of 6 Drug(s)
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [6]
Mivebresib DMCPF90 Phase 1 Mivebresib increases the phosphorylation of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [32]
carvacrol DMINM2D Investigative carvacrol increases the phosphorylation of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [44]
------------------------------------------------------------------------------------
38 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [7]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [8]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [9]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [10]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [11]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [12]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [13]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [14]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [15]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [16]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [17]
Dexamethasone DMMWZET Approved Dexamethasone affects the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [18]
Niclosamide DMJAGXQ Approved Niclosamide increases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [19]
Cannabidiol DM0659E Approved Cannabidiol increases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [20]
Diclofenac DMPIHLS Approved Diclofenac affects the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [17]
Nicotine DMWX5CO Approved Nicotine increases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [21]
Pioglitazone DMKJ485 Approved Pioglitazone decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [22]
Sorafenib DMS8IFC Approved Sorafenib decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [23]
Cantharidin DMBP5N3 Approved Cantharidin decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [25]
Omacetaxine mepesuccinate DMPU2WX Approved Omacetaxine mepesuccinate decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [26]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [27]
Curcumin DMQPH29 Phase 3 Curcumin decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [23]
Atorvastatin DMF28YC Phase 3 Trial Atorvastatin decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [28]
Contigoside B DMX9V8K Phase 2/3 Contigoside B affects the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [29]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [31]
ZSTK474 DMVIMQX Phase 1 ZSTK474 decreases the activity of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [33]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [34]
Geldanamycin DMS7TC5 Discontinued in Phase 2 Geldanamycin increases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [35]
Wortmannin DM8EVK5 Terminated Wortmannin decreases the activity of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [36]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [37]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [38]
Deguelin DMXT7WG Investigative Deguelin decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [39]
3R14S-OCHRATOXIN A DM2KEW6 Investigative 3R14S-OCHRATOXIN A increases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [31]
Tributylstannanyl DMHN7CB Investigative Tributylstannanyl decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [41]
OLEANOLIC_ACID DMWDMJ3 Investigative OLEANOLIC_ACID decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [42]
Methyl Mercury Ion DM6YEW4 Investigative Methyl Mercury Ion increases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [31]
Fascaplysin DMG5OZP Investigative Fascaplysin decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [43]
NU-7432 DMDNUM5 Investigative NU-7432 decreases the activity of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [45]
------------------------------------------------------------------------------------
⏷ Show the Full List of 38 Drug(s)
3 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Adenosine triphosphate DM79F6G Approved Adenosine triphosphate affects the binding of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [24]
BAICALEIN DM4C7E6 Phase 2 BAICALEIN affects the binding of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [30]
Rapamycin Immunosuppressant Drug DM678IB Investigative Rapamycin Immunosuppressant Drug decreases the response to substance of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA). [40]
------------------------------------------------------------------------------------

References

1 Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome. Am J Hum Genet. 2012 Jun 8;90(6):1108-15. doi: 10.1016/j.ajhg.2012.05.006. Epub 2012 May 31.
2 De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. Nat Genet. 2012 Jun 24;44(8):934-40. doi: 10.1038/ng.2331.
3 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
4 The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
5 Germline PIK3CA and AKT1 mutations in Cowden and Cowden-like syndromes. Am J Hum Genet. 2013 Jan 10;92(1):76-80. doi: 10.1016/j.ajhg.2012.10.021. Epub 2012 Dec 13.
6 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
7 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
8 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
9 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
10 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
11 Gene expression profiling reveals novel regulation by bisphenol-A in estrogen receptor-alpha-positive human cells. Environ Res. 2006 Jan;100(1):86-92.
12 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
13 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
14 Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
15 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
16 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
17 Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
18 Anti-diabetic effect of oligosaccharides from seaweed Sargassum confusum via JNK-IRS1/PI3K signalling pathways and regulation of gut microbiota. Food Chem Toxicol. 2019 Sep;131:110562. doi: 10.1016/j.fct.2019.110562. Epub 2019 Jun 7.
19 Niclosamide Exhibits Potent Anticancer Activity and Synergizes with Sorafenib in Human Renal Cell Cancer Cells. Cell Physiol Biochem. 2018;47(3):957-971. doi: 10.1159/000490140. Epub 2018 May 24.
20 Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
21 Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
22 Effects of metformin and pioglitazone combination on apoptosis and AMPK/mTOR signaling pathway in human anaplastic thyroid cancer cells. J Biochem Mol Toxicol. 2020 Oct;34(10):e22547. doi: 10.1002/jbt.22547. Epub 2020 Jun 26.
23 Novel carbocyclic curcumin analog CUR3d modulates genes involved in multiple apoptosis pathways in human hepatocellular carcinoma cells. Chem Biol Interact. 2015 Dec 5;242:107-22.
24 The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer. J Med Chem. 2008 Sep 25;51(18):5522-32. doi: 10.1021/jm800295d.
25 Cantharidin suppresses gastric cancer cell migration/invasion by inhibiting the PI3K/Akt signaling pathway via CCAT1. Chem Biol Interact. 2020 Feb 1;317:108939. doi: 10.1016/j.cbi.2020.108939. Epub 2020 Jan 13.
26 Homoharringtonine suppresses LoVo cell growth by inhibiting EphB4 and the PI3K/AKT and MAPK/EKR1/2 signaling pathways. Food Chem Toxicol. 2020 Feb;136:110960. doi: 10.1016/j.fct.2019.110960. Epub 2019 Nov 11.
27 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
28 Atorvastatin induces MicroRNA-145 expression in HEPG2 cells via regulation of the PI3K/AKT signalling pathway. Chem Biol Interact. 2018 May 1;287:32-40. doi: 10.1016/j.cbi.2018.04.005. Epub 2018 Apr 6.
29 Improved Preventive Effects of Combined Bioactive Compounds Present in Different Blueberry Varieties as Compared to Single Phytochemicals. Nutrients. 2018 Dec 29;11(1):61. doi: 10.3390/nu11010061.
30 Mechanism analysis of Buyang Huanwu decoction in treating atherosclerosis based on network pharmacology and in?vitro experiments. Chem Biol Drug Des. 2024 Jan;103(1):e14447. doi: 10.1111/cbdd.14447.
31 Inhibition of CXCL12-mediated chemotaxis of Jurkat cells by direct immunotoxicants. Arch Toxicol. 2016 Jul;90(7):1685-94. doi: 10.1007/s00204-015-1585-7. Epub 2015 Aug 28.
32 Superior efficacy of cotreatment with BET protein inhibitor and BCL2 or MCL1 inhibitor against AML blast progenitor cells. Blood Cancer J. 2019 Jan 15;9(2):4. doi: 10.1038/s41408-018-0165-5.
33 Synthesis and biological evaluation of novel analogues of the pan class I phosphatidylinositol 3-kinase (PI3K) inhibitor 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474). J Med Chem. 2011 Oct 27;54(20):7105-26. doi: 10.1021/jm200688y. Epub 2011 Sep 27.
34 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
35 Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
36 Expression and purification of PI3 kinase alpha and development of an ATP depletion and an alphascreen PI3 kinase activity assay. J Biomol Screen. 2008 Dec;13(10):1035-40. doi: 10.1177/1087057108326079. Epub 2008 Nov 25.
37 Prediction of the combined effects of multiple estrogenic chemicals on MCF-7 human breast cancer cells and a preliminary molecular exploration of the estrogenic proliferative effects and related gene expression. Ecotoxicol Environ Saf. 2018 Sep 30;160:1-9. doi: 10.1016/j.ecoenv.2018.05.025. Epub 2018 May 21.
38 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
39 A novel derivative of the natural agent deguelin for cancer chemoprevention and therapy. Cancer Prev Res (Phila). 2008 Dec;1(7):577-87. doi: 10.1158/1940-6207.CAPR-08-0184.
40 p70(s6k) integrates phosphatidylinositol 3-kinase and rapamycin-regulated signals for E2F regulation in T lymphocytes. Mol Cell Biol. 1999 Jul;19(7):4729-38. doi: 10.1128/MCB.19.7.4729.
41 Toxicogenomic analysis identifies the apoptotic pathway as the main cause of hepatotoxicity induced by tributyltin. Food Chem Toxicol. 2016 Nov;97:316-326. doi: 10.1016/j.fct.2016.09.027. Epub 2016 Sep 24.
42 SZC015, a synthetic oleanolic acid derivative, induces both apoptosis and autophagy in MCF-7 breast cancer cells. Chem Biol Interact. 2016 Jan 25;244:94-104. doi: 10.1016/j.cbi.2015.11.013. Epub 2015 Nov 21.
43 A marine sponge alkaloid derivative 4-chloro fascaplysin inhibits tumor growth and VEGF mediated angiogenesis by disrupting PI3K/Akt/mTOR signaling cascade. Chem Biol Interact. 2017 Sep 25;275:47-60.
44 TRPV3 enhances skin keratinocyte proliferation through EGFR-dependent signaling pathways. Cell Biol Toxicol. 2021 Apr;37(2):313-330. doi: 10.1007/s10565-020-09536-2. Epub 2020 Jun 13.
45 Discovery of potent chromen-4-one inhibitors of the DNA-dependent protein kinase (DNA-PK) using a small-molecule library approach. J Med Chem. 2005 Dec 1;48(24):7829-46.
46 BAD phosphorylation determines ovarian cancer chemosensitivity and patient survival. Clin Cancer Res. 2011 Oct 1;17(19):6356-66. doi: 10.1158/1078-0432.CCR-11-0735. Epub 2011 Aug 17.
47 The dual pathway inhibitor rigosertib is effective in direct patient tumor xenografts of head and neck squamous cell carcinomas. Mol Cancer Ther. 2013 Oct;12(10):1994-2005. doi: 10.1158/1535-7163.MCT-13-0206. Epub 2013 Jul 19.
48 Predictive biomarkers of sensitivity to the phosphatidylinositol 3' kinase inhibitor GDC-0941 in breast cancer preclinical models. Clin Cancer Res. 2010 Jul 15;16(14):3670-83. doi: 10.1158/1078-0432.CCR-09-2828. Epub 2010 May 7.
49 Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011 Jul;121(7):2750-67. doi: 10.1172/JCI45014.
50 Phosphoinositide 3-kinase (PI3K) pathway alterations are associated with histologic subtypes and are predictive of sensitivity to PI3K inhibitors in lung cancer preclinical models. Clin Cancer Res. 2012 Dec 15;18(24):6771-83. doi: 10.1158/1078-0432.CCR-12-2347. Epub 2012 Nov 7.
51 Knockin of mutant PIK3CA activates multiple oncogenic pathways. Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2835-40. doi: 10.1073/pnas.0813351106. Epub 2009 Feb 5.