Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO8JQJA)

DOT Name	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB)
Synonyms	PI3-kinase subunit beta; PI3K-beta; PI3Kbeta; PtdIns-3-kinase subunit beta; EC 2.7.1.153; Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit beta; PtdIns-3-kinase subunit p110-beta; p110beta; Serine/threonine protein kinase PIK3CB; EC 2.7.11.1
Gene Name	PIK3CB
UniProt ID	PK3CB_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	2.7.1.153; 2.7.11.1
Pfam ID	PF00454 ; PF00792 ; PF02192 ; PF00794 ; PF00613
Sequence	MCFSFIMPPAMADILDIWAVDSQIASDGSIPVDFLLPTGIYIQLEVPREATISYIKQMLW KQVHNYPMFNLLMDIDSYMFACVNQTAVYEELEDETRRLCDVRPFLPVLKLVTRSCDPGE KLDSKIGVLIGKGLHEFDSLKDPEVNEFRRKMRKFSEEKILSLVGLSWMDWLKQTYPPEH EPSIPENLEDKLYGGKLIVAVHFENCQDVFSFQVSPNMNPIKVNELAIQKRLTIHGKEDE VSPYDYVLQVSGRVEYVFGDHPLIQFQYIRNCVMNRALPHFILVECCKIKKMYEQEMIAI EAAINRNSSNLPLPLPPKKTRIISHVWENNNPFQIVLVKGNKLNTEETVKVHVRAGLFHG TELLCKTIVSSEVSGKNDHIWNEPLEFDINICDLPRMARLCFAVYAVLDKVKTKKSTKTI NPSKYQTIRKAGKVHYPVAWVNTMVFDFKGQLRTGDIILHSWSSFPDELEEMLNPMGTVQ TNPYTENATALHVKFPENKKQPYYYPPFDKIIEKAAEIASSDSANVSSRGGKKFLPVLKE ILDRDPLSQLCENEMDLIWTLRQDCREIFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPK LPPREALELLDFNYPDQYVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFL LERALGNRRIGQFLFWHLRSEVHIPAVSVQFGVILEAYCRGSVGHMKVLSKQVEALNKLK TLNSLIKLNAVKLNRAKGKEAMHTCLKQSAYREALSDLQSPLNPCVILSELYVEKCKYMD SKMKPLWLVYNNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYG CLATGDRSGLIEVVSTSETIADIQLNSSNVAAAAAFNKDALLNWLKEYNSGDDLDRAIEE FTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNFKSKFGIKRERVPFIL TYDFIHVIQQGKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKD IQYLKDSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTVRKDYRS
Function	Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol derivatives at position 3 of the inositol ring to produce 3-phosphoinositides. Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Involved in the activation of AKT1 upon stimulation by G-protein coupled receptors (GPCRs) ligands such as CXCL12, sphingosine 1-phosphate, and lysophosphatidic acid. May also act downstream receptor tyrosine kinases. Required in different signaling pathways for stable platelet adhesion and aggregation. Plays a role in platelet activation signaling triggered by GPCRs, alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) and ITAM (immunoreceptor tyrosine-based activation motif)-bearing receptors such as GP6. Regulates the strength of adhesion of ITGA2B/ ITGB3 activated receptors necessary for the cellular transmission of contractile forces. Required for platelet aggregation induced by F2 (thrombin) and thromboxane A2 (TXA2). Has a role in cell survival. May have a role in cell migration. Involved in the early stage of autophagosome formation. Modulates the intracellular level of PtdIns3P (phosphatidylinositol 3-phosphate) and activates PIK3C3 kinase activity. May act as a scaffold, independently of its lipid kinase activity to positively regulate autophagy. May have a role in insulin signaling as scaffolding protein in which the lipid kinase activity is not required. May have a kinase-independent function in regulating cell proliferation and in clathrin-mediated endocytosis. Mediator of oncogenic signal in cell lines lacking PTEN. The lipid kinase activity is necessary for its role in oncogenic transformation. Required for the growth of ERBB2 and RAS driven tumors. Has also a protein kinase activity showing autophosphorylation.
Tissue Specificity	Expressed ubiquitously.
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 ) PIP3 activates AKT signaling (R-HSA-1257604 ) Synthesis of PIPs at the plasma membrane (R-HSA-1660499 ) Downstream signal transduction (R-HSA-186763 ) 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 ) VEGFA-VEGFR2 Pathway (R-HSA-4420097 ) Interleukin-3, Interleukin-5 and GM-CSF signaling (R-HSA-512988 ) RAF/MAP kinase cascade (R-HSA-5673001 ) PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558 ) RET signaling (R-HSA-8853659 ) Erythropoietin activates Phosphoinositide-3-kinase (PI3K) (R-HSA-9027276 ) Interleukin receptor SHC signaling (R-HSA-912526 ) Regulation of signaling by CBL (R-HSA-912631 ) 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 ) PI3K Cascade (R-HSA-109704 )
BioCyc Pathway	MetaCyc:HS00644-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Nicotine	DMWX5CO	Approved	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB) increases the Bladder transitional cell carcinoma ADR of Nicotine.	[20]
Leptin	DM5LY1H	Investigative	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB) increases the Ovarian cancer ADR of Leptin.	[20]
TGX-221	DMM0LRE	Investigative	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB) increases the response to substance of TGX-221.	[21]
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22 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB).	[6]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB).	[9]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB).	[10]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB).	[3]
GDC0941	DM1YAK6	Phase 2	GDC0941 affects the activity of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB).	[11]
GDC-0980/RG7422	DMF3MV1	Phase 2	GDC-0980/RG7422 decreases the activity of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 affects the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB).	[14]
LY294002	DMY1AFS	Phase 1	LY294002 decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB).	[15]
ZSTK474	DMVIMQX	Phase 1	ZSTK474 decreases the activity of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB).	[16]
Dioscin	DM5H2W9	Preclinical	Dioscin decreases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB).	[17]
Wortmannin	DM8EVK5	Terminated	Wortmannin decreases the activity of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB).	[18]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB).	[13]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl increases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB).	[13]
Morin	DM2OGZ5	Investigative	Morin increases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB).	[19]
Methyl Mercury Ion	DM6YEW4	Investigative	Methyl Mercury Ion increases the expression of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB).	[13]
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⏷ Show the Full List of 22 Drug(s)

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB).	[7]
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References

1	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
2	Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
3	Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
4	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.
5	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
6	Arsenic trioxide reduces the expression of E2F1, cyclin E, and phosphorylation of PI3K signaling molecules in acute leukemia cells. Environ Toxicol. 2021 Sep;36(9):1785-1792. doi: 10.1002/tox.23299. Epub 2021 May 27.
7	DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
8	Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
9	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.
10	Resveratrol induces apoptosis and alters gene expression in human fibrosarcoma cells. Anticancer Res. 2015 Feb;35(2):767-74.
11	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.
12	GDC-0980 is a novel class I PI3K/mTOR kinase inhibitor with robust activity in cancer models driven by the PI3K pathway. Mol Cancer Ther. 2011 Dec;10(12):2426-36.
13	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.
14	BRD4-targeted therapy induces Myc-independent cytotoxicity in Gnaq/11-mutatant uveal melanoma cells. Oncotarget. 2015 Oct 20;6(32):33397-409. doi: 10.18632/oncotarget.5179.
15	The anti-MDR efficacy of YAN against A549/Taxol cells is associated with its inhibition on glycolysis and is further enhanced by 2-deoxy-d-glucose. Chem Biol Interact. 2022 Feb 25;354:109843. doi: 10.1016/j.cbi.2022.109843. Epub 2022 Feb 2.
16	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.
17	Molecular mechanism and inhibitory targets of dioscin in HepG2 cells. Food Chem Toxicol. 2018 Oct;120:143-154.
18	Effect of semi-synthesized quercetin water-soluble derivatives on recombinant human phosphatidylinositol 3-kinase p110beta catalytic subunit. Acta Pharmacol Sin. 2002 Apr;23(4):339-42.
19	Molecular mechanism of anti-cancerous potential of Morin extracted from mulberry in Hela cells. Food Chem Toxicol. 2018 Feb;112:466-475. doi: 10.1016/j.fct.2017.07.002. Epub 2017 Jul 6.
20	ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
21	Functional characterization of an isoform-selective inhibitor of PI3K-p110 as a potential anticancer agent. Cancer Discov. 2012 May;2(5):425-33. doi: 10.1158/2159-8290.CD-12-0003. Epub 2012 Apr 12.