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Molecule Details

General Information of the Molecule
Name
PI3-kinase beta (PIK3CB)
Synonyms
p110beta; PtdIns3kinase subunit p110beta; PtdIns3kinase subunit beta; PtdIns-3-kinase subunit p110-beta; PtdIns-3-kinase subunit beta; Phosphatidylinositol 4,5bisphosphate 3kinase catalytic subunitbeta isoform; Phosphatidylinositol 4,5bisphosphate 3kinase 110 kDa catalyticsubunit beta; Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform; Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit beta; PIK3C1; PI3kinase subunit beta; PI3Kbeta; PI3K-beta; PI3-kinase subunit beta
Gene Name
PIK3CB
Gene ID
5291
Sequence
MCFSFIMPPAMADILDIWAVDSQIASDGSIPVDFLLPTGIYIQLEVPREATISYIKQMLW
KQVHNYPMFNLLMDIDSYMFACVNQTAVYEELEDETRRLCDVRPFLPVLKLVTRSCDPGE
KLDSKIGVLIGKGLHEFDSLKDPEVNEFRRKMRKFSEEKILSLVGLSWMDWLKQTYPPEH
EPSIPENLEDKLYGGKLIVAVHFENCQDVFSFQVSPNMNPIKVNELAIQKRLTIHGKEDE
VSPYDYVLQVSGRVEYVFGDHPLIQFQYIRNCVMNRALPHFILVECCKIKKMYEQEMIAI
EAAINRNSSNLPLPLPPKKTRIISHVWENNNPFQIVLVKGNKLNTEETVKVHVRAGLFHG
TELLCKTIVSSEVSGKNDHIWNEPLEFDINICDLPRMARLCFAVYAVLDKVKTKKSTKTI
NPSKYQTIRKAGKVHYPVAWVNTMVFDFKGQLRTGDIILHSWSSFPDELEEMLNPMGTVQ
TNPYTENATALHVKFPENKKQPYYYPPFDKIIEKAAEIASSDSANVSSRGGKKFLPVLKE
ILDRDPLSQLCENEMDLIWTLRQDCREIFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPK
LPPREALELLDFNYPDQYVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFL
LERALGNRRIGQFLFWHLRSEVHIPAVSVQFGVILEAYCRGSVGHMKVLSKQVEALNKLK
TLNSLIKLNAVKLNRAKGKEAMHTCLKQSAYREALSDLQSPLNPCVILSELYVEKCKYMD
SKMKPLWLVYNNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYG
CLATGDRSGLIEVVSTSETIADIQLNSSNVAAAAAFNKDALLNWLKEYNSGDDLDRAIEE
FTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNFKSKFGIKRERVPFIL
TYDFIHVIQQGKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKD
IQYLKDSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTVRKDYRS
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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.
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Uniprot ID
PK3CB_HUMAN
EC Number
EC: 2.7.1.153
Pfam
PF00454 ; PF00792 ; PF02192 ; PF00794 ; PF00613
KEGG ID
hsa5291
TTD ID
T05031
A List of Drug Combination(s) Able to Regulate This Molecule
          Expression Regulation     Click to Show/Hide the Drug Combination Regulating This Molecule
                 Down-regulation     Click to Show/Hide
                    Drug Combination 1 Down-regulating the Expression of This Molecule [1]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Metformin   NP Info  + Nelfinavir   Drug Info 
                    Structure +
                    Drug Combination 2 Down-regulating the Expression of This Molecule [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Wogonin   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
                    Drug Combination 3 Down-regulating the Expression of This Molecule [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Bufalin   NP Info  + Sorafenib   Drug Info 
                    Structure +
                    Drug Combination 4 Down-regulating the Expression of This Molecule [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Sulforaphane   NP Info  + Acetazolamide   Drug Info 
                    Structure +
                    Drug Combination 5 Down-regulating the Expression of This Molecule [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Fisetin   NP Info  + Sorafenib   Drug Info 
                    Structure +
                    Drug Combination 6 Down-regulating the Expression of This Molecule [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Monocyte activating polypeptide II   NP Info  + Temozolomide   Drug Info 
                    Structure +
                    Drug Combination 7 Down-regulating the Expression of This Molecule [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Metformin   NP Info  + Trametinib   Drug Info 
                    Structure +
                    Drug Combination 8 Down-regulating the Expression of This Molecule [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Genistein   NP Info  + Centchroman   Drug Info 
                    Structure +
                    Drug Combination 9 Down-regulating the Expression of This Molecule [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Shikonin   NP Info  + 4-hydroxy-tamoxifen   Drug Info 
                    Structure +
                    Drug Combination 10 Down-regulating the Expression of This Molecule [10]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Ginsenoside Rg3   NP Info  + Endostar   Drug Info 
                    Structure +
                    Drug Combination 11 Down-regulating the Expression of This Molecule [11]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Kaempferol   NP Info  + Doxorubicin   Drug Info 
                    Structure +
                    Drug Combination 12 Down-regulating the Expression of This Molecule [12]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Osthole   NP Info  + Cisplatin   Drug Info 
                    Structure +
                    Drug Combination 13 Down-regulating the Expression of This Molecule [13]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Kaempferol   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
                    Drug Combination 14 Down-regulating the Expression of This Molecule [14]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Arsenic trioxide   NP Info  + Sorafenib   Drug Info 
                    Structure +
                    Drug Combination 15 Down-regulating the Expression of This Molecule [15]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Fisetin   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
                    Drug Combination 16 Down-regulating the Expression of This Molecule [16]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Semaglutide   NP Info  + Rosiglitazone   Drug Info 
                    Structure +
                    Drug Combination 17 Down-regulating the Expression of This Molecule [17]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Sulforaphane   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
                 Up-regulation     Click to Show/Hide
                    Drug Combination 1 Up-regulating the Expression of This Molecule [25]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Apocynin   NP Info  + Cyclophosphamide   Drug Info 
                    Structure +
                    Drug Combination 2 Up-regulating the Expression of This Molecule [26]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Apocynin   NP Info  + Edaravone   Drug Info 
                    Structure +
                    Drug Combination 3 Up-regulating the Expression of This Molecule [27]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Arsenic trioxide   NP Info  + Thalidomide   Drug Info 
                    Structure +
          Phosphorylation Regulation     Click to Show/Hide the Drug Combination Regulating This Molecule
                 Down-regulation     Click to Show/Hide
                    Drug Combination 1 Down-regulating the Phosphorylation of This Molecule [18]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Fucoxanthin   NP Info  + TNF-related apoptosis inducing ligand    Drug Info 
                    Structure +
                    Drug Combination 2 Down-regulating the Phosphorylation of This Molecule [19]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Costunolide   NP Info  + Doxorubicin   Drug Info 
                    Structure +
                    Drug Combination 3 Down-regulating the Phosphorylation of This Molecule [20]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Genistein   NP Info  + Cisplatin   Drug Info 
                    Structure +
                    Drug Combination 4 Down-regulating the Phosphorylation of This Molecule [21]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Cordycepin   NP Info  + Apatinib   Drug Info 
                    Structure +
                    Drug Combination 5 Down-regulating the Phosphorylation of This Molecule [22]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Nimustine hydrochloride   Drug Info 
                    Structure +
                    Drug Combination 6 Down-regulating the Phosphorylation of This Molecule [23]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Gingerol   NP Info  + Cisplatin   Drug Info 
                    Structure +
                    Drug Combination 7 Down-regulating the Phosphorylation of This Molecule [24]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Garcinol   NP Info  + Cisplatin   Drug Info 
                    Structure +
References
Reference 1 Combining metformin and nelfinavir exhibits synergistic effects against the growth of human cervical cancer cells and xenograft in nude mice. Sci Rep. 2017 Mar 2;7:43373.
Reference 2 Wogonin potentiates the antitumor effects of low dose 5-fluorouracil against gastric cancer through induction of apoptosis by down-regulation of NF-kappaB and regulation of its metabolism. Toxicol Lett. 2010 Sep 1;197(3):201-10.
Reference 3 Bufalin enhances the anti-proliferative effect of sorafenib on human hepatocellular carcinoma cells through downregulation of ERK. Mol Biol Rep. 2012 Feb;39(2):1683-9.
Reference 4 Simultaneous Targeting of Bladder Tumor Growth, Survival, and Epithelial-to-Mesenchymal Transition with a Novel Therapeutic Combination of Acetazolamide (AZ) and Sulforaphane (SFN). Target Oncol. 2016 Apr;11(2):209-27.
Reference 5 Fisetin, a phytochemical, potentiates sorafenib-induced apoptosis and abrogates tumor growth in athymic nude mice implanted with BRAF-mutated melanoma cells. Oncotarget. 2015 Sep 29;6(29):28296-311.
Reference 6 Combination of Endothelial-Monocyte-Activating Polypeptide-II with Temozolomide Suppress Malignant Biological Behaviors of Human Glioblastoma Stem Cells via miR-590-3p/MACC1 Inhibiting PI3K/AKT/mTOR Signal Pathway. Front Mol Neurosci. 2017 Mar 13;10:68.
Reference 7 Synergistic effect of MEK inhibitor and metformin combination in low grade serous ovarian cancer. Gynecol Oncol. 2017 Aug;146(2):319-326.
Reference 8 Genistein synergizes centchroman action in human breast cancer cells. Indian J Pharmacol. Nov-Dec 2016;48(6):637-642.
Reference 9 Shikonin and 4-hydroxytamoxifen synergistically inhibit the proliferation of breast cancer cells through activating apoptosis signaling pathway in vitro and in vivo. Chin Med. 2020 Mar 10;15:23.
Reference 10 Inhibiting effect of Endostar combined with ginsenoside Rg3 on breast cancer tumor growth in tumor-bearing mice. Asian Pac J Trop Med. 2016 Feb;9(2):180-3.
Reference 11 Kaempferol exhibits a synergistic effect with doxorubicin to inhibit proliferation, migration, and invasion of liver cancer. Oncol Rep. 2021 Apr;45(4):32.
Reference 12 Combination of Osthole and Cisplatin Against Rhabdomyosarcoma TE671 Cells Yielded Additive Pharmacologic Interaction by Means of Isobolographic Analysis. Anticancer Res. 2018 Jan;38(1):205-210.
Reference 13 Synergistic effect of kaempferol and 5?fluorouracil on the growth of colorectal cancer cells by regulating the PI3K/Akt signaling pathway. Mol Med Rep. 2019 Jul;20(1):728-734.
Reference 14 [Inhibitory effect of sorafenib combined with arsenic trioxide on hepatocellular carcinoma cells]. Nan Fang Yi Ke Da Xue Xue Bao. 2008 Apr;28(4):639-41.
Reference 15 Fisetin and 5-fluorouracil: Effective combination for PIK3CA-mutant colorectal cancer. Int J Cancer. 2019 Dec 1;145(11):3022-3032.
Reference 16 Combination therapy with semaglutide and rosiglitazone as a synergistic treatment for diabetic retinopathy in rodent animals. Life Sci. 2021 Mar 15;269:119013.
Reference 17 In Vitro Evaluation of Sulforaphane and a Natural Analog as Potent Inducers of 5-Fluorouracil Anticancer Activity. Molecules. 2018 Nov 21;23(11):3040.
Reference 18 Sensitization of TRAIL-resistant cervical cancer cells through combination of TRAIL and fucoxanthin treatments. Eur Rev Med Pharmacol Sci. 2017 Dec;21(24):5594-5601.
Reference 19 Costunolide enhances sensitivity of K562/ADR chronic myeloid leukemia cells to doxorubicin through PI3K/Akt pathway. Phytother Res. 2019 Jun;33(6):1683-1688.
Reference 20 Synergistic action of genistein and cisplatin on growth inhibition and cytotoxicity of human medulloblastoma cells. Pediatr Neurosurg. 2000 Sep;33(3):123-31.
Reference 21 Combination of Cordycepin and Apatinib Synergistically Inhibits NSCLC Cells by Down-Regulating VEGF/PI3K/Akt Signaling Pathway. Front Oncol. 2020 Sep 7;10:1732.
Reference 22 Curcumin potentiates the potent antitumor activity of ACNU against glioblastoma by suppressing the PI3K/AKT and NF-kappaB/COX-2 signaling pathways. Onco Targets Ther. 2017 Nov 15;10:5471-5482.
Reference 23 [6]-Gingerol enhances the cisplatin sensitivity of gastric cancer cells through inhibition of proliferation and invasion via PI3K/AKT signaling pathway. Phytother Res. 2019 May;33(5):1353-1362.
Reference 24 Garcinol Alone and in Combination With Cisplatin Affect Cellular Behavior and PI3K/AKT Protein Phosphorylation in Human Ovarian Cancer Cells. Dose Response. 2020 May 19;18(2):1559325820926732.
Reference 25 Acetovanillone prevents cyclophosphamide-induced acute lung injury by modulating PI3K/Akt/mTOR and Nrf2 signaling in rats. Phytother Res. 2021 May 9.
Reference 26 Edaravone and Acetovanillone Upregulate Nrf2 and PI3K/Akt/mTOR Signaling and Prevent Cyclophosphamide Cardiotoxicity in Rats. Drug Des Devel Ther. 2020 Nov 30;14:5275-5288.
Reference 27 Inhibitory Effects of Arsenic Trioxide and Thalidomide on Angiogenesis and Vascular Endothelial Growth Factor Expression in Leukemia Cells. Asian Pac J Cancer Prev. 2018 Apr 27;19(4):1127-1134.
Cite NPCDR
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Correspondence

X. N. Sun, Y. T. Zhang, Y. Zhou, X. C. Lian, L. L. Yan, T. Pan, T. Jin, H. Xie, Z. M. Liang, W. Q. Qiu, J. X. Wang, Z. R. Li, F. Zhu*, X. B. Sui*. NPCDR: natural product-based drug combination and its disease-specific molecular regulation. Nucleic Acids Research. 50(D1): 1324-1333 (2020). PMID: 34664659

Prof. Feng ZHU  (zhufeng@zju.edu.cn)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China


Prof. Xinbing SUI  (hzzju@hznu.edu.cn)

School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China