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Molecule Details

General Information of the Molecule
Name
Serine/threonine-protein kinase mTOR (mTOR)
Synonyms
Target of rapamycin; TOR kinase; Rapamycin target protein 1; Rapamycin target protein; Rapamycin and FKBP12 target 1; RAPT1; RAFT1; Mechanistic target of rapamycin; Mammalian target of rapamycin; FRAP2; FRAP1; FRAP; FKBP12-rapamycin complex-associated protein; FKBP-rapamycin associated protein; FK506-binding protein 12-rapamycin complex-associated protein 1
Gene Name
MTOR
Gene ID
2475
Sequence
MLGTGPAAATTAATTSSNVSVLQQFASGLKSRNEETRAKAAKELQHYVTMELREMSQEES
TRFYDQLNHHIFELVSSSDANERKGGILAIASLIGVEGGNATRIGRFANYLRNLLPSNDP
VVMEMASKAIGRLAMAGDTFTAEYVEFEVKRALEWLGADRNEGRRHAAVLVLRELAISVP
TFFFQQVQPFFDNIFVAVWDPKQAIREGAVAALRACLILTTQREPKEMQKPQWYRHTFEE
AEKGFDETLAKEKGMNRDDRIHGALLILNELVRISSMEGERLREEMEEITQQQLVHDKYC
KDLMGFGTKPRHITPFTSFQAVQPQQSNALVGLLGYSSHQGLMGFGTSPSPAKSTLVESR
CCRDLMEEKFDQVCQWVLKCRNSKNSLIQMTILNLLPRLAAFRPSAFTDTQYLQDTMNHV
LSCVKKEKERTAAFQALGLLSVAVRSEFKVYLPRVLDIIRAALPPKDFAHKRQKAMQVDA
TVFTCISMLARAMGPGIQQDIKELLEPMLAVGLSPALTAVLYDLSRQIPQLKKDIQDGLL
KMLSLVLMHKPLRHPGMPKGLAHQLASPGLTTLPEASDVGSITLALRTLGSFEFEGHSLT
QFVRHCADHFLNSEHKEIRMEAARTCSRLLTPSIHLISGHAHVVSQTAVQVVADVLSKLL
VVGITDPDPDIRYCVLASLDERFDAHLAQAENLQALFVALNDQVFEIRELAICTVGRLSS
MNPAFVMPFLRKMLIQILTELEHSGIGRIKEQSARMLGHLVSNAPRLIRPYMEPILKALI
LKLKDPDPDPNPGVINNVLATIGELAQVSGLEMRKWVDELFIIIMDMLQDSSLLAKRQVA
LWTLGQLVASTGYVVEPYRKYPTLLEVLLNFLKTEQNQGTRREAIRVLGLLGALDPYKHK
VNIGMIDQSRDASAVSLSESKSSQDSSDYSTSEMLVNMGNLPLDEFYPAVSMVALMRIFR
DQSLSHHHTMVVQAITFIFKSLGLKCVQFLPQVMPTFLNVIRVCDGAIREFLFQQLGMLV
SFVKSHIRPYMDEIVTLMREFWVMNTSIQSTIILLIEQIVVALGGEFKLYLPQLIPHMLR
VFMHDNSPGRIVSIKLLAAIQLFGANLDDYLHLLLPPIVKLFDAPEAPLPSRKAALETVD
RLTESLDFTDYASRIIHPIVRTLDQSPELRSTAMDTLSSLVFQLGKKYQIFIPMVNKVLV
RHRINHQRYDVLICRIVKGYTLADEEEDPLIYQHRMLRSGQGDALASGPVETGPMKKLHV
STINLQKAWGAARRVSKDDWLEWLRRLSLELLKDSSSPSLRSCWALAQAYNPMARDLFNA
AFVSCWSELNEDQQDELIRSIELALTSQDIAEVTQTLLNLAEFMEHSDKGPLPLRDDNGI
VLLGERAAKCRAYAKALHYKELEFQKGPTPAILESLISINNKLQQPEAAAGVLEYAMKHF
GELEIQATWYEKLHEWEDALVAYDKKMDTNKDDPELMLGRMRCLEALGEWGQLHQQCCEK
WTLVNDETQAKMARMAAAAAWGLGQWDSMEEYTCMIPRDTHDGAFYRAVLALHQDLFSLA
QQCIDKARDLLDAELTAMAGESYSRAYGAMVSCHMLSELEEVIQYKLVPERREIIRQIWW
ERLQGCQRIVEDWQKILMVRSLVVSPHEDMRTWLKYASLCGKSGRLALAHKTLVLLLGVD
PSRQLDHPLPTVHPQVTYAYMKNMWKSARKIDAFQHMQHFVQTMQQQAQHAIATEDQQHK
QELHKLMARCFLKLGEWQLNLQGINESTIPKVLQYYSAATEHDRSWYKAWHAWAVMNFEA
VLHYKHQNQARDEKKKLRHASGANITNATTAATTAATATTTASTEGSNSESEAESTENSP
TPSPLQKKVTEDLSKTLLMYTVPAVQGFFRSISLSRGNNLQDTLRVLTLWFDYGHWPDVN
EALVEGVKAIQIDTWLQVIPQLIARIDTPRPLVGRLIHQLLTDIGRYHPQALIYPLTVAS
KSTTTARHNAANKILKNMCEHSNTLVQQAMMVSEELIRVAILWHEMWHEGLEEASRLYFG
ERNVKGMFEVLEPLHAMMERGPQTLKETSFNQAYGRDLMEAQEWCRKYMKSGNVKDLTQA
WDLYYHVFRRISKQLPQLTSLELQYVSPKLLMCRDLELAVPGTYDPNQPIIRIQSIAPSL
QVITSKQRPRKLTLMGSNGHEFVFLLKGHEDLRQDERVMQLFGLVNTLLANDPTSLRKNL
SIQRYAVIPLSTNSGLIGWVPHCDTLHALIRDYREKKKILLNIEHRIMLRMAPDYDHLTL
MQKVEVFEHAVNNTAGDDLAKLLWLKSPSSEVWFDRRTNYTRSLAVMSMVGYILGLGDRH
PSNLMLDRLSGKILHIDFGDCFEVAMTREKFPEKIPFRLTRMLTNAMEVTGLDGNYRITC
HTVMEVLREHKDSVMAVLEAFVYDPLLNWRLMDTNTKGNKRSRTRTDSYSAGQSVEILDG
VELGEPAHKKTGTTVPESIHSFIGDGLVKPEALNKKAIQIINRVRDKLTGRDFSHDDTLD
VPTQVELLIKQATSHENLCQCYIGWCPFW
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Function
MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B, and the inhibitor of translation initiation PDCD4. Stimulates the pyrimidine biosynthesis pathway, both by acute regulation through RPS6KB1-mediated phosphorylation of the biosynthetic enzyme CAD, and delayed regulation, through transcriptional enhancement of the pentose phosphate pathway which produces 5-phosphoribosyl-1-pyrophosphate (PRPP), an allosteric activator of CAD at a later step in synthesis, this function is dependent on the mTORC1 complex. Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor. In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1. To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A. mTORC1 also negatively regulates autophagy through phosphorylation of ULK1. Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1. Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP. Also prevents autophagy by phosphorylating RUBCNL/Pacer under nutrient-rich conditions. mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor. Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules. As part of the mTORC2 complex MTOR may regulate other cellular processes including survival and organization of the cytoskeleton. Plays a critical role in the phosphorylation at 'Ser-473' of AKT1, a pro-survival effector of phosphoinositide 3-kinase, facilitating its activation by PDK1. mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B. mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422'. Regulates osteoclastogenesis by adjusting the expression of CEBPB isoforms. Plays an important regulatory role in the circadian clock function; regulates period length and rhythm amplitude of the suprachiasmatic nucleus (SCN) and liver clocks. Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
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Uniprot ID
MTOR_HUMAN
EC Number
EC: 2.7.11.1
Pfam
PF11865 ; PF02259 ; PF02260 ; PF08771 ; PF00454
KEGG ID
hsa2475
TTD ID
T75243
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 Bufalin   NP Info  + Sorafenib   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 Sulforaphane   NP Info  + Acetazolamide   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 Fisetin   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 Tanshinone IIA   NP Info  + Nutlin-3   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 Vinblastine   NP Info  + Temsirolimus   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 Cardamonin   NP Info  + Cisplatin   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  + Torin 2   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 Curcumin   NP Info  + Temozolomide   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 Thymoquinone   NP Info  + Gemcitabine   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 Betulinic Acid   NP Info  + Sorafenib   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 Ginsenoside Rg3   NP Info  + Endostar   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 Kaempferol   NP Info  + Doxorubicin   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 Oridonin   NP Info  + Imatinib   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 Metformin   NP Info  + Everolimus   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 Epigallocatechin gallate   NP Info  + Tamoxifen   Drug Info 
                    Structure +
                 Up-regulation     Click to Show/Hide
                    Drug Combination 1 Up-regulating the Expression of This Molecule [37]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Oridonin   NP Info  + Cetuximab   Drug Info 
                    Structure +
                    Drug Combination 2 Up-regulating the Expression of This Molecule [38]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Apocynin   NP Info  + Cyclophosphamide   Drug Info 
                    Structure +
                    Drug Combination 3 Up-regulating the Expression of This Molecule [39]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Apocynin   NP Info  + Edaravone   Drug Info 
                    Structure +
                    Drug Combination 4 Up-regulating the Expression of This Molecule [40]
                    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 Curcumin   NP Info  + 5-fluorouracil   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 Epigallocatechin gallate   NP Info  + Raloxifene   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 Resveratrol   NP Info  + Doxorubicin   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 Bufalin   NP Info  + Gefitinib   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 Genistein   NP Info  + Cisplatin   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 Lycopene   NP Info  + Eicosapentaenoic acid   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 Allyl isothiocyanate   NP Info  + Cisplatin   Drug Info 
                    Structure +
                    Drug Combination 8 Down-regulating the Phosphorylation of This Molecule [25]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Gossypol   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
                    Drug Combination 9 Down-regulating the Phosphorylation of This Molecule [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Cardamonin   NP Info  + Cisplatin   Drug Info 
                    Structure +
                    Drug Combination 10 Down-regulating the Phosphorylation of This Molecule [26]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Arsenic trioxide   NP Info  + Androgen   Drug Info 
                    Structure +
                    Drug Combination 11 Down-regulating the Phosphorylation of This Molecule [27]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Genistein   NP Info  + Gefitinib   Drug Info 
                    Structure +
                    Drug Combination 12 Down-regulating the Phosphorylation of This Molecule [28]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Norcantharidin   NP Info  + Crizotinib   Drug Info 
                    Structure +
                    Drug Combination 13 Down-regulating the Phosphorylation of This Molecule [29]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Artesunate   NP Info  + Sorafenib   Drug Info 
                    Structure +
                    Drug Combination 14 Down-regulating the Phosphorylation of This Molecule [30]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Emodin   NP Info  + Cytarabine   Drug Info 
                    Structure +
                    Drug Combination 15 Down-regulating the Phosphorylation of This Molecule [31]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Shikonin   NP Info  + Doxorubicin   Drug Info 
                    Structure +
                    Drug Combination 16 Down-regulating the Phosphorylation of This Molecule [32]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Tamoxifen   Drug Info 
                    Structure +
                    Drug Combination 17 Down-regulating the Phosphorylation of This Molecule [33]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Resveratrol   NP Info  + Temozolomide   Drug Info 
                    Structure +
                    Drug Combination 18 Down-regulating the Phosphorylation of This Molecule [34]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Triptolide   NP Info  + BIIB021   Drug Info 
                    Structure +
                    Drug Combination 19 Down-regulating the Phosphorylation of This Molecule [35]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Fisetin   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
                    Drug Combination 20 Down-regulating the Phosphorylation of This Molecule [36]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Resveratrol   NP Info  + Rapamycin   Drug Info 
                    Structure +
                 Up-regulation     Click to Show/Hide
                    Drug Combination 1 Up-regulating the Phosphorylation of This Molecule [37]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Oridonin   NP Info  + Cetuximab   Drug Info 
                    Structure +
Natural Product(s) of This Target
1 Cucurbitacin B  NP Info  Investigative Cucurbitaceae
2 Paeonol  NP Info  Investigative Paeonia suffruticosa
Drug(s) of This Target
1 Dactolisib  Drug Info  Phase 2 Solid tumour/cancer
2 Everolimus  Drug Info  Approved Renal cell carcinoma
3 Glasdegib  Drug Info  Approved Chronic myelomonocytic leukaemia
4 PP242  Drug Info  Investigative Colon cancer
5 Rapamycin  Drug Info  Approved Multiple myeloma
6 S-farnesylthiosalicylic acid  Drug Info  Phase 2 Lung cancer
7 Temsirolimus  Drug Info  Approved Renal cell carcinoma
8 Torin 2  Drug Info  Investigative Mature T-cell lymphoma
References
Reference 1 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 2 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 3 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 4 The combination of Nutlin-3 and Tanshinone IIA promotes synergistic cytotoxicity in acute leukemic cells expressing wild-type p53 by co-regulating MDM2-P53 and the AKT/mTOR pathway. Int J Biochem Cell Biol. 2019 Jan;106:8-20.
Reference 5 Sustained antitumor activity by co-targeting mTOR and the microtubule with temsirolimus/vinblastine combination in hepatocellular carcinoma. Biochem Pharmacol. 2012 May 1;83(9):1146-58.
Reference 6 Cardamonin enhances the anti-proliferative effect of cisplatin on ovarian cancer. Oncol Lett. 2018 Mar;15(3):3991-3997.
Reference 7 The Synergistic Effect of an ATP-Competitive Inhibitor of mTOR and Metformin on Pancreatic Tumor Growth. Curr Dev Nutr. 2020 Aug 10;4(9):nzaa131.
Reference 8 Curcumin sensitizes glioblastoma to temozolomide by simultaneously generating ROS and disrupting AKT/mTOR signaling. Oncol Rep. 2014 Oct;32(4):1610-6.
Reference 9 Thymoquinone Pretreatment Overcomes the Insensitivity and Potentiates the Antitumor Effect of Gemcitabine Through Abrogation of Notch1, PI3K/Akt/mTOR Regulated Signaling Pathways in Pancreatic Cancer. Dig Dis Sci. 2015 Apr;60(4):1067-80.
Reference 10 Synergistic activity of sorafenib and betulinic acid against clonogenic activity of non-small cell lung cancer cells. Cancer Sci. 2017 Nov;108(11):2265-2272.
Reference 11 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 12 Kaempferol exhibits a synergistic effect with doxorubicin to inhibit proliferation, migration, and invasion of liver cancer. Oncol Rep. 2021 Apr;45(4):32.
Reference 13 Oridonin in combination with imatinib exerts synergetic anti-leukemia effect in Ph+ acute lymphoblastic leukemia cells in vitro by inhibiting activation of LYN/mTOR signaling pathway. Cancer Biol Ther. 2012 Nov;13(13):1244-54.
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 Metformin and Everolimus: A Promising Combination for Neuroendocrine Tumors Treatment. Cancers (Basel). 2020 Aug 2;12(8):2143.
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 Tamoxifen and epigallocatechin gallate are synergistically cytotoxic to MDA-MB-231 human breast cancer cells. Anticancer Drugs. 2004 Oct;15(9):889-97.
Reference 18 Curcumin enhances cytotoxicity of chemotherapeutic agents in prostate cancer cells by inducing p21(WAF1/CIP1) and C/EBPbeta expressions and suppressing NF-kappaB activation. Prostate. 2002 May 15;51(3):211-8.
Reference 19 The combination of raloxifene and epigallocatechin gallate suppresses growth and induces apoptosis in MDA-MB-231 cells. Life Sci. 2008 Apr 23;82(17-18):943-8.
Reference 20 Resveratrol enhances the cytotoxic profile of docetaxel and doxorubicin in solid tumour cell lines in vitro. Cell Prolif. 2011 Dec;44(6):591-601.
Reference 21 [Effect of bufalin combined gefitinib on lung cancer H1975 cells and its mechanisms research]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2013 Aug;33(8):1081-5.
Reference 22 Synergistic action of genistein and cisplatin on growth inhibition and cytotoxicity of human medulloblastoma cells. Pediatr Neurosurg. 2000 Sep;33(3):123-31.
Reference 23 Concomitant supplementation of lycopene and eicosapentaenoic acid inhibits the proliferation of human colon cancer cells. J Nutr Biochem. 2009 Jun;20(6):426-34.
Reference 24 Synergistic effect of allyl isothiocyanate (AITC) on cisplatin efficacy in vitro and in vivo. Am J Cancer Res. 2015 Jul 15;5(8):2516-30.
Reference 25 Gossypol sensitizes the antitumor activity of 5-FU through down-regulation of thymidylate synthase in human colon carcinoma cells. Cancer Chemother Pharmacol. 2015 Sep;76(3):575-86.
Reference 26 Arsenic trioxide enhances the radiation sensitivity of androgen-dependent and -independent human prostate cancer cells. PLoS One. 2012;7(2):e31579.
Reference 27 Synergistic inhibitory effects by the combination of gefitinib and genistein on NSCLC with acquired drug-resistance in vitro and in vivo. Mol Biol Rep. 2012 Apr;39(4):4971-9.
Reference 28 Norcantharidin alone or in combination with crizotinib induces autophagic cell death in hepatocellular carcinoma by repressing c-Met-mTOR signaling. Oncotarget. 2017 Dec 4;8(70):114945-114955.
Reference 29 Artesunate promotes sensitivity to sorafenib in hepatocellular carcinoma. Biochem Biophys Res Commun. 2019 Oct 29;519(1):41-45.
Reference 30 Emodin and Its Combination with Cytarabine Induce Apoptosis in Resistant Acute Myeloid Leukemia Cells in Vitro and in Vivo. Cell Physiol Biochem. 2018;48(5):2061-2073.
Reference 31 Shikonin promotes adriamycin?induced apoptosis by upregulating caspase?3 and caspase?8 in osteosarcoma. Mol Med Rep. 2017 Aug;16(2):1347-1352.
Reference 32 Curcumin induces cell death and restores tamoxifen sensitivity in the antiestrogen-resistant breast cancer cell lines MCF-7/LCC2 and MCF-7/LCC9. Molecules. 2013 Jan 8;18(1):701-20.
Reference 33 Resveratrol enhances the antitumor effects of temozolomide in glioblastoma via ROS-dependent AMPK-TSC-mTOR signaling pathway. CNS Neurosci Ther. 2012 Jul;18(7):536-46.
Reference 34 Synergistic cytotoxicity of BIIB021 with triptolide through suppression of PI3K/Akt/mTOR and NF-KappaB signal pathways in thyroid carcinoma cells. Biomed Pharmacother. 2016 Oct;83:22-32.
Reference 35 Fisetin and 5-fluorouracil: Effective combination for PIK3CA-mutant colorectal cancer. Int J Cancer. 2019 Dec 1;145(11):3022-3032.
Reference 36 Resveratrol enhances the anti-tumor activity of the mTOR inhibitor rapamycin in multiple breast cancer cell lines mainly by suppressing rapamycin-induced AKT signaling. Cancer Lett. 2011 Feb 28;301(2):168-76.
Reference 37 Molecular mechanisms of apoptosis and autophagy elicited by combined treatment with oridonin and cetuximab in laryngeal squamous cell carcinoma. Apoptosis. 2019 Feb;24(1-2):33-45.
Reference 38 Acetovanillone prevents cyclophosphamide-induced acute lung injury by modulating PI3K/Akt/mTOR and Nrf2 signaling in rats. Phytother Res. 2021 May 9.
Reference 39 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.
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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