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Molecule Details

General Information of the Molecule
Name
Tumor necrosis factor (TNF)
Synonyms
Tumour necrosis factor alpha; Tumour necrosis factor; Tumor necrosis factor ligand superfamily member 2; TNFalpha; TNFSF2; TNFA; TNF-alpha; TNF-a; TNF alpha; Cachectin
Gene Name
TNF
Gene ID
7124
Sequence
MSTESMIRDVELAEEALPKKTGGPQGSRRCLFLSLFSFLIVAGATTLFCLLHFGVIGPQR
EEFPRDLSLISPLAQAVRSSSRTPSDKPVAHVVANPQAEGQLQWLNRRANALLANGVELR
DNQLVVPSEGLYLIYSQVLFKGQGCPSTHVLLTHTISRIAVSYQTKVNLLSAIKSPCQRE
TPEGAEAKPWYEPIYLGGVFQLEKGDRLSAEINRPDYLDFAESGQVYFGIIAL
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Function
It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Upregulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key 'Ser-418' residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective. Key mediator of cell death in the anticancer action of BCG-stimulated neutrophils in combination with DIABLO/SMAC mimetic in the RT4v6 bladder cancer cell line. Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance. Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR.
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Uniprot ID
TNFA_HUMAN
Pfam
PF00229
KEGG ID
hsa7124
TTD ID
T20178
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 Polydatin   NP Info  + N-palmitoylethanolamine   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 Thymoquinone   NP Info  + Bortezomib   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 Gentiopicroside + Leflunomide + Methotrexate
    Click to Show/Hide the Each NP or Drug Structure of This Combination
Gentiopicroside   NP Info     Drug Info 
   Drug Info 
                    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 Acteoside   NP Info  + Thymic stromal lymphopoietin   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 Ferulic acid   NP Info  + Atorvastatin   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 Apigenin   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 Trandolapril   NP Info  + Paricalcitol   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 Sesquiterpene lactone   NP Info  + Benznidazole   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 Epigallocatechin gallate   NP Info  + Cisplatin   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 Glatiramer acetate   NP Info  + Atorvastatin   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 Urolithin A   NP Info  + Cisplatin   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 Acovenoside A   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 Acteoside   NP Info  + Dextran sulfate sodium   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 Vitamin C + Diazinon + Ceftriaxone
    Click to Show/Hide the Each NP or Drug Structure of This Combination
Vitamin C   NP Info     Drug Info 
   Drug Info 
                    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 Semaglutide   NP Info  + Rosiglitazone   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 Acarbose   NP Info  + Cyclosporin   Drug Info 
                    Structure +
                 Up-regulation     Click to Show/Hide
                    Drug Combination 1 Up-regulating the Expression of This Molecule [18]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Miltefosine   NP Info  + Paromomycin   Drug Info 
                    Structure +
                    Drug Combination 2 Up-regulating the Expression of This Molecule [19]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Metformin   NP Info  + Sorafenib   Drug Info 
                    Structure +
                    Drug Combination 3 Up-regulating the Expression of This Molecule [20]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Vincristine   NP Info  + Combretastatin A-4 phosphate   Drug Info 
                    Structure +
                    Drug Combination 4 Up-regulating the Expression of This Molecule [21]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Anti-PD-1 antibody   Drug Info 
                    Structure +
          Secretion Regulation     Click to Show/Hide the Drug Combination Regulating This Molecule
                 Down-regulation     Click to Show/Hide
                    Drug Combination 1 Down-regulating the Secretion of This Molecule [17]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Aloin   NP Info  + Doxorubicin   Drug Info 
                    Structure +
Natural Product(s) of This Target
1 Astilbin  NP Info  Investigative Smilax glabra
2 Celastrol  NP Info  Preclinical Celastrus strigillosus
3 Magnolol  NP Info  Investigative Magnolia officinalis
4 Osthole  NP Info  Investigative Angelica pubescens
Drug(s) of This Target
1 Lenalidomide  Drug Info  Approved Multiple myeloma
2 Thalidomide  Drug Info  Approved Multiple myeloma
References
Reference 1 Palmitoylethanolamide and Polydatin combination reduces inflammation and oxidative stress in vascular injury. Pharmacol Res. 2017 Sep;123:83-92.
Reference 2 Thymoquinone overcomes chemoresistance and enhances the anticancer effects of bortezomib through abrogation of NF-KappaB regulated gene products in multiple myeloma xenograft mouse model. Oncotarget. 2014 Feb 15;5(3):634-48.
Reference 3 Hepatoprotective effect of gentiopicroside in combination with leflunomide and/or methotrexate in arthritic rats. Life Sci. 2021 Jan 15;265:118689.
Reference 4 Acteoside attenuates TSLP-induced mast cell proliferation via down-regulating MDM2. Int Immunopharmacol. 2015 May;26(1):23-9.
Reference 5 Promising role of ferulic acid, atorvastatin and their combination in ameliorating high fat diet-induced stress in mice. Life Sci. 2013 May 20;92(17-19):938-49.
Reference 6 Protective effects of apigenin and myricetin against cisplatin-induced nephrotoxicity in mice. Pharm Biol. 2017 Dec;55(1):766-774.
Reference 7 Combination therapy with paricalcitol and trandolapril reduces renal fibrosis in obstructive nephropathy. Kidney Int. 2009 Dec;76(12):1248-57.
Reference 8 Sesquiterpene lactone potentiates the immunomodulatory, antiparasitic and cardioprotective effects on anti-Trypanosoma cruzi specific chemotherapy. Int Immunopharmacol. 2019 Dec;77:105961.
Reference 9 Reversal of Cisplatin resistance by epigallocatechin gallate is mediated by downregulation of axl and tyro 3 expression in human lung cancer cells. Korean J Physiol Pharmacol. 2014 Feb;18(1):61-6.
Reference 10 Immunomodulatory synergy by combination of atorvastatin and glatiramer acetate in treatment of CNS autoimmunity. J Clin Invest. 2006 Apr;116(4):1037-44.
Reference 11 Protective effect of urolithin a on cisplatin-induced nephrotoxicity in mice via modulation of inflammation and oxidative stress. Food Chem Toxicol. 2019 Jul;129:108-114.
Reference 12 The Cardenolide Glycoside Acovenoside A Affords Protective Activity in Doxorubicin-Induced Cardiotoxicity in Mice. J Pharmacol Exp Ther. 2016 Aug;358(2):262-70.
Reference 13 In vivo treatment with the herbal phenylethanoid acteoside ameliorates intestinal inflammation in dextran sulphate sodium-induced colitis. Clin Exp Immunol. 2007 May;148(2):373-81.
Reference 14 Synergistic protective role of ceftriaxone and ascorbic acid against subacute diazinon-induced nephrotoxicity in rats. Cytotechnology. 2016 Mar;68(2):279-89.
Reference 15 Combination therapy with semaglutide and rosiglitazone as a synergistic treatment for diabetic retinopathy in rodent animals. Life Sci. 2021 Mar 15;269:119013.
Reference 16 Combination Therapy of Acarbose and Cyclosporine a Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis in Mice. Molecules. 2020 Apr 16;25(8):1822.
Reference 17 Aloin alleviates doxorubicin-induced cardiotoxicity in rats by abrogating oxidative stress and pro-inflammatory cytokines. Cancer Chemother Pharmacol. 2020 Sep;86(3):419-426.
Reference 18 Combination of paromomycin and miltefosine promotes TLR4-dependent induction of antileishmanial immune response in vitro. J Antimicrob Chemother. 2012 Oct;67(10):2373-8.
Reference 19 Synergistic effect of metformin on sorafenib in in vitro study using hepatocellular carcinoma cell lines. Ann Hepatobiliary Pancreat Surg. 2018 Aug;22(3):179-184.
Reference 20 Enhanced anticancer effect of Combretastatin A-4 phosphate when combined with vincristine in the treatment of hepatocellular carcinoma. Biomed Pharmacother. 2017 May;89:36-46.
Reference 21 Synergistic efficacy of curcumin and anti-programmed cell death-1 in hepatocellular carcinoma. Life Sci. 2021 Mar 19;279:119359.
Reference 22 Astilbin ameliorates cisplatin-induced nephrotoxicity through reducing oxidative stress and inflammation. Food Chem Toxicol. 2018 Apr;114:227-236.
Reference 23 Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52.
Reference 24 Magnolol exhibits anti-inflammatory and neuroprotective effects in a rat model of intracerebral haemorrhage. Brain Behav Immun. 2019 Mar;77:161-167.
Reference 25 Osthole confers neuroprotection against cortical stab wound injury and attenuates secondary brain injury. J Neuroinflammation. 2015 Sep 4;12:155.
Reference 26 Thalidomide and thalidomide analogues for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD007351.
Reference 27 Efficacy of different thalidomide regimens for patients with multiple myeloma and its relationship with TNF-alpha level. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008 Dec;16(6):1312-5.
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