Target Information

Target General Information

Target ID

T20178 (Former ID: TTDS00131)

Target 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

Target Type

Successful target

[1]

Disease

[+] 5 Target-related Diseases

Arterial occlusive disease [ICD-11: BD40]

Multiple myeloma [ICD-11: 2A83]

Pancreatitis [ICD-11: DC31-DC34]

Psoriasis [ICD-11: EA90]

Rheumatoid arthritis [ICD-11: FA20]

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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BioChemical Class

Cytokine: tumor necrosis factor

UniProt ID

TNFA_HUMAN

Sequence

MSTESMIRDVELAEEALPKKTGGPQGSRRCLFLSLFSFLIVAGATTLFCLLHFGVIGPQR
EEFPRDLSLISPLAQAVRSSSRTPSDKPVAHVVANPQAEGQLQWLNRRANALLANGVELR
DNQLVVPSEGLYLIYSQVLFKGQGCPSTHVLLTHTISRIAVSYQTKVNLLSAIKSPCQRE
TPEGAEAKPWYEPIYLGGVFQLEKGDRLSAEINRPDYLDFAESGQVYFGIIAL

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3D Structure

Click to Show 3D Structure of This Target

AlphaFold

ADReCS ID

BADD_A00402 ; BADD_A02863 ; BADD_A03065 ; BADD_A03633 ; BADD_A04357 ; BADD_A05322 ; BADD_A05438 ; BADD_A05639 ; BADD_A05823 ; BADD_A05962

HIT2.0 ID

T23VMI

Drugs and Modes of Action

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Approved Drug(s)

[+] 10 Approved Drugs

Adalimumab

Drug Info

Approved

Rheumatoid arthritis

[2], [3]

Certolizumab

Drug Info

Approved

Rheumatoid arthritis

[4]

Enbrel

Drug Info

Approved

Arthritis

[5]

Etanercept

Drug Info

Approved

Arthritis

[6]

Golimumab

Drug Info

Approved

Rheumatoid arthritis

[7]

Infliximab

Drug Info

Approved

Plaque psoriasis

[8], [9], [10]

Lenalidomide

Drug Info

Approved

Multiple myeloma

[11], [12], [13], [14]

Nafamostat

Drug Info

Approved

Pancreatitis

[15], [14]

Pentoxifylline

Drug Info

Approved

Intermittent claudication

[16], [17]

Thalidomide

Drug Info

Approved

Multiple myeloma

[18], [19]

Clinical Trial Drug(s)

[+] 24 Clinical Trial Drugs

ABP 501

Drug Info

Phase 3

Rheumatoid arthritis

[20]

CPL-7075

Drug Info

Phase 3

Diffuse systemic sclerosis

[21]

Golnerminogene pradenovac

Drug Info

Phase 3

Esophageal cancer

[22]

PF-06410293

Drug Info

Phase 3

Rheumatoid arthritis

[23]

PF-06438179

Drug Info

Phase 3

Rheumatoid arthritis

[23]

ABT-122

Drug Info

Phase 2

Rheumatoid arthritis

[24], [25], [23]

AN0128

Drug Info

Phase 2

Psoriatic disorder

[26]

AP-301-IH

Drug Info

Phase 2

Pneumonia

[27]

BAICALEIN

Drug Info

Phase 2

Influenza virus infection

[28]

DLX-105

Drug Info

Phase 2

Osteoarthritis

[29]

ESBA-105

Drug Info

Phase 2

Ocular disease

[30]

Ortataxel

Drug Info

Phase 2

Solid tumour/cancer

[31]

Pegsunercept

Drug Info

Phase 2

Rheumatoid arthritis

[32]

RDP58

Drug Info

Phase 2

Diarrhea

[33]

TNF alpha kinoid

Drug Info

Phase 2

Autoimmune diabetes

[34]

COVA322

Drug Info

Phase 1/2a

Psoriasis vulgaris

[35]

ART621

Drug Info

Phase 1/2

Psoriasis vulgaris

[36]

ABBV-257

Drug Info

Phase 1

Rheumatoid arthritis

[23]

AST-005

Drug Info

Phase 1

Psoriasis vulgaris

[37], [23]

AVX-470

Drug Info

Phase 1

Inflammatory bowel disease

[38]

CYT-609

Drug Info

Phase 1

Solid tumour/cancer

[39]

INB03

Drug Info

Phase 1

Solid tumour/cancer

[40]

PF-05230905

Drug Info

Phase 1

Rheumatoid arthritis

[41]

PMI-005

Drug Info

Phase 1

Osteoarthritis

[42]

Discontinued Drug(s)

[+] 10 Discontinued Drugs

CDP571

Drug Info

Discontinued in Phase 3

Crohn disease

[43]

Segard

Drug Info

Discontinued in Phase 3

Sepsis

[44]

Camobucol

Drug Info

Discontinued in Phase 2

Rheumatoid arthritis

[45]

CRx-191

Drug Info

Discontinued in Phase 2

Psoriatic disorder

[46]

AME-527

Drug Info

Discontinued in Phase 1/2

Rheumatoid arthritis

[47]

CYT-007-TNFQb

Drug Info

Discontinued in Phase 1/2

Allergic rhinitis

[48]

ALS-00T2-0501

Drug Info

Discontinued in Phase 1

Psoriasis vulgaris

[49]

FR-133605

Drug Info

Terminated

Arthritis

[52]

MDL-201112

Drug Info

Terminated

Colitis

[53]

TNFQb therapeutic vaccines

Drug Info

Terminated

Crohn disease

[54]

Preclinical Drug(s)

[+] 2 Preclinical Drugs

ABX-0401

Drug Info

Preclinical

Inflammatory bowel disease

[50]

Celastrol

Drug Info

Preclinical

Motor neurone disease

[51]

Mode of Action

[+] 3 Modes of Action

Inhibitor

[+] 28 Inhibitor drugs

Certolizumab

Drug Info

[4]

Lenalidomide

Drug Info

[58], [59]

Thalidomide

Drug Info

[63]

CPL-7075

Drug Info

[65]

PF-06438179

Drug Info

[68]

AN0128

Drug Info

[70], [71], [72]

AP-301-IH

Drug Info

[73]

BAICALEIN

Drug Info

[74]

Ortataxel

Drug Info

[77]

Pegsunercept

Drug Info

[78]

RDP58

Drug Info

[33]

ART621

Drug Info

[36]

ABBV-257

Drug Info

[23]

AST-005

Drug Info

[37], [23]

AVX-470

Drug Info

[23]

INB03

Drug Info

[40]

PF-05230905

Drug Info

[82]

PMI-005

Drug Info

[83]

Camobucol

Drug Info

[86]

CRx-191

Drug Info

[87]

CYT-007-TNFQb

Drug Info

[89]

ABX-0401

Drug Info

[91]

MDL-201112

Drug Info

[92]

2-Propanol, Isopropanol

Drug Info

[93]

IK-862

Drug Info

[95]

PKF-241-466

Drug Info

[96]

PKF-242-484

Drug Info

[96]

Y-39041

Drug Info

[97]

Modulator

[+] 10 Modulator drugs

Enbrel

Drug Info

[5]

Etanercept

Drug Info

[55], [56]

Golnerminogene pradenovac

Drug Info

[66]

ABT-122

Drug Info

[69]

COVA322

Drug Info

[80]

CYT-609

Drug Info

[81]

CDP571

Drug Info

[84]

ALS-00T2-0501

Drug Info

[90]

FR-133605

Drug Info

[52]

DOM-0215

Drug Info

[94]

Suppressor

[+] 1 Suppressor drugs

Celastrol

Drug Info

[51]

Chemical Structure based Activity Landscape of Target

Top

Drug Property Profile of Target

Top

(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

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Co-Targets

Co-Targets Info

Target Poor or Non Binders

Top

Target Poor or Non Binders

Target Poor or Non Binders Info

Target Regulators

Top

Target-regulating microRNAs

Target-regulating microRNAs Info

Target-interacting Proteins

Target-interacting Proteins Info

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways		Top
KEGG Pathway	[+] 46 KEGG Pathways	+
1	MAPK signaling pathway
2	Cytokine-cytokine receptor interaction
3	NF-kappa B signaling pathway
4	Sphingolipid signaling pathway
5	mTOR signaling pathway
6	Apoptosis
7	TGF-beta signaling pathway
8	Osteoclast differentiation
9	Antigen processing and presentation
10	Toll-like receptor signaling pathway
11	NOD-like receptor signaling pathway
12	RIG-I-like receptor signaling pathway
13	Hematopoietic cell lineage
14	Natural killer cell mediated cytotoxicity
15	T cell receptor signaling pathway
16	Fc epsilon RI signaling pathway
17	TNF signaling pathway
18	Adipocytokine signaling pathway
19	Type II diabetes mellitus
20	Non-alcoholic fatty liver disease (NAFLD)
21	Type I diabetes mellitus
22	Alzheimer's disease
23	Amyotrophic lateral sclerosis (ALS)
24	Pertussis
25	Legionellosis
26	Leishmaniasis
27	Chagas disease (American trypanosomiasis)
28	African trypanosomiasis
29	Malaria
30	Toxoplasmosis
31	Amoebiasis
32	Tuberculosis
33	Hepatitis C
34	Hepatitis B
35	Influenza A
36	HTLV-I infection
37	Herpes simplex infection
38	Proteoglycans in cancer
39	Asthma
40	Inflammatory bowel disease (IBD)
41	Systemic lupus erythematosus
42	Rheumatoid arthritis
43	Allograft rejection
44	Graft-versus-host disease
45	Hypertrophic cardiomyopathy (HCM)
46	Dilated cardiomyopathy
NetPath Pathway	[+] 7 NetPath Pathways	+
1	TCR Signaling Pathway
2	IL2 Signaling Pathway
3	IL3 Signaling Pathway
4	IL4 Signaling Pathway
5	Leptin Signaling Pathway
6	RANKL Signaling Pathway
7	IL1 Signaling Pathway
Panther Pathway	[+] 2 Panther Pathways	+
1	Apoptosis signaling pathway
2	Wnt signaling pathway
Pathwhiz Pathway	[+] 1 Pathwhiz Pathways	+
1	Fc Epsilon Receptor I Signaling in Mast Cells
PID Pathway	[+] 15 PID Pathways	+
1	IL27-mediated signaling events
2	Canonical NF-kappaB pathway
3	Calcineurin-regulated NFAT-dependent transcription in lymphocytes
4	Angiopoietin receptor Tie2-mediated signaling
5	Signaling events mediated by HDAC Class I
6	TNF receptor signaling pathway
7	Ceramide signaling pathway
8	amb2 Integrin signaling
9	RXR and RAR heterodimerization with other nuclear receptor
10	IL23-mediated signaling events
11	HIV-1 Nef: Negative effector of Fas and TNF-alpha
12	Caspase Cascade in Apoptosis
13	Cellular roles of Anthrax toxin
14	Downstream signaling in na&#xef
15
Reactome	[+] 7 Reactome Pathways	+
1	Transcriptional regulation of white adipocyte differentiation
2	TNFR1-induced proapoptotic signaling
3	Regulation of TNFR1 signaling
4	TNFR1-induced NFkappaB signaling pathway
5	TNFR1-mediated ceramide production
6	TNFR2 non-canonical NF-kB pathway
7	TNF signaling
WikiPathways	[+] 26 WikiPathways	+
1	Toll-like receptor signaling pathway
2	Monoamine Transport
3	SIDS Susceptibility Pathways
4	TGF Beta Signaling Pathway
5	Cytokines and Inflammatory Response
6	MAPK Signaling Pathway
7	EV release from cardiac cells and their functional effects
8	FAS pathway and Stress induction of HSP regulation
9	Apoptosis-related network due to altered Notch3 in ovarian cancer
10	Cardiac Hypertrophic Response
11	Transcriptional Regulation of White Adipocyte Differentiation
12	Aryl Hydrocarbon Receptor
13	Apoptosis
14	Nanoparticle triggered regulated necrosis
15	Amyotrophic lateral sclerosis (ALS)
16	Adipogenesis
17	Allograft Rejection
18	TNF alpha Signaling Pathway
19	TWEAK Signaling Pathway
20	Extrinsic Pathway for Apoptosis
21	Folate Metabolism
22	MicroRNAs in cardiomyocyte hypertrophy
23	Vitamin B12 Metabolism
24	Selenium Micronutrient Network
25	Regulation of toll-like receptor signaling pathway
26	Matrix Metalloproteinases

Target-Related Models and Studies

Top

Target Validation

Target Validation Info

References

Top

REF 1

Adalimumab for psoriasis patients who are non-responders to etanercept: open-label prospective evaluation. J Eur Acad Dermatol Venereol. 2009 Dec;23(12):1394-7.

REF 2

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4860).

REF 3

Molecular targets of rheumatoid arthritis. Inflamm Allergy Drug Targets. 2008 Mar;7(1):53-66.

REF 4

Emerging drugs for rheumatoid arthritis. Expert Opin Emerg Drugs. 2008 Mar;13(1):175-96.

REF 5

Oral pentoxifylline inhibits release of tumor necrosis factor-alpha from human peripheral blood monocytes : a potential treatment for aseptic loose... J Bone Joint Surg Am. 2001 Jul;83(7):1057-61.

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Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.

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ClinicalTrials.gov (NCT02390700) Observational Study of Golimumab Intravenous Infusion

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Drug insight: tumor necrosis factor-converting enzyme as a pharmaceutical target for rheumatoid arthritis. Nat Clin Pract Rheumatol. 2008 Jun;4(6):300-9.

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Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2018

REF 11

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Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.

REF 13

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Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

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New drugs in development for the treatment of endometriosis. Expert Opin Investig Drugs. 2008 Aug;17(8):1187-202.

REF 18

REF 19

Thalidomide in multiple myeloma--clinical trials and aspects of drug metabolism and toxicity. Expert Opin Drug Metab Toxicol. 2008 Jul;4(7):973-85.

REF 20

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REF 21

ClinicalTrials.gov (NCT03398837) Trial to Evaluate Efficacy and Safety of Lenabasum in Diffuse Cutaneous Systemic Sclerosis (RESOLVE-1). U.S. National Institutes of Health.

REF 22

ClinicalTrials.gov (NCT00051467) A Study of TNFerade Biologic With 5-FU and Radiation Therapy for First-Line Treatment of Unresectable Locally Advanced Pancreatic Cancer. U.S. National Institutes of Health.

REF 23

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 24

ClinicalTrials.gov (NCT02349451) A Phase 2 Study to Investigate the Safety, Tolerability and Efficacy of ABT-122 in Subjects With Active Psoriatic Arthritis Who Have an Inadequate Response to Methotrexate. U.S. National Institutes of Health.

REF 25

ClinicalTrials.gov (NCT02433340) Phase 2, Multicenter, Open-Label Extension (OLE) Study With ABT-122 in Rheumatoid Arthritis Subjects Who Have Completed the Preceding M12-963 Study

REF 26

Clinical pipeline report, company report or official report of Anacor Pharmaceuticals.

REF 27

ClinicalTrials.gov (NCT02095626) Study in Intensive Care Patients Regarding the Effect of Inhaled AP-301 After Primary Graft Dysfunction After Lung Transplantation. U.S. National Institutes of Health.

REF 28

ClinicalTrials.gov (NCT03830684) A Randomized, Double-blind, Placebo-controlled, Multicenter and Phase IIa Clinical Trial for the Effectiveness and Safety of Baicalein Tablets in the Treatment of Improve Other Aspects of Healthy Adult With Influenza Fever. U.S. National Institutes of Health.

REF 29

ClinicalTrials.gov (NCT01624376) Randomized, Double-blind, Placebo-controlled Study in Patients With Fistulizing Crohn's Disease. U.S. National Institutes of Health.

REF 30

ClinicalTrials.gov (NCT00823173) Exploratory Study on Topical ESBA105 in Acute Anterior Uveitis. U.S. National Institutes of Health.

REF 31

Broad-spectrum modulation of ATP-binding cassette transport proteins by the taxane derivatives ortataxel (IDN-5109, BAY 59-8862) and tRA96023. Cancer Chemother Pharmacol. 2004 May;53(5):363-9.

REF 32

ClinicalTrials.gov (NCT00537667) The SPECTRA Study. U.S. National Institutes of Health.

REF 33

RDP58, a locally active TNF inhibitor, is effective in the dextran sulphate mouse model of chronic colitis. Inflamm Res. 2002 Nov;51(11):522-31.

REF 34

ClinicalTrials.gov (NCT01911234) Clinical Efficacy of TNF-Kinoid in Patients With Rheumatoid Arthritis. U.S. National Institutes of Health.

REF 35

ClinicalTrials.gov (NCT02243787) Safety and Tolerability Study of COVA322 in Patients With Stable Chronic Moderate-to-severe Plaque Psoriasis

REF 36

Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63.

REF 37

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 38

ClinicalTrials.gov (NCT01759056) Evaluation of an Oral Anti-TNF Antibody in Patients With Active Ulcerative Colitis. U.S. National Institutes of Health.

REF 39

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025369)

REF 40

Clinical pipeline report, company report or official report of INmune Bio.

REF 41

ClinicalTrials.gov (NCT01284036) A Single Dose Study Of The Safety And Investigational Product Level Measurement In Healthy Subjects. U.S. National Institutes of Health.

REF 42

ClinicalTrials.gov (NCT01010919) A Study of Chicory for Treatment of Osteoarthritis of the Hip or Knee. U.S. National Institutes of Health.

REF 43

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003884)

REF 44

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002771)

REF 45

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015375)

REF 46

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025635)

REF 47

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019215)

REF 48

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021664)

REF 49

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023971)

REF 50

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020354)

REF 51

Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52.

REF 52

Effect of FR133605, a novel cytokine suppressive agent, on bone and cartilage destruction in adjuvant arthritic rats. J Rheumatol. 1996 Oct;23(10):1778-83.

REF 53

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007330)

REF 54

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800034853)

REF 55

The potential of biologics for the treatment of asthma. Nat Rev Drug Discov. 2012 Dec;11(12):958-72.

REF 56

Etanercept, a TNF antagonist for treatment for psoriatic arthritis and psoriasis. Skin Therapy Lett. 2003 Jan;8(1):1-4.

REF 57

Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.

REF 58

Thalidomide and thalidomide analogues for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD007351.

REF 59

The thalidomide saga. Int J Biochem Cell Biol. 2007;39(7-8):1489-99.

REF 60

Clinical pipeline report, company report or official report of AstraZeneca (2009).

REF 61

Targeted therapies in myelodysplastic syndromes: ASH 2003 review. Semin Hematol. 2004 Apr;41(2 Suppl 4):13-20.

REF 62

Tumor necrosis factor alpha in the pathogenesis of cerebral malaria. Cell Mol Life Sci. 2003 Aug;60(8):1623-35.

REF 63

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.

REF 64

Case study: biosimilar anti TNFalpha (Adalimumab) analysis of Fc effector functions. BMC Proc. 2013; 7(Suppl 6): P30.

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Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.

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TNFerade, an adenovector carrying the transgene for human tumor necrosis factor alpha, for patients with advanced solid tumors: surgical experience... Ann Surg Oncol. 2005 Oct;12(10):825-30.

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Apoptosis and the FLIP and NF-kappa B proteins as pharmacodynamic criteria for biosimilar TNF-alpha antagonists. Biologics. 2014 Jul 31;8:211-20.

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Biosimilars in the therapy of inflammatory bowel diseases. Eur J Gastroenterol Hepatol. 2014 Jun;26(6):581-7.

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DOI: 10.1136/annrheumdis-2015-eular.4042

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Inhibition of experimental periodontitis by a topical boron-based antimicrobial. J Dent Res. 2008 Feb;87(2):148-52.

REF 71

Identification of a novel boron-containing antibacterial agent (AN0128) with anti-inflammatory activity, for the potential treatment of cutaneous d... Bioorg Med Chem Lett. 2006 Dec 1;16(23):5963-7.

REF 72

Anacor Announces Positive Results From Phase 2 Trial Of Novel Anti-Inflammatory Agent For The Treatment Of Atopic Dermatitis. Anacor Pharmaceuticals. Friday 16 June 2006.

REF 73

AP301, a synthetic peptide mimicking the lectin-like domain of TNF, enhances amiloride-sensitive Na(+) current in primary dog, pig and rat alveolar type II cells. Pulm Pharmacol Ther. 2013 Jun;26(3):356-63.

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Discovery of the inhibitors of tumor necrosis factor alpha with structure-based virtual screening. Bioorg Med Chem Lett. 2010 Nov 1;20(21):6195-8.

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Cyclic AMP inhibition of tumor necrosis factor alpha production induced by amyloidogenic C-terminal peptide of Alzheimer's amyloid precursor protein in macrophages: involvement of multiple intracellular pathways and cyclic AMP response element binding protein. Mol Pharmacol. 2003 Mar;63(3):690-8.

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Pharmacokinetics and posterior segment biodistribution of ESBA105, an anti-TNF-alpha single-chain antibody, upon topical administration to the rabbit eye. Invest Ophthalmol Vis Sci. 2009 Feb;50(2):771-8.

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New developments in immunosuppressive therapy for heart transplantation. Expert Opin Emerg Drugs. 2009 Mar;14(1):1-21.

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Diabetes-enhanced tumor necrosis factor-alpha production promotes apoptosis and the loss of retinal microvascular cells in type 1 and type 2 models of diabetic retinopathy. Am J Pathol. 2008 May;172(5):1411-8.

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Modulation of Anti-Tumor Necrosis Factor Alpha (TNF-alpha) Antibody Secretion in Mice Immunized with TNF-alpha Kinoid. Clin Vaccine Immunol. 2012 May; 19(5): 699-703.

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Bispecific antibodies rise again. Nat Rev Drug Discov. 2014 Nov;13(11):799-801.

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Phase I and Pharmacokinetic Studies of CYT-6091, a Novel PEGylated Colloidal Gold-rhTNF Nanomedicine. Clin Cancer Res. 2010 December 15; 16(24): 6139-6149.

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Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033173)

REF 83

US patent application no. 2008,0269,123, Methods for treating polycystic kidney disease (pkd) or other cyst forming diseases.

REF 84

CDP571, a humanized monoclonal antibody to tumour necrosis factor-alpha, for steroid-dependent Crohn's disease: a randomized, double-blind, placebo... Aliment Pharmacol Ther. 2006 Mar 1;23(5):617-28.

REF 85

Randomized, placebo-controlled trial of the anti-tumor necrosis factor antibody fragment afelimomab in hyperinflammatory response during severe sepsis: The RAMSES Study. Crit Care Med. 2001 Apr;29(4):765-9.

REF 86

AGIX-4207 [2-[4-[[1-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]thio]-1-methylethyl]thio]-2,6-bis(1,1-dimethylethyl)phenoxy]acetic acid], a novel ... J Pharmacol Exp Ther. 2005 May;313(2):492-501.

REF 87

CombinatoRx Drug Candidate CRx-191 Demonstrates Positive Phase 2 Results In Psoriasis. CombinatoRx. 2008.

REF 88

IND Filed for AME-527, Monoclonal Antibody That Is a Potential Treatment for Rheumatoid Arthritis. P&T Community. 2015.

REF 89

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