Target Information
| Target General Information | Top | |||||
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| Target ID |
T97257
(Former ID: TTDR00511)
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| Target Name |
Transforming growth factor beta 1 (TGFB1)
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| Synonyms |
Transforming growth factor beta-1 proprotein; Transforming growth factor beta-1; TGFB; TGF-beta1; TGF-beta 1
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| Gene Name |
TGFB1
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Idiopathic interstitial pneumonitis [ICD-11: CB03] | |||||
| Function |
Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active subunit of TGF-beta-1, respectively.
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| BioChemical Class |
Growth factor
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| UniProt ID | ||||||
| Sequence |
MPPSGLRLLLLLLPLLWLLVLTPGRPAAGLSTCKTIDMELVKRKRIEAIRGQILSKLRLA
SPPSQGEVPPGPLPEAVLALYNSTRDRVAGESAEPEPEPEADYYAKEVTRVLMVETHNEI YDKFKQSTHSIYMFFNTSELREAVPEPVLLSRAELRLLRLKLKVEQHVELYQKYSNNSWR YLSNRLLAPSDSPEWLSFDVTGVVRQWLSRGGEIEGFRLSAHCSCDSRDNTLQVDINGFT TGRRGDLATIHGMNRPFLLLMATPLERAQHLQSSRHRRALDTNYCFSSTEKNCCVRQLYI DFRKDLGWKWIHEPKGYHANFCLGPCPYIWSLDTQYSKVLALYNQHNPGASAAPCCVPQA LEPLPIVYYVGRKPKVEQLSNMIVRSCKCS Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| ADReCS ID | BADD_A01246 ; BADD_A01249 ; BADD_A03745 ; BADD_A05045 | |||||
| HIT2.0 ID | T53AOE | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Pirfenidone | Drug Info | Approved | Idiopathic pulmonary fibrosis | [2], [3], [4] | |
| Clinical Trial Drug(s) | [+] 7 Clinical Trial Drugs | + | ||||
| 1 | A435 | Drug Info | IND submitted | Aggressive cancer | [5] | |
| 2 | TG-C | Drug Info | Phase 3 | Arthritis | [6] | |
| 3 | LY2157299 | Drug Info | Phase 2/3 | Arteriosclerosis | [7], [8] | |
| 4 | Disitertide | Drug Info | Phase 2 | Macular degeneration | [9] | |
| 5 | ABBV-151 | Drug Info | Phase 1 | Solid tumour/cancer | [10] | |
| 6 | ACE-1334 | Drug Info | Phase 1 | Systemic sclerosis | [11] | |
| 7 | SRK-181 | Drug Info | Phase 1 | Solid tumour/cancer | [12] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | Mannose phosphate | Drug Info | Discontinued in Phase 2 | Lesion | [13] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Modulator | [+] 4 Modulator drugs | + | ||||
| 1 | Pirfenidone | Drug Info | [1] | |||
| 2 | TG-C | Drug Info | [6], [14] | |||
| 3 | Mannose phosphate | Drug Info | [20] | |||
| 4 | ART-144 | Drug Info | [21] | |||
| Inhibitor | [+] 5 Inhibitor drugs | + | ||||
| 1 | A435 | Drug Info | [5] | |||
| 2 | LY2157299 | Drug Info | [15], [16] | |||
| 3 | Disitertide | Drug Info | [9] | |||
| 4 | ABBV-151 | Drug Info | [17] | |||
| 5 | SRK-181 | Drug Info | [19] | |||
| Antagonist | [+] 1 Antagonist drugs | + | ||||
| 1 | ACE-1334 | Drug Info | [18] | |||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| MAPK signaling pathway | hsa04010 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Cytokine-cytokine receptor interaction | hsa04060 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| FoxO signaling pathway | hsa04068 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Cell cycle | hsa04110 | Affiliated Target |
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| Class: Cellular Processes => Cell growth and death | Pathway Hierarchy | ||
| Cellular senescence | hsa04218 | Affiliated Target |
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| Class: Cellular Processes => Cell growth and death | Pathway Hierarchy | ||
| TGF-beta signaling pathway | hsa04350 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Osteoclast differentiation | hsa04380 | Affiliated Target |
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| Class: Organismal Systems => Development and regeneration | Pathway Hierarchy | ||
| Hippo signaling pathway | hsa04390 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Th17 cell differentiation | hsa04659 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Intestinal immune network for IgA production | hsa04672 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Relaxin signaling pathway | hsa04926 | Affiliated Target |
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| Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
| Click to Show/Hide the Information of Affiliated Human Pathways | |||
| Degree | 35 | Degree centrality | 3.76E-03 | Betweenness centrality | 2.27E-03 |
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| Closeness centrality | 2.51E-01 | Radiality | 1.44E+01 | Clustering coefficient | 1.73E-01 |
| Neighborhood connectivity | 4.15E+01 | Topological coefficient | 5.73E-02 | Eccentricity | 11 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "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 | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-regulating Transcription Factors | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| References | Top | |||||
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| REF 1 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| 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: 7532). | |||||
| REF 3 | 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81. | |||||
| REF 4 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 5 | Clinical pipeline report, company report or official report of Klus Pharma | |||||
| REF 6 | ClinicalTrials.gov (NCT02072070) Efficacy and Safety Study of TissueGene-C to Degenerative Arthritis. U.S. National Institutes of Health. | |||||
| REF 7 | 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: 7797). | |||||
| REF 8 | ClinicalTrials.gov (NCT02008318) A Study of LY2157299 in Participants With Myelodysplastic Syndromes. U.S. National Institutes of Health. | |||||
| REF 9 | Perspectives of TGF-beta inhibition in pancreatic and hepatocellular carcinomas. Oncotarget. 2014 January; 5(1): 78-94. | |||||
| REF 10 | ClinicalTrials.gov (NCT03821935) Study to Determine the Safety, Tolerability, Pharmacokinetics and RP2D of ABBV-151 as a Single Agent and in Combination With ABBV-181 in Participants With Locally Advanced or Metastatic Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 11 | ClinicalTrials.gov (NCT04948554) A Phase 1b Randomized, Double-Blind, Placebo-Controlled, Multiple-Ascending Dose Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of ACE-1334 Plus Standard of Care in Participants With Systemic Sclerosis. U.S.National Institutes of Health. | |||||
| REF 12 | ClinicalTrials.gov (NCT04291079) SRK-181 Alone or in Combination With Anti-PD-(L)1 Antibody Therapy in Patients With Locally Advanced or Metastatic Solid Tumors (DRAGON). U.S. National Institutes of Health. | |||||
| REF 13 | Mannose phosphate isomerase regulates fibroblast growth factor receptor family signaling and glioma radiosensitivity. PLoS One. 2014 Oct 14;9(10):e110345. | |||||
| REF 14 | Clinical pipeline report, company report or official report of Tissue Gene, Inc. | |||||
| REF 15 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 16 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 17 | Clinical pipeline report, company report or official report of AbbVie. | |||||
| REF 18 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2023. Adis Insight | |||||
| REF 19 | Clinical pipeline report, company report or official report of Scholar Rock. | |||||
| REF 20 | The mannose-6-phosphate analogue, PXS64, inhibits fibrosis via TGF-beta1 pathway in human lung fibroblasts. Immunol Lett. 2015 Jun;165(2):90-101. | |||||
| REF 21 | Pharmaceutical products of TORREYA partners. December 2011. | |||||
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