Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV5XHVH)

DOT Name Transforming growth factor beta-1 proprotein (TGFB1)
Gene Name TGFB1
Related Disease
Camurati-Engelmann disease ( )
Inflammatory bowel disease, immunodeficiency, and encephalopathy ( )
UniProt ID
TGFB1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1KLA; 1KLC; 1KLD; 3KFD; 4KV5; 5FFO; 5VQP; 6OM2; 6P7J; 7Y1R; 7Y1T
Pfam ID
PF00019 ; PF00688
Sequence
MPPSGLRLLPLLLPLLWLLVLTPGRPAAGLSTCKTIDMELVKRKRIEAIRGQILSKLRLA
SPPSQGEVPPGPLPEAVLALYNSTRDRVAGESAEPEPEPEADYYAKEVTRVLMVETHNEI
YDKFKQSTHSIYMFFNTSELREAVPEPVLLSRAELRLLRLKLKVEQHVELYQKYSNNSWR
YLSNRLLAPSDSPEWLSFDVTGVVRQWLSRGGEIEGFRLSAHCSCDSRDNTLQVDINGFT
TGRRGDLATIHGMNRPFLLLMATPLERAQHLQSSRHRRALDTNYCFSSTEKNCCVRQLYI
DFRKDLGWKWIHEPKGYHANFCLGPCPYIWSLDTQYSKVLALYNQHNPGASAAPCCVPQA
LEPLPIVYYVGRKPKVEQLSNMIVRSCKCS
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; [Latency-associated peptide]: Required to maintain the Transforming growth factor beta-1 (TGF-beta-1) chain in a latent state during storage in extracellular matrix. Associates non-covalently with TGF-beta-1 and regulates its activation via interaction with 'milieu molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS, that control activation of TGF-beta-1. Interaction with LRRC33/NRROS regulates activation of TGF-beta-1 in macrophages and microglia (Probable). Interaction with LRRC32/GARP controls activation of TGF-beta-1 on the surface of activated regulatory T-cells (Tregs). Interaction with integrins (ITGAV:ITGB6 or ITGAV:ITGB8) results in distortion of the Latency-associated peptide chain and subsequent release of the active TGF-beta-1 ; [Transforming growth factor beta-1]: Multifunctional protein that regulates the growth and differentiation of various cell types and is involved in various processes, such as normal development, immune function, microglia function and responses to neurodegeneration. Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains remain non-covalently linked rendering TGF-beta-1 inactive during storage in extracellular matrix. At the same time, LAP chain interacts with 'milieu molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS that control activation of TGF-beta-1 and maintain it in a latent state during storage in extracellular milieus. TGF-beta-1 is released from LAP by integrins (ITGAV:ITGB6 or ITGAV:ITGB8): integrin-binding to LAP stabilizes an alternative conformation of the LAP bowtie tail and results in distortion of the LAP chain and subsequent release of the active TGF-beta-1. Once activated following release of LAP, TGF-beta-1 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal. While expressed by many cells types, TGF-beta-1 only has a very localized range of action within cell environment thanks to fine regulation of its activation by Latency-associated peptide chain (LAP) and 'milieu molecules'. Plays an important role in bone remodeling: acts as a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts. Can promote either T-helper 17 cells (Th17) or regulatory T-cells (Treg) lineage differentiation in a concentration-dependent manner. At high concentrations, leads to FOXP3-mediated suppression of RORC and down-regulation of IL-17 expression, favoring Treg cell development. At low concentrations in concert with IL-6 and IL-21, leads to expression of the IL-17 and IL-23 receptors, favoring differentiation to Th17 cells. Stimulates sustained production of collagen through the activation of CREB3L1 by regulated intramembrane proteolysis (RIP). Mediates SMAD2/3 activation by inducing its phosphorylation and subsequent translocation to the nucleus. Positively regulates odontoblastic differentiation in dental papilla cells, via promotion of IPO7-mediated translocation of phosphorylated SMAD2 to the nucleus and subsequent transcription of target genes. Can induce epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types.
Tissue Specificity
Highly expressed in bone . Abundantly expressed in articular cartilage and chondrocytes and is increased in osteoarthritis (OA) . Colocalizes with ASPN in chondrocytes within OA lesions of articular cartilage .
KEGG Pathway
MAPK sig.ling pathway (hsa04010 )
Cytokine-cytokine receptor interaction (hsa04060 )
FoxO sig.ling pathway (hsa04068 )
Cell cycle (hsa04110 )
Efferocytosis (hsa04148 )
Cellular senescence (hsa04218 )
TGF-beta sig.ling pathway (hsa04350 )
Osteoclast differentiation (hsa04380 )
Hippo sig.ling pathway (hsa04390 )
Th17 cell differentiation (hsa04659 )
Intesti.l immune network for IgA production (hsa04672 )
Relaxin sig.ling pathway (hsa04926 )
Non-alcoholic fatty liver disease (hsa04932 )
AGE-RAGE sig.ling pathway in diabetic complications (hsa04933 )
Leishmaniasis (hsa05140 )
Chagas disease (hsa05142 )
Malaria (hsa05144 )
Toxoplasmosis (hsa05145 )
Amoebiasis (hsa05146 )
Tuberculosis (hsa05152 )
Hepatitis B (hsa05161 )
Human T-cell leukemia virus 1 infection (hsa05166 )
Pathways in cancer (hsa05200 )
Proteoglycans in cancer (hsa05205 )
Colorectal cancer (hsa05210 )
Re.l cell carcinoma (hsa05211 )
Pancreatic cancer (hsa05212 )
Chronic myeloid leukemia (hsa05220 )
Hepatocellular carcinoma (hsa05225 )
Gastric cancer (hsa05226 )
Inflammatory bowel disease (hsa05321 )
Rheumatoid arthritis (hsa05323 )
Hypertrophic cardiomyopathy (hsa05410 )
Dilated cardiomyopathy (hsa05414 )
Diabetic cardiomyopathy (hsa05415 )
Reactome Pathway
Influenza Virus Induced Apoptosis (R-HSA-168277 )
Cell surface interactions at the vascular wall (R-HSA-202733 )
Molecules associated with elastic fibres (R-HSA-2129379 )
Downregulation of TGF-beta receptor signaling (R-HSA-2173788 )
TGF-beta receptor signaling activates SMADs (R-HSA-2173789 )
TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) (R-HSA-2173791 )
Syndecan interactions (R-HSA-3000170 )
ECM proteoglycans (R-HSA-3000178 )
SMAD2/3 Phosphorylation Motif Mutants in Cancer (R-HSA-3304356 )
TGFBR2 MSI Frameshift Mutants in Cancer (R-HSA-3642279 )
TGFBR2 Kinase Domain Mutants in Cancer (R-HSA-3645790 )
TGFBR1 KD Mutants in Cancer (R-HSA-3656532 )
TGFBR1 LBD Mutants in Cancer (R-HSA-3656535 )
Transcriptional regulation of white adipocyte differentiation (R-HSA-381340 )
UCH proteinases (R-HSA-5689603 )
Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807 )
RUNX3 regulates CDKN1A transcription (R-HSA-8941855 )
Regulation of RUNX3 expression and activity (R-HSA-8941858 )
RUNX3 regulates p14-ARF (R-HSA-8951936 )
Platelet degranulation (R-HSA-114608 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Camurati-Engelmann disease DISTJPCE Definitive Autosomal dominant [1]
Inflammatory bowel disease, immunodeficiency, and encephalopathy DISIR0ZL Strong Autosomal recessive [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 9 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Cisplatin DMRHGI9 Approved Transforming growth factor beta-1 proprotein (TGFB1) decreases the response to substance of Cisplatin. [90]
Calcitriol DM8ZVJ7 Approved Transforming growth factor beta-1 proprotein (TGFB1) affects the response to substance of Calcitriol. [91]
Vorinostat DMWMPD4 Approved Transforming growth factor beta-1 proprotein (TGFB1) increases the Corneal defect ADR of Vorinostat. [92]
Gemcitabine DMSE3I7 Approved Transforming growth factor beta-1 proprotein (TGFB1) decreases the response to substance of Gemcitabine. [90]
Lapatinib DM3BH1Y Approved Transforming growth factor beta-1 proprotein (TGFB1) decreases the response to substance of Lapatinib. [94]
Gabapentin DM6T924 Approved Transforming growth factor beta-1 proprotein (TGFB1) increases the Diabetic complications renal ADR of Gabapentin. [92]
Alfacalcidol DM1237M Phase 4 Transforming growth factor beta-1 proprotein (TGFB1) affects the response to substance of Alfacalcidol. [91]
Rapamycin Immunosuppressant Drug DM678IB Investigative Transforming growth factor beta-1 proprotein (TGFB1) increases the response to substance of Rapamycin Immunosuppressant Drug. [95]
Irbesartan DMTP1DC Investigative Transforming growth factor beta-1 proprotein (TGFB1) affects the response to substance of Irbesartan. [96]
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⏷ Show the Full List of 9 Drug(s)
This DOT Affected the Regulation of Drug Effects of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Glutathione DMAHMT9 Approved Transforming growth factor beta-1 proprotein (TGFB1) decreases the abundance of Glutathione. [93]
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95 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [3]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [4]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [5]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [6]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the activity of Transforming growth factor beta-1 proprotein (TGFB1). [7]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [8]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [9]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [10]
Arsenic DMTL2Y1 Approved Arsenic decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [11]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [12]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [13]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [14]
Triclosan DMZUR4N Approved Triclosan increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [15]
Methotrexate DM2TEOL Approved Methotrexate decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [16]
Decitabine DMQL8XJ Approved Decitabine increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [17]
Marinol DM70IK5 Approved Marinol increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [18]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [19]
Progesterone DMUY35B Approved Progesterone decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [20]
Fluorouracil DMUM7HZ Approved Fluorouracil increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [21]
Fulvestrant DM0YZC6 Approved Fulvestrant increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [22]
Dexamethasone DMMWZET Approved Dexamethasone decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [23]
Cannabidiol DM0659E Approved Cannabidiol increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [24]
Troglitazone DM3VFPD Approved Troglitazone decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [25]
Rosiglitazone DMILWZR Approved Rosiglitazone decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [26]
Azathioprine DMMZSXQ Approved Azathioprine increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [27]
Ethanol DMDRQZU Approved Ethanol increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [28]
Aspirin DM672AH Approved Aspirin decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [29]
Dasatinib DMJV2EK Approved Dasatinib decreases the activity of Transforming growth factor beta-1 proprotein (TGFB1). [30]
Mitomycin DMH0ZJE Approved Mitomycin increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [31]
Obeticholic acid DM3Q1SM Approved Obeticholic acid decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [32]
Sulindac DM2QHZU Approved Sulindac increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [33]
Capsaicin DMGMF6V Approved Capsaicin decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [34]
Alitretinoin DMME8LH Approved Alitretinoin decreases the activity of Transforming growth factor beta-1 proprotein (TGFB1). [35]
Palbociclib DMD7L94 Approved Palbociclib increases the activity of Transforming growth factor beta-1 proprotein (TGFB1). [36]
Acocantherin DM7JT24 Approved Acocantherin decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [37]
Prednisolone DMQ8FR2 Approved Prednisolone decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [38]
Sorafenib DMS8IFC Approved Sorafenib decreases the activity of Transforming growth factor beta-1 proprotein (TGFB1). [39]
Diphenylpyraline DMW4X37 Approved Diphenylpyraline increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [40]
Isoproterenol DMK7MEY Approved Isoproterenol decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [41]
Adenosine DMM2NSK Approved Adenosine increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [42]
Tacrolimus DMZ7XNQ Approved Tacrolimus increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [4]
Bleomycin DMNER5S Approved Bleomycin increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [43]
Ciprofloxacin XR DM2NLS9 Approved Ciprofloxacin XR increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [44]
Mitotane DMU1GX0 Approved Mitotane decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [45]
Sodium chloride DMM3950 Approved Sodium chloride increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [46]
Busulfan DMXYJ9C Approved Busulfan increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [47]
Phenylephrine DMZHUO5 Approved Phenylephrine increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [41]
Carvedilol DMHTEAO Approved Carvedilol decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [48]
Ketamine DMT5HA4 Approved Ketamine increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [49]
Prednisone DM2HG4X Approved Prednisone decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [50]
Lamivudine DMI347A Approved Lamivudine decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [52]
Cetrorelix DMFD9Q6 Approved Cetrorelix decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [54]
Valsartan DMREUQ6 Approved Valsartan decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [55]
Emetine DMCT2YF Approved Emetine decreases the activity of Transforming growth factor beta-1 proprotein (TGFB1). [30]
Benazepril DMH1M9B Approved Benazepril decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [56]
Domperidone DMBDPY0 Approved Domperidone decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [57]
Carfilzomib DM48K0X Approved Carfilzomib decreases the activity of Transforming growth factor beta-1 proprotein (TGFB1). [30]
Vinorelbine DMVXFYE Approved Vinorelbine decreases the activity of Transforming growth factor beta-1 proprotein (TGFB1). [30]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [58]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [59]
Curcumin DMQPH29 Phase 3 Curcumin decreases the activity of Transforming growth factor beta-1 proprotein (TGFB1). [60]
HMPL-004 DM29XGY Phase 3 HMPL-004 decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [61]
Genistein DM0JETC Phase 2/3 Genistein decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [63]
Disulfiram DMCL2OK Phase 2 Trial Disulfiram decreases the activity of Transforming growth factor beta-1 proprotein (TGFB1). [30]
Flavopiridol DMKSUOI Phase 2 Flavopiridol decreases the activity of Transforming growth factor beta-1 proprotein (TGFB1). [30]
URSOLIC ACID DM4SOAW Phase 2 URSOLIC ACID decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [64]
CI-1033 DMSI8N3 Phase 2 CI-1033 decreases the activity of Transforming growth factor beta-1 proprotein (TGFB1). [30]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [65]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [66]
AMEP DMFELMQ Phase 1 AMEP increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [68]
JWH-015 DMGTSCP Patented JWH-015 decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [69]
PMID26394986-Compound-10 DMP8RQ4 Patented PMID26394986-Compound-10 decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [70]
Nemorubicin DMX7Q3H Preclinical Nemorubicin decreases the activity of Transforming growth factor beta-1 proprotein (TGFB1). [30]
Acteoside DM0YHKB Terminated Acteoside increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [71]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [72]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [73]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [74]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [75]
Coumarin DM0N8ZM Investigative Coumarin increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [76]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [77]
Deguelin DMXT7WG Investigative Deguelin increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [78]
3R14S-OCHRATOXIN A DM2KEW6 Investigative 3R14S-OCHRATOXIN A increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [79]
Paraquat DMR8O3X Investigative Paraquat increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [80]
Glyphosate DM0AFY7 Investigative Glyphosate decreases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [81]
Nickel chloride DMI12Y8 Investigative Nickel chloride increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [82]
D-glucose DMMG2TO Investigative D-glucose increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [25]
Phencyclidine DMQBEYX Investigative Phencyclidine increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [84]
Butanoic acid DMTAJP7 Investigative Butanoic acid increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [85]
Chlorpyrifos DMKPUI6 Investigative Chlorpyrifos increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [86]
Tributylstannanyl DMHN7CB Investigative Tributylstannanyl increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [87]
Cycloheximide DMGDA3C Investigative Cycloheximide decreases the activity of Transforming growth factor beta-1 proprotein (TGFB1). [30]
PP-242 DM2348V Investigative PP-242 decreases the activity of Transforming growth factor beta-1 proprotein (TGFB1). [30]
Cordycepin DM72Y01 Investigative Cordycepin increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [42]
ELLAGIC ACID DMX8BS5 Investigative ELLAGIC ACID increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [88]
Oleic acid DM54O1Z Investigative Oleic acid increases the expression of Transforming growth factor beta-1 proprotein (TGFB1). [89]
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⏷ Show the Full List of 95 Drug(s)
5 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Amlodipine DMBDAZV Approved Amlodipine decreases the response to substance of Transforming growth factor beta-1 proprotein (TGFB1). [51]
Imiquimod DM1TMA3 Approved Imiquimod increases the secretion of Transforming growth factor beta-1 proprotein (TGFB1). [53]
Masitinib DMRSNEU Phase 3 Masitinib increases the secretion of Transforming growth factor beta-1 proprotein (TGFB1). [62]
LY294002 DMY1AFS Phase 1 LY294002 decreases the response to substance of Transforming growth factor beta-1 proprotein (TGFB1). [67]
Hexadecanoic acid DMWUXDZ Investigative Hexadecanoic acid increases the secretion of Transforming growth factor beta-1 proprotein (TGFB1). [83]
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References

1 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
2 Human TGF-1 deficiency causes severe inflammatory bowel disease and encephalopathy. Nat Genet. 2018 Mar;50(3):344-348. doi: 10.1038/s41588-018-0063-6. Epub 2018 Feb 26.
3 The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
4 Oxidative stress in kidney transplant patients with calcineurin inhibitor-induced hypertension: effect of ramipril. J Cardiovasc Pharmacol. 2002 Oct;40(4):625-31.
5 Human oligodendrocytes derived from embryonic stem cells: Effect of noggin on phenotypic differentiation in vitro and on myelination in vivo. Mol Cell Neurosci. 2007 Mar;34(3):310-23. doi: 10.1016/j.mcn.2006.11.008. Epub 2006 Dec 28.
6 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
7 Doxorubicin inhibits TGF-beta signaling in human lung carcinoma A549 cells. Eur J Pharmacol. 2008 Aug 20;590(1-3):67-73. doi: 10.1016/j.ejphar.2008.05.030. Epub 2008 May 29.
8 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
9 Estradiol downregulates miR-21 expression and increases miR-21 target gene expression in MCF-7 breast cancer cells. Nucleic Acids Res. 2009 May;37(8):2584-95. doi: 10.1093/nar/gkp117. Epub 2009 Mar 5.
10 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
11 Pattern of expression of apoptosis and inflammatory genes in humans exposed to arsenic and/or fluoride. Sci Total Environ. 2010 Jan 15;408(4):760-7. doi: 10.1016/j.scitotenv.2009.11.016. Epub 2009 Dec 4.
12 Influence of quercetin and x-ray on collagen synthesis of cultured human keloid-derived fibroblasts. Chin Med Sci J. 2006 Sep;21(3):179-83.
13 [Effect of endogenous TGF-beta1 and TNF-alpha on the As(2)O(3) inducing apoptosis of HL-60 cells]. Zhonghua Xue Ye Xue Za Zhi. 2003 May;24(5):231-4.
14 PPAR-alpha ligands inhibit H2O2-mediated activation of transforming growth factor-beta1 in human mesangial cells. Antioxid Redox Signal. 2002 Dec;4(6):877-84. doi: 10.1089/152308602762197416.
15 Primary Human Hepatocyte Spheroids as Tools to Study the Hepatotoxic Potential of Non-Pharmaceutical Chemicals. Int J Mol Sci. 2021 Oct 12;22(20):11005. doi: 10.3390/ijms222011005.
16 The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
17 Integrative analysis of epigenetic modulation in melanoma cell response to decitabine: clinical implications. PLoS One. 2009;4(2):e4563. doi: 10.1371/journal.pone.0004563. Epub 2009 Feb 23.
18 Autocrine and paracrine regulation of lymphocyte CB2 receptor expression by TGF-beta. Biochem Biophys Res Commun. 2002 Jan 11;290(1):91-6. doi: 10.1006/bbrc.2001.6179.
19 Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity. Arch Toxicol. 2018 Jan;92(1):469-485.
20 Progesterone and 17beta-estradiol enhance regulatory responses to human papillomavirus type 16 virus-like particles in peripheral blood mononuclear cells from healthy women. Clin Vaccine Immunol. 2010 Apr;17(4):609-17. doi: 10.1128/CVI.00441-09. Epub 2010 Feb 3.
21 Transcriptional profiling of MCF7 breast cancer cells in response to 5-Fluorouracil: relationship with cell cycle changes and apoptosis, and identification of novel targets of p53. Int J Cancer. 2006 Sep 1;119(5):1164-75.
22 Antiestrogens induce transforming growth factor beta-mediated immunosuppression in breast cancer. Cancer Res. 2010 Feb 15;70(4):1314-22. doi: 10.1158/0008-5472.CAN-09-3292. Epub 2010 Feb 9.
23 Role of endogenous TGF-beta in glucocorticoid-induced lung type II cell differentiation. Am J Physiol Lung Cell Mol Physiol. 2007 Jan;292(1):L249-57. doi: 10.1152/ajplung.00088.2006. Epub 2006 Sep 22.
24 Transcriptomic Analysis of Stem Cells Treated with Moringin or Cannabidiol: Analogies and Differences in Inflammation Pathways. Int J Mol Sci. 2019 Nov 30;20(23):6039. doi: 10.3390/ijms20236039.
25 Troglitazone inhibits synthesis of transforming growth factor-beta1 and reduces matrix production in human peritoneal mesothelial cells. Nephrology (Carlton). 2006 Dec;11(6):516-23. doi: 10.1111/j.1440-1797.2006.00654.x.
26 [Effect of Rosiglitazone on the proliferation and the production of transforming growth factor-beta 1 in cultured human Tenon' s capsule fibroblasts]. Zhonghua Yan Ke Za Zhi. 2008 May;44(5):413-7.
27 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
28 Cytokine response and oxidative stress produced by ethanol, acetaldehyde and endotoxin treatment in HepG2 cells. Isr Med Assoc J. 2001 Feb;3(2):131-6.
29 Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
30 Identification and Profiling of Environmental Chemicals That Inhibit the TGF/SMAD Signaling Pathway. Chem Res Toxicol. 2019 Dec 16;32(12):2433-2444. doi: 10.1021/acs.chemrestox.9b00228. Epub 2019 Nov 11.
31 Effects of mitomycin-C on normal dermal fibroblasts. Laryngoscope. 2006 Apr;116(4):514-7. doi: 10.1097/01.MLG.0000205590.62824.0A.
32 Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
33 Enhanced apoptosis and transforming growth factor-beta1 expression in colorectal adenomas and carcinomas after Sulindac therapy. Dis Colon Rectum. 2001 Jul;44(7):1008-15. doi: 10.1007/BF02235490.
34 Induction of the endoplasmic reticulum stress protein GADD153/CHOP by capsaicin in prostate PC-3 cells: a microarray study. Biochem Biophys Res Commun. 2008 Aug 8;372(4):785-91.
35 Hepatocyte growth factor receptor signaling mediates the anti-fibrotic action of 9-cis-retinoic acid in glomerular mesangial cells. Am J Pathol. 2005 Oct;167(4):947-57. doi: 10.1016/S0002-9440(10)61185-6.
36 Cdk4/6 inhibition induces epithelial-mesenchymal transition and enhances invasiveness in pancreatic cancer cells. Mol Cancer Ther. 2012 Oct;11(10):2138-48. doi: 10.1158/1535-7163.MCT-12-0562. Epub 2012 Aug 6.
37 Ouabain impairs cell migration, and invasion and alters gene expression of human osteosarcoma U-2 OS cells. Environ Toxicol. 2017 Nov;32(11):2400-2413. doi: 10.1002/tox.22453. Epub 2017 Aug 10.
38 Steroid therapy and urinary transforming growth factor-beta1 in IgA nephropathy. Am J Kidney Dis. 2001 Dec;38(6):1191-8. doi: 10.1053/ajkd.2001.29209.
39 Sorafenib inhibits transforming growth factor 1-mediated epithelial-mesenchymal transition and apoptosis in mouse hepatocytes. Hepatology. 2011 May;53(5):1708-18. doi: 10.1002/hep.24254.
40 Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers. J Allergy Clin Immunol. 2016 Dec;138(6):1690-1700. doi: 10.1016/j.jaci.2016.02.038. Epub 2016 Apr 24.
41 The regulation of human vascular smooth muscle extracellular matrix protein production by alpha- and beta-adrenoceptor stimulation. J Hypertens. 2002 Feb;20(2):287-94. doi: 10.1097/00004872-200202000-00019.
42 Adenosine and Cordycepin Accelerate Tissue Remodeling Process through Adenosine Receptor Mediated Wnt/-Catenin Pathway Stimulation by Regulating GSK3b Activity. Int J Mol Sci. 2021 May 25;22(11):5571. doi: 10.3390/ijms22115571.
43 Pulmonary fibrosis model using micro-CT analyzable human PSC-derived alveolar organoids containing alveolar macrophage-like cells. Cell Biol Toxicol. 2022 Aug;38(4):557-575. doi: 10.1007/s10565-022-09698-1. Epub 2022 Mar 10.
44 Ciprofloxacin decreases survival in HT-29 cells via the induction of TGF-beta1 secretion and enhances the anti-proliferative effect of 5-fluorouracil. Br J Pharmacol. 2009 Jun;157(3):362-70. doi: 10.1111/j.1476-5381.2009.00161.x. Epub 2009 Apr 9.
45 The effect of mitotane on viability, steroidogenesis and gene expression in NCI295R adrenocortical cells. Mol Med Rep. 2013 Mar;7(3):893-900.
46 Osmotic Induction of Angiogenic Growth Factor Expression in Human Retinal Pigment Epithelial Cells. PLoS One. 2016 Jan 22;11(1):e0147312. doi: 10.1371/journal.pone.0147312. eCollection 2016.
47 Antineoplastic agent busulfan regulates a network of genes related to coagulation and fibrinolysis. Eur J Clin Pharmacol. 2012 Jun;68(6):923-35. doi: 10.1007/s00228-011-1209-y.
48 [Arterial hypertension and oxidative stress induced by cyclosporin. Effect of carvedilol]. Ann Ital Med Int. 2001 Apr-Jun;16(2):101-5.
49 Ketamine-induced bladder fibrosis involves epithelial-to-mesenchymal transition mediated by transforming growth factor-1. Am J Physiol Renal Physiol. 2017 Oct 1;313(4):F961-F972. doi: 10.1152/ajprenal.00686.2016. Epub 2017 Mar 22.
50 Cytokine abnormalities in a patient with eosinophilic fasciitis. Ann Allergy Asthma Immunol. 2003 Apr;90(4):452-5. doi: 10.1016/S1081-1206(10)61832-7.
51 Effects of amlodipine on TGF--induced Smad2, 4 expressions in adriamycin toxicity of rat mesangial cells. Arch Toxicol. 2011 Jun;85(6):663-8. doi: 10.1007/s00204-011-0667-4. Epub 2011 Feb 20.
52 Effect of lamivudine treatment on plasma levels of transforming growth factor beta1, tissue inhibitor of metalloproteinases-1 and metalloproteinase-1 in patients with chronic hepatitis B. World J Gastroenterol. 2004 Sep 15;10(18):2661-5. doi: 10.3748/wjg.v10.i18.2661.
53 Cannabidiol selectively modulates interleukin (IL)-1 and IL-6 production in toll-like receptor activated human peripheral blood monocytes. Toxicology. 2021 Dec;464:153016. doi: 10.1016/j.tox.2021.153016. Epub 2021 Nov 2.
54 Luteinizing Hormone-Releasing Hormone (LHRH)-I antagonist cetrorelix inhibits myeloma cell growth in vitro and in vivo. Mol Cancer Ther. 2011 Jan;10(1):148-58. doi: 10.1158/1535-7163.MCT-10-0829. Epub 2010 Nov 9.
55 [The relationship between the gene polymorphism of TGF-beta1 and early renal injury in patients with essential hypertension, and the effect of the gene polymorphism of TGF- beta1 on the individual treatment with valsartan]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2007 Aug;24(4):428-31.
56 Transforming growth factor-beta1 is associated with kidney damage in patients with essential hypertension: renoprotective effect of ACE inhibitor and/or angiotensin II receptor blocker. Nephrol Dial Transplant. 2008 Sep;23(9):2841-6. doi: 10.1093/ndt/gfn159. Epub 2008 Apr 5.
57 Plasma cytokine concentration and the cytokine producing ability of whole blood cell cultures from healthy females with pharmacologically induced hyperprolactinemia. Int J Tissue React. 1999;21(2):43-9.
58 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
59 Resveratrol Inhibits Proliferation and Induces Apoptosis of Pathological Scar Fibroblasts Through the Mechanism Involving TGF-1/Smads Signaling Pathway. Cell Biochem Biophys. 2015 Apr;71(3):1267-72. doi: 10.1007/s12013-014-0317-6.
60 Transcriptional regulation by transforming growth factor beta of the expression of retinoic acid and retinoid X receptor genes in osteoblastic cells is mediated through AP-1. J Biol Chem. 1996 Dec 6;271(49):31602-6. doi: 10.1074/jbc.271.49.31602.
61 Andrographolide down-regulates hypoxia-inducible factor-1 in human non-small cell lung cancer A549 cells. Toxicol Appl Pharmacol. 2011 Feb 1;250(3):336-45. doi: 10.1016/j.taap.2010.11.014. Epub 2010 Dec 4.
62 Additive cell protective and oxidative stress reducing effects of combined treatment with cromolyn sodium and masitinib on MPTP-induced toxicity in SH-SY5Y neuroblastoma cells. Chem Biol Interact. 2022 Feb 25;354:109808. doi: 10.1016/j.cbi.2022.109808. Epub 2022 Jan 7.
63 Anti-inflammatory effects of dietary phenolic compounds in an in vitro model of inflamed human intestinal epithelium. Chem Biol Interact. 2010 Dec 5;188(3):659-67.
64 Inhibition of cell proliferation, invasion and migration by ursolic acid in human lung cancer cell lines. Toxicol In Vitro. 2011 Oct;25(7):1274-80. doi: 10.1016/j.tiv.2011.04.014. Epub 2011 Apr 20.
65 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
66 The BET bromodomain inhibitor JQ1 suppresses growth of pancreatic ductal adenocarcinoma in patient-derived xenograft models. Oncogene. 2016 Feb 18;35(7):833-45.
67 Role of the Akt/FoxO3a pathway in TGF-beta1-mediated mesangial cell dysfunction: a novel mechanism related to diabetic kidney disease. J Am Soc Nephrol. 2006 Dec;17(12):3325-35. doi: 10.1681/ASN.2006070754. Epub 2006 Nov 2.
68 Glyphosate and Aminomethylphosphonic Acid (AMPA) Modulate Glutathione S-Transferase in Non-Tumorigenic Prostate Cells. Int J Mol Sci. 2023 Mar 28;24(7):6323. doi: 10.3390/ijms24076323.
69 Alcohol and Cannabinoids Differentially Affect HIV Infection and Function of Human Monocyte-Derived Dendritic Cells (MDDC). Front Microbiol. 2015 Dec 22;6:1452. doi: 10.3389/fmicb.2015.01452. eCollection 2015.
70 Thyroid hormone-induced expression of inflammatory cytokines interfere with resveratrol-induced anti-proliferation of oral cancer cells. Food Chem Toxicol. 2019 Oct;132:110693. doi: 10.1016/j.fct.2019.110693. Epub 2019 Jul 20.
71 Acteoside inhibits human promyelocytic HL-60 leukemia cell proliferation via inducing cell cycle arrest at G0/G1 phase and differentiation into monocyte. Carcinogenesis. 2007 Sep;28(9):1928-36. doi: 10.1093/carcin/bgm126. Epub 2007 Jul 18.
72 Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
73 NF-kappaB and activator protein 1 response elements and the role of histone modifications in IL-1beta-induced TGF-beta1 gene transcription. J Immunol. 2006 Jan 1;176(1):603-15. doi: 10.4049/jimmunol.176.1.603.
74 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
75 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
76 A synthetic coumarin derivative (4-flourophenylacetamide-acetyl coumarin) impedes cell cycle at G0/G1 stage, induces apoptosis, and inhibits metastasis via ROS-mediated p53 and AKT signaling pathways in A549 cells. J Biochem Mol Toxicol. 2020 Oct;34(10):e22553. doi: 10.1002/jbt.22553. Epub 2020 Jun 24.
77 Early response of alpha2(I) collagen to acetaldehyde in human hepatic stellate cells is TGF-beta independent. Hepatology. 2005 Aug;42(2):343-52. doi: 10.1002/hep.20798.
78 Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
79 Ochratoxin A upregulates biomarkers associated with hypoxia and transformation in human kidney cells. Toxicol In Vitro. 2019 Jun;57:211-216. doi: 10.1016/j.tiv.2019.03.016. Epub 2019 Mar 12.
80 Vascular endothelial growth factor reduced and connective tissue growth factor induced by triamcinolone in ARPE19 cells under oxidative stress. Invest Ophthalmol Vis Sci. 2005 Mar;46(3):1062-8. doi: 10.1167/iovs.04-0761.
81 Evaluation of estrogen receptor alpha activation by glyphosate-based herbicide constituents. Food Chem Toxicol. 2017 Oct;108(Pt A):30-42.
82 Reversal of Sp1 transactivation and TGF1/SMAD1 signaling by H(2)S prevent nickel-induced fibroblast activation. Toxicol Appl Pharmacol. 2018 Oct 1;356:25-35. doi: 10.1016/j.taap.2018.07.029. Epub 2018 Jul 26.
83 Thioacetamide potentiates high cholesterol and high fat diet induced steato-hepatitic changes in livers of C57BL/6J mice: A novel eight weeks model of fibrosing NASH. Toxicol Lett. 2019 Apr;304:21-29. doi: 10.1016/j.toxlet.2019.01.001. Epub 2019 Jan 6.
84 Effect of exposure to Asian sand dust-Particulate matter on liver Tenascin-C expression in human cancer cell and mouse hepatic tissue. J Toxicol Sci. 2019;44(9):633-641. doi: 10.2131/jts.44.633.
85 Cytokine responses of intestinal epithelial-like Caco-2 cells to non-pathogenic and opportunistic pathogenic yeasts in the presence of butyric acid. Biosci Biotechnol Biochem. 2007 Oct;71(10):2428-34.
86 Organophosphorus Pesticides Induce Cytokine Release from Differentiated Human THP1 Cells. Am J Respir Cell Mol Biol. 2019 Nov;61(5):620-630. doi: 10.1165/rcmb.2018-0257OC.
87 Low-dose tributyltin triggers human chondrocyte senescence and mouse articular cartilage aging. Arch Toxicol. 2023 Feb;97(2):547-559. doi: 10.1007/s00204-022-03407-x. Epub 2022 Nov 1.
88 Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants. Life Sci. 2002 Mar 1;70(15):1821-39.
89 Sorafenib reduces steatosis-induced fibrogenesis in a human 3D co-culture model of non-alcoholic fatty liver disease. Environ Toxicol. 2021 Feb;36(2):168-176. doi: 10.1002/tox.23021. Epub 2020 Sep 12.
90 A novel 3-dimensional culture system uncovers growth stimulatory actions by TGF in pancreatic cancer cells. Cancer Biol Ther. 2011 Aug 1;12(3):198-207. doi: 10.4161/cbt.12.3.15979. Epub 2011 Aug 1.
91 Association of transforming growth factor beta1 genotype with therapeutic response to active vitamin D for postmenopausal osteoporosis. J Bone Miner Res. 2000 Mar;15(3):415-20. doi: 10.1359/jbmr.2000.15.3.415.
92 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
93 Synthesis of Reactive Sulfur Species in Cultured Vascular Endothelial Cells after Exposure to TGF-(1): Induction of Cystathionine -Lyase and Cystathionine -Synthase Expression Mediated by the ALK5-Smad2/3/4 and ALK5-Smad2/3-ATF4 Pathways. Int J Mol Sci. 2021 Oct 29;22(21):11762. doi: 10.3390/ijms222111762.
94 Niclosamide inhibits epithelial-mesenchymal transition and tumor growth in lapatinib-resistant human epidermal growth factor receptor 2-positive breast cancer. Int J Biochem Cell Biol. 2016 Feb;71:12-23. doi: 10.1016/j.biocel.2015.11.014. Epub 2015 Nov 28.
95 Defective TGF-beta signaling sensitizes human cancer cells to rapamycin. Oncogene. 2008 Feb 14;27(8):1055-62. doi: 10.1038/sj.onc.1210721. Epub 2007 Aug 13.
96 Transforming growth factor beta1 genotype and change in left ventricular mass during antihypertensive treatment--results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA). Clin Cardiol. 2004 Mar;27(3):169-73. doi: 10.1002/clc.4960270315.