Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXTG0C7)

DOT Name Thymidylate synthase
Synonyms TS; TSase; EC 2.1.1.45
Gene Name TYMS
UniProt ID
TYSY_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1HVY ; 1HW3 ; 1HW4 ; 1HZW ; 1I00 ; 1JU6 ; 1JUJ ; 1YPV ; 2ONB ; 2RD8 ; 2RDA ; 3EAW ; 3EBU ; 3ED7 ; 3EDW ; 3EF9 ; 3EGY ; 3EHI ; 3EJL ; 3GG5 ; 3GH0 ; 3GH2 ; 3H9K ; 3HB8 ; 3N5E ; 3N5G ; 3OB7 ; 4E28 ; 4FGT ; 4G2O ; 4G6W ; 4GD7 ; 4GYH ; 4H1I ; 4JEF ; 4KPW ; 4O1U ; 4O1X ; 4UP1 ; 5HS3 ; 5WRN ; 5X4W ; 5X4X ; 5X4Y ; 5X5A ; 5X5D ; 5X5Q ; 5X66 ; 5X67 ; 5X69 ; 6OJU ; 6OJV ; 6PF3 ; 6PF4 ; 6PF5 ; 6PF6 ; 6QXG ; 6QXH ; 6QYQ ; 6R2E ; 6ZXO
EC Number
2.1.1.45
Pfam ID
PF00303
Sequence
MPVAGSELPRRPLPPAAQERDAEPRPPHGELQYLGQIQHILRCGVRKDDRTGTGTLSVFG
MQARYSLRDEFPLLTTKRVFWKGVLEELLWFIKGSTNAKELSSKGVKIWDANGSRDFLDS
LGFSTREEGDLGPVYGFQWRHFGAEYRDMESDYSGQGVDQLQRVIDTIKTNPDDRRIIMC
AWNPRDLPLMALPPCHALCQFYVVNSELSCQLYQRSGDMGLGVPFNIASYALLTYMIAHI
TGLKPGDFIHTLGDAHIYLNHIEPLKIQLQREPRPFPKLRILRKVEKIDDFKAEDFQIEG
YNPHPTIKMEMAV
Function
Catalyzes the reductive methylation of 2'-deoxyuridine 5'-monophosphate (dUMP) to thymidine 5'-monophosphate (dTMP), using the cosubstrate, 5,10- methylenetetrahydrofolate (CH2H4folate) as a 1-carbon donor and reductant and contributes to the de novo mitochondrial thymidylate biosynthesis pathway.
KEGG Pathway
Pyrimidine metabolism (hsa00240 )
One carbon pool by folate (hsa00670 )
Metabolic pathways (hsa01100 )
Nucleotide metabolism (hsa01232 )
Antifolate resistance (hsa01523 )
Reactome Pathway
G1/S-Specific Transcription (R-HSA-69205 )
Interconversion of nucleotide di- and triphosphates (R-HSA-499943 )
BioCyc Pathway
MetaCyc:HS11096-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 10 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Methotrexate DM2TEOL Approved Thymidylate synthase decreases the response to substance of Methotrexate. [55]
Fluorouracil DMUM7HZ Approved Thymidylate synthase decreases the response to substance of Fluorouracil. [55]
Cytarabine DMZD5QR Approved Thymidylate synthase affects the response to substance of Cytarabine. [56]
Etoposide DMNH3PG Approved Thymidylate synthase affects the response to substance of Etoposide. [56]
Daunorubicin DMQUSBT Approved Thymidylate synthase affects the response to substance of Daunorubicin. [56]
Capecitabine DMTS85L Approved Thymidylate synthase decreases the response to substance of Capecitabine. [57]
Prednisone DM2HG4X Approved Thymidylate synthase affects the response to substance of Prednisone. [56]
Mercaptopurine DMTM2IK Approved Thymidylate synthase affects the response to substance of Mercaptopurine. [56]
Floxuridine DM04LR2 Approved Thymidylate synthase decreases the response to substance of Floxuridine. [58]
Tegafur DM31ZQM Approved Thymidylate synthase affects the response to substance of Tegafur. [59]
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⏷ Show the Full List of 10 Drug(s)
62 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Thymidylate synthase. [1]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Thymidylate synthase. [2]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Thymidylate synthase. [3]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Thymidylate synthase. [4]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Thymidylate synthase. [5]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Thymidylate synthase. [6]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Thymidylate synthase. [7]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Thymidylate synthase. [8]
Quercetin DM3NC4M Approved Quercetin increases the expression of Thymidylate synthase. [9]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Thymidylate synthase. [10]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Thymidylate synthase. [11]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Thymidylate synthase. [12]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Thymidylate synthase. [13]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Thymidylate synthase. [12]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Thymidylate synthase. [14]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Thymidylate synthase. [15]
Marinol DM70IK5 Approved Marinol decreases the expression of Thymidylate synthase. [16]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Thymidylate synthase. [17]
Progesterone DMUY35B Approved Progesterone decreases the expression of Thymidylate synthase. [18]
Menadione DMSJDTY Approved Menadione affects the expression of Thymidylate synthase. [19]
Folic acid DMEMBJC Approved Folic acid increases the expression of Thymidylate synthase. [20]
Troglitazone DM3VFPD Approved Troglitazone decreases the expression of Thymidylate synthase. [21]
Azathioprine DMMZSXQ Approved Azathioprine decreases the expression of Thymidylate synthase. [22]
Paclitaxel DMLB81S Approved Paclitaxel increases the expression of Thymidylate synthase. [6]
Malathion DMXZ84M Approved Malathion decreases the expression of Thymidylate synthase. [23]
Mitomycin DMH0ZJE Approved Mitomycin increases the expression of Thymidylate synthase. [6]
Simvastatin DM30SGU Approved Simvastatin decreases the expression of Thymidylate synthase. [24]
Benzatropine DMF7EXL Approved Benzatropine increases the expression of Thymidylate synthase. [25]
Palbociclib DMD7L94 Approved Palbociclib decreases the expression of Thymidylate synthase. [26]
Bicalutamide DMZMSPF Approved Bicalutamide decreases the expression of Thymidylate synthase. [27]
Gefitinib DM15F0X Approved Gefitinib decreases the expression of Thymidylate synthase. [28]
Docetaxel DMDI269 Approved Docetaxel decreases the expression of Thymidylate synthase. [29]
AC220 DM8Y4JS Approved AC220 decreases the expression of Thymidylate synthase. [30]
Pemetrexed DMMX2E6 Approved Pemetrexed decreases the activity of Thymidylate synthase. [31]
Raltitrexed DMT9K8G Approved Raltitrexed decreases the activity of Thymidylate synthase. [31]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Thymidylate synthase. [32]
Resveratrol DM3RWXL Phase 3 Resveratrol increases the expression of Thymidylate synthase. [33]
Camptothecin DM6CHNJ Phase 3 Camptothecin increases the expression of Thymidylate synthase. [6]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of Thymidylate synthase. [34]
Belinostat DM6OC53 Phase 2 Belinostat decreases the expression of Thymidylate synthase. [35]
phorbol 12-myristate 13-acetate DMJWD62 Phase 2 phorbol 12-myristate 13-acetate increases the expression of Thymidylate synthase. [36]
Tanespimycin DMNLQHK Phase 2 Tanespimycin decreases the expression of Thymidylate synthase. [37]
Amsilarotene DMOB01U Phase 2 Amsilarotene decreases the expression of Thymidylate synthase. [38]
Plevitrexed DM7Y60I Phase 2 Plevitrexed decreases the activity of Thymidylate synthase. [39]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Thymidylate synthase. [40]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Thymidylate synthase. [41]
BETULINIC ACID DMBUI2A Phase 1 BETULINIC ACID decreases the expression of Thymidylate synthase. [42]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Thymidylate synthase. [43]
Phenolphthalein DM5SICT Withdrawn from market Phenolphthalein decreases the activity of Thymidylate synthase. [44]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN decreases the expression of Thymidylate synthase. [45]
Oxamflatin DM1TG3C Terminated Oxamflatin decreases the expression of Thymidylate synthase. [46]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Thymidylate synthase. [47]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Thymidylate synthase. [46]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of Thymidylate synthase. [33]
geraniol DMS3CBD Investigative geraniol decreases the expression of Thymidylate synthase. [48]
Rapamycin Immunosuppressant Drug DM678IB Investigative Rapamycin Immunosuppressant Drug decreases the expression of Thymidylate synthase. [49]
Cycloheximide DMGDA3C Investigative Cycloheximide decreases the expression of Thymidylate synthase. [50]
U0126 DM31OGF Investigative U0126 decreases the expression of Thymidylate synthase. [51]
Wogonin DMGCF51 Investigative Wogonin increases the expression of Thymidylate synthase. [52]
SU9516 DMQHG0R Investigative SU9516 decreases the expression of Thymidylate synthase. [53]
6-O-Cyclohexylmethyl Guanine DMDIW08 Investigative 6-O-Cyclohexylmethyl Guanine decreases the expression of Thymidylate synthase. [27]
Distamycin A DMPVNDK Investigative Distamycin A decreases the expression of Thymidylate synthase. [54]
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⏷ Show the Full List of 62 Drug(s)

References

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