Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTP1UKZ)

• DTT Name: Thymidylate synthase messenger RNA (TYMS mRNA)
• Synonyms: TSase (mRNA); TS (mRNA); OK/SW-cl.29 (mRNA)
• Gene Name: TYMS
• DTT Type: Successful target; [1]
• Related Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• BioChemical Class: mRNA target
• UniProt ID: TYSY_HUMAN
• TTD ID: T79249
• EC Number: EC 2.1.1.45
• Sequence:
  MPVAGSELPRRPLPPAAQERDAEPRPPHGELQYLGQIQHILRCGVRKDDRTGTGTLSVFG
  MQARYSLRDEFPLLTTKRVFWKGVLEELLWFIKGSTNAKELSSKGVKIWDANGSRDFLDS
  LGFSTREEGDLGPVYGFQWRHFGAEYRDMESDYSGQGVDQLQRVIDTIKTNPDDRRIIMC
  AWNPRDLPLMALPPCHALCQFYVVNSELSCQLYQRSGDMGLGVPFNIASYALLTYMIAHI
  TGLKPGDFIHTLGDAHIYLNHIEPLKIQLQREPRPFPKLRILRKVEKIDDFKAEDFQIEG
  YNPHPTIKMEMAV
• Function: 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-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Solid tumour/cancer	2A00-2F9Z	Approved	[1]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
TS antisense + raltitrexed	DMIV75Q	Solid tumour/cancer	2A00-2F9Z	Investigative	[1]

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Thymidylate synthase (TYMS) DME Info
• Gene Name: TYMS

2 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Solid tumour/cancer	2A00-2F9Z	Approved	[2]
Methotrexate	DM2TEOL	leukaemia	2A60-2B33	Approved	[3]

1 Investigative Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2'-deoxyuridylic acid	DMPV1LU	Discovery agent	N.A.	Investigative	[4]

References

• [1] Design and development of antisense drugs. Expert Opin. Drug Discov. 2008 3(10):1189-1207.
• [2] 5-Fluorouracil pharmacogenomics: still rocking after all these years? Pharmacogenomics. 2011 Feb;12(2):251-65.
• [3] The pharmacogenetics of methotrexate. Rheumatology (Oxford). 2007 Oct;46(10):1520-4.
• [4] Distribution of mutations in human thymidylate synthase yielding resistance to 5-fluorodeoxyuridine. J Biol Chem. 2002 Sep 27;277(39):36304-11.