thymidylate synthetase

Target id: 2642

Nomenclature: thymidylate synthetase

Family: 2.1.1.- Methyltransferases, Nucleoside synthesis and metabolism

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for thymidylate synthetase in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 313 18p11.31-p11.21 TYMS thymidylate synthetase
Mouse - 307 5 B1 Tyms thymidylate synthase
Rat - 307 9q38 Tyms thymidylate synthetase
Previous and Unofficial Names
TMS | Tsase
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of human thymidylate synthase bound to a peptide inhibitor
PDB Id:  3N5E
Resolution:  2.26Å
Species:  Human
References:  2
Enzyme Reaction
EC Number: 2.1.1.45

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
plevitrexed Mm Inhibition 9.4 pKi 6
pKi 9.4 (Ki 4.4x10-10 M) [6]
Description: Measured using partially purified thymidylate synthase from mouse L1210 leukemia cells.
ONX-0801 Mm Inhibition 8.9 pKi 5
pKi 8.9 (Ki 1.2x10-9 M) [5]
Description: Thymidylate synthase isolated from mouse L1210 lymphocytic leukemia cells.
pemetrexed Hs Inhibition 7.0 pKi 8
pKi 7.0 (Ki 1.09x10-7 M) [8]
raltitrexed Mm Inhibition 6.4 pKi 1
pKi 6.4 (Ki 4.18x10-7 M) [1]
raltitrexed Hs Inhibition 6.5 pIC50 4
pIC50 6.5 (IC50 2.9x10-7 M) [4]
capecitabine Hs Inhibition - - 3,7
[3,7]
View species-specific inhibitor tables

References

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1. Bisset GM, Pawelczak K, Jackman AL, Calvert AH, Hughes LR. (1992) Syntheses and thymidylate synthase inhibitory activity of the poly-gamma-glutamyl conjugates of N-[5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino ]-2-thenoyl]-L-glutamic acid (ICI D1694) and other quinazoline antifolates. J. Med. Chem.35 (5): 859-66. [PMID:1372358]

2. Cardinale D, Guaitoli G, Tondi D, Luciani R, Henrich S, Salo-Ahen OM, Ferrari S, Marverti G, Guerrieri D, Ligabue A et al.. (2011) Protein-protein interface-binding peptides inhibit the cancer therapy target human thymidylate synthase. Proc. Natl. Acad. Sci. U.S.A.108 (34): E542-9. [PMID:21795601]

3. Carlini LE, Meropol NJ, Bever J, Andria ML, Hill T, Gold P, Rogatko A, Wang H, Blanchard RL. (2005) UGT1A7 and UGT1A9 polymorphisms predict response and toxicity in colorectal cancer patients treated with capecitabine/irinotecan. Clin. Cancer Res.11 (3): 1226-36. [PMID:15709193]

4. Gangjee A, Zhao Y, Ihnat MA, Thorpe JE, Bailey-Downs LC, Kisliuk RL. (2012) Novel tricyclic indeno[2,1-d]pyrimidines with dual antiangiogenic and cytotoxic activities as potent antitumor agents. Bioorg. Med. Chem.20 (14): 4217-25. [PMID:22739090]

5. Gibbs DD, Theti DS, Wood N, Green M, Raynaud F, Valenti M, Forster MD, Mitchell F, Bavetsias V, Henderson E et al.. (2005) BGC 945, a novel tumor-selective thymidylate synthase inhibitor targeted to alpha-folate receptor-overexpressing tumors. Cancer Res.65 (24): 11721-8. [PMID:16357184]

6. Marsham PR, Wardleworth JM, Boyle FT, Hennequin LF, Kimbell R, Brown M, Jackman AL. (1999) Design and synthesis of potent non-polyglutamatable quinazoline antifolate thymidylate synthase inhibitors. J. Med. Chem.42 (19): 3809-20. [PMID:10508430]

7. Papamichael D. (1999) The use of thymidylate synthase inhibitors in the treatment of advanced colorectal cancer: current status. Oncologist4 (6): 478-87. [PMID:10631692]

8. Shih C, Habeck LL, Mendelsohn LG, Chen VJ, Schultz RM. (1998) Multiple folate enzyme inhibition: mechanism of a novel pyrrolopyrimidine-based antifolate LY231514 (MTA). Adv. Enzyme Regul.38: 135-52. [PMID:9762351]

How to cite this page

2.1.1.- Methyltransferases: thymidylate synthetase. Last modified on 05/06/2017. Accessed on 19/10/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2642.