thymidylate synthetase | 2.1.1.- Methyltransferases | IUPHAR/BPS Guide to PHARMACOLOGY

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thymidylate synthetase

Target not currently curated in GtoImmuPdb

Target id: 2642

Nomenclature: thymidylate synthetase

Abbreviated Name: TYMS

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

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
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
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:

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

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter 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
View species-specific inhibitor tables
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0034097 response to cytokine IEA


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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. Oncologist, 4 (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 28/11/2018. Accessed on 05/08/2020. IUPHAR/BPS Guide to PHARMACOLOGY,