Literature summary for 2.4.2.4 extracted from

  • de Moura Sperotto, N.D.; Deves Roth, C.; Rodrigues-Junior, V.S.; Ev Neves, C.; Reisdorfer Paula, F.; da Silva Dadda, A.; Bergo, P.; Freitas de Freitas, T.; Souza Macchi, F.; Moura, S.; Duarte de Souza, A.P.; Campos, M.M.; Valim Bizarro, C.; Santos, D.S.; Basso, L.A.; Machado, P.
    Design of novel inhibitors of human thymidine phosphorylase synthesis, enzyme inhibition, in vitro toxicity, and impact on human glioblastoma cancer (2019), J. Med. Chem., 62, 1231-1245 .
    View publication on PubMed

Inhibitors

Inhibitors Comment Organism Structure
1H-pyrrolo[2,3-d]pyrimidine-2,4(3H,7H)-dione
-
Homo sapiens
5-bromo-6-[[(1,3-dihydroxypropan-2-yl)amino]methyl]pyrimidine-2,4(1H,3H)-dione
-
Homo sapiens
5-bromo-6-[[(2,3-dihydroxypropyl)amino]methyl]pyrimidine-2,4(1H,3H)-dione
-
Homo sapiens
5-bromo-6-[[(2-hydroxyethyl)amino]methyl]pyrimidine-2,4(1H,3H)-dione
-
Homo sapiens
5-chloro-6-[1-(2-iminopyrrolidinyl)methyl] uracil hydrochloride
-
Homo sapiens
5-chloro-6-[[(1,3-dihydroxypropan-2-yl)amino]methyl]pyrimidine-2,4(1H,3H)-dione
-
Homo sapiens
5-chloro-6-[[(2-hydroxyethyl)amino]methyl]pyrimidine-2,4(1H,3H)-dione
-
Homo sapiens
5-iodo-6-[[(piperidin-1-yl)amino]methyl]pyrimidine-2,4(1H,3H)-dione
-
Homo sapiens
6-(((1,3-dihydroxypropan-2-yl)amino)methyl)-5-iodopyrimidine-2,4(1H,3H)-dione the inhibitor shows a noncompetitive inhibition mode with both thymidine and inorganic phosphate substrates. Effect of 8g on cell viabilities of different cancer cell lines, overview Homo sapiens
6-[[(2,3-dihydroxypropyl)(methyl)amino]methyl]-5-iodopyrimidine-2,4(1H,3H)-dione
-
Homo sapiens
6-[[(2-hydroxyethyl)amino]methyl]-5-iodopyrimidine-2,4(1H,3H)-dione
-
Homo sapiens
6-amino-5-bromopyrimidine-2,4(1H,3H)-dione
-
Homo sapiens
6-[[bis(2-ethoxyethyl)amino]methyl]-5-iodopyrimidine-2,4(1H,3H)-dione
-
Homo sapiens
6-[(dimethylamino)methyl]-5-iodopyrimidine-2,4(1H,3H)-dione
-
Homo sapiens
6-[(dipentylamino)methyl]-5-iodopyrimidine-2,4(1H,3H)-dione
-
Homo sapiens
6-[(dipropylamino)methyl]-5-iodopyrimidine-2,4(1H,3H)-dione
-
Homo sapiens
additional information designed as transition-state analogues by mimicking the oxacarbenium ion, the pyrimidine-2,4-diones are synthesized and evaluated as inhibitors of hTP activity, kinetic mechanisms for the most potent molecule and evaluation of the interaction mode using molecular docking, overview Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
thymidine + phosphate Homo sapiens
-
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
-
r

Organism

Organism UniProt Comment Textmining
Homo sapiens P19971
-
-

Source Tissue

Source Tissue Comment Organism Textmining
glioblastoma cell
-
Homo sapiens
-
U-87MG cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
thymidine + phosphate
-
Homo sapiens thymine + 2-deoxy-alpha-D-ribose 1-phosphate
-
r

Synonyms

Synonyms Comment Organism
HTP
-
Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.00002
-
5-chloro-6-[1-(2-iminopyrrolidinyl)methyl] uracil hydrochloride pH and temperature not specified in the publication Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.036
-
pH and temperature not specified in the publication Homo sapiens 6-[[(2,3-dihydroxypropyl)(methyl)amino]methyl]-5-iodopyrimidine-2,4(1H,3H)-dione
0.001
-
pH and temperature not specified in the publication Homo sapiens 5-chloro-6-[[(1,3-dihydroxypropan-2-yl)amino]methyl]pyrimidine-2,4(1H,3H)-dione
0.012
-
pH and temperature not specified in the publication Homo sapiens 6-[[(2-hydroxyethyl)amino]methyl]-5-iodopyrimidine-2,4(1H,3H)-dione
0.017
-
pH and temperature not specified in the publication Homo sapiens 6-amino-5-bromopyrimidine-2,4(1H,3H)-dione
0.1
-
above, pH and temperature not specified in the publication Homo sapiens 5-bromo-6-[[(2,3-dihydroxypropyl)amino]methyl]pyrimidine-2,4(1H,3H)-dione
0.1
-
above, pH and temperature not specified in the publication Homo sapiens 6-[(dipropylamino)methyl]-5-iodopyrimidine-2,4(1H,3H)-dione
0.087
-
pH and temperature not specified in the publication Homo sapiens 6-[[bis(2-ethoxyethyl)amino]methyl]-5-iodopyrimidine-2,4(1H,3H)-dione
0.00012
-
pH and temperature not specified in the publication Homo sapiens 6-(((1,3-dihydroxypropan-2-yl)amino)methyl)-5-iodopyrimidine-2,4(1H,3H)-dione
0.04
-
pH and temperature not specified in the publication Homo sapiens 1H-pyrrolo[2,3-d]pyrimidine-2,4(3H,7H)-dione
0.04
-
pH and temperature not specified in the publication Homo sapiens 5-bromo-6-[[(2,3-dihydroxypropyl)amino]methyl]pyrimidine-2,4(1H,3H)-dione
0.034
-
pH and temperature not specified in the publication Homo sapiens 5-iodo-6-[[(piperidin-1-yl)amino]methyl]pyrimidine-2,4(1H,3H)-dione
0.000035
-
pH and temperature not specified in the publication Homo sapiens 5-chloro-6-[1-(2-iminopyrrolidinyl)methyl] uracil hydrochloride
0.028
-
pH and temperature not specified in the publication Homo sapiens 6-[(dipentylamino)methyl]-5-iodopyrimidine-2,4(1H,3H)-dione
0.024
-
pH and temperature not specified in the publication Homo sapiens 5-bromo-6-[[(2-hydroxyethyl)amino]methyl]pyrimidine-2,4(1H,3H)-dione
0.0056
-
pH and temperature not specified in the publication Homo sapiens 5-bromo-6-[[(1,3-dihydroxypropan-2-yl)amino]methyl]pyrimidine-2,4(1H,3H)-dione
0.0084
-
pH and temperature not specified in the publication Homo sapiens 6-[(dimethylamino)methyl]-5-iodopyrimidine-2,4(1H,3H)-dione
0.039
-
pH and temperature not specified in the publication Homo sapiens 5-chloro-6-[[(2-hydroxyethyl)amino]methyl]pyrimidine-2,4(1H,3H)-dione

General Information

General Information Comment Organism
malfunction overexpression of human thymidine phosphorylase (hTP) has been associated with cancer aggressiveness and poor prognosis by triggering proangiogenic and antiapoptotic signaling Homo sapiens