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Literature summary for 3.1.4.1 extracted from

  • Lv, P.C.; Agama, K.; Marchand, C.; Pommier, Y.; Cushman, M.
    Design, synthesis, and biological evaluation of O-2-modified indenoisoquinolines as dual topoisomerase I-tyrosyl-DNA phosphodiesterase I inhibitors (2014), J. Med. Chem., 57, 4324-4336.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.1.4.1

Application

Application Comment Organism
medicine the enzyme is a promising and attractive target for cancer treatment Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
(5Z)-5-(2,3,4-trihydroxybenzylidene)-1,3-thiazolidine-2,4-dithione
-
 Homo sapiens
2-(3-(dimethylamino)propoxy)-3-methoxy-6-(3-morpholinopropyl)-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
-
 Homo sapiens
2-(3-(ethylamino)propoxy)-3-methoxy-6-(3-morpholinopropyl)-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
-
 Homo sapiens
2-(3-aminopropoxy)-3-methoxy-6-(3-morpholinopropyl)-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
-
 Homo sapiens
3-methoxy-6-(3-morpholinopropyl)-2-(3-(piperidin-1-yl)-propoxy)-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
-
 Homo sapiens
3-methoxy-6-(3-morpholinopropyl)-2-(3-(pyrrolidin-1-yl)-propoxy)-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
-
 Homo sapiens
6,6'-[propane-1,3-diylbis(iminopropane-3,1-diyl)]bis(5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione)
-
 Homo sapiens
6-(3-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
 Homo sapiens
furamidine
-
 Homo sapiens
additional information structure-based drug design, synthesis, and biological evaluation of O-2-modified indenoisoquinolines as dual topoisomerase I-tyrosyl-DNA phosphodiesterase I inhibitors, structure-activity relationships, molecular docking studies, and molecular modeling, overview. No inhibition by 2-(allyloxy)-3-methoxy-6-(3-morpholinopropyl)-5H-[1,3]-dioxolo[4',5':5,6]indeno [1,2-c]isoquinoline-5,12(6H)-dione, 3-methoxy-2-(3-morpholinopropoxy)-6-(3-morpholinopropyl)-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione, 3-methoxy-2-(3-(4-methylpiperazin-1-yl)propoxy)-6-(3-morpholinopropyl)-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]-isoquinoline-5,12(6H)-dione, methyl 2-((3-methoxy-6-(3-morpholinopropyl)-5,12-dioxo-6,12-dihydro-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]-isoquinolin-2-yl)oxy)acetate, and 2-((12-hydroxy-3-methoxy-6-(3-morpholinopropyl)-5-oxo-6,12-dihydro-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]-isoquinolin-2-yl)oxy)acetohydrazide. Antiproliferative potencies of selected O-2-modified indenoisoquinolines, overview Homo sapiens
NSC88915 a steroid inhibitor Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens the enzyme catalyzes the hydrolysis of 3' phosphotyrosyl linkers and other 3'-end blocking lesions. When Top1 nicks double-stranded DNA, a covalent cleavage complex is formed that can be repaired by the enzyme, the mechanism involves the following steps: first, as Lys265 and Lys495 residues in the catalytic site coordinate the oxygen atoms of the phosphate group, His263 attacks the phosphorus atom linked to the oxygen of the Top1 catalytic residue, Tyr723, at the 3' end of DNA. Second, the TDP1-DNA covalent intermediate formed is hydrolyzed by a His493-activated water molecule, leading to the generation of a DNA product with a 3' phosphate ?
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information the enzyme catalyzes the hydrolysis of 3' phosphotyrosyl linkers and other 3'-end blocking lesions. When Top1 nicks double-stranded DNA, a covalent cleavage complex is formed that can be repaired by the enzyme, the mechanism involves the following steps: first, as Lys265 and Lys495 residues in the catalytic site coordinate the oxygen atoms of the phosphate group, His263 attacks the phosphorus atom linked to the oxygen of the Top1 catalytic residue, Tyr723, at the 3' end of DNA. Second, the TDP1-DNA covalent intermediate formed is hydrolyzed by a His493-activated water molecule, leading to the generation of a DNA product with a 3' phosphate Homo sapiens ?
-
 ?
additional information substrate is a 5'-[32P]-labeled single-stranded DNA oligonucleotide containing a 3' phosphotyrosine (N14Y) Homo sapiens ?
-
 ?

Synonyms

Synonyms Comment Organism
TDP1
-
 Homo sapiens
tyrosyl-DNA phosphodiesterase I
-
 Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
22
-
 assay at room temperature Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
 assay at Homo sapiens

General Information

General Information Comment Organism
evolution tyrosyl-DNA phosphodiesterase I is a member of the phospholipase D superfamily of enzymes Homo sapiens
physiological function the enzyme plays a critical role in the cellular repair of topoisomerase 1-mediated DNA damage Homo sapiens