Literature summary for 1.17.4.1 extracted from

Petrelli, R.; Meli, M.; Vita, P.; Torquati, I.; Ferro, A.; Vodnala, M.; DAlessandro, N.; Tolomeo, M.; Del Bello, F.; Kusumanchi, P.; Franchetti, P.; Grifantini, M.; Jayaram, H.N.; Hofer, A.; Cappellacci, L.
From the covalent linkage of drugs to novel inhibitors of ribonucleotide reductase synthesis and biological evaluation of valproic esters of 3-C-methyladenosine (2014), Bioorg. Med. Chem. Lett., 24, 5304-5309 .

Search for more literature for 1.17.4.1

Activating Compound

Activating Compound	Comment	Organism	Structure
ATP	allosteric effector of CDP reaction	Homo sapiens

Application

Application	Comment	Organism
drug development	ribonucleotide reductase is a key enzyme in DNA synthesis and cell growth control and represents an excellent target for anticancer therapy. 5'-O-valproyl-3'-C-methyladenosine inhibits ribonucleotide reductase activity by competing with ATP as an allosteric effector and concomitantly reduces the intracellular deoxyribonucleoside triphosphate pools. In contrast to previously used ribonucleotide reductase nucleoside analogs does not require intracellular kinases for its activity and therefore holds promise against drug resistant tumors with downregulated nucleoside kinases	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
5'-O-valproyl-3'-C-methyladenosine	inhibits ribonucleotide reductase activity by competing with ATP as an allosteric effector and concomitantlyreduces the intracellular deoxyribonucleoside triphosphate pools. In contrast to previously used ribonucleotide reductase nucleoside analogs does not require intracellular kinases for its activity and therefore holds promise against drug resistant tumors with downregulated nucleoside kinases	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P23921	ribonucleoside-diphosphate reductase large subunit	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
HL-60 cell	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
ADP + thioredoxin	-	Homo sapiens	2'-dADP + thioredoxin disulfide + H2O	-	?
CDP + thioredoxin	-	Homo sapiens	2'-dCDP + thioredoxin disulfide + H2O	-	?

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism	Structure
0.4	-	5'-O-valproyl-3'-C-methyladenosine	pH and temperature not specified in the publication	Homo sapiens

General Information

General Information	Comment	Organism
metabolism	key enzyme in DNA synthesis and cell growth control	Homo sapiens

Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.

Release 2023.1 (January 2023)