Literature summary for 1.1.1.239 extracted from

Guise, C.P.; Abbattista, M.R.; Singleton, R.S.; Holford, S.D.; Connolly, J.; Dachs, G.U.; Fox, S.B.; Pollock, R.; Harvey, J.; Guilford, P.; Donate, F.; Wilson, W.R.; Patterson, A.V.
The bioreductive prodrug PR-104A is activated under aerobic conditions by human aldo-keto reductase 1C3 (2010), Cancer Res., 70, 1573-1584.

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Application

Application	Comment	Organism
medicine	enzyme is involved in activation of prodrug PR-104A designed to exploit tumor hypoxia. AKR1C3 protein is detected by Western blot in 7 of 23 cell lines and correlates with oxic PR-104A metabolism. AKR1C3 is unable to sensitize cells to 10 other bioreductive prodrugs and is associated with single-agent PR-104 activity across a panel of 9 human tumor xenograft models. Overexpression in two AKR1C3-negative tumor xenograft models strongly enhances PR-104 antitumor activity. Marked upregulation of AKR1C3 is found in a subset including hepatocellular, bladder, renal, gastric, and non-small cell lung carcinoma	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
carcinoma cell	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
2-[(2-bromoethyl)(2-[[(2-hydroxyethyl)amino]methyl]-4,6-dinitrophenyl)amino]ethyl methanesulfonate + 2 NADH + 2 H+	i.e. PR-104A, phosphate ester prodrug designed to exploit tumor hypoxia	Homo sapiens	2-[(2-bromoethyl)[4-(hydroxyamino)-2-[[(2-hydroxyethyl)amino]methyl]-6-nitrophenyl]amino]ethyl methanesulfonate + 2 NAD+ + H2O	i.e. PR-104H, enzyme acts as nitroreductase for activation of PR-104A	?

Expression

Organism	Comment	Expression
Homo sapiens	marked upregulation of AKR1C3 is found in a subset including hepatocellular, bladder, renal, gastric, and non-small cell lung carcinoma	up

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Release 2023.1 (January 2023)