4-Hydroxyquinazoline

4-HQN (491-36-1) is an inhibitor of poly(ADP-ribose) polymerase (PARP) (IC50= 9.5 μM).1Displays mixed inhibition with respect to NAD+. Protective against ischemia-reperfusion induced ROS production, and subsequent mitochondrial and cell damage in rat heart.24-HQN is anti-inflammatory in LPS-induced endotoxic micein vivo; decreases NF-κB and AP-1 activation.3

off-white to light beige crystalline powder

4-Hydroxyquinazoline is been used to inhibit PARP (poly(ADP-ribose) synthetase) which catalyzes covalent attachment of the ADP-ribose moiety of NAD+ to various proteins. This compound specifically and potently inhibits PARP-1. 4-HQN demonstrates the ability to decrease activation of transcription factor NFκB and AP-1 in lipopolysaccharide-induced shock. Mechanistic studies indicate that 4-HQN activates PI3-kinase/Akt pathway in the liver, spleen, and lung and down-regulates two elements of the MAP kinase system. Additionally, this agent has been observed to decrease ischemia-reperfusion-induced increase of protein oxidation, single-strand DNA breaks, lipid peroxidation, and mitochondrial reactive oxygen species production in the reperfusion period.

4-Hydroxyquinazoline shows anti-microbial and anti-carcinogenic activity as seen in studies due to the quinazoline moiety.

ChEBI: 1H-quinazolin-4-one is a member of quinazolines.

The Journal of Organic Chemistry, 16, p. 1669, 1951 DOI: 10.1021/jo50005a003

Not classified

Inhibitor of poly(ADP-ribose) polymerase (PARP) (IC 50 = 9.5 μ M); displays mixed inhibition with respect to NAD + . Protective against ischemia-reperfusion induced ROS production, and subsequent mitochondrial and cell damage in rat heart. Anti-inflammatory in LPS-induced endotoxic mice in vivo ; decreases NF- κ B and AP-1 activation.

[1] M BANASIK. Specific inhibitors of poly(ADP-ribose) synthetase and mono(ADP-ribosyl)transferase.[J]. The Journal of Biological Chemistry, 1992, 267 3: 1569-1575.
[2] R. HALMOSI. Effect of poly(ADP-ribose) polymerase inhibitors on the ischemia-reperfusion-induced oxidative cell damage and mitochondrial metabolism in Langendorff heart perfusion system.[J]. Molecular Pharmacology, 2001, 59 6 1: 1497-1505. DOI:10.1124/mol.59.6.1497
[3] BALAZS VERES. Regulation of kinase cascades and transcription factors by a poly(ADP-ribose) polymerase-1 inhibitor, 4-hydroxyquinazoline, in lipopolysaccharide-induced inflammation in mice.[J]. Journal of Pharmacology and Experimental Therapeutics, 2004, 310 1: 247-255. DOI:10.1124/jpet.104.065151