Matches in SemOpenAlex for { <https://semopenalex.org/work/W2073537302> ?p ?o ?g. }
- W2073537302 endingPage "1071" @default.
- W2073537302 startingPage "1047" @default.
- W2073537302 abstract "Poly(ADP-ribose) polymerase (PARP) is a DNA-binding protein that is activated by nicks in the DNA molecule. It regulates the activity of various enzymes, including itself, that are involved in the control of DNA metabolism. Evidence obtained with both benzamide and isoquinolinone PARP inhibitors and the PARP-1(-/-) phenotype, clearly indicate that PARP plays an important role in NO/ROS-induced cell damage during inflammation, ischaemia and neurodegeneration. PARP is involved in the maintenance of genomic stability and PARP inhibition may also potentiate the cytotoxic action of agents used in cancer therapy. Benzamides, although not very potent (IC50 ~ 20 – 50 μM) PARP inhibitors, have been widely used to probe PARP functions, because of their lack of toxicity both in vitro and in vivo, even at high doses. In the early 1990s, a new class of very potent PARP inhibitors (i.e., at least 100-fold more potent thatn benzamide), the dihydroisoquinolinones, benzamide derivatives with the carbamoyl group constrained into the antiorientation, was discovered. At the same time, a large structure–activity surevey identified over 13 chemical classes of PARP inhibitors, the most potent calss sharing a common structural feature, the presence of a carbonyl group built into a polyaromatic heterocyclic skeleton or a carbamoyl group attached to an aromatic ring. Recently, a better knowledge of the PARP catalytic domain and the use of its crystal structure have led to the design and synthesis of the tricyclic lactam indoles, active at low nanomolar concentrations, and with favourable physical properties and in vivo characteristics. In the last few years the interest in PARP as a therapeutic target has been rapidly growing. This article reviews the patents filed for new PARP inhibitors over the last three years, up to February 2002, and their development status." @default.
- W2073537302 created "2016-06-24" @default.
- W2073537302 creator A5091250799 @default.
- W2073537302 date "2002-07-01" @default.
- W2073537302 modified "2023-10-11" @default.
- W2073537302 title "New inhibitors of poly(ADP-ribose) polymerase and their potential therapeutic targets" @default.
- W2073537302 cites W1516722054 @default.
- W2073537302 cites W1519767585 @default.
- W2073537302 cites W1519922008 @default.
- W2073537302 cites W154144866 @default.
- W2073537302 cites W1541897964 @default.
- W2073537302 cites W1546873627 @default.
- W2073537302 cites W1570879094 @default.
- W2073537302 cites W1584549675 @default.
- W2073537302 cites W1605052148 @default.
- W2073537302 cites W1679032940 @default.
- W2073537302 cites W1904188511 @default.
- W2073537302 cites W1966934669 @default.
- W2073537302 cites W1967029035 @default.
- W2073537302 cites W1968263866 @default.
- W2073537302 cites W1969175804 @default.
- W2073537302 cites W1971953001 @default.
- W2073537302 cites W1973912514 @default.
- W2073537302 cites W1974725853 @default.
- W2073537302 cites W1975255909 @default.
- W2073537302 cites W1975487247 @default.
- W2073537302 cites W1978367221 @default.
- W2073537302 cites W1980093190 @default.
- W2073537302 cites W1981955278 @default.
- W2073537302 cites W1982785786 @default.
- W2073537302 cites W1983786528 @default.
- W2073537302 cites W1984616391 @default.
- W2073537302 cites W1985411684 @default.
- W2073537302 cites W1986727165 @default.
- W2073537302 cites W1990712903 @default.
- W2073537302 cites W1992092971 @default.
- W2073537302 cites W1992413029 @default.
- W2073537302 cites W1995862213 @default.
- W2073537302 cites W1997253947 @default.
- W2073537302 cites W2005458257 @default.
- W2073537302 cites W2005706069 @default.
- W2073537302 cites W2005765181 @default.
- W2073537302 cites W2006079819 @default.
- W2073537302 cites W2006693847 @default.
- W2073537302 cites W2009567717 @default.
- W2073537302 cites W2009926364 @default.
- W2073537302 cites W2012874800 @default.
- W2073537302 cites W2016313163 @default.
- W2073537302 cites W2017326736 @default.
- W2073537302 cites W2018346130 @default.
- W2073537302 cites W2019278298 @default.
- W2073537302 cites W2020539068 @default.
- W2073537302 cites W2021643429 @default.
- W2073537302 cites W2033761616 @default.
- W2073537302 cites W2034401615 @default.
- W2073537302 cites W2035598559 @default.
- W2073537302 cites W2037593967 @default.
- W2073537302 cites W2040556202 @default.
- W2073537302 cites W2042222447 @default.
- W2073537302 cites W2042293867 @default.
- W2073537302 cites W2045060059 @default.
- W2073537302 cites W2045643757 @default.
- W2073537302 cites W2049696886 @default.
- W2073537302 cites W2050674095 @default.
- W2073537302 cites W2052157498 @default.
- W2073537302 cites W2054323181 @default.
- W2073537302 cites W2062764486 @default.
- W2073537302 cites W2063495656 @default.
- W2073537302 cites W2064396602 @default.
- W2073537302 cites W2069049558 @default.
- W2073537302 cites W2069471046 @default.
- W2073537302 cites W2072744580 @default.
- W2073537302 cites W2073729004 @default.
- W2073537302 cites W2075454634 @default.
- W2073537302 cites W2075745805 @default.
- W2073537302 cites W2075874875 @default.
- W2073537302 cites W2077559325 @default.
- W2073537302 cites W2078484961 @default.
- W2073537302 cites W2084097772 @default.
- W2073537302 cites W2084676673 @default.
- W2073537302 cites W2085459880 @default.
- W2073537302 cites W2086992094 @default.
- W2073537302 cites W2088694204 @default.
- W2073537302 cites W2092807015 @default.
- W2073537302 cites W2092989846 @default.
- W2073537302 cites W2094266637 @default.
- W2073537302 cites W2099594706 @default.
- W2073537302 cites W2099904057 @default.
- W2073537302 cites W2102150242 @default.
- W2073537302 cites W2108669634 @default.
- W2073537302 cites W2112671059 @default.
- W2073537302 cites W2125292551 @default.
- W2073537302 cites W2128739804 @default.
- W2073537302 cites W2129554445 @default.
- W2073537302 cites W2131835065 @default.
- W2073537302 cites W2136956854 @default.
- W2073537302 cites W2138364349 @default.
- W2073537302 cites W2140029877 @default.