Serendipitous discovery of a prodrug of a PARP-1 inhibitor

Chemical Biology and Drug Design

Volumn 82, Issue 3, 2013, Pages 348-350

  Dunn, Derek ^a   Husten, Jean ^a   Aimone, Lisa D ^a   Ator, Mark A ^a   Chatterjee, Sankar ^a  

^a CEPHALON INC   (United States)

Author keywords

Oncology; PARP 1; Pyrrolocarbazole

Indexed keywords

NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE 1 INHIBITOR; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; PRODRUG; PYRROLOCARBAZOLE; UNCLASSIFIED DRUG;

ACYLATION; ALKYLATION; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; CONTROLLED STUDY; DNA DAMAGE; DRUG BLOOD LEVEL; DRUG SCREENING; DRUG SOLUBILITY; DRUG SYNTHESIS; ELECTRON TRANSPORT; ENZYME ACTIVE SITE; ENZYME ASSAY; LETTER; MALE; MOLECULAR DOCKING; NONHUMAN; PC12 CELL; PRIORITY JOURNAL; RAT;

ONCOLOGY; PARP-1; PYRROLOCARBAZOLE;

ANIMALS; CARBAZOLES; CHICKENS; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; HALF-LIFE; PHTHALIMIDES; POLY(ADP-RIBOSE) POLYMERASES; PRODRUGS; PROTEIN BINDING; RATS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84882760215     PISSN: 17470277     EISSN: 17470285     Source Type: Journal    
DOI: 10.1111/cbdd.12165     Document Type: Letter

References (12)

1. Chambon P., Weil J.D., Mandel P. (1963) Nicotinamide mononucleotide activation of new DNA-dependent polyadenylic acid synthesizing nuclear enzyme. Biochem Biophys Res Comm;11:39-43.
2. Gibson B.A., Kraus W.L. (2012) New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs. Nat Rev Mol Cell Biol;13:411-424.
3. Boehler C., Gauthier L.R., Mortusewicz O., Biard D.S., Saliou J.-M., Bresson A., Sanglier-Cianferani S., Smith S., Schreiber V., Boussin F., Dantzer F. (2011) Poly(ADP-ribose) polymerase 3 (PARP3), a newcomer in cellular response to DNA damage and mitotic progression. PNAS;108:2783-2788.
4. Rouleau M., Patel A., Hendzel M.J., Kaufmann S.H., Poirier G.G. (2010) PARP inhibition: PARP1 and beyond. Nat Rev Cancer;10:293-301.
5. Ferraris D.V. (2010) Evolution of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors. From concept to clinic. J Med Chem;53:4561-4584.
6. Fogelman D.R., Wolff R.A., Kopetz S., Javle M., Bradley C., Mok I., Cabanillas F., Abbruzzese J.L. (2011) Evidence for the efficacy of Iniparib, a PARP-1 inhibitor, in BRCA2-associated pancreatic cancer. Anticancer Res;31:1417-1420.
7. Leung M., Rosen D., Fields S., Cesano A., Budman D.R. (2011) Poly(ADP-ribose) polymerase-1 inhibition: preclinical and clinical development of synthetic lethality. Mol Med;17:854-862.
8. Annunziata C.M., O'Shaughnessy J. (2010) Poly (ADP-ribose) polymerase as a novel therapeutic target in cancer. Clin Cancer Res;16:4517-4526.
9. Ator M.A., Bihovsky R., Chatterjee S., Dunn D., Hudkins R.L. (2001) Multicyclic compounds and the use thereof. US Patent 7, 122, 679;1-74.
10. Tao M., Park C.H., Bihovsky R., Wells G.J., Husten J., Ator M.A., Hudkins R.L. (2006) Synthesis and structure-activity relationships of novel poly(ADP-ribose) polymerase-1 inhibitors. Bioorg Med Chem Lett;16:938-942.
11. Miknyoczki S.J., Jones-Bolin S., Pritchard S., Hunter R., Zhao H., Wan W., Ator M.A., Bihovsky R., Hudkins R., Chatterjee S., Klein-Szanto A., Dionne C., Ruggeri B. (2003) Chemopotentiation of Temozolomide, Irinotecan, and Cisplatin activity by CEP-6800, a poly(ADP-ribose) polymerase inhibitor. Mol Cancer Ther;2:371-382.
12. Ruf A., de Murcia G., Schultz G.E. (1998) Inhibitor and NAD+ binding to poly(ADP-ribose) polymerase as derived from crystal structures and homology modeling. Biochemistry;37:3893-3900.