PARP inhibitors as antitumor agents: a patent update (2013-2015)

References

• Papeo G, Casale E, Montagnoli A, et al. PARP inhibitors in cancer therapy: an update. Expert Opin Ther Pat. 2013;23(4):503–514.
   PubMed Web of Science ®Google Scholar
• Curtin NJ, Szabo C. Therapeutic applications of PARP inhibitors: anticancer therapy and beyond. Mol Aspects Med. 2013;34(6):1217–1256.
   PubMed Web of Science ®Google Scholar
• Sonnenblick A, de Azambuja E, Azim HA, et al. An update on PARP inhibitors—moving to the adjuvant setting. Nat Rev Clin Oncol. 2014;12(1):27–41.
   PubMed Web of Science ®Google Scholar
• Ryu KW, Kim D-S, Kraus WL. New facets in the regulation of gene expression by adp-ribosylation and poly(adp-ribose) polymerases. Chem Rev. 2015;115(6):2453–2481.
   PubMed Web of Science ®Google Scholar
• Huang S-MA, Mishina YM, Liu S, et al. Tankyrase inhibition stabilizes axin and antagonizes WNT signalling. Nature. 2009;461(7264):614–620.
   PubMed Web of Science ®Google Scholar
• Peukert S, Schwahn U. New inhibitors of poly (adp-ribose) polymerase (PARP). Expert Opin Ther Pat. 2004;14(11):1531–1551.
   Web of Science ®Google Scholar
• Jagtap P, Szabó C. Poly(adp-ribose) polymerase and the therapeutic effects of its inhibitors. Nat Rev Drug Discov. 2005;4(5):421–440.
   PubMed Web of Science ®Google Scholar
• Ferraris DV. Evolution of poly(adp-ribose) polymerase-1 (PARP-1) inhibitors. From concept to clinic. J Med Chem. 2010;53(12):4561–4584.
   PubMed Web of Science ®Google Scholar
• McLornan DP, List A, Mufti GJ. Applying synthetic lethality for the selective targeting of cancer. N Engl J Med. 2014;371(18):1725–1735.
   PubMed Web of Science ®Google Scholar
• Lord CJ, Tutt ANJ, Ashworth A. Synthetic lethality and cancer therapy: lessons learned from the development of PARP inhibitors. Annu Rev Med. 2015;66 Caskey CT (Ed). 455–470.
   PubMed Web of Science ®Google Scholar
• Walsh CS. Two decades beyond BRCA1/2: homologous recombination, hereditary cancer risk and a target for ovarian cancer therapy. Gynecol Oncol. 2015;137(2):343–350.
   PubMed Web of Science ®Google Scholar
• Postel-Vinay S, Bajrami I, Friboulet L, et al. A high-throughput screen identifies PARP-1/2 inhibitors as a potential therapy for ERCC1-deficient non-small cell lung cancer. Oncogene. 2013;32(47):5377–5387.
   PubMed Web of Science ®Google Scholar
• Somyajit K, Mishra A, Jameei A, et al. Enhanced non-homologous end joining contributes toward synthetic lethality of pathological rad51c mutants with poly (adp-ribose) polymerase. Carcinogenesis. 2015;36(1):13–24.
   PubMed Web of Science ®Google Scholar
• Bridges KA, Toniatti C, Buser CA, et al. Niraparib (MK-4827), a novel poly(adp-ribose) polymerase inhibitor, radiosensitizes human lung and breast cancer cells. Oncotarget. 2014;5(13):5076–5086.
   PubMed Web of Science ®Google Scholar
• Gani C, Coackley C, Kumareswaran R, et al. In vivo studies of the PARP inhibitor, AZD-2281, in combination with fractionated radiotherapy: an exploration of the therapeutic ratio. Radiother Oncol. 2015;116(3):486–494.
   PubMed Web of Science ®Google Scholar
• Engert F, Schneider C, Weibeta LM, et al. PARP inhibitors sensitize ewing sarcoma cells to temozolomide-induced apoptosis via the mitochondrial pathway. Mol Cancer Ther. 2015;14(12):2818–2830.
   PubMed Web of Science ®Google Scholar
• Karginova O, Siegel MB, Van Swearingen AED, et al. Efficacy of carboplatin alone and in combination with ABT888 in intracranial murine models of BRCA-mutated and BRCA-wild-type triple-negative breast cancer. Mol Cancer Ther. 2015;14(4):920–930.
   PubMed Web of Science ®Google Scholar
• Wulf GM, Juvekar A, Lyssiotis CA, et al. Combination of a PI3K and a PARP inhibitor to treat high-grade serous ovarian or triple-negative breast cancer. Cancer Res. 2014;74(19):CT338–CT338.
   Google Scholar
• Sui H, Shi C, Yan Z, et al. Combination of erlotinib and a PARP inhibitor inhibits growth of A2780 tumor xenografts due to increased autophagy. Drug Des Dev Ther. 2015;9:3183–3190.
   PubMed Web of Science ®Google Scholar
• Konstantinopoulos PA, Wilson AJ, Saskowski J, et al. Suberoylanilide hydroxamic acid (SAHA) enhances olaparib activity by targeting homologous recombination DNA repair in ovarian cancer. Gynecol Oncol. 2014;133(3):599–606.
   PubMed Web of Science ®Google Scholar
• Pulliam N, Taverna P, Lyons J, et al. Novel combination therapy of DNMT inhibitor SGI-110 and PARP inhibitor BMN-673 (talazoparib) for BRCA-proficient ovarian cancer. Cancer Res. 2015;75(15):2943–2943.
   Web of Science ®Google Scholar
• Kumar R, Li DQ, Muller S, et al. Epigenomic regulation of oncogenesis by chromatin remodeling. Oncogene. 2016;35(34):4423-4436.
   PubMed Web of Science ®Google Scholar
• Papeo G, Forte B, Orsini P, et al. Poly (adp-ribose) polymerase inhibition in cancer therapy: are we close to maturity? Expert Opin Ther Pat. 2009;19(10):1377–1400.
   PubMed Web of Science ®Google Scholar
• Angion Biomedica Corp. Small molecule inhibitors of PARP activity. US2013303567. 2013.
   Google Scholar
• Nerviano Medical Sciences S.r.l. 4-Carboxamido-isoindolinone derivatives as selective PARP-1 inhibitors. WO2014064149. 2014.
   Google Scholar
• Nerviano Medical Sciences S.r.l. 3-Oxo-2,3-dihydro-1H-indazole-4-carboxamide derivatives as PARP-1 inhibitors. US2014235675. 2014.
   Google Scholar
• Medshine Discovery Inc. 4H-pyrazolo[1,5-[alpha]]benzimidazole compound analogue as PARP inhibitor. CN104974161. 2015.
   Google Scholar
• Sigma-Tau Ind Farmaceuti. 7-Azaindole derivatives as PARP inhibitors. WO2015011008. 2015.
   Google Scholar
• Cincinelli R, Musso L, Merlini L, et al. 7-azaindole-1-carboxamides as a new class of PARP-1 inhibitors. Bioorg Med Chem. 2014;22(3):1089–1103.
   PubMed Web of Science ®Google Scholar
• Impact Therapeutics Inc. 1-(Arylmethyl)quinazoline-2,4(1H,3H)-diones as PARP inhibitors and the use thereof. US2014023642. 2014.
   Google Scholar
• Janssen Pharmaceutica NV Quinazolinedione derivatives as PARP inhibitors. US2014100239. 2014.
   Google Scholar
• Janssen Pharmaceutica NV Phthalazine derivatives as PARP inhibitors. US2015072972. 2015.
   Google Scholar
• Chengdu Di`ao Pharmaceutical Group Co. Poly (adp-ribose) polymerase inhibitor. WO2013078771. 2013.
   Google Scholar
• Shanghai Institute of Materia Medica. Piperazinotriazole compound, preparation method therefor, and use thereof in drug preparation. US2015166544. 2015.
   Google Scholar
• Nerviano Medical Sciences S.r.l. 3-phenyl-isoquinolin-1(2h)-one derivatives as PARP-1 inhibitors. WO2013076090. 2013
   Google Scholar
• Lupin Ltd. Tetrahydroquinazolinone derivatives as PARP inhibitors. WO2014009872. 2014.
   Google Scholar
• BioMarin Phamaceutical Inc. Methods of using dihydropyridophthalazinone inhibitors of poly (adp-ribose)polymerase (PARP). WO2011130661. 2011.
   Google Scholar
• BioMarin Phamaceutical Inc. Dihydropyridophthalazinone inhibitors of poly (adp-ribose) polymerase (PARP) for the treatment of multiple myeloma. WO2013028495. 2013.
   Google Scholar
• Bing W, Daniel C. Dihydropyridophthalazinone inhibitors of poly(adp-ribose)polymerase (PARP). US2013053365. 2013.
   Google Scholar
• Janssen Pharmaceutica NV Tetrahydrophenanthridinones and tetrahydrocyclopentaquinolinones as PARP and tubulin polymerization inhibitors. US2015353526. 2015.
   Google Scholar
• BeiGene Ltd. Fused tetra or penta-cyclic pyridophthalazinones as PARP inhibitors. TW201444839. 2014.
   Google Scholar
• BeiGene Ltd. Fused tetra or penta-cyclic dihydrodiazepinocarbazolones as PARP inhibitors. TW201444842. 2014.
   Google Scholar
• Suzhou Kangrun Pharmaceutical Inc. Aza-phenalene-3-ketone derivative, preparation method thereof and application of aza-phenalene-3-ketone derivative as PARP inhibitor. CN104945406. 2015.
   Google Scholar
• China Pharmaceutical University. Tricyclic indole compound (I) with PARP (Poly-ADP-Ribose Polymerase) inhibiting activity, preparation method and application thereof. CN103772395. 2014.
   Google Scholar
• Santen Pharmaceutical Co. Novel compound having PARP inhibitory activity. US2014243320. 2014.
   Google Scholar
• Abbvie Inc. Combination therapy with PARP inhibitors. US2015005355. 2015.
   Google Scholar
• Abbvie Inc. Combination therapy with PARP inhibitors. US2015005354. 2015.
   Google Scholar
• Abbvie Inc. Combination therapy with PARP inhibitors. US2013225647. 2013.
   Google Scholar
• Nektar Therapeutics. Combination-based treatment method. WO2015108876. 2015.
   Google Scholar
• Beth Isarel Hospiral. Compositions and methods for the treatment of proliferative diseases. WO2013049581. 2013.
   Google Scholar
• Univ. Jefferson. Use of PARP inhibitors to treat breast cancer. WO2014052550. 2014.
   Google Scholar
• Univ. Johns Hopkins. Therapy regimen and methods to sensitize cancer cells treated with epigenetic therapy to PARP inhibitors in multiple cancers. WO2015112598. 2015.
   Google Scholar
• Oncozyme Pharma Inc. Combinations comprising diamidine compounds and PARP inhibitors for use INu treating cancer. WO2014008592. 2014.
   Google Scholar
• Eisai R&D Man Co. Ltd. Use of eribulin and poly (adp ribose) polymerase (PARP) inhibitors as combination therapy for the treatment of cancer. WO2015184145. 2015
   Google Scholar
• Gen Hospital Corp. Methods and assays for determining reduced brca1 pathway function in a cancer cell. WO2015100257. 2015
   Google Scholar
• Univ. California. Biomarkers for prediction of response to PARP inhibition in breast cancer. WO2013133876. 2013.
   Google Scholar
• Univ. Texas. gene signature to predict homologous recombination (hr) deficient cancer. WO2014138101. 2014.
   Google Scholar
• Inst. Nat. Sante. Rech. Med. Methods for screening a brca1 loss-of-function in a subject suffering from a cancer. WO2013076295. 2013
   Google Scholar
• Inst. Curie. Methods for detecting inactivation of the homologous recombination pathway (brca1/2) in human tumors. WO2013182645. 2013
   Google Scholar
• Genomic Vision. Methods for the detection, visualization and high resolution physical mapping of genomic rearrangements in breast and ovarian cancer genes and loci brca1 and brca2 using genomic morse code in conjunction with molecular combing. WO2013064895. 2013.
   Google Scholar
• Univ. Sheffield. Use of RNAi inhibiting PARP activity for the manufacture of a medicament for the treatment of cancer. US2015005327. 2015
   Google Scholar
• Myriad Genetics Inc. Methods and materials for assessing loss of heterozygosity. WO2013096843. 2013.
   Google Scholar
• Clovis Oncology Inc. Use of PARP inhibitors to treat breast or ovarian cancer patients showing a loss of heterozygosity. WO2015108986. 2015.
   Google Scholar
• King S College London. Biomarkers correlated to PARP inhibitor treatment success in AML patients. WO2015040378. 2015
   Google Scholar
• Univ. California. Biomarkers of response to inhibition of poly-adp ribose polymerase (PARP) in cancer. WO2014205105. 2014
   Google Scholar
• Inst. Cancer Res. D B A the Res. INST Of Fox Chase Cancer CT. Methods for determining PARP inhibitor and platinum resistance in cancer therapy. US2015344968. 2015.
   Google Scholar
• Sobol Jr Robert W. N-Methylpurine dna glycosylase and polymerase beta as biomarkers for alkylator chemotherapy potentiation. US2013316349. 2013
   Google Scholar
• Univ. Emory. Selective chemotherapy treatments and diagnostic methods related thereto. WO2015168544. 2015.
   Google Scholar
• Mayo Foundation. Methods and materials for assessing responsiveness to PARP inhibitors and platinating agents. US2013224312. 2013
   Google Scholar
• Toshimitsu H, Yoshimoto Y, Augustine CK, et al. Inhibition of poly(adp-ribose) polymerase enhances the effect of chemotherapy in an animal model of regional therapy for the treatment of advanced extremity malignant melanoma. Ann Surg Oncol. 2010;17(8):2247–2254.
   PubMed Web of Science ®Google Scholar
• Penning TD, Zhu G-D, Gandhi VB, et al. Discovery of the poly (adp-ribose) polymerase (PARP) inhibitor 2-[(r)-2-methylpyrrolidin-2-yl]-1h-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer. J Med Chem. 2008;52(2):514–523.
   Web of Science ®Google Scholar
• Lin F, de Gooijer MC, Roig EM, et al. ABCB1, ABCG2, and PTEN determine the response of glioblastoma to temozolomide and ABT-888 therapy. Clin Cancer Res. 2014;20(10):2703–2713.
   PubMed Web of Science ®Google Scholar
• Mariano G, Ricciardi MR, Trisciuoglio D, et al. PARP inhibitor ABT-888 affects response of MDA-MB-231 cells to doxorubicin treatment, targeting snail expression. Oncotarget. 2015;6(17):15008–15021.
   PubMed Web of Science ®Google Scholar
• Reiss KA, Herman JM, Zahurak M, et al. A phase I study of veliparib (ABT-888) in combination with low-dose fractionated whole abdominal radiation therapy in patients with advanced solid malignancies and peritoneal carcinomatosis. Clin Cancer Res. 2015;21(1):68–76.
   PubMed Web of Science ®Google Scholar
• Coleman RL, Sill MW, Bell-McGuinn K, et al. A phase II evaluation of the potent, highly selective PARP inhibitor veliparib in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who carry a germline BRCA1 or BRCA2 mutation - an nrg oncology/gynecologic oncology group study. Gynecol Oncol. 2015;137(3):386–391.
   PubMed Web of Science ®Google Scholar
• Kummar S, Oza AM, Fleming GF, et al. Randomized trial of oral cyclophosphamide and veliparib in high-grade serous ovarian, primary peritoneal, or fallopian tube cancers, or BRCA-mutant ovarian cancer. Clin Cancer Res. 2015;21(7):1574–1582.
   PubMed Web of Science ®Google Scholar
• Middleton MR, Friedlander P, Hamid O, et al. Randomized phase II study evaluating veliparib (ABT-888) with temozolomide in patients with metastatic melanoma. Ann Oncol. 2015;26(10):2173–2179.
   PubMed Web of Science ®Google Scholar
• Gabrielson A, Tesfaye AA, Marshall JL, et al. Phase II study of temozolomide and veliparib combination therapy for sorafenib-refractory advanced hepatocellular carcinoma. Cancer Chemoth Pharm. 2015;76(5):1073–1079.
   PubMed Web of Science ®Google Scholar
• Jones P, Altamura S, Boueres J, et al. Discovery of 2-{4-[(3s)-piperidin-3-yl]phenyl}-2h-indazole-7-carboxamide (MK-4827): a novel oral poly(adp-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and −2 mutant tumors. J Med Chem. 2009;52(22):7170–7185.
   PubMed Web of Science ®Google Scholar
• Chung CK, Bulger PG, Kosjek B, et al. Process development of C-N cross-coupling and enantioselective biocatalytic reactions for the asymmetric synthesis of niraparib. Org Process Res Dev. 2014;18(1):215–227.
   Web of Science ®Google Scholar
• Murai J, Huang S-Y, Das BB, et al. Trapping of PARP-1 and PARP-2 by clinical PARP inhibitors. Cancer Res. 2012;72(21):5588–5599.
   PubMed Web of Science ®Google Scholar
• Genther Williams SM, Kuznicki AM, Andrade P, et al. Treatment with the PARP inhibitor, niraparib, sensitizes colorectal cancer cell lines to irinotecan regardless of msi/mss status. Cancer Cell Int. 2015;15(1):14–14.
   PubMed Web of Science ®Google Scholar
• Sandhu SK, Schelman WR, Wilding G, et al. The poly(adp-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a phase I dose-escalation trial. Lancet Oncol. 2013;14(9):882–892.
   PubMed Web of Science ®Google Scholar
• Abdullah I, Chee CF, Lee Y-K, et al. Benzimidazole derivatives as potential dual inhibitors for PARP-1 and dhodh. Bio Med Chem. 2015;23(15):4669–4680.
   PubMed Web of Science ®Google Scholar
• Zhu Q, Wang X, Hu Y, et al. Discovery and sar study of 2-(1-propylpiperidin-4-yl)-3h-imidazo 4,5-c pyridine-7-carboxamide: a potent inhibitor of poly(adp-ribose) polymerase-1 (PARP-1) for the treatment of cancer. Bio Med Chem. 2015;23(20):6551–6559.
   PubMed Web of Science ®Google Scholar
• Zhu Q, Wang X, Chu Z, et al. Design, synthesis and biological evaluation of novel imidazo 4,5-c pyridinecarboxamide derivatives as PARP-1 inhibitors. Bio Med Chem Lett. 2013;23(7):1993–1996.
   PubMed Web of Science ®Google Scholar
• Papeo G, Posteri H, Borghi D, et al. Discovery of 2-[1-(4,4-difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1h-isoindole-4-carboxamide (NMS-P118): a potent, orally available, and highly selective PARP-1 inhibitor for cancer therapy. J Med Chem. 2015;58(17):6875–6898.
   PubMed Web of Science ®Google Scholar
• Patel MR, Bhatt A, Steffen JD, et al. Discovery and structure–activity relationship of novel 2,3-dihydrobenzofuran-7-carboxamide and 2,3-dihydrobenzofuran-3(2h)-one-7-carboxamide derivatives as poly(adp-ribose)polymerase-1 inhibitors. J Med Chem. 2014;57(13):5579–5601.
   PubMed Web of Science ®Google Scholar
• Langelier MF, Planck JL, Roy S, et al. Structural basis for DNA damage-dependent poly(adp-ribosyl)ation by human parp-1. Science. 2012;336(6082):728–732.
   PubMed Web of Science ®Google Scholar
• Menear KA, Adcock C, Boulter R, et al. 4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2h-phthalazin-1-one: a novel bioavailable inhibitor of poly(adp-ribose) polymerase-1. J Med Chem. 2008;51(20):6581–6591.
   PubMed Web of Science ®Google Scholar
• Liu JF, Tolaney SM, Birrer M, et al. A phase I trial of the poly(adp-ribose) polymerase inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer. Eur J Cancer. 2013;49(14):2972–2978.
   PubMed Web of Science ®Google Scholar
• Ledermann J, Harter P, Gourley C, et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase II trial. Lancet Oncol. 2014;15(8):852–861.
   PubMed Web of Science ®Google Scholar
• Bixel K, Hays JL. Olaparib in the management of ovarian cancer. Pharmgenomics Pers Med. 2015;8:127–135.
   PubMedGoogle Scholar
• Del Conte G, Sessa C, von Moos R, et al. Phase I study of olaparib in combination with liposomal doxorubicin in patients with advanced solid tumours. Brit J Cancer. 2014;111(4):651–659.
   PubMed Web of Science ®Google Scholar
• Kaufman B, Shapira-Frommer R, Schmutzler RK, et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015;33(3):244–U134.
   PubMed Web of Science ®Google Scholar
• Jaspers JE, Kersbergen A, Boon U, et al. Loss of 53bp1 causes PARP inhibitor resistance in BRCA1-mutated mouse mammary tumors. Cancer Discov. 2013;3(1):68–81.
   PubMed Web of Science ®Google Scholar
• Williams R. Discontinued drugs in 2011: oncology drugs. Expert Opin Inv Drug. 2013;22(1):9–34.
   PubMed Web of Science ®Google Scholar
• Shanghai Hengrui Pharm Co. Ltd. Phthalazinone ketone derivative, preparation method thereof, and pharmaceutical use thereof. WO2012019427. 2012
   Google Scholar
• Maciag AE, Holland RJ, Kim Y, et al. Nitric oxide (NO) releasing poly adp-ribose polymerase 1 (PARP-1) inhibitors targeted to glutathione s-transferase p1-overexpressing cancer cells. J Med Chem. 2014;57(6):2292–2302.
   PubMed Web of Science ®Google Scholar
• Zmuda F, Malviya G, Blair A, et al. Synthesis and evaluation of a radioiodinated tracer with specificity for poly(adp-ribose) polymerase-1 (PARP-1) in vivo. J Med Chem. 2015;58(21):8683–8693.
   PubMed Web of Science ®Google Scholar
• Johannes JW, Almeida L, Daly K, et al. Discovery of AZ0108, an orally bioavailable phthalazinone PARP inhibitor that blocks centrosome clustering. Bioorg Med Chem Lett. 2015;25(24):5743–5747.
   PubMed Web of Science ®Google Scholar
• Ye N, Chen C-H, Chen T, et al. Design, synthesis, and biological evaluation of a series of benzo[de][1,7]naphthyridin-7(8h)-ones bearing a functionalized longer chain appendage as novel PARP-1 inhibitors. J Med Chem. 2013;56(7):2885–2903.
   PubMed Web of Science ®Google Scholar
• Yao H, Ji M, Zhu Z, et al. Discovery of 1-substituted benzyl-quinazoline-2,4(1h,3h)-dione derivatives as novel poly(adp-ribose)polymerase-1 inhibitors. Bioorg Med Chem. 2015;23(4):681–693.
   PubMed Web of Science ®Google Scholar
• Wang L-X, Zhou X-B, M-L X, et al. Synthesis and biological evaluation of substituted 4-(thiophen-2-ylmethyl)-2h-phthalazin-1-ones as potent PARP-1 inhibitors. Bioorg Med Chem Lett. 2014;24(16):3739–3743.
   PubMed Web of Science ®Google Scholar
• Hannigan K, Kulkarni SS, Bdzhola VG, et al. Identification of novel PARP-1 inhibitors by structure-based virtual screening. Bioorg Med Chem Lett. 2013;23(21):5790–5794.
   PubMed Web of Science ®Google Scholar
• Tuong Vy Thi L, Suh JH, Kim N, et al. In silico identification of poly(adp-ribose)polymerase-1 inhibitors and their chemosensitizing effects against cisplatin-resistant human gastric cancer cells. Bioorg Med Chem Lett. 2013;23(9):2642–2646.
   PubMed Web of Science ®Google Scholar
• Giannini G, Battistuzzi G, Vesci L, et al. Novel PARP-1 inhibitors based on a 2-propanoyl-3h-quinazolin-4-one scaffold. Bioorg Med Chem Lett. 2014;24(2):462–466.
   PubMed Web of Science ®Google Scholar
• Gillmore AT, Badland M, Crook CL, et al. Multkilogram scale-up of a reductive alkylation route to a novel PARP inhibitor. Org Process Res Dev. 2012;16(12):1897–1904.
   Web of Science ®Google Scholar
• Liu JF, Konstantinopoulos PA, Matulonis UA. PARP inhibitors in ovarian cancer: current status and future promise. Gynecol Oncol. 2014;133(2):362–369.
   PubMed Web of Science ®Google Scholar
• Plummer R, Lorigan P, Steven N, et al. A phase II study of the potent PARP inhibitor, rucaparib (PF-01367338, AG014699), with temozolomide in patients with metastatic melanoma demonstrating evidence of chemopotentiation. Cancer Chemoth Pharm. 2013;71(5):1191–1199.
   PubMed Web of Science ®Google Scholar
• Falzacappa MVV, Ronchini C, Faretta M, et al. The combination of the PARP inhibitor rucaparib and 5-FU is an effective strategy for treating acute leukemias. Mol Cancer Ther. 2015;14(4):889–898.
   PubMed Web of Science ®Google Scholar
• Znojek P, Willmore E, Curtin NJ. Preferential potentiation of topoisomerase I poison cytotoxicity by PARP inhibition in S phase. Brit J Cancer. 2014;111(7):1319–1326.
   PubMed Web of Science ®Google Scholar
• Murray J, Thomas H, Berry P, et al. Tumour cell retention of rucaparib, sustained PARP inhibition and efficacy of weekly as well as daily schedules. Brit J Cancer. 2014;110(8):1977–1984.
   PubMed Web of Science ®Google Scholar
• Durmus S, Sparidans RW, van Esch A, et al. Breast cancer resistance protein (BCRP/ABCG2) and p-glycoprotein (P-gp/ABCB1) restrict oral availability and brain accumulation of the PARP inhibitor rucaparib (AG-014699). Pharmaceut Res. 2015;32(1):37–46.
   PubMed Web of Science ®Google Scholar
• Wang B, Chu D, Feng Y, et al. Discovery and characterization of (8s,9r)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1h-1,2,4-triazol-5-yl)-2,7,8,9-tetrahydro-3h-pyrido 4,3,2-de phthalazin-3-one (BMN673, talazoparib), a novel, highly potent, and orally efficacious poly(adp-ribose) polymerase-1/2 inhibitor, as an anticancer agent. J Med Chem. 2016;59(1):335–357.
   PubMed Web of Science ®Google Scholar
• Murai J, Huang S-YN, Renaud A, et al. Stereospecific PARP trapping by BMN673 and comparison with olaparib and rucaparib. Mol Cancer Ther. 2014;13(2):433–443.
   PubMed Web of Science ®Google Scholar
• Aoyagi-Scharber M, Gardberg AS, Yip BK, et al. Structural basis for the inhibition of poly(adp-ribose) polymerases 1 and 2 by BMN673, a potent inhibitor derived from dihydropyridophthalazinone. Acta Crystallogr F-Struct Biol Commun. 2014;70(9):1143–1149.
   PubMed Web of Science ®Google Scholar
• Cardnell RJ, Feng Y, Diao L, et al. Proteomic markers of DNA repair and PI3K pathway activation predict response to the PARP inhibitor BMN673 in small cell lung cancer. Clin Cancer Res. 2013;19(22):6322–6328.
   PubMed Web of Science ®Google Scholar
• Andrei A-Z, Hall A, Smith AL, et al. Increased in vitro and in vivo sensitivity of BRCA2-associated pancreatic cancer to the poly(adp-ribose) polymerase-1/2 inhibitor BMN673. Cancer Lett. 2015;364(1):8–16.
   PubMed Web of Science ®Google Scholar
• Huang J, Wang L, Cong Z, et al. The PARP-1 inhibitor BMN673 exhibits immunoregulatory effects in a BRCA1(-/-) murine model of ovarian cancer. Biochem Bioph Res Co. 2015;463(4):551–556.
   PubMed Web of Science ®Google Scholar
• Shen Y, Rehman FL, Feng Y, et al. BMN673, a novel and highly potent PARP-1/2 inhibitor for the treatment of human cancers with DNA repair deficiency. Clin Cancer Res. 2013;19(18):5003–5015.
   PubMed Web of Science ®Google Scholar
• Smith MA, Reynolds CP, Kang MH, et al. Synergistic activity of PARP inhibition by talazoparib (BMN673) with temozolomide in pediatric cancer models in the pediatric preclinical testing program. Clin Cancer Res. 2015;21(4):819–832.
   PubMed Web of Science ®Google Scholar
• Murai J, Pommier Y. The combination of the PARP inhibitor talazoparib (BMN673) with the ATR inhibitor VE-821 overcomes the drug resistance of schlafen 11-deficient cells. Cancer Res. 2015;75(15):2849–2849.
   Web of Science ®Google Scholar
• Mgi Gp Inc. Diazabenzo[de]anthracen-3-one compounds and methods for inhibiting PARP. WO2006078711. 2006.
   Google Scholar
• Mgi Gp Inc. PARP inhibitor compounds, compositions and methods of use. WO2009046205. 2009.
   Google Scholar
• Russo AL, Kwon H-C, Burgan WE, et al. In vitro and in vivo radiosensitization of glioblastoma cells by the poly (adp-ribose) polymerase inhibitor E7016. Clin Cancer Res. 2009;15(2):607–612.
   PubMed Web of Science ®Google Scholar
• McGonigle S, Chen Z, Wu J, et al. E7449: a dual inhibitor of PARP-1/2 and tankyrase1/2 inhibits growth of DNA repair deficient tumors and antagonizes Wnt signaling. Oncotarget. 2015;6(38):41307–41323.
   PubMed Web of Science ®Google Scholar
• Cephalon Inc. Novel multicyclic compounds and the use thereof. US2006276497. 2006.
   Google Scholar
• Cephalon Inc. Method of radio-sensitizing tumors using a radio-sensitizing agent. WO2008063644. 2008.
   Google Scholar
• Cephalon Inc. Novel forms of a multicyclic compound. WO2011028580. 2011.
   Google Scholar
• Plummer R, Stephens P, Aissat-Daudigny L, et al. Phase I dose-escalation study of the PARP inhibitor CEP-9722 as monotherapy or in combination with temozolomide in patients with solid tumors. Cancer Chemoth Pharm. 2014;74(2):257–265.
   PubMed Web of Science ®Google Scholar
• Jian W, Xu HG, Chen J, et al. Activity of CEP-9722, a poly (adp-ribose) polymerase inhibitor, in urothelial carcinoma correlates inversely with homologous recombination repair response to DNA damage. Anticancer Drug. 2014;25(8):878–886.
   Google Scholar
• Awada A, Campone M, Varga A, et al. An open-label, dose-escalation study to evaluate the safety and pharmacokinetics of CEP-9722 (a PARP-1 and PARP-2 inhibitor) in combination with gemcitabine and cisplatin in patients with advanced solid tumors. Anticancer Drug. 2016;27(4):342–348.
   Google Scholar
• Jagtap PG, Baloglu E, Southan G, et al. Facile and convenient syntheses of 6,11-dihydro-5h-indeno[1,2-c]isoquinolin-5-ones and 6,11-dihydro-5h-indolo[3,2-c]isoquinolin-5-one. Org Lett. 2005;7(9):1753–1756.
   PubMed Web of Science ®Google Scholar
• Jagtap PG, Baloglu E, Southan GJ, et al. Discovery of potent poly(adp-ribose) polymerase-1 inhibitors from the modification of indeno[1,2-c]isoquinolinone. J Med Chem. 2005;48(16):5100–5103.
   PubMed Web of Science ®Google Scholar
• Zhou D, Chu W, Xu J, et al. Synthesis, F-18 radiolabeling, and evaluation of poly (adp-ribose) polymerase-1 (PARP-1) inhibitors for in vivo imaging of PARP-1 using positron emission tomography. Bioorg Med Chem. 2014;22(5):1700–1707.
   PubMed Web of Science ®Google Scholar
• Xie Z, Zhou Y, Zhao W, et al. Identification of novel PARP-1 inhibitors: drug design, synthesis and biological evaluation. Bioorg Med Chem Lett. 2015;25(20):4557–4561.
   PubMed Web of Science ®Google Scholar
• Chen J, Peng H, He J, et al. Synthesis of isoquinolinone-based tricycles as novel poly(adp-ribose) polymerase-1 (PARP-1) inhibitors. Bioorg Med Chem Lett. 2014;24(12):2669–2673.
   PubMed Web of Science ®Google Scholar
• Song M, Li J-L, Li X-P, et al. Targeting human poly(adp-ribose) polymerase-1 with natural medicines and its potential applications in ovarian cancer therapeutics. Arch Pharm (Weinheim). 2015;348(11):817–823.
   Web of Science ®Google Scholar
• Michels J, Vitale I, Saparbaev M, et al. Predictive biomarkers for cancer therapy with PARP inhibitors. Oncogene. 2014;33(30):3894–3907.
   PubMed Web of Science ®Google Scholar
• Shen Y, Aoyagi-Scharber M, Wang B. Trapping poly(adp-ribose) polymerase. J Pharmacol Exp Ther. 2015;353(3):446–457.
   PubMed Web of Science ®Google Scholar
• Lord CJ, Ashworth A. Mechanisms of resistance to therapies targeting BRCA-mutant cancers. Nat Med. 2013;19(11):1381–1388.
   PubMed Web of Science ®Google Scholar
• Rottenberg S, Jaspers JE, Kersbergen A, et al. High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs. Proc Natl Acad Sci USA. 2008;105(44):17079–17084.
   PubMed Web of Science ®Google Scholar
• Ha K, Fiskus W, Choi DS, et al. Histone deacetylase inhibitor treatment induces ‘BRCAness’ and synergistic lethality with PARP inhibitor and cisplatin against human triple negative breast cancer cells. Oncotarget. 2014;5(14):5637–5650.
   PubMed Web of Science ®Google Scholar
• Livraghi L, Garber JE. PARP inhibitors in the management of breast cancer: current data and future prospects. BMC Med. 2015;13(1):188–203.
   PubMed Web of Science ®Google Scholar
• Cambronne XA, Stewart ML, Kim D, et al. Biosensor reveals multiple sources for mitochondrial NAD+. Science. 2016;352(6292):1474–1477.
   PubMed Web of Science ®Google Scholar
• Yergeri M. Current overview on the usage of poly(adp-ribose)polymerase (PARP) inhibitors in treating cancer. Clin Cancer Drugs. 2014;1(2):127–148.
   Google Scholar
• Univ. Northeastern. Nanoparticle drug delivery system and method of treating cancer and neurotrauma. WO2015031536. 2015.
   Google Scholar
• Brown JS, Kaye SB, Yap TA. PARP inhibitors: the race is on. Brit J Cancer. 2016;114(7):713–715.
   PubMed Web of Science ®Google Scholar
• Ljungman M. Targeting the DNA damage response in cancer. Chem Rev. 2009;109(7):2929–2950.
   PubMed Web of Science ®Google Scholar