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 (BMN 673, Talazoparib), a Novel, Highly Potent, and Orally Efficacious Poly(ADP-ribose) Polymerase-1/2 Inhibitor, as an Anticancer Agent

Journal of Medicinal Chemistry

Volumn 59, Issue 1, 2016, Pages 335-357

  Wang, Bing ^a   Chu, Daniel ^a   Feng, Ying ^a   Shen, Yuqiao ^a   Aoyagi Scharber, Mika ^a   Post, Leonard E ^a  

^a BIOMARIN PHARMACEUTICAL INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 (BENZYLIDENEAMINO) 6 FLUOROISOBENZOFURAN 1 (3H)ONE; 4 (BENZYLIDENEAMINO)ISOBENZOFURAN 1 (3H)ONE; 4 AMINOISOBENZOFURAN 1 (3H)ONE; 4 [(4 CHLOROBENZYLIDENE)AMINO]ISOBENZOFURAN 1 (3H)ONE; 4 [(4 FLUOROBENZYLIDENE)AMINO]ISOBENZOFURAN 1 (3H)ONE; 4 [[4 [(DIMETHYLAMINO)METHYL]BENZYLIDENE]AMINO] 6 FLUOROISOBENZOFURAN 1 (3H)ONE; 4 [[4 [(DIMETHYLAMINO)METHYL]BENZYLIDENE]AMINO]ISOBENZOFURAN 1 (3H)ONE; 6 FLUORO 4 [(4 FLUOROBENZYLIDENE)AMINO]ISOBENZOFURAN 1 (3H)ONE; 8,9 BIS[4 [(DIMETHYLAMINO)METHYL]PHENYL] 8,9 DIHYDRO 2H PYRIDO[4,3,2 DE]PHTHALAZIN 3 (7H)ONE; 8,9 DI (1 METHYL IMIDAZOL 2 YL) 8,9 DIHYDRO 2H PYRIDO[4,3,2 DE]PHTHALAZIN 3 (7H)ONE; 8,9 DI (3 PYRIDYL) 8,9 DIHYDRO 2H PYRIDO[4,3,2 DE]PHTHALAZIN 3 (7H)ONE; 8,9 DI(2 PYRIDYL) 8,9 DIHYDRO 2H PYRIDO[4,3,2 DE]PHTHALAZIN 3 (7H)ONE; 8,9 DI(4 PYRIDYL) 8,9 DIHYDRO 2H PYRIDO[4,3,2 DE]PHTHALAZIN 3 (7H)ONE; 8,9 DIPHENYL 8,9 DIHYDRO 2H PYRIDO[4,3,2 DE]PHTHALAZIN 3 (7H)ONE; ANTINEOPLASTIC AGENT; CARBOPLATIN; CISPLATIN; METHYL 2,3 BIS[4 [(DIMETHYLAMINO)METHYL]PHENYL] 4 OXO 1,2,3,4 TETRAHYDROQUINOLINE 5 CARBOXYLATE; METHYL 3 [3 (DIETHOXYMETHYL)PHENYL] 4 OXO 2 PHENYL 1,2,3,4 TETRAHYDROQUINOLINE 5 CARBOXYLATE; METHYL 4 OXO 2,3 DI(1 METHYL IMIDAZOL 2 YL) 1,2,3,4 TETRAHYDROQUINOLINE 5 CARBOXYLATE; METHYL 4 OXO 2,3 DI(2 PYRIDYL) 1,2,3,4 TETRAHYDROQUINOLINE 5 CARBOXYLATE; METHYL 4 OXO 2,3 DI(3 PYRIDYL) 1,2,3,4 TETRAHYDROQUINOLINE 5 CARBOXYLATE; METHYL 4 OXO 2,3 DI(4 PYRIDYL) 1,2,3,4 TETRAHYDROQUINOLINE 5 CARBOXYLATE; METHYL 4 OXO 2,3 DIARYL 1,2,3,4 TETRAHYDROQUINOLINE 5 CARBOXYLATE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE 1; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; OLAPARIB; TALAZOPARIB; TETRAHYDROPYRIDOPHTHALAZINONE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; BRCA1 PROTEIN; BRCA1 PROTEIN, HUMAN; BRCA2 PROTEIN; BRCA2 PROTEIN, HUMAN; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; PARP1 PROTEIN, HUMAN; PARP2 PROTEIN, HUMAN; PHTHALAZINE DERIVATIVE; PROTEIN BINDING;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST CANCER; CANCER CELL; CELL PROLIFERATION; CHIRALITY; CONTROLLED STUDY; DRUG EFFICACY; DRUG POTENCY; DRUG STRUCTURE; EC50; ENZYME ACTIVITY; FEMALE; HUMAN; IC50; MOUSE; NONHUMAN; PROSTATE CANCER; SINGLE DRUG DOSE; STEREOSPECIFICITY; STRUCTURE ACTIVITY RELATION; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; DRUG DEVELOPMENT; DRUG EFFECTS; DRUG SCREENING; GENETICS; GERMLINE MUTATION; KINETICS; NUDE MOUSE; PHASE 1 CLINICAL TRIAL (TOPIC); RAT; STEREOISOMERISM; SYNTHESIS;

ANIMALS; ANTINEOPLASTIC AGENTS; BRCA1 PROTEIN; BRCA2 PROTEIN; CELL PROLIFERATION; CLINICAL TRIALS, PHASE I AS TOPIC; DRUG DISCOVERY; FEMALE; GERM-LINE MUTATION; HUMANS; KINETICS; MICE; MICE, NUDE; MODELS, MOLECULAR; PHTHALAZINES; POLY(ADP-RIBOSE) POLYMERASE INHIBITORS; POLY(ADP-RIBOSE) POLYMERASES; PROTEIN BINDING; RATS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84955157633     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.5b01498     Document Type: Article

References (45)

1. Hassa, P. O.; Hottiger, M. O. The diverse biological roles of mammalian PARPS, a small but powerful family of poly-ADP-ribose polymerases Front. Biosci., Landmark Ed. 2008, 13, 3046-3082 10.2741/2909
2. Rouleau, M.; Patel, A.; Hendzel, M. J.; Kaufmann, S. H.; Poirier, G. G. PARP inhibition: PARP1 and beyond Nat. Rev. Cancer 2010, 10, 293-301 10.1038/nrc2812
3. Curtin, N. J.; Szabo, C. Therapeutic applications of PARP inhibitors: anticancer therapy and beyond Mol. Aspects Med. 2013, 34, 1217-1256 10.1016/j.mam.2013.01.006
4. Krishnakumar, R.; Kraus, W. L. The PARP side of the nucleus: molecular actions, physiological outcomes, and clinical targets Mol. Cell 2010, 39, 8-24 10.1016/j.molcel.2010.06.017
5. Langelier, M. F.; Pascal, J. M. PARP-1 mechanism for coupling DNA damage detection to poly(ADP-ribose) synthesis Curr. Opin. Struct. Biol. 2013, 23, 134-143 10.1016/j.sbi.2013.01.003
6. Curtin, N. J. DNA repair dysregulation from cancer driver to therapeutic target Nat. Rev. Cancer 2012, 12, 801-817 10.1038/nrc3399
7. Amé, J. C.; Rolli, V.; Schreiber, V.; Niedergang, C.; Apiou, F.; Decker, P.; Muller, S.; Höger, T.; Ménissier-de Murcia, J.; de Murcia, G. PARP-2, A novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase J. Biol. Chem. 1999, 274, 17860-17868 10.1074/jbc.274.25.17860
8. Schreiber, V.; Dantzer, F.; Ame, J. C.; de Murcia, G. Poly(ADP-ribose): novel functions for an old molecule Nat. Rev. Mol. Cell Biol. 2006, 7, 517-528 10.1038/nrm1963
9. Lord, C. J.; Ashworth, A. The DNA damage response and cancer therapy Nature 2012, 481, 287-294 10.1038/nature10760
10. Ekblad, T.; Camaioni, E.; Schüler, H.; Macchiarulo, A. PARP inhibitors: polypharmacology versus selective inhibition FEBS J. 2013, 280, 3563-3575 10.1111/febs.12298
11. Lupo, B.; Trusolino, L. Inhibition of poly(ADP-ribosyl)ation in cancer: old and new paradigms revisited Biochim. Biophys. Acta, Rev. Cancer 2014, 1846, 201-215 10.1016/j.bbcan.2014.07.004
12. Menear, K. A.; Adcock, C.; Boulter, R.; Cockcroft, X.; Copsey, L.; Cranston, A.; Dillon, K. J.; Drzewiecki, J.; Garman, S.; Gomez, S.; Javaid, H.; Kerrigan, F.; Knights, C.; Lau, A.; Loh, V. M.; Matthews, I. T. W.; Moore, S.; O'Connor, M. J.; Smith, G. C. M.; Martin, N. M. B. 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, 6581-6591 10.1021/jm8001263
13. Thomas, H. D.; Calabrese, C. R.; Batey, M. A.; Canan, S.; Hostomsky, Z.; Kyle, S.; Maegley, K. A.; Newell, D. R.; Skalitzky, D.; Wang, L.-Z.; Webber, S. E.; Curtin, N. J. Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial Mol. Cancer Ther. 2007, 6, 945-956 10.1158/1535-7163.MCT-06-0552
14. Canan-Koch, S. S.; Thoresen, L. H.; Tikhe, J. G.; Maegley, K. A.; Yu, X.-H.; Zook, S. E.; Kumpf, R. A.; Zhang, C.; Boritzki, T. J.; Mansour, R. N.; Zhang, K. E.; Ekker, A.; Calabrese, C. R.; Curtin, N. J.; Kyle, S.; Thomas, H. D.; Wang, L.-Z.; Calvert, A. H.; Golding, B. T.; Griffin, R. J.; Newell, D. R.; Webber, S. E.; Hostomsky, Z. Novel tricyclic poly(ADP-ribose) polymerase-1 inhibitors with potent anticancer chemopotentiating activity: Design, synthesis, and X-ray cocrystal structure J. Med. Chem. 2002, 45, 4961-4974 10.1021/jm020259n
15. Jones, P.; Altamura, S.; Boueres, J.; Ferrigno, F.; Fonsi, M.; Giomini, C.; Lamartina, S.; Monteagudo, E.; Ontoria, J. M.; Orsale, M. V.; Palumbi, M. C.; Pesci, S.; Roscilli, G.; Scarpelli, R.; Schultz-Fademrecht, C.; Toniatti, C.; Rowley, M. 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, 7170-7185 10.1021/jm901188v
16. Jones, P.; Wilcoxen, K.; Rowley, M.; Toniatti, C. Niraparib: a poly (ADP-ribose) polymerase (PARP) inhibitor for the treatment of tumors with defective homologous recombination J. Med. Chem. 2015, 58, 3302-3314 10.1021/jm5018237
17. Donawho, C. K.; Luo, Y.; Luo, Y.; Penning, T. D.; Bauch, J. L.; Bouska, J. J.; Bontcheva-Diaz, V. D.; Cox, B. F.; DeWeese, T. L.; Dillehay, L. E.; Ferguson, D. C.; Ghoreishi-Haack, N. S.; Grimm, D. R.; Guan, R.; Han, E. K.; Holley-Shanks, R. R.; Hristov, B.; Idler, K. B.; Jarvis, K.; Johnson, E. F.; Kleinberg, L. R.; Klinghofer, V.; Lasko, L. M.; Liu, X.; Marsh, K. C.; McGonigal, T. P.; Meulbroek, J. A.; Olson, A. M.; Palma, J. P.; Rodriguez, L. E.; Shi, Y.; Stavropoulos, J. A.; Tsurutani, A. C.; Zhu, G. D.; Rosenberg, S.; Giranda, V. L.; Frost, D. J. ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models Clin. Cancer Res. 2007, 13, 2728-2737 10.1158/1078-0432.CCR-06-3039
18. Penning, T. D.; Zhu, G. D.; Gandhi, V. B.; Gong, J.; Thomas, S.; Lubisch, W.; Grandel, R.; Wernet, W.; Park, C. H.; Fry, E. H.; Luo, Y.; Liu, X.; Shi, Y.; Klinghofer, V.; Johnson, E. F.; Frost, D. J.; Donawho, C. K.; Bontcheva-Diaz, V.; Bouska, J. J.; Olson, A. M.; Marsh, K. C.; Rosenberg, S. H.; Giranda, V. L. Discovery and SAR of 2-(1-propylpiperidin-4-yl)-1H-benzimidazole-4-carbox-amide: A potent inhibitor of poly(ADP-ribose) polymerase (PARP) for the treatment of cancer Bioorg. Med. Chem. 2008, 16, 6965-6975 10.1016/j.bmc.2008.05.044
19. Penning, T. D.; Zhu, G. D.; Gandhi, V. B.; Gong, J.; Liu, X.; Shi, Y.; Klinghofer, V.; Johnson, E. F.; Donawho, C. K.; Frost, D. J.; Bontcheva-Diaz, V.; Bouska, J. J.; Osterling, D. J.; Olson, A. M.; Marsh, K. C.; Luo, Y.; Giranda, V. L. 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. 2009, 52, 514-523 10.1021/jm801171j
20. Shen, Y.; Rehman, F. L.; Feng, Y.; Boshuizen, J.; Bajrami, I.; Elliott, R.; Wang, B.; Lord, C. J.; Post, L. E.; Ashworth, A. BMN 673, a novel and highly potent PARP1/2 inhibitor for the treatment of human cancers with DNA repair deficiency Clin. Cancer Res. 2013, 19, 5003-5015 10.1158/1078-0432.CCR-13-1391
21. Gangloff, A. R.; Brown, J.; de Jong, R.; Dougan, D. R.; Grimshaw, C. E.; Hixon, M.; Jennings, A.; Kamran, R.; Kiryanov, A.; O'Connell, S.; Taylor, E.; Vu, P. Discovery of novel benzo[b][1,4]oxazin-3(4H)-ones as poly(ADP-ribose)polymerase inhibitors Bioorg. Med. Chem. Lett. 2013, 23, 4501-4505 10.1016/j.bmcl.2013.06.055
22. Ye, N.; Chen, C. H.; Chen, T.; Song, Z.; He, J. X.; Huan, X. J.; Song, S. S.; Liu, Q.; Chen, Y.; Ding, J.; Xu, Y.; Miao, Z. H.; Zhang, A. 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 PARP1 inhibitors J. Med. Chem. 2013, 56, 2885-2903 10.1021/jm301825t
23. Papeo, G.; Posteri, H.; Borghi, D.; Busel, A. A.; Caprera, F.; Casale, E.; Ciomei, M.; Cirla, A.; Corti, E.; D'Anello, M.; Fasolini, M.; Forte, B.; Galvani, A.; Isacchi, A.; Khvat, A.; Krasavin, M. Y.; Lupi, R.; Orsini, P.; Perego, R.; Pesenti, E.; Pezzetta, D.; Rainoldi, S.; Riccardi-Sirtori, F.; Scolaro, A.; Sola, F.; Zuccotto, F.; Felder, E. R.; Donati, D.; Montagnoli, A. 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, 6875-6898 10.1021/acs.jmedchem.5b00680
24. Shalinsky, D. R.; et al., Preclinical chemosensitization by PARP inhibitors. In PARP Inhibitors for Cancer Therapy; Curtin, N.; Sharma, R., Eds.; Humana Press: New York, 2015; pp 225-260.
25. Bryant, H. E.; Schultz, N.; Thomas, H.; Parker, K. M.; Flower, D.; Lopez, E.; Kyle, S.; Meuth, M.; Curtin, N. J.; Helleday, T. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase Nature 2005, 434, 913-917 10.1038/nature03443
26. Farmer, H.; McCabe, N.; Lord, C. J.; Tutt, A. N. J.; Johnson, D. A.; Richardson, T. B.; Santarosa, M.; Dillon, K. J.; Hickson, I.; Knights, C.; Martin, N. M.; Jackson, S. P.; Smith, G. C.; Ashworth, A. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy Nature 2005, 434, 917-921 10.1038/nature03445
27. Ashworth, A. A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair J. Clin. Oncol. 2008, 26, 3785-3790 10.1200/JCO.2008.16.0812
28. Helleday, T. The underlying mechanism for the PARP and BRCA synthetic lethality: clearing up the misunderstandings Mol. Oncol. 2011, 5, 387-393 10.1016/j.molonc.2011.07.001
29. Turner, N. C.; Ashworth, A. Biomarkers of PARP inhibitor sensitivity Breast Cancer Res. Treat. 2011, 127, 283-286 10.1007/s10549-011-1375-8
30. Murai, J.; Huang, S. Y.; Das, B. B.; Renaud, A.; Zhang, Y.; Doroshow, J. H.; Ji, J.; Takeda, S.; Pommier, Y. Trapping of PARP1 and PARP2 by clinical PARP inhibitors Cancer Res. 2012, 72, 5588-5599 10.1158/0008-5472.CAN-12-2753
31. De Lorenzo, S. B.; Patel, A. G.; Hurley, R. M.; Kaufmann, S. H. The elephant and the blind men: making sense of PARP inhibitors in homologous recombination deficient tumor cells Front. Oncol. 2013, 3, 228 10.3389/fonc.2013.00228
32. Murai, J.; Huang, S. Y.; Renaud, A.; Zhang, Y.; Ji, J.; Takeda, S.; Morris, J.; Teicher, B.; Doroshow, J. H.; Pommier, Y. Stereospecific PARP trapping by BMN 673 and comparison with olaparib and rucaparib Mol. Cancer Ther. 2014, 13, 433-443 10.1158/1535-7163.MCT-13-0803
33. Shen, J.; Aoyagi-Scharber, M.; Wang, B. Trapping poly(ADP-ribose) polymerase J. Pharmacol. Exp. Ther. 2015, 353, 446-457 10.1124/jpet.114.222448
34. Ferraris, D. V. Evolution of poly(ADP-ribose) polymerase inhibitors. From concept to clinic J. Med. Chem. 2010, 53, 4561-4584 10.1021/jm100012m
35. Penning, T. D.; Zhu, G. D.; Gong, J.; Thomas, S.; Gandhi, V. B.; Liu, X.; Shi, Y.; Klinghofer, V.; Johnson, E. F.; Park, C. H.; Fry, E. H.; Donawho, C. K.; Frost, D. J.; Buchanan, F. G.; Bukofzer, G. T.; Rodriguez, L. E.; Bontcheva-Diaz, V.; Bouska, J. J.; Osterling, D. J.; Olson, A. M.; Marsh, K. C.; Luo, Y.; Giranda, V. L. Optimization of phenyl-substituted benzimidazole carboxamide poly (ADP-ribose) polymerase inhibitors: identification of (S)-2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-1H-benzimidazole-4-carboxamide (A-966492), a highly potent and efficacious inhibitor J. Med. Chem. 2010, 53, 3142-3153 10.1021/jm901775y
36. Aoyagi-Scharber, M.; Gardberg, A. S.; Yip, B. K.; Wang, B.; Shen, Y.; Fitzpatrick, P. A. Structural basis for the inhibition of poly(ADP-ribose) polymerases 1 and 2 by BMN 673, a potent inhibitor derived from tetrahydropyridophthalazinone Acta Crystallogr., Sect. F: Struct. Biol. Commun. 2014, 70, 1143-1149 10.1107/S2053230X14015088
37. de Bono, J.; Mina, L. A.; Gonzalez, M.; Curtin, N. J.; Wang, E.; Henshaw, J. W.; Chadha, M.; Sachdev, J. C.; Matei, D.; Jameson, G. S.; Ong, M.; Basu, B.; Wainberg, Z. A.; Byers, L.; Chugh, R. First-in-human trial of novel oral PARP inhibitor BMN 673 in patients with solid tumors, ASCO, Chicago, IL, May 31-June 4, 2013; Abstract 2580.
38. Wainberg, Z. A.; Rafii, S.; Ramanathan, R. K.; Mina, L. A.; Byers, L. A.; Chugh, R.; Goldman, J. W.; Sachdev, J.; Matei, D.; Wheler, J. J.; Henshaw, J. W.; Zhang, C.; Gallant, G. J. A.; de Bono, J. S. Safety and antitumor activity of the PARP inhibitor BMN 673 in a phase 1 trial recruiting metastatic small-cell lung cancer (SCLC) and germline BRCA mutation carrier cancer patients, ASCO, Chicago, IL, May 30-June 3, 2014; Abstract 7522.
39. Smith, M. A.; Reynolds, C. P.; Kang, M. H.; Kolb, E. A.; Gorlick, R.; Carol, H.; Lock, R. B.; Keir, S. T.; Maris, J. M.; Billups, C. A.; Lyalin, D.; Kurmasheva, R. T.; Houghton, P. J. Synergistic activity of PARP inhibition by talazoparib (BMN 673) with Temozolomide in pediatric cancer models in the pediatric preclinical testing program Clin. Cancer Res. 2015, 21, 819-832 10.1158/1078-0432.CCR-14-2572
40. Stewart, E.; Goshorn, R.; Bradley, C.; Griffiths, L. M.; Benavente, C.; Twarog, N. R.; Miller, G. M.; Caufield, W.; Freeman, B. B.; Bahrami, A.; Pappo, A.; Wu, J.; Loh, A.; Karlström, Å.; Calabrese, C.; Gordon, B.; Tsurkan, L.; Hatfield, M. J.; Potter, P. M.; Snyder, S. E.; Thiagarajan, S.; Shirinifard, A.; Sablauer, A.; Shelat, A. A.; Dyer, M. A. Targeting the DNA Repair Pathway in Ewing Sarcoma Cell Rep. 2014, 9, 829-840 10.1016/j.celrep.2014.09.028
41. Flack, H. D.; Bernardinelli, G. Reporting and evaluating absolute-structure and absolute-configuration determinations J. Appl. Crystallogr. 2000, 33, 1143-1148 10.1107/S0021889800007184
42. Kabsch, W. Integration, scaling, space-group assignment and post-refinement Acta Crystallogr., Sect. D: Biol. Crystallogr. 2010, 66, 133-144 10.1107/S0907444909047374
43. Litton, J. K.; Blum, J. L.; Im, Y. H.; Martin, M.; Mina, L.; Roche, H.; Rugo, H. S.; Visco, F.; Zhang, C.; Lokker, N. A.; Lounsbury, D. L.; Eiermann, W. A phase 3, open-label, randomized, parallel, 2-arm international study of the oral PARP inhibitor talazoparib (BMN 673) in germline BRCA mutation subjects with locally advanced and/or metastatic breast cancer (EMBRCA), ASCO, Chicago, IL, May 29-Jun 2, 2015; Poster TPS1107.
44. Turner, N. C.; Balmaña, J.; Fasching, P. A.; Hurvitz, S. A.; Telli, M. L.; Visco, F.; Wardley, A. M.; Zhang, C.; Lokker, N. A.; Lounsbury, D. L.; Robson, M. E. A phase 2 study (2-stage, 2-cohort) of the oral PARP inhibitor talazoparib (BMN 673) in patients with germline BRCA mutation and locally advanced and/or metastatic breast cancer (ABRAZO), ASCO, Chicago, IL, May 29-Jun 2, 2015; Poster TPS1108.
45. Case, D. A.; et al., AMBER 10; University of California: San Francisco, CA, 2008.