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Danusertib

Description of Danusertib: Danusertib is a small-molecule 3-aminopyrazole derivative with potential antineoplastic activity. Aurora kinase inhibitor PHA-739358 binds to and inhibits the Aurora kinases, which may result in cell growth arrest and apoptosis in tumor cells in which Aurora kinases are overexpressed. This agent may preferentially bind to and inhibit Aurora B kinase. Aurora kinases, a family of serine-threonine kinases, are important regulators of cellular proliferation and division. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus) .

Current developer: Entremed.

PHA-739358 exhibits inhibitory activity against all known Aurora kinases as well as other cancer-relevant kinases such as the Bcr-Abl tyrosine kinase, including its multidrug-resistant T315I mutant. This mutation is responsible for up to 25% of all clinically observed resistances in CML patients undergoing Imatinib therapy. However, this particular mutation is predicted to play an even more important clinical role in the future, since in addition to Imatinib, it also confers resistance to second-generation Bcr-Abl inhibitors such as Nilotinib, Dasatinib, and Bosutinib. Therefore, combined Aurora and Bcr-Abl inhibition (the latter including high-grade resistance conferring mutations) with compounds such as Danusertib represents a promising new strategy for treatment of Bcr-Abl positive leukemias, especially those in second and third line of treatment. see http://www.ncbi.nlm.nih.gov/pubmed/20072840.  

1. Fancelli, Daniele; Moll, Jurgen. Discovery of PHA-739358. Kinase Inhibitor Drugs (2009), 281-307. CODEN: 69MSJO AN 2010:651182

2. Taktikos, Katharina. Procedure and analysis of a phase I-study with an aurora kinase inhibitor for the treatment of acute leukemia. (2009), No pp. CAN 152:397460 AN 2010:413962

3. Martinelli, Giovanni; Iacobucci, Ilaria; Papayannidis, Cristina; Soverini, Simona. New targets for Ph+ leukaemia therapy. Best Practice & Research, Clinical Haematology (2009), 22(3), 445-454. CODEN: BPRCA5 AN 2009:1522997

4. Wang, Yaolin; Wang, Yan; Liu, Ming; Bishop, Walter Robert; Seidel-Dugan, Cynthia. Anti-IGF-1 receptor antibody combined with chemotherapeutic agent, antitumor agent, radiotherapy or surgery for treating or preventing colorectal cancer. PCT Int. Appl. (2009), 52pp. CODEN: PIXXD2 WO 2009142810 A2 20091126 CAN 151:569615 AN 2009:1470605

5. Steeghs, Neeltje; Eskens, Ferry A. L. M.; Gelderblom, Hans; Verweij, Jaap; Nortier, Johan W. R.; Ouwerkerk, Jan; van Noort, Conny; Mariani, Mariangela; Spinelli, Riccardo; Carpinelli, Patrizia; Laffranchi, Bernard; de Jonge, Maja J. A. Phase I pharmacokinetic and pharmacodynamic study of the aurora kinase inhibitor danusertib in patients with advanced or metastatic solid tumors. Journal of Clinical Oncology (2009), 27(30), 5094-5101. CODEN: JCONDN ISSN:0732-183X. AN 2009:1448047

6. Wang, Yaolin; Wang, Yan; Lu, Brian Der-Hua; Liu, Ming; Seidel-Dugan, Cynthia; Yao, Siu-Long. Sequential administration of chemotherapeutic agents and anti-(insulin-like growth factor 1 receptor) for treatment of cancer. PCT Int. Appl. (2009), 104 pp. CODEN: PIXXD2 WO 2009137378 A2 20091112 CAN 151:521177 AN 2009:1395230

7. Cohen, Roger B.; Jones, Suzanne F.; Aggarwal, Charu; von Mehren, Margaret; Cheng, Jonathan; Spigel, David R.; Greco, F. Anthony; Mariani, Mariangela; Rocchetti, Maurizio; Ceruti, Roberta; Comis, Silvia; Laffranchi, Bernard; Moll, Jurgen; Burris, Howard A. A Phase I Dose-Escalation Study of Danusertib (PHA-739358) Administered as a 24-Hour Infusion with and without Granulocyte Colony-Stimulating Factor in a 14-Day Cycle in Patients with Advanced Solid Tumors. Clinical Cancer Research (2009), 15(21), 6694-6701. CODEN: CCREF4 ISSN:1078-0432. AN 2009:1340094

8. Martinelli, Giovanni; Papayannidis, Cristina; Iacobucci, Ilaria; Soverini, Simona; Cilloni, Daniela; Baccarani, Michele. Aurora kinase inhibitors: which role in the treatment of chronic myelogenous leukemia patients resistant to imatinib? Hematology Reviews (2009), 1 1-8. CODEN: HREEBR ISSN:1970-6790. CAN 152:540724 AN 2009:1333791

9. Ratushny, Vladimir; Golemis, Erica A.; Astsaturov, Igor; Serebriiskii, Iiya G.; Weiner, Louis M. Synergistic combination therapy for treatment of cancer comprising Aurora kinase inhibitor, EGFR inhibitor and optionally antiproliferative agent. PCT Int. Appl. (2009), 26 pp. CODEN: PIXXD2 WO 2009114703 A2 20090917 CAN 151:344824 AN 2009:1136438

10. Benten, Daniel; Keller, Gunhild; Quaas, Alexander; Schrader, Jorg; Gontarewicz, Artur; Balabanov, Stefan; Braig, Melanie; Wege, Henning; Moll, Jurgen; Lohse, Ansgar W.; Brummendorf, Tim H. Aurora kinase inhibitor PHA-739358 suppresses growth of hepatocellular carcinoma in vitro and in a xenograft mouse model. Neoplasia (Ann Arbor, MI, United States) (2009), 11(9), 934-944. CODEN: NEOPFL ISSN:1522-8002. CAN 152:372945 AN 2009:1062566

11. Adrian, Francisco; Dierks, Christine; Gray, Nathanael S.; Warmuth, Markus. Compositions and methods for treating antitumor resistant cancers using a combination of a ATP-competitive BCR-ABL inhibitor and a non-ATP BCR-ABL inhibitor. PCT Int. Appl. (2009), 56pp. CODEN: PIXXD2 WO 2009091476 A1 20090723 CAN 151:189956 AN 2009:885621

12. Bertucci, Francois; Birnbaum, Daniel; Finetti, Pascal. Protein kinase genes showing altered levels of expression in breast cancer tissue and their diagnostic use. PCT Int. Appl. (2009), 97pp. CODEN: PIXXD2 WO 2009083780 A1 20090709 CAN 151:145654 AN 2009:825033

13. Wang, Yan; Wang, Yaolin; Levitan, Diane; Seidel-Dugan, Cynthia; Liu, Ming; Ding, Wei. Gene expression biomarkers for detecting IGF1R inhibitor-resistant or -sensitive cancers and uses in anti-IGF1R antibody combination chemotherapy. PCT Int. Appl. (2009), 165pp. CODEN: PIXXD2 WO 2009079587 A2 20090625 CAN 151:116583 AN 2009:769153

14. Low, Jonathan; Chakravartty, Arunava; Blosser, Wayne; Dowless, Michele; Chalfant, Christopher; Bragger, Patty; Stancato, Louis. Phenotypic fingerprinting of small molecule cell cycle kinase inhibitors for drug discovery. Current Chemical Genomics (2009), 3 13-21. CODEN: CCGUAQ ISSN:1875-3973. CAN 152:254294 AN 2009:623851

15. Ocheni, Sunday; Iwanski, Gabriela B.; Schafhausen, Philippe; Zander, Axel Rolf; Ayuk, Francis; Klyuchnikov, Evgeny; Zabelina, Tatjana; Fiedler, Walter; Schnittger, Susanne; Hochhaus, Andreas; Brummendorf, Tim H.; Kroger, Nicolaus; Bacher, Ulrike. Characterisation of extramedullary relapse in patients with chronic myeloid leukemia in advanced disease after allogeneic stem cell transplantation. Leukemia & Lymphoma (2009), 50(4), 551-558. CODEN: LELYEA ISSN:1042-8194. CAN 151:439972 AN 2009:462507

16. Pinel, S.; Barbault-Foucher, S.; Lott-Desroches, M.-C.; Astier, A. Inhibitors of aurora kinases. Annales Pharmaceutiques Francaises (2009), 67(2), 69-77. CODEN: APFRAD ISSN:0003-4509. CAN 151:298 AN 2009:421565

17. Hsieh, Hsing-Pang; Coumar, Mohane S.; Lin, Chen-Wei; Reddy, Gadarla Randheer; Tsai, Ming-Tsung; Lin, Wen-Hsing; Hsu, Tsu-An; Wu, Su-Ying. Discovery and development of novel furano-pyrimidine analogs as Aurora kinase inhibitors. Abstracts of Papers, 237th ACS National Meeting, Salt Lake City, UT, United States, March 22-26, 2009 (2009), MEDI-221. CODEN: 69LNK5 AN 2009:305575

18. Dierks, Christine; Warmuth, Markus. Methods and compositions of a hedgehog signaling antagonist and a BCR-ABL inhibitor for treating cancers. PCT Int. Appl. (2009), 49pp. CODEN: PIXXD2 WO 2009026075 A1 20090226 CAN 150:252611 AN 2009:237899

19. Dulsat, C.; Mealy, N.; Castaner, R. Danusertib Aurora kinase inhibitor. Oncolytic. PHA-739358. Drugs of the Future (2008), 33(8), 662-667. CODEN: DRFUD4 ISSN:0377-8282. CAN 150:463076 AN 2008:1465094

20. Wang, Yan; Zong, Chen; Seidel-Dugan, Cynthia; Wang, Yaolin; Yao, Siu-Long; Lu, Brian Der-Hua; Ladha, Mohamed H. Methods of treating cancer using IGF1R inhibitors. PCT Int. Appl. (2008), 103pp. CODEN: PIXXD2 WO 2008076278 A2 20080626 CAN 149:102715 AN 2008:771165

21. Noronha, Glenn; Cao, Jianguo; Chow, Chun P.; Dneprovskaia, Elena; Fine, Richard M.; Hood, John; Kang, Xinshan; Klebansky, Boris; Lohse, Dan; Mak, Chi Ching; McPherson, Andrew; Palanki, Moorthy S. S.; Pathak, Ved P.; Renick, Joel; Soll, Richard; Zeng, Binqi. Inhibitors of ABL and the ABL-T315I mutation. Current Topics in Medicinal Chemistry (Sharjah, United Arab Emirates) (2008), 8(10), 905-921. CODEN: CTMCCL ISSN:1568-0266. CAN 149:118502 AN 2008:742461

22. Gontarewicz, Artur; Balabanov, Stefan; Keller, Gunhild; Colombo, Riccardo; Graziano, Alessio; Pesenti, Enrico; Benten, Daniel; Bokemeyer, Carsten; Fiedler, Walter; Moll, Juergen; Bruemmendorf, Tim H. Simultaneous targeting of Aurora kinases and Bcr-Abl kinase by the small molecule inhibitor PHA-739358 is effective against imatinib-resistant BCR-ABL mutations including T315I. Blood (2008), 111(8), 4355-4364. CODEN: BLOOAW ISSN:0006-4971. CAN 149:191175 AN 2008:493142

23. Alvarado, Yesid; Cortes, Jorge E. Emerging role of Aurora kinase inhibitors in chronic myeloid leukemia. Clinical Leukemia (2007), 1(6), 325-330. CODEN: CLLEAW ISSN:1931-6925. CAN 148:393556 AN 2008:210298

24. Wang, Yan. Blood levels of insulin-like growth factor-binding protein 2 as a marker for monitoring the effectiveness of inhibitors of insulin-like growth factor I receptors in cancer therapy. PCT Int. Appl. (2008), 133pp. CODEN: PIXXD2 WO 2008005469 A2 20080110 CAN 148:135980 AN 2008:43490

25. Carpinelli, Patrizia; Ceruti, Roberta; Giorgini, Maria Laura; Cappella, Paolo; Gianellini, Laura; Croci, Valter; Degrassi, Anna; Texido, Gemma; Rocchetti, Maurizio; Vianello, Paola; Rusconi, Luisa; Storici, Paola; Zugnoni, Paola; Arrigoni, Claudio; Soncini, Chiara; Alli, Cristina; Patton, Veronica; Marsiglio, Aurelio; Ballinari, Dario; Pesenti, Enrico; Fancelli, Daniele; Moll, Juergen. PHA-739358, a potent inhibitor of Aurora kinases with a selective target inhibition profile relevant to cancer. Molecular Cancer Therapeutics (2007), 6(12, Pt. 1), 3158-3168. 

26. Pulici, Maurizio. Aurora Kinase Inhibition: Identification and Expansion of Novel Scaffolds Leading to a Potent and Selective Compound with Favorable Antitumor Kinase Inhibition Profile. Frontiers in CNS and Oncology Medicinal Chemistry, ACS-EFMC, Siena, Italy, October 7-9 (2007), COMC-109. CODEN: 69KAR2 AN 2007:1171083

27. Modugno, Michele; Casale, Elena; Soncini, Chiara; Rosettani, Pamela; Colombo, Riccardo; Lupi, Rosita; Rusconi, Luisa; Fancelli, Daniele; Carpinelli, Patrizia; Cameron, Alexander D.; Isacchi, Antonella; Moll, Juergen. Crystal Structure of the T315I Abl Mutant in Complex with the Aurora Kinases Inhibitor PHA-739358. Cancer Research (2007), 67(17), 7987-7990.

28. Gontarewicz Artur; Brummendorf Tim H Danusertib (formerly PHA-739358)--a novel combined pan-Aurora kinases and third generation Bcr-Abl tyrosine kinase inhibitor. Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer (2010), 184 199-214.

29. Cooper Susannah; Giles Francis J; Savona Michael R Overcoming resistance in chronic myelogenous leukemia. Leukemia & lymphoma (2009), 50(11), 1785-93. J

30. Tomillero A; Moral M A Gateways to clinical trials. Methods and findings in experimental and clinical pharmacology (2008), 30(7), 543-88. 

31. Tomillero A; Moral M A Gateways to clinical trials. Methods and findings in experimental and clinical pharmacology (2008), 30(3), 231-51. J

32. Carpinelli Patrizia; Moll Jurgen Aurora kinases and their inhibitors: more than one target and one drug. Advances in experimental medicine and biology (2008), 610 54-73.