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 Tozasertib

Tozasertib lactate is the lactate salt of tozasertib, a synthetic, small-molecule Aurora kinase inhibitor with potential antitumor activity. Tozasertib binds to and inhibits Aurora kinases (AKs), thereby inducing apoptosis in tumor cells in which AKs are overexpressed. AKs, a family of serine-threonine kinases, are essential for mitotic progression, spindle formation, centrosome maturation, chromosomal segregation, and cytokinesis. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Current developer:   Merck and Vertex

According CNBC news  published on 20 Nov, 2007, Vertex Pharmaceuticals said Merck & Co halted enrollment on trials of their investigational leukemia drug MK-0457 due to a potential heart safety issue in one patient. They suspended trials involving MK-0457, also known as VX-680, pending a full analysis of efficacy and safety data after preliminary data showed that one patient experienced QTc prolongation. The companies also said they discontinued development of their Aurora kinase inhibitor MK-6592, or VX-667, after the investigational drug failed to meet pharmacokinetic objectives in a Phase 1 trial.

1. Golec, Julian M. C. Discovery of MK-0457 (VX-680). Kinase Inhibitor Drugs (2009), 255-279. CODEN: 69MSJO AN 2010:651181

2. Hamilton, Thomas C.; Williams, Stephen J.; Cvetkovic, Dusica. Cancer compositions, animal models, and methods of use thereof. U.S. Pat. Appl. Publ. (2010), 17pp. CODEN: USXXCO US 2010083391 A1 20100401 CAN 152:422240 AN 2010:409182

3. Liang, Yiqiong; Chen, Baoan; Chen, Yali. Research on Aurora kinase inhibitor MK-0457 in therapy for some hematological malignancies. Zhongguo Shiyan Xueyexue Zazhi (2009), 17(3), 810-815. CODEN: ZSXZAF ISSN:1009-2137. AN 2010:389138

4. George, Donna L.; Leu, Julia I-Ju; Murphy, Maureen. Modulators of HSP70/DnaK function, particularly 2-phenylethynesulfonamide (PES) derivatives, for use in potentiating the anticancer and antibacterial effects. PCT Int. Appl. (2010), 76pp. CODEN: PIXXD2 WO 2010033771 A2 20100325 CAN 152:398183 AN 2010:384489

5. Ulisse, Salvatore; Arlot-Bonnemains, Yannick; Baldini, Enke; Morrone, Stefania; Carocci, Silvia; Di Luigi, Luigi; D'Armiento, Massimino. Inhibition of the aurora kinases suppresses in vitro NT2-D1 cell growth and tumorigenicity. Journal of Endocrinology (2010), 204(2), 135-142. CODEN: JOENAK ISSN:0022-0795. CAN 152:326567 AN 2010:209056

6. McDermott, Ultan; Pusapati, Raju V.; Christensen, James G.; Gray, Nathanael S.; Settleman, Jeff. Acquired Resistance of Non-Small Cell Lung Cancer Cells to MET Kinase Inhibition Is Mediated by a Switch to Epidermal Growth Factor Receptor Dependency. Cancer Research (2010), 70(4), 1625-1634. CODEN: CNREA8 ISSN:0008-5472. CAN 152:469649 AN 2010:192741

7. Nicolini, Franck E.; Mauro, Michael J.; Martinelli, Giovanni; Kim, Dong-Wook; Soverini, Simona; Muller, Martin C.; Hochhaus, Andreas; Cortes, Jorge; Chuah, Charles; Dufva, Inge H.; Apperley, Jane F.; Yagasaki, Fumiharu; Pearson, Jay D.; Peter, Senaka; Rodriguez, Cesar Sanz; Preudhomme, Claude; Giles, Francis; Goldman, John M.; Zhou, Wei. Epidemiologic study on survival of chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia patients with BCR-ABL T315I mutation. Blood (2009), 114(26), 5271-5278. CODEN: BLOOAW ISSN:0006-4971. CAN 152:189122 AN 2010:27178

8. Donato, Nicholas J.; Fang, Dexing; Sun, Hanshi; Giannola, Diane; Peterson, Luke F.; Talpaz, Moshe. Targets and effectors of the cellular response to aurora kinase inhibitor MK-0457 (VX-680) in imatinib sensitive and resistant chronic myelogenous leukemia. Biochemical Pharmacology (2010), 79(5), 688-697. CODEN: BCPCA6 ISSN:0006-2952. CAN 152:278887 AN 2009:1584013

9. 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

10. 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

11. 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

12. Aguilera, Dolly G.; Tsimberidou, Apostolia M. Dasatinib in chronic myeloid leukemia: a review. Therapeutics and Clinical Risk Management (2009), 5 281-289. CODEN: TCRMA6 ISSN:1178-203X. CAN 151:235303 AN 2009:928660

13. 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

14. 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

15. Bebbington, David; Binch, Hayley; Charrier, Jean-Damien; Everitt, Simon; Fraysse, Damien; Golec, Julian; Kay, David; Knegtel, Ronald; Mak, Chau; Mazzei, Francesca; Miller, Andrew; Mortimore, Michael; O'Donnell, Michael; Patel, Sanjay; Pierard, Francoise; Pinder, Joanne; Pollard, John; Ramaya, Sharn; Robinson, Daniel; Rutherford, Alistair; Studley, John; Westcott, James. The discovery of the potent aurora inhibitor MK-0457 (VX-680). Bioorganic & Medicinal Chemistry Letters (2009), 19(13), 3586-3592. CODEN: BMCLE8 ISSN:0960-894X. CAN 151:211346 AN 2009:695127

16. Anderson, Kelly; Lai, Zhihong; McDonald, Octerloney B.; Stuart, J. Darren; Nartey, Eldridge N.; Hardwicke, Mary Ann; Newlander, Ken; Dhanak, Dashyant; Adams, Jerry; Patrick, Denis; Copeland, Robert A.; Tummino, Peter J.; Yang, Jingsong. Biochemical characterization of GSK1070916, a potent and selective inhibitor of Aurora B and Aurora C kinases with an extremely long residence time1. Biochemical Journal (2009), 420(2), 259-265. CODEN: BIJOAK ISSN:0264-6021. CAN 151:142033 AN 2009:585799

17. Ramachandra, Sumant; Bishop, Robert Walter; Masat, Linda; Huang, Chao Bai; Takeuchi, Toshihiko; Kantak, Seema. Human anti-VEGF antibodies and conjugates for treatment of angiogenesis conditions. PCT Int. Appl. (2009), 195pp. CODEN: PIXXD2 WO 2009055343 A2 20090430 CAN 150:492909 AN 2009:519479

18. Dreier, Megan R.; Grabovich, Aaron Z.; Katusin, Jamie D.; Taylor, William R. Short and long-term tumor cell responses to Aurora kinase inhibitors. Experimental Cell Research (2009), 315(7), 1085-1099. CODEN: ECREAL ISSN:0014-4827. CAN 151:259916 AN 2009:419730

19. Sanchez-Guijo, Fermin M.; Lopez-Jimenez, Javier; Gonzalez, Tomas; Santamaria, Carlos; Gonzalez, Marcos; del Canizo, Maria-Consuelo. Multitargeted sequential therapy with MK-0457 and dasatinib followed by stem cell transplantation for T315I mutated chronic myeloid leukemia. Leukemia Research (2009), 33(6), e20-e22. CODEN: LEREDD ISSN:0145-2126. CAN 151:395398 AN 2009:414422

20. 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

21. Okabe, Seiichi; Tauchi, Tetsuzo; Ohyashiki, Junko H.; Ohyashiki, Kazuma. Mechanism of MK-0457 efficacy against BCR-ABL positive leukemia cells. Biochemical and Biophysical Research Communications (2009), 380(4), 775-779. CODEN: BBRCA9 ISSN:0006-291X. CAN 150:506424 AN 2009:263026

22. 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

23. Wang, Yan; Pachter, Jonathan A.; Hailey, Judith Anne; Brams, Peter; Williams, Denise; Srinivasan, Mohan; Feingersh, Mary Diane. Anti-insulin-like growth factor 1 receptor therapy. PCT Int. Appl. (2009), 129pp. CODEN: PIXXD2 WO 2009005673 A1 20090108 CAN 150:119716 AN 2009:25215

24. Zhao, Baoguang; Smallwood, Angela; Yang, Jingsong; Koretke, Kristin; Nurse, Kelvin; Calamari, Amy; Kirkpatrick, Robert B.; Lai, Zhihong. Modulation of kinase-inhibitor interactions by auxiliary protein binding: crystallography studies on Aurora A interactions with VX-680 and with TPX2. Protein Science (2008), 17(10), 1791-1797. CODEN: PRCIEI ISSN:0961-8368. CAN 149:486337 AN 2008:1241540

25. Kojima, Kensuke; Konopleva, Marina; Tsao, Twee; Nakakuma, Hideki; Andreeff, Michael. Concomitant inhibition of Mdm2-p53 interaction and Aurora kinases activates the p53-dependent postmitotic checkpoints and synergistically induces p53-mediated mitochondrial apoptosis along with reduced endoreduplication in acute myelogenous leukemia. Blood (2008), 112(7), 2886-2895. CODEN: BLOOAW ISSN:0006-4971. CAN 149:505710 AN 2008:1208721

26. Fiskus, Warren; Wang, Yongchao; Joshi, Rajeshree; Rao, Rekha; Yang, Yonghua; Chen, Jianguang; Kolhe, Ravindra; Balusu, Ramesh; Eaton, Kelly; Lee, Pearl; Ustun, Celalettin; Jillella, Anand; Buser, Carolyn A.; Peiper, Stephen; Bhalla, Kapil. Cotreatment with Vorinostat Enhances Activity of MK-0457 (VX-680) against Acute and Chronic Myelogenous Leukemia Cells. Clinical Cancer Research (2008), 14(19), 6106-6115. CODEN: CCREF4 ISSN:1078-0432. CAN 150:344450 AN 2008:1194852

27. Lin, Yvonne G.; Immaneni, Anand; Merritt, William M.; Mangala, Lingegowda S.; Kim, Seung Wook; Shahzad, Mian M. K.; Tsang, Yvonne T. M.; Armaiz-Pena, Guillermo N.; Lu, Chunhua; Kamat, Aparna A.; Han, Liz Y.; Spannuth, Whitney A.; Nick, Alpa M.; Landen, Charles N., Jr.; Wong, Kwong K.; Gray, Michael J.; Coleman, Robert L.; Bodurka, Diane C.; Brinkley, William R.; Sood, Anil K. Targeting Aurora Kinase with MK-0457 Inhibits Ovarian Cancer Growth. Clinical Cancer Research (2008), 14(17), 5437-5446. CODEN: CCREF4 ISSN:1078-0432. CAN 150:297979 AN 2008:1065359

28. Dai, Yun; Chen, Shuang; Venditti, Charis A.; Pei, Xin-Yan; Nguyen, Tri K.; Dent, Paul; Grant, Steven. Vorinostat synergistically potentiates MK-0457 lethality in chronic myelogenous leukemia cells sensitive and resistant to imatinib mesylate. Blood (2008), 112(3), 793-804. CODEN: BLOOAW ISSN:0006-4971. CAN 149:258816 AN 2008:942111

29. 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

30. 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

31. Tonegawa, Susumu; Hayashi, Mansuo; Karaman, Mazen; Zarrinkar, Patrick P.; Treiber, Daniel K. Small molecule inhibitors of p21-activated kinase for treatment of fragile X syndrome and other neurodevelopmental disorders. PCT Int. Appl. (2008), 78pp. CODEN: PIXXD2 WO 2008060448 A2 20080522 CAN 148:577404 AN 2008:614861

32. Martinelli, Giovanni; Iacobucci, Ilaria; Soverini, Simona; Palandri, Francesca; Castagnetti, Fausto; Rosti, Gianantonio; Baccarani, Michele. Nilotinib: a novel encouraging therapeutic option for chronic myeloid leukemia patients with imatinib resistance or intolerance. Biologics: Targets & Therapy (2007), 1(2), 121-127. CODEN: BTTICT ISSN:1177-5475. CAN 148:509265 AN 2008:344350

33. 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

34. Dubost, David C. A novel lactic acid formulation of MK-0457 useful for the treatment of cancer. PCT Int. Appl. (2008), 29 pp. CODEN: PIXXD2 WO 2008013807 A2 20080131 CAN 148:198643 AN 2008:124306

35. Tyler, Rebecca K.; Shpiro, Natalia; Marquez, Rodolfo; Eyers, Patrick A. VX-680 inhibits Aurora A and Aurora B kinase activity in human cells. Cell Cycle (2007), 6(22), 2846-2854. CODEN: CCEYAS ISSN:1538-4101. CAN 148:345951 AN 2008:61307

36. 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

37. Mcdermott, Ultan; Sharma, Sreenath V.; Dowell, Lori; Greninger, Patricia; Montagut, Clara; Lamb, Jennifer; Archibald, Heidi; Raudales, Raul; Tam, Angela; Lee, Diana; Rothenberg, S. Michael; Supko, Jeffrey G.; Sordella, Raffaella; Ulkus, Lindsey E.; Lafrate, A. John; Maheswaran, Shyamala; Njauw, Ching Ni; Tsao, Hensin; Drew, Lisa; Hanke, Jeff H.; Ma, Xiao-Jun; Erlander, Mark G.; Gray, Nathanael S.; Haber, Daniel A.; Settleman, Jeffrey. Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling. Proceedings of the National Academy of Sciences of the United States of America (2007), 104(50), 19936-19941. CODEN: PNASA6 ISSN:0027-8424. CAN 148:276277 AN 2008:21101

38. Maekawa, Taira; Ashihara, Eishi; Kimura, Shinya. The Bcr-Abl tyrosine kinase inhibitor imatinib and promising new agents against Philadelphia chromosome-positive leukemias. International Journal of Clinical Oncology (2007), 12(5), 327-340. CODEN: IJCOF6 ISSN:1341-9625. CAN 148:298631 AN 2007:1153309

39. Ballard, J. E.; Prueksaritanont, T.; Tang, C. Hepatic metabolism of MK-0457, a potent Aurora kinase inhibitor: interspecies comparison and role of human cytochrome P450 and flavin-containing monooxygenase. Drug Metabolism and Disposition (2007), 35(9), 1447-1451. CODEN: DMDSAI ISSN:0090-9556. CAN 147:291318 AN 2007:976890

40. Wang, Y.; Serradell, N. VX-680/MK-0457 aurora kinase inhibitor oncolytic. Drugs of the Future (2007), 32(2), 144-147. CODEN: DRFUD4 ISSN:0377-8282. CAN 147:157036 AN 2007:525216

41. Cheetham, G. M. T.; Charlton, P. A.; Golec, J. M. C.; Pollard, J. R. Structural basis for potent inhibition of the Aurora kinases and a T315I multi-drug resistant mutant form of Abl kinase by VX-680. Cancer Letters (Amsterdam, Netherlands) (2007), 251(2), 323-329. CODEN: CALEDQ ISSN:0304-3835. CAN 147:157642 AN 2007:495841

42. Harrington, Elizabeth A.; Bebbington, David; Moore, Jeff; Rasmussen, Richele K.; Ajose-Adeogun, Abi O.; Nakayama, Tomoko; Graham, Joanne A.; Demur, Cecile; Hercend, Thierry; Diu-Hercend, Anita; Su, Michael; Golec, Julian M. C.; Miller, Karen M. VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. [Erratum to document cited in CA140:399485]. Nature Medicine (New York, NY, United States) (2007), 13(4), 511. CODEN: NAMEFI ISSN:1078-8956. CAN 146:434451 AN 2007:382972

43. Giles, Francis J.; Cortes, Jorge; Jones, Dan; Bergstrom, Donald; Kantarjian, Hagop; Freedman, Steven J. MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T315I BCR-ABL mutation. Blood (2007), 109(2), 500-502. CODEN: BLOOAW ISSN:0006-4971. CAN 146:266132 AN 2007:288789

44. Martinelli, Giovanni; Soverini, Simona. MK-0457: a light at the end of the tunnel? Blood (2007), 109(2), 396-397. CODEN: BLOOAW ISSN:0006-4971. AN 2007:288776

45. Carella, Angelo Michele. Imatinib mesylate, a selective inhibitor of BCR-ABL, in chronic myeloid leukemia: There is hope that imatinib mesylate and second generation kinase inhibitors can makechronic myeloid leukemia a curable disease. Expert Review of Anticancer Therapy (2007), 7(3), 249-251. CODEN: ERATBJ ISSN:1473-7140. CAN 147:108622 AN 2007:262457

46. Sanchez-Guijo Fermin M; Lopez-Jimenez Javier; Gonzalez Tomas; Santamaria Carlos; Gonzalez Marcos; Del Canizo Maria-Consuelo Multitargeted sequential therapy with MK-0457 and dasatinib followed by stem cell transplantation for T315I mutated chronic myeloid leukemia. Leukemia research (2009), 33(6), e20-2. Journal code: 7706787. E-ISSN:1873-5835. PubMed ID 19038446 AN 2009256558