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 MKC-1

MKC-1 is an orally bioavailable, small-molecule, bisindolylmaleimide cell cycle inhibitor with potential antineoplastic activity. MKC-1 and its metabolites inhibit tubulin polymerization, blocking the formation of the mitotic spindle, which may result in cell cycle arrest at the G2/M phase and apoptosis. In addition, this agent has been shown to inhibit the activities of the oncogenic kinase Akt, the mTOR pathway, and importin-beta, a protein essential to the transport of other proteins from the cytosol into the nucleus. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

According to EntreMed's website: MKC-1 is an orally-active, small molecule, cell cycle inhibitor with in vitro and in vivo efficacy against a broad range of human solid tumor cell lines, including multi-drug resistant cell lines. MKC-1 acts through multiple mechanisms of action, arresting cellular mitosis and inducing cell death (apoptosis) by binding to a number of different cellular proteins including tubulin and members of the importin β family. MKC-1 also inhibits activation of the oncogenic kinase Akt and the mTOR pathway.

MKC-1 has demonstrated broad antitumor effects in multiple preclinical models, including paclitaxel-resistant models, and was evaluated in several Phase 1 and 2 clinical studies involving nearly 270 patients prior to the licensing of the drug from Hoffman La Roche. These studies have provided extensive pharmacokinetic and safety data. Since acquired by EntreMed, MKC-1 has shown single agent antitumor activity in breast cancer patients and in combination with Alimta® in NSCLC patients. MKC-1 has completed multiple Phase 2 clinical trials for cancer and has a robust data set.

 Current developer:   EntreMed, Inc.

1. Dulsat, C.; Castaner, R.; Bolos, J. MKC-1: antimitotic agent apoptosis inducer oncolytic. Drugs of the Future (2009), 34(4), 270-275. 

2. Zhao, Sheng-Yin; Shao, Zhi-Yu; Qin, Wei-Min; Zhang, Deng-Qing. Recent progress in indolylmaleimide derivatives as protein kinase C inhibitors. Youji Huaxue (2008), 28(10), 1676-1684.

3. Habib, Nabil. Treatment of cancer and other diseases. PCT Int. Appl. (2007), 86pp. CODEN: PIXXD2 WO 2007064691 A1 20070607

4. Kelland, Lloyd R. Cyclin-dependent kinase inhibitors and combination therapy: experimental and clinical status. Inhibitors of Cyclin-Dependent Kinases as Anti-Tumor Agents (2007), 371-388. 

5. Yaffe, Michael B.; Clapperton, Julie A.; Manke, Isaac A.; Lowery, Drew M.; Ho, Timmy; Haire, Lesley F.; Smerdon, Stephen J. The x-ray crystal structure of BRCA1 tandem BRCT repeat and BACH1 phosphopeptide complex and methods and compositions for antitumor drug design. PCT Int. Appl. (2005), 360 pp. CODEN: PIXXD2 WO 2005115454 A2 20051208 

6. Penning, Maarten Tjerk; Van den Broek, Sebastiaan Johannes Jacobus; Voest, Emile Eugene; Beerepoot, Laurens Victor; Mehra, Niven. Methods of detecting CD133 antigen (AC133) expression level and use as biomarker for human cancer diagnosis and therapy monitor. PCT Int. Appl. (2005), 55 pp. CODEN: PIXXD2 WO 2005083123 A1 20050909

7. Penning, Maarten Tjerk; Beerepoot, Laurens Victor; Van Den Broek, Sebastiaan Johannes Jacobus; Mehra, Niven; Voest, Emile Eugene. Methods for detecting AC133 antigen mRNA for diagnosis and treatment of cancer and other diseases. Eur. Pat. Appl. (2005), 28 pp. CODEN: EPXXDW EP 1571225 A1 20050907 

8. Lacasse, Eric; McManus, Daniel. Human protein IAP (inhibitor of apoptosis protein) nucleobase oligomers, including dsRNA, shRNA, and siRNA, and their use for enhancing apoptosis in cancer therapy. PCT Int. Appl. (2005), 112 pp. CODEN: PIXXD2 WO 2005042558 A1 20050512 

9. Lacasse, Eric; McManus, Daniel; Durkin, Jon P. Sequences of antisense IAP (inhibitor of apoptosis protein) oligomers and their use for treatment of proliferative diseases with a chemotherapeutic agent. PCT Int. Appl. (2005), 285 pp. CODEN: PIXXD2 WO 2005042030 A1 20050512 

10. Schultz, Clyde L. Hydrogels used to deliver medicaments to the eye for the treatment of posterior segment diseases. U.S. Pat. Appl. Publ. (2005), 7 pp., Cont.-in-part of U.S. Ser. No. 821,718. CODEN: USXXCO US 2005074497 A1 20050407 

11. Lee, Margaret S.; Nichols, James M.; Zhang, Yanzhen; Keith, Curtis. Combinations of chlorpromazine compounds and antiproliferative drugs for the treatment of neoplasms. PCT Int. Appl. (2005), 65 pp. CODEN: PIXXD2 WO 2005027842 A2 20050331 

12. Dupont, Jakob; Bienvenu, Bryan; Aghajanian, Carol; Pezzulli, Sandra; Sabbatini, Paul; Vongphrachanh, Phothisath; Chang, Christine; Perkell, Christina; Ng, Kenneth; Passe, Sharon; Breimer, Lars; Zhi, Jianguo; DeMario, Mark; Spriggs, David; Soignet, Steven L. Phase I and pharmacokinetic study of the novel oral cell-cycle inhibitor Ro 31-7453 in patients with advanced solid tumors. Journal of Clinical Oncology (2004), 22(16), 3366-3374. CODEN: JCONDN ISSN:0732-183X. CAN 142:232516 AN 2004:945843

13. Salazar, Ramon; Bissett, Donald; Twelves, Chris; Breimer, Lars; DeMario, Mark; Campbell, Sophia; Zhi, Jay; Ritland, Steve; Cassidy, Jim. A phase I clinical and pharmacokinetic study of Ro 31-7453 given as a 7- or 14-day oral twice daily schedule every 4 weeks in patients with solid tumors. Clinical Cancer Research (2004), 10(13), 4374-4382. 

14. Timmermans, Eveline Catherina Anna Clasina; Van Gemen, Bob. Methods for quantifying ratio between two nucleic acids by NASBA for diagnosis and treatment of HIV-1, tumor or angiogenic disorders. Eur. Pat. Appl. (2004), 32 pp. 

15. Timmermans, Eveline Catherina Anna Clasina; Van Gemen, Bob. Methods for quantifying ratio between two nucleic acids by NASBA for diagnosis and treatment of HIV-1, tumor or angiogenic disorders. Eur. Pat. Appl. (2004), 37 pp. CODEN: EPXXDW EP 1418241 A1 20040512 CAN 140:386996 AN 2004:386629

16. Come, Jon H.; Becker, Frank; Kley, Nikolai A.; Reichel, Christoph. Three hybrid assay system for isolating ligand-binding polypeptides and for isolating small mol. ligands. U.S. Pat. Appl. Publ. (2004), 238 pp., Cont.-in-part of U.S. Ser. No. 91,177. CODEN: USXXCO US 2004043388 A1 20040304 

17. Van der Kuyl, Antoinette Cornelia; Cornelissen, Marion. Angiogenesis-related gene expression analysis of blood and skin samples for diagnosis and post-chemotherapy treatment evaluation of Kaposi's sarcoma and other human cancers. U.S. Pat. Appl. Publ. (2003), 36 pp., Cont.-in-part of U.S. Ser. No. 55,728. CODEN: USXXCO US 2003219772 A1 20031127 

18. Breimer, Lars Holger; Dhingra, Kapil; Dhingra, Urvashi Hooda; Ritland, Steve. Method using bisindolymaleimide compounds in combination with gemcitabine for cancer therapy. PCT Int. Appl. (2003), 42 pp. CODEN: PIXXD2 WO 2003043632 A2 20030530 CAN 138:396202 AN 2003:417622

19. Breimer, Lars Holger; Dhingra, Kapil; Dhingra, Urvashi Hooda; Ritland, Steve. Method for administration of cancer therapeutic bisindolymaleimides. PCT Int. Appl. (2002), 20 pp. CODEN: PIXXD2 WO 2002102373 A1 20021227 

20. Breimer, Lars Holger; Dhingra, Kapil; Dhingra, Urvashi Hooda; Ritland, Steve. Combination of a bis(3-indolyl)pyrrolinedione derivative and paclitaxel for cancer therapy. PCT Int. Appl. (2002), 37 pp. CODEN: PIXXD2 WO 2002064214 A2 20020822 
21. Van der Kuyl, Antoinette Cornelia; Cornelissen, Marion. RT-PCR based methods for determining cancer treatment efficacy using expression profiles of marker genes. Eur. Pat. Appl. (2002), 38 pp. CODEN: EPXXDW EP 1225233 A2 20020724 

22. Albano, Antonio A.; Phuapradit, Wantanee; Sandhu, Harpreet K.; Shah, Navnit Hargovindas. Amorphous form of indolylpyrroledione derivative as cell cycle inhibitor. PCT Int. Appl. (2002), 29 pp. CODEN: PIXXD2 WO 2002028855 A2 20020411 

23. Jiang, Xinglong. Methylation of indoles using dimethyl carbonate. PCT Int. Appl. (2001), 35 pp. CODEN: PIXXD2 WO 2001081305 A2 20011101 

24. Fotouhi, Nader; Kong, Norman; Liu, Emily Aijun; Lovey, Allen John; Mullin, John Guilfoyle, Jr. Preparation of substituted pyrroles as antiproliferative agents for the treatment of cancer. PCT Int. Appl. (2001), 60 pp. CODEN: PIXXD2 WO 2001027106 A1 20010419 

25. Albano, Antonio A.; Phuapradit, Wantanee; Sandhu, Harpreet K.; Shah, Navnit Hargovindas. Stable complexes of poorly soluble compounds. Eur. Pat. Appl. (2000), 22 pp. CODEN: EPXXDW EP 988863 A2 20000329

26. Mager, Peter P. Interactive multivariate analysis of bisindolylmaleimides as potent protein kinase C antagonists. Drug Design and Discovery (1993), 10(3), 231-48. CODEN: DDDIEV ISSN:1055-9612. CAN 120:182350 AN 1994:182350

27. Davis, Peter D.; Hill, Christopher H.; Lawton, Geoffrey; Nixon, John S.; Wilkinson, Sandra E.; Hurst, Steven A.; Keech, Elizabeth; Turner, Susan E. Inhibitors of protein kinase C. 1. 2,3-bisarylmaleimides. Journal of Medicinal Chemistry (1992), 35(1), 177-84. 

28. Davis, Peter David; Hill, Christopher Huw; Lawton, Geoffrey. Preparation of 3-(3-indolyl)pyrrole-2,5-diones and analogs as protein kinase inhibitors. Eur. Pat. Appl. (1989), 38 pp.