2264 R. P. Verma, C. Hansch / Bioorg. Med. Chem. 15 (2007) 2223–2268 Table 46. MMP inhibitors in clinical trials No. MMP inhibitors Structure Company name 1 ABT-518 2 AG-3340 (Prinomastat) 3 AG-3433 4 BAY 12-9566 5 BB-94 (Batimastst) 6 BB-2516 (Marimastat) HO N O O O H O O S O OCF3 Comments Status Reference Abbott Cancer Phase I 144 O O O S O HO N N H N Agouron Cancer Macular degeneration Phase III Phase II 7,15 7 S CN O HO H O N HO O S O HO N H S HO S N H O O OH O N O O H N H N O O O N H N H Cl Agouron Cancer Phase I 15 Bayer Cancer Phase III 7,15 Arthritis Phase II (withdrawn) 15 British Biotech Cancer Phase II 15 British Biotech Cancer Phase III 7,15 7 BB-3644 Not Released British Biotech Cancer Phase I 7 8 CGS-27023A HO NH 9 D-1927 N O O O HCl N N S O O SH O N H O OCH3 H N O N H Novartis Arthritis Phase I 7 Cancer Phase I 7 Chiroscience Cancer Preclinical 7 Inflammation Phase II 15
Table 46 (continued) No. MMP inhibitors Structure Company name 10 D-2163 (BMS-275291) chemo-preventive and chemo-therapeutic ability. The mechanisms of inhibition of <strong>MMPs</strong> by bio-drugs may be of significant importance to understanding the mechanism by which nutraceuticals elicit their anti-tumoral and anti-metastatic effects. References and notes 1. Aranapakam, V.; Grosu, G. T.; Davis, J. M.; Hu, B.; Ellingboe, J.; Baker, J. L.; Skotnicki, J. S.; Zask, A.; DiJoseph, J. F.; Sung, A.; Sharr, M. A.; Killar, L. M.; Walter, T.; Jin, G.; Cowling, R. J. Med. Chem. 2003, 46, 2361. 2. Engel, C. K.; Pirard, B.; Schimanski, S.; Kirsch, R.; Habermann, J.; Klingler, O.; Schlotte, V.; Weithmann, K. U.; Wendt, K. U. Chem. Biol. 2005, 12, 181. 3. Amin, E. A.; Welsh, W. J. J. Med. Chem. 2001, 44, 3849. 4. Raspollini, M. R.; Castiglione, F.; Degl’Innocenti, D. R.; Garbini, F.; Coccia, M. E.; Taddei, G. L. Fertil. Steril. 2005, 84, 1049. 5. Venkatesan, A. M.; Davis, J. M.; Grosu, G. T.; Baker, J.; Zask, A.; Levin, J. I.; Ellingboe, J.; Skotnicki, J. S.; DiJoseph, J. F.; Sung, A.; Jin, G.; Xu, W.; McCarthy, D. J.; Barone, D. J. Med. Chem. 2004, 47, 6255. 6. Brown, S.; Meroueh, S. O.; Fridman, R.; Mobashery, S. Curr. Top. Med. Chem. 2004, 4, 1227. 7. Whittaker, M.; Floyd, C. D.; Brown, P.; Gearing, J. H. Chem. Rev. 1999, 99, 2735. 8. Raitio, A.; Tuomas, H.; Kokkonen, N.; Salo, T.; Sorsa, T.; Hanemaaijer, R.; Oikarinen, A. Arch. Dermatol. Res. 2005, 297, 242. 9. Cheng, M.; De, B.; Pikul, S.; Almstead, N. G.; Natchus, M. G.; Anastasio, M. V.; McPhail, S. J.; Snider, C. E.; Taiwo, Y. O.; Chen, L.; Dunaway, C. M.; Gu, F.; Dowty, M. E.; Mieling, G. E.; Janusz, M. J.; Wang- Weigand, S. J. Med. Chem. 2000, 43, 369. 10. Kontogiorgis, C. A.; Papaioannou, P.; Hadjipavlou- Litina, D. J. Curr. Med. Chem. 2005, 12, 339. N O O N SH O N H O H N O N H Comments Status Reference Chiroscience Cancer Phase III 145 11 Metastat Not Released CollaGenex Cancer Preclinical 7 12 RS-130,830 13 RO 32-3555 R. P. Verma, C. Hansch / Bioorg. Med. Chem. 15 (2007) 2223–2268 2265 HO N H O O HO N H O N N O O O S O O N O Cl Roche Bioscience Arthritis Phase II 15 Roche Arthritis Phase III (withdrawn) 11. Mannello, F.; Tonti, G.; Papa, S. Curr. Cancer Drug Targets 2005, 5, 285. 12. Coussens, L. M.; Fingleton, B.; Matrisian, L. M. Science 2002, 295, 2387. 13. Overall, C. M.; López-Otín, C. Nat. Rev. Cancer 2002, 2, 657. 14. Benoit de Coignac, A.; Elson, G.; Gauchat, J.-F. Pierre Fabre Medicament, France, Patent No. WO 2001016335. 15. Skiles, J. W.; Monovich, L. G.; Jeng, A. Y. Annu. Rep. Med. Chem. 2000, 35, 167. 16. Babine, R. E.; Bender, S. L. Chem. Rev. 1997, 97, 1359. 17. Khandelwal, A.; Lukacova, V.; Kroll, D. M.; Çömez, D.; Raha, S.; Balaz, S. QSAR Comb. Sci. 2004, 23, 754. 18. Lovejoy, B.; Cleasby, A.; Hassell, A. M.; Longley, K.; Luther, M. A.; Weigl, D.; McGeehan, G.; McElroy, A. B.; Drewry, D.; Lambert, M. H.; Jorden, S. R. Science 1994, 263, 375. 19. Bertini, I.; Calderone, V.; Fragai, M.; Luchinat, C.; Mangani, S.; Terni, B. Angew. Chem., Int. Ed. 2003, 42, 2673. 20. Cuniasse, P.; Devel, L.; Makaritis, A.; Beau, F.; Georgiadis, D.; Matziari, M.; Yiotakis, A.; Dive, V. Biochimie 2005, 87, 393. 21. Morgunova, E.; Tuuttila, A.; Bergmann, U.; Isupov, M.; Lindqvist, Y.; Schneider, G.; Tryggvason, K. Science 1999, 284, 1667. 22. Bode, W. Structure 1995, 3, 541. 23. Natchus, M. G.; Bookland, R. G.; De, B.; Almstead, N. G.; Pikul, S.; Janusz, M. J.; Heitmeyer, S. A.; Hookfin, E. B.; Hsieh, L. C.; Dowty, M. E.; Dietsch, C. R.; Patel, V. S.; Garver, S. M.; Gu, F.; Pokross, M. E.; Mieling, G. E.; Baker, T. R.; Foltz, D. J.; Peng, S. X.; Bornes, D. M.; Strojnowski, M. J.; Taiwo, Y. O. J. Med. Chem. 2000, 43, 4948. 24. Welch, A. R.; Holman, C. M.; Huber, M.; Brenner, M. C.; Browner, M. F.; Van Wart, H. E. Biochemistry 1996, 35, 10103. 25. Kiyama, R.; Tamura, Y.; Watanabe, F.; Tsuzuki, H.; Ohtani, M.; Yodo, M. J. Med. Chem. 1999, 42, 1723. 15
Change language