Design and Synthesis of Nonpeptide Inhibitors of Hepatocyte Growth Factor Activation

ACS Medicinal Chemistry Letters

Volumn 7, Issue 2, 2016, Pages 177-181

  Venukadasula, Phanindra K M ^a   Owusu, Benjamin Y ^a   Bansal, Namita ^a   Ross, Larry J ^a   Hobrath, Judith V ^a   Bao, Donghui ^a   Truss, Jackie W ^a   Stackhouse, Murray ^a   Messick, Troy E ^b   Klampfer, Lidija ^a   Galemmo, Robert A ^a  

^a SOUTHERN RESEARCH INSTITUTE   (United States)

^b WISTAR INSTITUTE   (United States)

Author keywords

hepsin; HGFA; iHGFa; matriptase; Serine protease; SRI 31215; triplex protease inhibitor

Indexed keywords

ANTINEOPLASTIC AGENT; BLOOD CLOTTING FACTOR 10A; HEPSIN; MATRIPTASE; PROTEINASE INHIBITOR; SCATTER FACTOR; SRI 31215; THROMBIN; TRYPSIN; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL; COLON CANCER; CRYSTAL STRUCTURE; DRUG CLEARANCE; DRUG DESIGN; DRUG HALF LIFE; DRUG SOLUBILITY; DRUG STRUCTURE; DRUG SYNTHESIS; ENANTIOMER; EPITHELIAL MESENCHYMAL TRANSITION; HUMAN; IN VITRO STUDY; IN VIVO STUDY; LIVER MICROSOME; MEMBRANE PERMEABILITY; NONHUMAN; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN EXPRESSION; VOLUME OF DISTRIBUTION;

EID: 84958952414     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/acsmedchemlett.5b00357     Document Type: Article

References (30)

1. Comoglio, P. M.; Giordano, S.; Trusolino, L. Drug Development of MET Inhibitors: Targeting Oncogene Addiction and Expedience Nat. Rev. Drug Discovery 2008, 7, 504-16 10.1038/nrd2530
2. Wilson, T. R.; Fridlyand, J.; Yan, Y.; Penuel, E.; Burton, L.; Chan, E.; Peng, J.; Lin, E.; Wang, Y.; Sosman, J.; Ribas, A.; Li, J.; Moffat, J.; Sutherlin, D. P.; Koeppen, H.; Merchant, M.; Neve, R.; Settleman, J. Widespread Potential for Growth-Factor-Driven Resistance to Anticancer Kinase Inhibitors Nature 2012, 487, 505-9 10.1038/nature11249
3. Eder, J. P.; Vande Woude, G. F.; Boerner, S. A.; LoRusso, P. M. Novel Therapeutic Inhibitors of the c-Met Signaling Pathway in Cancer Clin. Cancer Res. 2009, 15, 2207-2214 10.1158/1078-0432.CCR-08-1306
4. Sharma, N.; Adjei, A. A. In the Clinic: Ongoing Clinical Trials Evaluating c-MET-Inhibiting Drugs Ther. Adv. Med. Oncol. 2011, 3, S37-50 10.1177/1758834011423403
5. Bhowmick, N. A.; Neilson, E. G.; Moses, H. L. Stromal Fibroblasts in Cancer Initiation and Progression Nature 2004, 432, 332-337 10.1038/nature03096
6. Ferracini, R.; Di Renzo, M. F.; Scotlandi, K.; Baldini, N.; Olivero, M.; Lollini, P.; Cremona, O.; Campanacci, M.; Comoglio, P. M. The Met/HGF Receptor is Over-expressed in Human Osteosarcomas and is Activated by either a Paracrine or an Autocrine Circuit Oncogene 1995, 10, 739-49
7. Seneviratne, D.; Ma, J.; Tan, X.; Kwon, Y. K.; Muhammad, E.; Melhem, M.; DeFrances, M. C.; Zarnegar, R. Genomic Instability Causes HGF Gene Activation in Colon Cancer Cells, Promoting their Resistance to Necroptosis Gastroenterology 2015, 148, 181-191 10.1053/j.gastro.2014.09.019
8. Owen, K. A.; Qiu, D.; Alves, J.; Schumacher, A. M.; Kilpatrick, L. M.; Li, J.; Harris, J. L.; Ellis, V. Pericellular Activation of Hepatocyte Growth Factor by the Transmembrane Serine Proteases Matriptase and Hepsin, but not by the Membrane-Associated Protease uPA Biochem. J. 2010, 426, 219-228 10.1042/BJ20091448
9. Lee, S. L.; Dickson, R. B.; Lin, C. Y. Activation of Hepatocyte Growth Factor and Urokinase/Plasminogen Activator by Matriptase, an Epithelial Membrane Serine Protease J. Biol. Chem. 2000, 275, 36720-36725 10.1074/jbc.M007802200
10. Herter, S.; Piper, D. E.; Aaron, W.; Gabriele, T.; Cutler, G.; Cao, P.; Bhatt, A. S.; Choe, Y.; Craik, C. S.; Walker, N.; Meininger, D.; Hoey, T.; Austin, R. J. Hepatocyte Growth Factor is a Preferred In Vitro Substrate for Human Hepsin, a Membrane-Anchored Serine Protease Implicated in Prostate and Ovarian Cancers Biochem. J. 2005, 390, 125-136 10.1042/BJ20041955
11. Kawaguchi, M.; Kataoka, H. Mechanisms of Hepatocyte Growth Factor Activation in Cancer Tissues Cancers 2014, 6, 1890-1904 10.3390/cancers6041890
12. Forbs, D.; Thiel, S.; Stella, M. C.; Sturzebecher, A.; Schweinitz, A.; Steinmetzer, T.; Stürzebecher, J.; Uhland, K. In Vitro Inhibition of Matriptase Prevents Invasive Growth of Cell Lines of Prostate and Colon Carcinoma Int. J. Oncol. 2005, 27, 1061-1070 10.3892/ijo.27.4.1061
13. Szabo, R.; Rasmussen, A. L.; Moyer, A. B.; Kosa, P.; Schafer, J. M.; Molinolo, A. A.; Gutkind, J. S.; Bugge, T. H. c-Met-Induced Epithelial Carcinogenesis is Initiated by the Serine Protease Matriptase Oncogene 2011, 30, 2003-16 10.1038/onc.2010.586
14. Kataoka, H.; Hamasuna, R.; Itoh, H.; Kitamura, N.; Koono, M. Activation of Hepatocyte Growth Factor/Scatter Factor in Colorectal Carcinoma Cancer Res. 2000, 60, 6148-59
15. Parr, C.; Watkins, G.; Mansel, R. E.; Jiang, W. G. The Hepatocyte Growth Factor Regulatory Factors in Human Breast Cancer Clin. Cancer Res. 2004, 10, 202-211 10.1158/1078-0432.CCR-0553-3
16. Ye, J.; Kawaguchi, M.; Haruyama, Y.; Kanemaru, A.; Fukushima, T.; Yamamoto, K.; Lin, C. Y.; Kataoka, H. Loss of Hepatocyte Growth Factor Activator Inhibitor Type 1 Participates in Metastatic Spreading of Human Pancreatic Cancer Cells in a Mouse Orthotopic Transplantation Model Cancer Sci. 2014, 105, 44-51 10.1111/cas.12306
17. Kawaguchi, M.; Takeda, N.; Hoshiko, S.; Yorita, K.; Baba, T.; Sawaguchi, A.; Nezu, Y.; Yoshikawa, T.; Fukushima, T.; Kataoka, H. Membrane-Bound Serine Protease Inhibitor HAI-1 is Required for Maintenance of Intestinal Epithelial Integrity Am. J. Pathol. 2011, 179, 1815-1826 10.1016/j.ajpath.2011.06.038
18. Hoshiko, S.; Kawaguchi, M.; Fukushima, T.; Haruyama, Y.; Yorita, K.; Tanaka, H.; Seiki, M.; Inatsu, H.; Kitamura, K.; Kataoka, H. Hepatocyte Growth Factor Activator Inhibitor Type 1 is a Suppressor of Intestinal Tumorigenesis Cancer Res. 2013, 73, 2659-2670 10.1158/0008-5472.CAN-12-3337
19. Oberst, M. D.; Johnson, M. D.; Dickson, R. B.; Lin, C. Y.; Singh, B.; Stewart, M.; Williams, A.; al-Nafussi, A.; Smyth, J. F.; Gabra, H.; Sellar, G. C. Expression of the Serine Protease Matriptase and its Inhibitor HAI-1 in Epithelial Ovarian Cancer: Correlation with Clinical Outcome and Tumor Clinicopathological Parameters Clin. Cancer Res. 2002, 8, 1101-1107
20. Zeng, L.; Cao, J.; Zhang, X. Expression of Serine Protease SNC19/Matriptase and its Inhibitor Hepatocyte Growth Factor Activator Inhibitor Type 1 in Normal and Malignant Tissues of Gastrointestinal Tract World J. Gastroenterol. 2005, 11, 6202-6207 10.3748/wjg.v11.i39.6202
21. Nakamura, K.; Abarzua, F.; Kodama, J.; Hongo, A.; Nasu, Y.; Kumon, H.; Hiramatsu, Y. Expression of Hepatocyte Growth Factor Activator Inhibitors (HAI-1 and HAI-2) in Ovarian Cancer Int. J. Oncol. 2009, 34, 345-353 10.3892/ijo-00000157
22. Hamasuna, R.; Kataoka, H.; Meng, J. Y.; Wakisaka, S.; Koono, M. Reduced Expression of Hepatocyte Growth Factor Activator Inhibitor Type-2/Placental Bikunin (HAI-2/PB) in Human Glioblastomas: Implication for Anti-Invasive Role of HAI-2/PB in Glioblastoma Cells Int. J. Cancer 2001, 93, 339-345 10.1002/ijc.1349
23. Morris, M. R.; Gentle, D.; Abdulrahman, M.; Maina, E. N.; Gupta, K.; Banks, R. E.; Wiesener, M. S.; Kishida, T.; Yao, M.; Teh, B.; Latif, F.; Maher, E. R. Tumor Suppressor Activity and Epigenetic Inactivation of Hepatocyte Growth Factor Activator Inhibitor Type 2/SPINT2 in Papillary and Clear Cell Renal Cell Carcinoma Cancer Res. 2005, 65, 4598-06
24. Franco, F. M.; Jones, D. E.; Harris, P. K.; Han, Z.; Wildman, S. A.; Jarvis, C. M.; Janetka, J. W. Structure-based discovery of small molecule hepsin and HGFA protease inhibitors: Evaluation of potency and selectivity derived from distinct binding pockets Bioorg. Med. Chem. 2015, 23, 2328-43 10.1016/j.bmc.2015.03.072
25. Han, Z.; Harris, P. K. W.; Jones, D. E.; Chugani, R.; Kim, T.; Agarwal, M.; Shen, W.; Wildman, S. A.; Janetka, J. W. Inhibitors of HGFA, Matriptase and Hepsin Serine Proteases: a Nonkinase Strategy to Block Cell Signaling in Cancer ACS Med. Chem. Lett. 2014, 5, 1219-1224 10.1021/ml500254r
26. Galemmo, R. A., Jr.; Wells, B. L.; Rossi, K. A.; Alexander, R. S.; Dominguez, C.; Maduskuie, T. P.; Stouten, P. F.; Wright, M. R.; Aungst, B. J.; Wong, P. C.; Knabb, R. M.; Wexler, R. R. The De Novo Design and Synthesis of Cyclic Urea Inhibitors of Factor Xa: Optimization of the S4 Ligand Bioorg. Med. Chem. Lett. 2000, 10, 301-304 10.1016/S0960-894X(99)00688-5
27. Galemmo, R. A., Jr.; Maduskuie, T. P.; Dominguez, C.; Rossi, K. A.; Knabb, R. M.; Wexler, R. R.; Stouten, P. F. The De Novo Design and Synthesis of Cyclic Urea Inhibitors of Factor Xa: Initial SAR Studies Bioorg. Med. Chem. Lett. 1998, 8, 2705-2710 10.1016/S0960-894X(98)00471-5
28. Bode, W.; Mayr, I.; Baumann, U.; Huber, R.; Stone, S. R.; Hofsteenge, J. The Refined 1.9 Å Crystal Structure of Human α-Thrombin: Interaction with D-Phe-Pro-Arg Chloromethylketone and Significance of the Tyr-Pro-Pro-Tyr Insertion Segment EMBO J. 1989, 8, 3467-3475
29. Owusu, B. Y.; Bansal, N.; Venukadasula, P. K. M.; Ross, L. J.; Messick, T. E.; Goel, S.; Galemmo, R. A., Jr.; Klampfer, L. Inhibition of HGF Activation, a Novel Approach to Block Oncogenic HGF/MET Signaling. Submitted.
30. Lam, P. Y.; Clark, C. G.; Li, R.; Pinto, D. J.; Orwat, M. J.; Galemmo, R. A.; Fevig, J. M.; Teleha, C. A.; Alexander, R. S.; Rossi, K. A.; Wright, M. R.; Bai, S. A.; He, K.; Luettgen, J. M.; Wong, P. C.; Knabb, R. M.; Wexler, R. R. Structure-Based Design of Novel Guanidine/Benzamidine Mimics: Potent and Orally Bioavailable Factor Xa Inhibitors as Novel Anticoagulants J. Med. Chem. 2003, 46, 4405-4418 10.1021/jm020578e