Discovery and characterization of OC144-093, a novel inhibitor of P- glycoprotein-mediated multidrug resistance

Cancer Research

Volumn 60, Issue 11, 2000, Pages 2964-2972

  Newman, Michael J ^a   Rodarte, Jennifer C ^a   Benbatoul, Khalid D ^a,c   Romano, Suzanne J ^a   Zhang, Chengzhi ^a,d   Krane, Sonja ^a,e   Moran, Edmund J ^a,f   Uyeda, Roy T ^a   Dixon, Ross ^a   Guns, Emma S ^b   Mayer, Lawrence D ^b  

^a Ontogen Corporation   (United States)

^b BRITISH COLUMBIA CANCER AGENCY   (Canada)

^c LIGAND PHARMACEUTICALS INC   (United States)

^d BAYER CORPORATION   (United States)

^e Havemeyer Hall ^*  (United States)

^f Advanced Medicine Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DOXORUBICIN; GLYCOPROTEIN P; IMIDAZOLE DERIVATIVE; MULTIDRUG RESISTANCE PROTEIN; OC 144093; PACLITAXEL; UNCLASSIFIED DRUG; VINBLASTINE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST CANCER; COLORECTAL CARCINOMA; CONTROLLED STUDY; DRUG EFFECT; DRUG SCREENING; FEMALE; HUMAN; HUMAN CELL; LYMPHOMA; MALIGNANT NEOPLASTIC DISEASE; MOUSE; MULTIDRUG RESISTANCE; NONHUMAN; OVARY CANCER; PRIORITY JOURNAL; PROTEIN EXPRESSION; UTERUS CANCER;

ADENOSINE TRIPHOSPHATASES; ANIMALS; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC AGENTS, PHYTOGENIC; CELL DIVISION; DOGS; DOSE-RESPONSE RELATIONSHIP, DRUG; DOXORUBICIN; DRUG RESISTANCE, MULTIPLE; DRUG RESISTANCE, NEOPLASM; FEMALE; HUMANS; IMIDAZOLES; INHIBITORY CONCENTRATION 50; KINETICS; MICE; MICE, SCID; P-GLYCOPROTEIN; PACLITAXEL; RATS; TIME FACTORS; TUMOR CELLS, CULTURED; VINBLASTINE;

EID: 0034214366     PISSN: 00085472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (46)

1. Ling, V. Multidrug resistance: molecular mechanisms and clinical relevance. Cancer Chemother. Pharmacol., 40 (Suppl.): S3-S8, 1997.
2. Sikic, B. I. Pharmacologic approaches to reversing multidrug resistance. Semin. Hematol., 34: 40-47, 1997.
3. Cole, S. P., and Deeley, R. G. Multidrug resistance mediated by the ATP-binding cassette transporter protein MRP. Bioessays, 20: 931-940, 1998.
4. Belinsky, M. G., Bain, L. J., Balsara, B. B., Testa, J. R., and Kruh, G. D. Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT subfamily of transporter proteins. J. Natl. Cancer Inst., 90: 1735-1741, 1998.
5. Schinkel, A. H. Pharmacological insights from P-glycoprotein knockout mice. Int. J. Clin. Pharmacol. Ther., 36: 9-13, 1998.
6. Luker, G. D., Nilsson, K. R., Covey, D. F., and Piwnica-Worms, D. Multidrug resistance (MDR1) P-glycoprotein enhances esterification of plasma membrane cholesterol. J. Biol. Chem., 274: 6979-6991, 1999.
7. Ramachandran, C., and Melnick, S. J. Multidrug resistance in human tumors-molecular diagnosis and clinical significance. Mol. Diagn., 4: 81-94, 1999.
8. Mechetner, E., Kyshtoobayeva, A., Zonis, S., Kim, H., Stroup, R., Garcia, R., Parker, R. J., and Fruehauf, J. P. Levels of multidrug resistance (MDR1) P-glycoprotein expression by human breast cancer correlate with in vitro resistance to taxol and doxorubicin. Clin. Cancer Res., 4: 389-398, 1998.
9. Nussler, V., Pelka-Fleischer, R., Zwierzina, H., Nerl, C., Beckert, B., Gieseler, F., Diem, H., Ledderose, G., Gullis, E., Sauer, H., and Wilmanns, W. P-glycoprotein expression in patients with acute leukemia-clinical relevance. Leukemia, 10 (Suppl. 3): S23-S31, 1996.
10. Del Poeta, G., Stasi, R., Aronica, G., Venditti, A., Cox, M. C. Bruno, A., Buccisano, F., Masi, M., Tribalto, M., Amadori, S., and Papa, G. Clinical relevance of P-glycoprotein expression in de novo acute myeloid leukemia. Blood, 87: 1997-2004, 1996.
11. Del Poeta, G., Venditti, A., Aronica, G., Stasi, R., Cox, M. C., Buccisano, F., Bruno, A., Tamburini, A., Suppo, G., Simone, M. D., Epiceno, A. M., Del Moro, B., Masi, M., Papa, G., and Amadori, S. P-Glycoprotein expression in de novo acute myeloid leukemia. Leuk. Lymphoma. 27: 257-274, 1997.
12. Senent, L., Jarque, I., Martin, G., Sempere, A., Gonzalez-Garcia, Y., Gomis, F., Perez-Sirvent, M., De La Ruhia, J., and Sanz, M. A. P-glycoprotein expression and prognostic value in acute myeloid leukemia. Haematologica, 83: 783-787, 1998.
13. van der Zee, A. G., Hollema, H., Suurmeijer, A. J., Krans, M., Sluiter, W. J., Willemse, P. H., Aalders, J. G., and de Vries, E. G. Value of P-glycoprotein, glutathione S-transferase pi, c-erbB-2, and p53 as prognostic factors in ovarian carcinomas. J. Clin. Oncol., 13: 70-78, 1995.
14. Kavallaris, M., Leary, J. A., Barrett, J. A., and Friedlander, M. L. MDR1 and multidrug resistance-associated protein (MRP) gene expression in epithelial ovarian tumors. Cancer Lett., 102: 7-16, 1996.
15. Trock, B. J., Leonessa, F., and Clarke, R. Multidrug resistance in breast cancer: a meta-analysis of MDR1/gp170 expression and its possible functional significance. J. Natl. Cancer Inst., 89: 917-931, 1997.
16. Chen, G., Jaffrezou, J. P., Fleming, W. H., Duran, G. E., and Sikic, B. I. Prevalence of multidrug resistance related to activation of the mdr1 gene in human sarcoma mutants derived by single-step doxorubicin selection. Cancer Res., 54: 4980-4987, 1994.
17. Beketic-Oreskovic, L., Duran, G. E., Chen, G., Dumontet, C., and Sikic, B. I. Decreased mutation rate for cellular resistance to doxorubicin and suppression of mdr1 gene activation by the cyclosporin PSC 833. J. Natl. Cancer Inst., 87: 1593-1602, 1995.
18. Abolhoda, A., Wilson, A. E., Ross, H., Danenberg, P. V., Burt, M., and Scotto, K. W. Rapid activation of MDR1 gene expression in human metastatic sarcoma after in vivo exposure to doxorubicin. Clin. Cancer Res., 5: 3352-3356, 1999.
19. Sikic, B. I., Fisher, G. A., Lum, B. L., Halsey, J., Beketic-Oreskovic, L., and Chen, G. Modulation and preventíon of multidrug resistance by inhibitors of P-glycoprotein. Cancer Chemother. Pharmacol., 40 (Suppl.): S13-S19, 1997.
20. Bates, S. E. Drug resistance: still on the learning curve. Clin. Cancer Res., 5: 3346-3348, 1999.
21. Germann, U. A., Shlyakhter, D., Mason, V. S., Zelle, R. E., Duffy, J. P., Galullo, V., Armistead, D. M., Saunders, J. O., Boger, J., and Harding, M. W. Cellular and biochemical characterization of VX-710 as a chemosensitizer: reversal of P-glycoprotein-mediated multidrug resistance in vitro. Anticancer Drugs, 8: 125-140, 1997.
22. Atadja, P., Watanabe, T., Xu, H., and Cohen, D. PSC-833, a frontier in modulation of P-glycoprotein mediated multidrug resistance. Cancer Metastasis Rev., 17: 163-168, 1998.
23. Dale, I. L., Tuffley, W., Callaghan, R., Holmes, J. A., Martin, K., Luscombe, M., Mistry, P., Ryder, H., Stewart, A. J., Charlton, P., Twentyman, P. R., and Bevan, P. Reversal of P-glycoprotein-mediated multidrug resistance by XR9051, a novel dike-topiperazine derivative. Br. J. Cancer, 78: 885-892, 1998.
24. Rowinsky, E. K., Smith, L., Wang, Y. M., Chaturvedi, P., Villalona, M., Campbell, E., Aylesworth, C., Eckhardt, S. G., Hammond, L., Kraynak, M., Drengler, R., Stephenson, J., Jr., Harding, M. W., and Von Hoff, D. D. Phase I and pharmacokinetic study of paclitaxel in combination with biricodar, a novel agent that reverses multi-drug resistance conferred by overexpression of both MDR1 and MRP. J. Clin. Oncol., 16: 2964-2976, 1998.
25. Hyafil, F., Vergely, C., Du Vignaud, P., and Grand-Perret, T. In vitro and in vivo reversal of multidrug resistance by GF120918, an acridonecarboxamide derivative. Cancer Res., 53: 4595-4602, 1993.
26. Dantzig, A. H., Shepard, R. L., Cao, J., Law, K. L., Ehlhardt, W. J., Baughman, T, M., Bumol, T. F., and Starling, J. J. Reversal of P-glycoprotein-mediated multidrug resistance by a potent cyclopropyldibenzosuberane modulator, LY335979. Cancer Res., 56: 4171-4179, 1996.
27. Starling, J. J., Shepard, R. L., Cao, J., Law, K. L., Norman, B. H., Kroin, J. S., Ehlhardt, W. J., Baughman, T. M., Winter, M. A., Bell, M. G., Shih, C., Gruber, J., Elmquist, W. F., and Dantzig, A. H. Pharmacological characterization of LY335979: a potent cyclopropyldibenzosuberane modulator of P-glycoprotein. Adv. Enzyme Regul., 37: 335-347, 1997.
28. Monks, A., Scudiero, D., Skehan, P., Shoemaker, R., Paull, K., Vistica, D., Hose, C., Langley, J., Cronise, P., Vaigro-Wolff, A., et al. Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. J. Natl. Cancer Inst., 83: 757-766, 1991.
29. May, G. L., Wright, L. C., Dyne, M., Mackinnon, W. B., Fox, R. M., and Mountford, C. E. Plasma membrane lipid composition of vinblostine sensitive and resistant human leukaemic lymphoblasts. Int. J. Cancer, 42: 728-733, 1988.
30. Sarkadi, B., Price, E., Boucher, R., Germann, U., and Scarborough, G. Expression of the human multidrug resistance cDNA in insect cells generates a high activity drug stimulated membrane ATPase. J. Biol. Chem., 267: 4854-4858, 1992.
31. Chifflet, S., Torriglia, A., Chiesa, R., and Tolosa, S. A method for the determination of inorganic phosphate in the presence of labile organic phosphate and high concentrations of protein: application to lens ATPases. Anal. Biochem., 168: 1-4, 1988.
32. Johnson, R. K., Chitnis, M. P., Embrey, W. M., and Gregory, E. B. In vivo characteristics of resistance and cross-resistance of an Adriamycin-resistant subline of P388 leukemia. Cancer Treat. Rep., 62: 1535-1547, 1978.
33. MDR 1: ascites models of human breast cancer. Br. J. Cancer, 73: 154-161, 1996.
34. Lai, G. M., Chen, Y. N., Mickley, L. A., Fojo, A. T., and Bates, S. E. P-Glycoprotein expression and schedule dependence of Adriamycin cytotoxicity in human colon carcinoma cell lines. Int. J. Cancer, 49: 696-703, 1991.
35. Cargill, J., and Maiefski, R. Reaction Chamber and Other Apparatus for Use in the Generation of Chemical Libraries. United States Patent, 5,770,157, 1998.
36. Schneider, E., Horton, J., Yang, C., Nakagawa, M., and Cowan, K. Multidrug resistance associated protein gene overexpression and reduced drug sensitivity of topoisomerase II in a human breast carcinoma MCF7 cell line selected for etoposide resistance. Cancer Res., 54: 152-158, 1994.
37. Boesch, D., and Loor, F. Extent and persistence of P-glycoprotein inhibition in multidrug-resistant P388 cells after exposure to resistance-modifying agents. Anti-cancer Drugs, 5: 229-238, 1994.
38. Archinal-Mattheis, A., Rzepka, R. W., Watanabe, T., Kokubu, N., Itoh, Y., Combates, N. J., Bair, K. W., and Cohen, D. Analysis of the interactions of SDZ PSC 833 ([3′-keto-Bmt1]-Val2]-Cyclosporin), a multidrug resistance modulator, with P-glycoprotein. Oncol. Res., 7: 603-610, 1995.
39. Desai, P. B., Duan, J. Z., Zhu, Y. W., and Kouzi, S. Human liver microsomal metabolism of paclitaxel and drug interactions. Eur. J. Drug Metab. Pharmacokinet., 23: 417-424, 1998.
40. Fischer, V., Rodriguez-Gascon, A., Heitz, F., Tynes, R., Hauck, C., Cohen, D., and Vickers, A. E. The multidrug resistance modulator valspodar (PSC 833) is metabolized by human cytochrome P450 3A. Implications for drug-drug interactions and pharmacological activity of the main metabolite. Drug Metab. Dispos., 26: 802-811, 1998.
41. Mistry, P., Plumb, J., Eccles, S., Watson, S., Dale, I., Ryder, H., Box, G., Charlton, P., Templeton, D., and Bevan, P. B. In vivo efficacy of XR9051, a potent modulator of P-glycoprotein mediated multidrug resistance. Br. J. Cancer, 79: 1672-1678, 1999.
42. Roe, M., Folkes, A., Ashworth, P., Brumwell, J., Chima, L., Hunjan, S., Pretswell, I., Dangerfield, W., Ryder, H., and Charlton, P. Reversal of P-glycoprotein mediated multidrug resistance by novel anthranilamide derivatives. Bioorg. Med. Chem. Lett., 9: 595-600, 1999.
43. Mistry, P., Stewart, A., Plumb, J., Callaghan, R., Martin, C., Dangerfield, W., Bootle, D., Liddle, C., Templeton, D., and Charlton, P. In vitro and in vivo evaluation of XR9576, a novel potent modulator of P-glycoprotein (P-gp) mediated multidrug resistance (MDR). Proc. Am. Assoc. Cancer Res., 40: 313, 1999.
44. Rubin, E., Zamek, R., Medina, M., Much, J., Toppmeyer, D., Luffer-Atlas, D., Chaudhary, A., Green, L., Marder, P., Jordan, C., Skerjanec, A., and Slapak, C. A Phase I trial of LY335979, a potent multidrug resistance modulator, administered orally in combination with doxorubicin. Proc. Am. Soc. Clin. Oncol., 18: 183a, 1999.
45. Steiner, J. A., Mellows, G., Stewart, A. J., Norris, D. B., and Bevan, P. An oral and intravenous Phase I clinical trial of a potent P-glycoprotein modulator, XR9576, in healthy volunteers. Proc. Am. Assoc. Cancer Res., 5: 3832s, Abstract 512, 1999.
46. Dixon, R., and Toyonaga, B. P-Glycoprotein inhibitor OC144-093: Phase 1 intravenous and oral pharmacokinetics of a novel multidrug resistance modulator. Proc. Am. Assoc. Cancer Res., 41: 607, 2000.