Multidrug resistance inhibitors

Saponara S, Ferrara A, Gorelli B, Shah A, Kawase M, Motohashi N, Molnar J, Sgaragli G, Fusi F (2007) 3,5-Dibenzoyl-4-(3-phenoxyphenyl)-l,4-dihydro-2,6-dimethylpyridine (DP7) a new multidrug resistance inhibitor devoid of effects on Langendorff-perfused rat heart. Eur J Pharmacol 563 160-163... 

Le, L.H., Moore, M.J., Siu, L.L., Oza, A.M., MacLean, M., Fisher, B. etal. (2005) Phase I study of the multidrug resistance inhibitor zosuquidar administered in combination with vinorelbine in patients with advanced solid tumours. Cancer Chemotherapy and Pharmacology, 56 (2), 154—160. 

Mounier C, Guilhot F, Garnache F, Berthou C, Kara-Slimane F, Harousseau J-L. Quinine as a multidrug resistance inhibitor a phase 3 multicentric randomized study in adult de novo acute myelogenous leukemia. Blood 2003 102 1202-1210. 

Toppmeyer D, Seidman AD, Poliak M, Russell C, Tkaczuk K, Verma S, Overmoyer B, Garg V, Ette E, Harding MW, Demetri GD. Safety and efficacy of the multidrug resistance inhibitor Incel (biricodar VX-710) in combination with pachtaxel for advanced breast cancer refractory to pachtaxel. Clin Cancer Res 2002 8 610 1%. 

Gandhi L, Harding MW, Neubauer M, Langer CJ, Moore M, Ross HI et al. A phase II study of the safety and efficacy of the multidrug resistance inhibitor VX-710 combined with doxorubicin and vincristine in patients with recurrent small cell lung cancer. Cancer 2007 109 924-932. 

Hambhn, M. R. Tegos, G. P. Inactivation of microorganisms with multidrug resistance inhibitors and phenothiaziniums. PCX Int. Appl. WO 2006034219, 2006 Chem. Abstr. 2006,144, 343545. 

Major Appiications Fuel cell power generation system, liquid crystal displays, solor cells, sensors, thermochromic materials,coloring wood,n detergents, assessment of tobacco smoke, cosmetics,14 detect bacterial infections,i multidrug resistance inhibitors, treatment of bums, endodontic, diabetes, obesity, 5 cancer,2o age-related macular degeneration, viral diseases Safety/Toxicity Acute toxicity, combustion toxicity, 4 cytotoxicity, genotoxicity, mutagenicity, nephrotoxicity, phototoxicity, soil toxicity ... 

Aukunuru, JV, Sunkara, G, Bandi, N, Thoreson, WB, and Kompella, UB, 2001. Expression of multidrug resistance-associated protein (MRP) in human retinal pigment epithelial cells and its interaction with BAPSG, a novel aldose reductase inhibitor. Pharm Res 18, 565-572. 

Cytostatic drugs for which inhibitors are primarily needed are often not only substrates of P-gp but also inducers of P-gp overexpression with one or even several type II units. An important point to clarify would be whether or not type II units are required to achieve a cytostatic effect. If they were not required, it might be possible to eliminate the P-gp-inducing effect that causes multidrug resistance by eliminating type II units. So far, the only other possibility of overcoming multidrug resistance is to inhibit the transporters involved. Inhibition can be achieved essentially by two different concepts ... 

Huisman, M.T., Smit, J.W., Crommentuyn, K.M., Zelcer, N., Wiltshire, H.R., Beijnen, J.H. and Schinkel, A.H. (2002) Multidrug resistance protein 2 (MRP2) transports HIV protease inhibitors, and transport can be enhanced by other drugs. AIDS, 16, 2295-2301. 

Teodori E, Dei S, Martelli C, Scapecchi S, Gualtieri F (2006) The functions and structure of ABC transporters Implications for the design of new inhibitors of P-gp and MRP1 to control multidrug resistance (MDR). Curr Drug Targets 7 893-909. 

Cyclopamine also interferes with cholesterol metabolism that results in decreased cholesterol synthesis and the accumulation of late biosynthetic intermediates. Cyclopamine was evaluated as an inhibitor of multi-drug resistance in tumor cells. Intrinsic or acquired resistance of tumor cells to cytotoxic drugs is a major cause of failure of chemotherapy. Both cyclopamine and the spirosolane alkaloid tomatidine from tomatoes act as potent and elfective chemosensitizers in multidrug-resistant cells (Lavie et ah, 2001). Therefore, plant steroidal alkaloids, such as cyclopamine and tomatidine, or their analogs, may serve as chemosensitizers in combination with chemotherapy and conventional cytotoxic drugs for treating multidrug-resistant cancers. 

Pereda-Miranda R, Kaatz GW, Gibbons S (2006) Polyacylated Oligosaccharides from Medicinal Mexican Morning Glory Species as Antibacterials and Inhibitors of Multidrug Resistance in Staphylococcus aureus. J Nat Prod 69 406... 

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