Multidrug resistance-associated polypeptide

Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues

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435 6, 536 231, C07K 100, C12Q 168, C07H 2102

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active

060779365

ABSTRACT:
Compositions and methods are disclosed for improving the effectiveness of a chemotherapeutic regimen to eradicate multidrug-resistant transformed cells from the body of a mammal, preferably from the body of a human. The present disclosure capitalizes on the discovery of a novel multidrug-resistance associated protein (MRP), herein designated MRP-.beta.. The disclosed compositions include MRP-.beta. nucleic acids, including probes and antisense oligonucleotides, MRP-.beta. polypeptides and antibodies, MRP-.beta. expressing host cells, and non-human mammals transgenic or nullizygous for MRP-.beta.. The disclosed methods include methods for attenuating aberrant MRP-.beta. gene expression, protein production and/or protein function. In addition, methods are disclosed for identifying and using a modulator, such as an inhibitor, of MRP-.beta.. Preferably, the modulator is a small molecule.

REFERENCES:
Wilson et al. Nature 368: 32-38 (Genbank accession No. Q19048) 1994.
Suzuki, T., et al., "cDNA cloning of a short type of multidrug resistance protein homologue, SMRP, from a human lung cancer cell line" Biochemical and Biophysical Research Communications 238(3):790-4 (1997).
Kool, M., et al., "Four homologs of the multidrug resistance protein MRP1" Eighty-Eighth Annual Meeting of the American Association for Cancer Research, San Diego, CA, Apr. 12-15, 1997, Proceedings of the American Association for Cancer Research Annual Meeting, 38(0), (1997), abstract #2941.
Genbankl.RTM. Accession No. H17207 for ym42a06.rl Soares infant brain 1NIB Homo sapiens cDNA clone 50857 5' similar to SP:MRP.sub.-- Human P33527 Multidrug Resistance-Associated; mRNA sequence.

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