ABCMdb

PMID: 17504223

Xia CQ, Milton MN, Gan LS
Evaluation of drug-transporter interactions using in vitro and in vivo models.
Curr Drug Metab. 2007 May;8(4):341-63., [PubMed]

Sentences

No. Mutations Sentence Comment

119 ABCG2 p.Gln141Lys ABCG2 p.Val12Met ABCG2 p.Gln166Glu ABCG2 p.Ser441Asn ABCG2 p.Ala149Pro ABCG2 p.Pro269Ser ABCG2 p.Arg163Lys The function of seven single nucleotide polymorphisms (SNPs) in BCRP (V12M, Q141K, A149P, R163K, Q166E, P269S, and S441N BCRP) was determined using membrane vesicles from HEK293 cells infected with the recombinant adenoviruses containing the corresponding BCRP cDNAs [45]. Login to comment 120 ABCG2 p.Gln141Lys ABCG2 p.Ser441Asn The expression levels of Q141K and S441N BCRP proteins were significantly lower compared to the wild type protein and the other five variants. Login to comment 121 ABCG2 p.Gln141Lys ABCG2 p.Val12Met ABCG2 p.Gln166Glu ABCG2 p.Ala149Pro ABCG2 p.Pro269Ser ABCG2 p.Arg163Lys Furthermore, the transport rate of estrone sulfate, dehydroepiandrosterone sulfate (DHEAS), methotrexate, and p-aminohippurate was almost the same for the wild type, V12M, Q141K, A149P, R163K, Q166E, and P269S BCRP variants when it is normalized by the expression levels of BCRP protein. Login to comment 122 ABCG2 p.Gln141Lys ABCG2 p.Ser441Asn These results suggest that Q141K SNPs may be associated with a lower expression level, and S441N SNPs may affect both the expression level and cellular localization. Login to comment 124 ABCG2 p.Arg482Gly Using a similar method, methotrexate has been demonstrated to be a substrate for wild type BCRP but not for the R482G BCRP mutant [44]. Login to comment