ABCMdb

PMID: 16520651

Ahmed-Belkacem A, Pozza A, Macalou S, Perez-Victoria JM, Boumendjel A, Di Pietro A
Inhibitors of cancer cell multidrug resistance mediated by breast cancer resistance protein (BCRP/ABCG2).
Anticancer Drugs. 2006 Mar;17(3):239-43., [PubMed]

Sentences

No. Mutations Sentence Comment

15 ABCG2 p.Arg482Gly In addition, the effects of the hotspot mutation R482G/T, which are well known to change the pattern of transported substrates, have not been systematically characterized for the inhibitors. Login to comment 19 ABCG2 p.Arg482Gly It chemosensitized S1M1-3.2 and MCF-7/BCRP cells to mitoxantrone, doxorubicin and topotecan, promoted the accumulation of radioactive doxorubicin, and also efficiently inhibited (IC50 = 1.3 mmol/l) the ATPase activity of insect cell membranes enriched with recombinant R482G mutant ABCG2 [8]. Login to comment 34 ABCG2 p.Arg482Gly Similar effects were produced by homocamptothecins, containing a seven-membered ring E [15]; interestingly, the best compound, BN-80915, was better transported by mutant (R482G/T) than wild-type (R482) ABCG2. Login to comment 47 ABCG2 p.Arg482Thr Interestingly, however, they were able to inhibit only wild-type (R482) ABCG2, but not the mutant (R482T) transporter [23], as this was also the case with the third-generation P-gp inhibitor VX-710 (biricodar, Incel) [24]. Login to comment 59 ABCG2 p.Arg482Thr Cyclosporin A was considered, however, as a broad-spectrum inhibitor on the basis of its 3-fold induced increase in mitoxantrone accumulation and cell growth sensitization [29], and was reported as a potent ATPase inhibitor of recombinant R482T mutant ABCG2 in insect cell membranes [8]. Login to comment 69 ABCG2 p.Arg482Thr Interestingly, the R482T hotspot mutation altered the impact of prenylation on the inhibitory potency; tectochrysin being the best compound with an IC50 of 1.9 mmol/l. Login to comment 81 ABCG2 p.Gln141Lys Iressa transport/binding appears to be dependent on natural ABCG2 polymorphisms such as Q141K [36]. Login to comment 88 ABCG2 p.Arg482Thr The interaction was altered 2-fold by the R482T/G hotspot mutations. Login to comment