PMID: 19427995

Tiwari AK, Sodani K, Wang SR, Kuang YH, Ashby CR Jr, Chen X, Chen ZS
Nilotinib (AMN107, Tasigna) reverses multidrug resistance by inhibiting the activity of the ABCB1/Pgp and ABCG2/BCRP/MXR transporters.
Biochem Pharmacol. 2009 Jul 15;78(2):153-61. Epub 2009 Apr 11., 2009-07-15 [PubMed]
Sentences
No. Mutations Sentence Comment
217 ABCG2 p.Arg482Gly
X
ABCG2 p.Arg482Gly 19427995:217:453
status: VERIFIED
view ABCG2 p.Arg482Gly details
 Robey et al. [34] have shown that the efficacy of ABCG2 transporters are also altered in these mutant cell lines, for e.g. novobiocin can only block wild-type ABCG2 and is nearly ineffective against mutant variants, however, FTC was shown to block both wild-type as well as mutant ABCG2. Our result shows that like FTC, nilotinib significantly enhanced the sensitivity of ABCG2 substrates not only in cells overexpressing wild-type R482 but also in the R482G/T variants of ABCG2. Our results, which indicate that specific TKIs interact with the ABCG2 and ABCB1 transporters, support the findings previously published by us and other groups. Login to comment