ABCC1 p.Asp88Val
| Predicted by SNAP2: | A: N (61%), C: N (53%), E: N (61%), F: D (71%), G: D (59%), H: D (75%), I: D (71%), K: D (75%), L: D (71%), M: D (80%), N: N (57%), P: D (80%), Q: N (57%), R: D (85%), S: N (61%), T: N (66%), V: D (66%), W: D (80%), Y: D (75%), |
| Predicted by PROVEAN: | A: D, C: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] Resistance to antifolates. Oncogene. 2003 Oct 20;22(47):7431-57. Zhao R, Goldman ID
Resistance to antifolates.
Oncogene. 2003 Oct 20;22(47):7431-57., 2003-10-20 [PMID:14576850]
Abstract [show]
The antifolates were the first class of antimetabolites to enter the clinics more than 50 years ago. Over the following decades, a full understanding of their mechanisms of action and chemotherapeutic potential evolved along with the mechanisms by which cells develop resistance to these drugs. These principals served as a basis for the subsequent exploration and understanding of the mechanisms of resistance to a variety of diverse antineoplastics with different cellular targets. This section describes the bases for intrinsic and acquired antifolate resistance within the context of the current understanding of the mechanisms of actions and cytotoxic determinants of these agents. This encompasses impaired drug transport into cells, augmented drug export, impaired activation of antifolates through polyglutamylation, augmented hydrolysis of antifolate polyglutamates, increased expression and mutation of target enzymes, and the augmentation of cellular tetrahydrofolate-cofactor pools in cells. This chapter also describes how these insights are being utilized to develop gene therapy approaches to protect normal bone marrow progenitor cells as a strategy to improve the efficacy of bone marrow transplantation. Finally, clinical studies are reviewed that correlate the cellular pharmacology of methotrexate with the clinical outcome in children with neoplastic diseases treated with this antifolate.
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No. Sentence Comment
276 Of interest was the demonstration that in a cell line resistant to MTX due to a mutation in the fourth TMD of hRFC (Arg133Leu), the induction of a second mutation in the second TMD (Asp88Val), which alone also impaired function, restored the activity of the carrier and drug sensitivity (Liu and Matherly, 2001).
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ABCC1 p.Asp88Val 14576850:276:182
status: NEW