Small molecule inhibitors of divalent metal transporter-1

American Journal of Physiology - Gastrointestinal and Liver Physiology

Volumn 296, Issue 4, 2009, Pages

  Buckett, Peter D ^a   Wessling Resnick, Marianne ^a  

^a HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

Author keywords

Iron; Iron transport inhibitors

Indexed keywords

COPPER; NATURAL RESISTANCE ASSOCIATED MACROPHAGE PROTEIN 2; NSC 11079; NSC 124808; NSC 13831; NSC 27236; NSC 306711; NSC 331973; NSC 48010; NSC 48874; NSC 75600; PROTEIN INHIBITOR; TRIENTINE; UNCLASSIFIED DRUG; DMRT1 PROTEIN; IRON; TRANSCRIPTION FACTOR;

ARTICLE; CHELATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; CYTOTOXICITY; DRUG EFFECT; DRUG INHIBITION; DRUG STRUCTURE; HUMAN; HUMAN CELL; IRON TRANSPORT; PRIORITY JOURNAL; PROTEIN EXPRESSION; CELL LINE; CHEMICAL STRUCTURE; DRUG ANTAGONISM; METABOLISM; STRUCTURE ACTIVITY RELATION;

CELL LINE; HUMANS; IRON RADIOISOTOPES; MOLECULAR STRUCTURE; STRUCTURE-ACTIVITY RELATIONSHIP; TRANSCRIPTION FACTORS;

EID: 67149134750     PISSN: 01931857     EISSN: 15221547     Source Type: Journal    
DOI: 10.1152/ajpgi.90342.2008     Document Type: Article

References (16)

1. Adams PC, Barton JC. Haemochromatosis. Lancet 370: 1855-1860, 2007.
2. Anderson GJ, Powell LW. HFE and non-HFE hemochromatosis. Int J Hematol 76: 203-207, 2002.
3. Breuer W, Hershko C, Cabantchik ZI. The importance of non-transferrin bound iron in disorders of iron metabolism. Transfus Sci 23:185-192, 2000.
4. Brown JX, Buckett PD, Wessling-Resnick M. Identification of small molecule inhibitors that distinguish between non-transferrin bound iron uptake and transferrin-mediated iron transport. Chem Biol 11: 407-416, 2004.
5. Fleming MD, Romano MA, Su MA, Garrick LM, Garrick MD, Andrews NC. Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport. Proc Natl Acad Sci USA 95: 1148-1153, 1998.
6. Fleming MD, Trenor CC 3rd, Su MA, Foernzler D, Beier DR, Dietrich WF, Andrews NC. Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene. Nat Genet 16: 383-386, 1997.
7. Garrick MD, Singleton ST, Vargas F, Kuo HC, Zhao L, Knopfel M, Davidson T, Costa M, Paradkar P, Roth JA, Garrick LM. DMT1: which metals does it transport? Biol Res 39: 79-85, 2006.
8. Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, Nussberger S, Gollan JL, Hediger MA. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388:482-488, 1997.
9. Horonchik L, Wessling-Resnick M. The small-molecule iron transport inhibitor ferristatin/NSC306711 promotes degradation of the transferrin receptor. Chem Biol 15: 647-653, 2008.
10. Kushner JP, Porter JP, Olivieri NF. Secondary iron overload. Hematology Am Soc Hematol Educ Program: 47-61, 2001.
11. 2+ channel blockers reverse iron overload by a new mechanism via divalent metal transporter-1. Nat Med 13: 448-454, 2007.
12. Mackenzie B, Shawki A, Ahio AJ, Stonehuerner JD, Zhao L, Ghadersohl S, Garrick LM, Garrick MD. A role for the devalent metal-ion transporter (DMT1) is doubtful in the mechanism by which calcium-channel blockers reverse iron overload. FASEB J 22: 1192, 2008.
13. Mackenzie B, Takanaga H, Hubert N, Rolfs A, Hediger MA. Functional properties of multiple isoforms of human divalent metal-ion transporter 1 (DMT1). Biochem J 403: 59-69, 2007.
14. Picard V, Govoni G, Jabado N, Gros P. Nramp 2 (DCT1/DMT1) expressed at the plasma membrane transports iron and other divalent cations into a calcein-accessible cytoplasmic pool. J Biol Chem 275: 35738-35745, 2000.
15. Savigni DL, Wege D, Cliff GS, Meesters ML, Morgan EH. Iron and transition metal transport into erythrocytes mediated by nifedipine degradation products and related compounds. Biochem Pharmacol 65: 1215-1226, 2003.
16. Wetli HA, Buckett PD, Wessling-Resnick M. Small-molecule screening identifies the selanazal drug ebselen as a potent inhibitor of DMT1-mediated iron uptake. Chem Biol 13: 965-972, 2006.