Oral ferroportin inhibitor ameliorates ineffective erythropoiesis in a model of β-thalassemia
Open accessAbstract
β-Thalassemia is a genetic anemia caused by partial or complete loss of β-globin synthesis, leading to ineffective erythropoiesis and RBCs with a short life span. Currently, there is no efficacious oral medication modifying anemia for patients with β-thalassemia. The inappropriately low levels of the iron regulatory hormone hepcidin enable excessive iron absorption by ferroportin, the unique cellular iron exporter in mammals, leading to organ iron overload and associated morbidities. Correction of unbalanced iron absorption and recycling by induction of hepcidin synthesis or treatment with hepcidin mimetics ameliorates β-thalassemia. However, hepcidin modulation or replacement strategies currently in clinical development all require parenteral drug administration. We identified oral ferroportin inhibitors by screening a library of small molecular weight compounds for modulators of ferroportin internalization. Restricting iron availability by VIT-2763, the first clinical stage oral ferroportin inhibitor, ameliorated anemia and the dysregulated iron homeostasis in the Hbbth3/+ mouse model of β-thalassemia intermedia. VIT-2763 not only improved erythropoiesis but also corrected the proportions of myeloid precursors in spleens of Hbbth3/+ mice. VIT-2763 is currently being developed as an oral drug targeting ferroportin for the treatment of β-thalassemia.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The potentiation of hepcidin activity by iron may have immediate consequences for the development of hepcidin mimetics currently in clinical trials.
“The potentiation of hepcidin activity by iron may therefore have immediate consequences for the development of hepcidin mimetics currently in clinical trials 16 .”
From Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms (2020) · cites this paper as [16]
The Introduction (page unavailable) says that synthetic hepcidin and a hepcidin peptidomimetic have been tested in phase I clinical studies, supporting the clinical-development context. But the paper does not say that iron potentiates hepcidin activity or that such potentiation has consequences for developing those drugs; its experiments instead compare hepcidin with the ferroportin inhibitor VIT-2763. (LLM, conf=0.84)
Experimental — accuracy not yet measuredAlthough several approaches to restore aberrant FPN function have been evaluated in clinical trials, none have thus far succeeded.
“Although several approaches to restore aberrant FPN function have been evaluated in clinical trials 16-18 , none have thus far succeeded.”
From Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms (2020) · cites this paper as [16]
The Introduction (page not provided) names three hepcidin-related approaches tested in phase I clinical studies and says no oral ferroportin inhibitor or hepcidin-mimetic drug was available for treatment. It does not report that those trials failed or establish that none of the approaches succeeded; some are described as still in clinical development. (LLM, conf=0.82)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Hepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization
Nemeth, E., Tuttle, M. S., Powelson, J., Vaughn, M. B., Donovan, A., Ward, D. M., Ganz, T., & Kaplan, J. (2004) · Science · doi:10.1126/science.1104742 · Cited by 4,803 · see citing works
Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter
Donovan, A., Brownlie, A., Zhou, Y., Shepard, J., Pratt, S. J., Moynihan, J., Paw, B. H., Drejer, A., Barut, B., Zapata, A., et al. (2000) · Nature · doi:10.1038/35001596 · Cited by 1,667 · see citing works
McKie, A. T., Marciani, P., Rolfs, A., Brennan, K., Wehr, K., Barrow, D., Miret, S., Bomford, A., Peters, T. J., Farzaneh, F., et al. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80425-6 · Cited by 1,422 · see citing works
Dysmetabolic Hyperferritinemia: All Iron Overload Is Not Hemochromatosis
Makker, J. S., Hanif, A., Bajantri, B., & Chilimuri, S. S. (2015) · Case Reports in Gastroenterology · doi:10.1159/000373883 · Cited by 1,353 · see citing works
A Red carpet for iron metabolism
Muckenthaler, M. U., Rivella, S., Hentze, M. W., & Galy, B. (2017) · Cell · doi:10.1016/j.cell.2016.12.034 · Cited by 1,319 · see citing works
Essential role for Nix in autophagic maturation of erythroid cells
Sandoval, H., Thiagarajan, P., Dasgupta, S. K., Schumacher, A., Prchal, J. T., Chen, M., & Wang, J. (2008) · Nature · doi:10.1038/nature07006 · Cited by 1,185 · see citing works
Identification of erythroferrone as an erythroid regulator of iron metabolism
Kautz, L., Jung, G., Valore, E. V., Rivella, S., Nemeth, E., & Ganz, T. (2014) · Nature Genetics · doi:10.1038/ng.2996 · Cited by 1,127 · see citing works
Taher, A. T., Weatherall, D. J., & Cappellini, M. D. (2018) · The Lancet · doi:10.1016/s0140-6736(17)31822-6 · Cited by 807 · see citing works
Olivieri, N. F. (1999) · New England Journal of Medicine · doi:10.1056/nejm199907083410207 · Cited by 718 · see citing works
Phosphatidylserine Receptor Is Required for Clearance of Apoptotic Cells
Li, M. O., Sarkisian, M. R., Mehal, W. Z., RAKIC, P. T., & Flavell, R. A. (2003) · Science · doi:10.1126/science.1087621 · Cited by 403 · see citing works
From Erythroblasts to Mature Red Blood Cells: Organelle Clearance in Mammals
Moras, M., Lefevre, S. D., & Ostuni, M. A. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.01076 · Cited by 343 · see citing works
Hepcidin-Induced Endocytosis of Ferroportin Is Dependent on Ferroportin Ubiquitination
Qiao, B., Sugianto, P., Fung, E., del-Castillo-Rueda, A., Moran-Jimenez, M.-J., Ganz, T., & Nemeth, E. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.03.018 · Cited by 334 · see citing works
Aschemeyer, S., Qiao, B., Stefanova, D., Valore, E. V., Sek, A. C., Ruwe, T. A., Vieth, K. R., Jung, G., Casu, C., Rivella, S., et al. (2018) · Blood · doi:10.1182/blood-2017-05-786590 · Cited by 325 · see citing works
Rivera, S., Nemeth, E., Gabayan, V., Lopez, M. A., Farshidi, D., & Ganz, T. (2005) · Blood · doi:10.1182/blood-2005-04-1766 · Cited by 308 · see citing works
Nemeth, E., Preza, G. C., Jung, C.-L., Kaplan, J., Waring, A. J., & Ganz, T. (2006) · Blood · doi:10.1182/blood-2005-05-2049 · Cited by 273 · see citing works
A mouse model for beta 0-thalassemia.
Yang, B., Kirby, S. L., Lewis, J., Detloff, P. J., Maeda, N., & Smithies, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.25.11608 · Cited by 272 · see citing works
Oxidation and erythrocyte senescence
Kiefer, C. R., & Snyder, L. M. (2000) · Current Opinion in Hematology · doi:10.1097/00062752-200003000-00007 · Cited by 254 · see citing works
Liu, J., Zhang, J., Ginzburg, Y. Z., Li, H., Xue, F., Franceschi, L. D., Chasis, J. A., Mohandas, N., & An, X. (2013) · Blood · doi:10.1182/blood-2012-09-456079 · Cited by 248 · see citing works
Preza, G. C., Ruchala, P., Pinon, R., Ramos, E., Qiao, B., Peralta, M. A., Sharma, S., Waring, A., Ganz, T., & Nemeth, E. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57693 · Cited by 234 · see citing works
Reducing TMPRSS6 ameliorates hemochromatosis and β-thalassemia in mice
Guo, S., Casu, C., Gardenghi, S., Booten, S. L., Aghajan, M., Peralta, R. Q., Watt, A., Freier, S., Monia, B. P., & Rivella, S. (2013) · Journal of Clinical Investigation · doi:10.1172/jci66969 · Cited by 224 · see citing works
Hepcidin as a therapeutic tool to limit iron overload and improve anemia in β-thalassemic mice
Gardenghi, S., Ramos, P., Marongiu, M. F., Melchiori, L., Breda, L., Guy, E., Muirhead, K., Rao, N., Roy, C. N., Andrews, N. C., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci41717 · Cited by 220 · see citing works
The IRP1-HIF-2α Axis Coordinates Iron and Oxygen Sensing with Erythropoiesis and Iron Absorption
Anderson, S. A., Nizzi, C. P., Chang, Y.-I., Deck, K. M., Schmidt, P. J., Galy, B., Damnernsawad, A., Broman, A. T., Kendziorski, C., Hentze, M. W., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.01.007 · Cited by 211 · see citing works
Schmidt, P. J., Toudjarska, I., Sendamarai, A. K., Racie, T., Milstein, S., Bettencourt, B. R., Hettinger, J., Bumcrot, D., & Fleming, M. D. (2013) · Blood · doi:10.1182/blood-2012-09-453977 · Cited by 204 · see citing works
Schwartz, A. J., Das, N. K., Ramakrishnan, S. K., Jain, C., Jurkovic, M. T., Wu, J., Nemeth, E., Lakhal-Littleton, S., Colacino, J. A., & Shah, Y. M. (2018) · Journal of Clinical Investigation · doi:10.1172/jci122359 · Cited by 203 · see citing works
Transferrin therapy ameliorates disease in β-thalassemic mice
Li, H., Rybicki, A. C., Suzuka, S. M., von Bonsdorff, L., Breuer, W., Hall, C. B., Cabantchik, Z. I., Bouhassira, E. E., Fabry, M. E., & Ginzburg, Y. Z. (2010) · Nature Medicine · doi:10.1038/nm.2073 · Cited by 192 · see citing works
Oxidative stress in β-thalassaemia and sickle cell disease
Voskou, S., Aslan, M., Fanis, P., Phylactides, M., & Kleanthous, M. (2015) · Redox Biology · doi:10.1016/j.redox.2015.07.018 · Cited by 172 · see citing works
Kattamis, A., Papassotiriou, I., Palaiologou, D., Apostolakou, F., Galani, A., Ladis, V., Sakellaropoulos, N., & Papanikolaou, G. (2006) · PubMed · Cited by 156 · see citing works
Pasricha, S., Frazer, D. M., Bowden, D. K., & Anderson, G. J. (2013) · Blood · doi:10.1182/blood-2012-12-471441 · Cited by 154 · see citing works
Erythrocytic ferroportin reduces intracellular iron accumulation, hemolysis, and malaria risk
Zhang, D.-L., Wu, J., Shah, B. N., Greutélaers, K. C., Ghosh, M. C., Ollivierre, H., Su, X.-Z., Thuma, P. E., Bedu-Addo, G., Mockenhaupt, F. P., et al. (2018) · Science · doi:10.1126/science.aal2022 · Cited by 150 · see citing works
Suragani, R. N. V. S., Cawley, S. M., Li, R., Wallner, S., Alexander, M. J., Mulivor, A. W., Gardenghi, S., Rivella, S., Grinberg, A. V., Pearsall, R. S., et al. (2014) · Blood · doi:10.1182/blood-2013-06-511238 · Cited by 148 · see citing works
Minihepcidin peptides as disease modifiers in mice affected by β-thalassemia and polycythemia vera
Casu, C., Oikonomidou, P. R., Chen, H., Nandi, V., Ginzburg, Y., Prasad, P., Fleming, R. E., Shah, Y. M., Valore, E. V., Nemeth, E., et al. (2016) · Blood · doi:10.1182/blood-2015-10-676742 · Cited by 148 · see citing works
Ross, S. L., Tran, L., Winters, A., Lee, K.-J., Plewa, C., Foltz, I., King, C., Miranda, L. P., Allen, J., Beckman, H., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.03.017 · Cited by 145 · see citing works
High nontransferrin bound iron levels and heart disease in thalassemia major
Piga, A. G., Longo, F., Duca, L., Roggero, S., Vinciguerra, T., Calabrese, R., Hershko, C., & Cappellini, M. D. (2008) · American Journal of Hematology · doi:10.1002/ajh.21317 · Cited by 144 · see citing works
α-Globin as a molecular target in the treatment of β-thalassemia
Mettananda, S., Gibbons, R. J., & Higgs, D. R. (2015) · Blood · doi:10.1182/blood-2015-03-633594 · Cited by 139 · see citing works
The role of ineffective erythropoiesis in non-transfusion-dependent thalassemia
Rivella, S. (2012) · Blood Reviews · doi:10.1016/s0268-960x(12)70005-x · Cited by 126 · see citing works
Rivella, S. (2015) · Haematologica · doi:10.3324/haematol.2014.114827 · Cited by 122 · see citing works
Taniguchi, R., Kato, H. E., Font, J., Deshpande, C. N., Wada, M., Ito, K., Ishitani, R., Jormakka, M., & Nureki, O. (2015) · Nature Communications · doi:10.1038/ncomms9545 · Cited by 120 · see citing works
Iron metabolism under conditions of ineffective erythropoiesis in β-thalassemia
Rivella, S. (2019) · Blood · doi:10.1182/blood-2018-07-815928 · Cited by 120 · see citing works
Olson, K. A., Beatty, A. L., Heidecker, B., Regan, M. C., Brody, E. N., Foreman, T. M., Kato, S., Mehler, R. E., Singer, B. S., Hveem, K., et al. (2015) · European Heart Journal · doi:10.1093/eurheartj/ehv385 · Cited by 117 · see citing works
An erythroid chaperone that facilitates folding of α-globin subunits for hemoglobin synthesis
Yu, X., Kong, Y., Doré, L. C., Abdulmalik, O. Y., Katein, A. M., Zhou, S., Choi, J. K., Gell, D. A., Mackay, J. P., Gow, A. J., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31664 · Cited by 107 · see citing works
Zhang, D.-L., Ghosh, M. C., Ollivierre, H., Li, Y., & Rouault, T. A. (2018) · Blood · doi:10.1182/blood-2018-04-842997 · Cited by 107 · see citing works
Jagadeeswaran, R., Vazquez, B., Thiruppathi, M., Ganesh, B. B., Ibañez, V., Cui, S., Engel, J. D., Diamond, A. M., Molokie, R. E., DeSimone, J., et al. (2017) · Experimental Hematology · doi:10.1016/j.exphem.2017.02.003 · Cited by 98 · see citing works
Pharmacokinetics of Anti-hepcidin Monoclonal Antibody Ab 12B9m and Hepcidin in Cynomolgus Monkeys
Xiao, J. J., Krzyżański, W., Wang, Y., Li, H., Rose, M. J., Ma, M., Wu, Y., Hinkle, B., & Ruixo, J. J. P. (2010) · The AAPS Journal · doi:10.1208/s12248-010-9222-0 · Cited by 80 · see citing works
Oral ferroportin inhibitor VIT‐2763: First‐in‐human, phase 1 study in healthy volunteers
Richard, F., van Lier, J. J., Roubert, B., Haboubi, T., Göhring, U., & Dürrenberger, F. (2019) · American Journal of Hematology · doi:10.1002/ajh.25670 · Cited by 72 · see citing works
Self-citationControlling -globin: a review of -globin expression and its impact on -thalassemia
Voon, H. P. J., & Vadolas, J. (2008) · Haematologica · doi:10.3324/haematol.13490 · Cited by 65 · see citing works
Gelderman, M. P., Baek, J. H., Yalamanoglu, A., Puglia, M., Vallelian, F., Burla, B., Vostal, J., Schaer, D. J., & Buehler, P. W. (2015) · Haematologica · doi:10.3324/haematol.2014.117325 · Cited by 63 · see citing works
Leecharoenkiat, A., Wannatung, T., Lithanatudom, P., Svasti, S., Fucharoen, S., Chokchaichamnankit, D., Srisomsap, C., & Smith, D. R. (2011) · Blood Cells, Molecules & Diseases · doi:10.1016/j.bcmd.2011.06.005 · Cited by 45 · see citing works
A structural model of human ferroportin and of its iron binding site
Bonaccorsi di Patti, M. C., Polticelli, F., Cece, G., Cutone, A., Felici, F., Persichini, T., & Musci, G. (2014) · The FEBS Journal · doi:10.1111/febs.12825 · Cited by 44 · see citing works
Garcia‐Santos, D., Hamdi, A., Saxova, Z., Fillebeen, C., Pantopoulos, K., Horváthová, M., & Ponka, P. (2017) · Blood · doi:10.1182/blood-2017-07-798728 · Cited by 40 · see citing works
Siwaponanan, P., Siegers, J. Y., Ghazali, R., Ng, T., McColl, B., Ng, G. Z., SUTTON, P. R. N., Wang, N., Ooi, I., Thiengtavor, C., et al. (2017) · Blood · doi:10.1182/blood-2016-07-730135 · Cited by 36 · see citing works
Baek, J. H., Yalamanoglu, A., Gao, Y. S., Guenster, R., Spahn, D. R., Schaer, D. J., & Buehler, P. W. (2017) · JCI Insight · doi:10.1172/jci.insight.93577 · Cited by 27 · see citing works
European Hematology Association
Alexander, W. (2014) · PubMed Central · Cited by 15 · see citing works
Mitochondrial Changes in β0-Thalassemia/Hb E Disease
Khungwanmaythawee, K., Sornjai, W., Paemanee, A., Jaratsittisin, J., Fucharoen, S., Svasti, S., Lithanatudom, P., Roytrakul, S., & Smith, D. R. (2016) · PLoS ONE · doi:10.1371/journal.pone.0153831 · Cited by 15 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [32]32. Kiefer CR, Snyder LM. Oxidation and eryth- rocyte senescence. Curr Opin Hematol. 2000;7(2):113-116.
- [43]43. Olivieri NF. The beta-thalassemias. N Engl J Med. 1999;341(2):99-109.
Cited by
Sorted by citations
Iron metabolism and iron disorders revisited in the hepcidin era
Camaschella, C., Nai, A., & Silvestri, L. (2020) · Haematologica · doi:10.3324/haematol.2019.232124 · Cited by 734 · see citing works
Iron Homeostasis and Ferroptosis in Human Diseases: Mechanisms and Therapeutic Prospects
Ru, Q., Li, Y., Chen, L., Wu, Y., Min, J., & Wang, F. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01969-z · Cited by 724 · see citing works
Hepcidin-Ferroportin Interaction Controls Systemic Iron Homeostasis
Nemeth, E., & Ganz, T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126493 · Cited by 540 · see citing works
“How the new structural model accom od tes other hepcidin agonists ranging from minihepcidin peptides [23] to small molecules [24] remains to be determined.”
BackgroundTaher, A. T., Musallam, K. M., & Cappellini, M. D. (2021) · New England Journal of Medicine · doi:10.1056/nejmra2021838 · Cited by 486 · see citing works
Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms
Billesbølle, C. B., Azumaya, C. M., Kretsch, R. C., Powers, A. S., Gonen, S., Schneider, S., Arvedson, T., Dror, R. O., Cheng, Y., & Manglik, A. (2020) · Nature · doi:10.1038/s41586-020-2668-z · Cited by 344 · see citing works
Beta Thalassemia: New Therapeutic Options Beyond Transfusion and Iron Chelation
Motta, I., Bou‐Fakhredin, R., Taher, A. T., & Cappellini, M. D. (2020) · Drugs · doi:10.1007/s40265-020-01341-9 · Cited by 103 · see citing works
Ineffective erythropoiesis and its treatment
Cazzola, M. (2021) · Blood · doi:10.1182/blood.2021011045 · Cited by 98 · see citing works
Oral ferroportin inhibitor VIT‐2763: First‐in‐human, phase 1 study in healthy volunteers
Richard, F., van Lier, J. J., Roubert, B., Haboubi, T., Göhring, U., & Dürrenberger, F. (2019) · American Journal of Hematology · doi:10.1002/ajh.25670 · Cited by 72 · see citing works
Self-citationInterplay Between Iron Overload and Osteoarthritis: Clinical Significance and Cellular Mechanisms
Cai, C., Hu, W., & Chu, T. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.817104 · Cited by 69 · see citing works
Mukhopadhyay, S., Encarnación-Rosado, J., Lin, E. Y., Sohn, A. S. W., Zhang, H., Mancias, J. D., & Kimmelman, A. C. (2023) · Science Advances · doi:10.1126/sciadv.adf9284 · Cited by 65 · see citing works
2021 update on clinical trials in β‐thalassemia
Musallam, K. M., Bou‐Fakhredin, R., Cappellini, M. D., & Taher, A. T. (2021) · American Journal of Hematology · doi:10.1002/ajh.26316 · Cited by 61 · see citing works
Cell‐type‐specific insights into iron regulatory processes
Mleczko‐Sanecka, K., & Silvestri, L. (2020) · American Journal of Hematology · doi:10.1002/ajh.26001 · Cited by 59 · see citing works
Ineffective Erythropoiesis in β-Thalassaemia: Key Steps and Therapeutic Options by Drugs
Longo, F., Piolatto, A., Ferrero, G. B., & Piga, A. G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22137229 · Cited by 51 · see citing works
Nutrient transporters: connecting cancer metabolism to therapeutic opportunities
Nwosu, Z. C., Song, M. G., di Magliano, M. P., Lyssiotis, C. A., & Kim, S. E. (2023) · Oncogene · doi:10.1038/s41388-023-02593-x · Cited by 47 · see citing works
TMPRSS6 as a Therapeutic Target for Disorders of Erythropoiesis and Iron Homeostasis
Ganz, T., Nemeth, E., Rivella, S., Goldberg, P., Dibble, A., McCaleb, M. L., Guo, S., Monia, B. P., & Barrett, T. D. (2023) · Advances in Therapy · doi:10.1007/s12325-022-02421-w · Cited by 44 · see citing works
Casu, C., Pettinato, M., Liu, A., Aghajan, M., Presti, V. L., Lidonnici, M. R., Munoz, K. A., O’Hara, E., Olivari, V., Modica, S. M. D., et al. (2020) · Blood · doi:10.1182/blood.2019004719 · Cited by 43 · see citing works
The cardinal roles of ferroportin and its partners in controlling cellular iron in and out
Yang, Q., Liu, W., Zhang, S., & Liu, S. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118135 · Cited by 45 · see citing works
Non-Transfusion-Dependent Thalassemia: A Panoramic Review
Shash, H. A. (2022) · Medicina · doi:10.3390/medicina58101496 · Cited by 36 · see citing works
β-Thalassemia: evolving treatment options beyond transfusion and iron chelation
Langer, A. L., & Esrick, E. B. (2021) · Hematology · doi:10.1182/hematology.2021000313 · Cited by 34 · see citing works
Structural and functional annotation of solute carrier transporters: implication for drug discovery
Dvorak, V., & Superti‐Furga, G. (2023) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2023.2244760 · Cited by 33 · see citing works
The mutual crosstalk between iron and erythropoiesis
Camaschella, C., Pagani, A., Silvestri, L., & Nai, A. (2022) · International Journal of Hematology · doi:10.1007/s12185-022-03384-y · Cited by 33 · see citing works
Nyffenegger, N., Zennadi, R., Kalleda, N., Flace, A., Ingoglia, G., Buzzi, R. M., Doucerain, C., Buehler, P. W., Schaer, D. J., Dürrenberger, F., et al. (2022) · Blood · doi:10.1182/blood.2021014716 · Cited by 30 · see citing works
Self-citation20 years of Hepcidin: How far we have come
Colucci, S., Marques, O., & Altamura, S. (2021) · Seminars in Hematology · doi:10.1053/j.seminhematol.2021.05.001 · Cited by 28 · see citing works
Porter, J. B., Taher, A. T., Viprakasit, V., Kattamis, A., Coates, T. D., Garbowski, M., Dürrenberger, F., Manolova, V., Richard, F., & Cappellini, M. D. (2021) · Expert Review of Hematology · doi:10.1080/17474086.2021.1935854 · Cited by 28 · see citing works
Self-citationThe Role of Iron in Benign and Malignant Hematopoiesis
Sinha, S., Pereira-Reis, J., Guerra, A., Rivella, S., & Duarte, D. (2020) · Antioxidants and Redox Signaling · doi:10.1089/ars.2020.8155 · Cited by 29 · see citing works
Nyffenegger, N., Flace, A., Doucerain, C., Dürrenberger, F., & Manolova, V. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22020873 · Cited by 27 · see citing works
Self-citationStructures of ferroportin in complex with its specific inhibitor vamifeport
Lehmann, E. F., Liziczai, M., Drożdżyk, K., Altermatt, P., Langini, C., Manolova, V., Sundström, H., Dürrenberger, F., Dutzler, R., & Manatschal, C. (2023) · eLife · doi:10.7554/elife.83053 · Cited by 25 · see citing works
Self-citationNovel therapeutic approaches in thalassemias, sickle cell disease, and other red cell disorders
Pinto, V. M., Mazzi, F., & Franceschi, L. D. (2024) · Blood · doi:10.1182/blood.2023022193 · Cited by 27 · see citing works
Porter, J. B., Scrimgeour, A., Martínez, A., James, L., Aleku, M., Wilson, R. J., Muckenthaler, M. U., Boyce, M. J., Wilkes, D., Schaeper, U., et al. (2023) · American Journal of Hematology · doi:10.1002/ajh.27015 · Cited by 25 · see citing works
Ferroptosis as an emerging target in sickle cell disease
Fortuna, V., Lima, J. C., Oliveira, G. F., de Oliveira, Y. S. C., Getachew, B., Nekhai, S. A., Aschner, M., & Tizabi, Y. (2024) · Current Research in Toxicology · doi:10.1016/j.crtox.2024.100181 · Cited by 25 · see citing works
Dietary iron restriction improves markers of disease severity in murine sickle cell anemia
Parrow, N. L., Violet, P.-C., George, N. A., Ali, F., Bhanvadia, S., Wong, R., Tisdale, J. F., Fitzhugh, C. D., Levine, M., Thein, S. L., et al. (2020) · Blood · doi:10.1182/blood.2020006919 · Cited by 23 · see citing works
Innovative Treatments for Rare Anemias
Cappellini, M. D., Marcon, A., Fattizzo, B., & Motta, I. (2021) · HemaSphere · doi:10.1097/hs9.0000000000000576 · Cited by 23 · see citing works
Han, Y., Gao, C., Liu, Y., Zhang, H., Wang, S., Zhao, H., Bao, W., Guo, X., Vinchi, F., Lobo, C. A., et al. (2023) · Blood · doi:10.1182/blood.2023021658 · Cited by 21 · see citing works
Li, H., Kazmi, J. S., Lee, S. K., Zhang, D., Gao, X., Maryanovich, M., Torres, L. S., Verma, D., Kelly, L., Ginzburg, Y. Z., et al. (2022) · Blood · doi:10.1182/blood.2022016218 · Cited by 19 · see citing works
Guerra, A., Parhiz, H., & Rivella, S. (2023) · Haematologica · doi:10.3324/haematol.2023.283057 · Cited by 19 · see citing works
Buehler, P. W., Swindle, D. C., Pak, D. I., Fini, M. A., Hassell, K. L., Nuss, R., Wilkerson, R. B., D’Alessandro, A., & Irwin, D. C. (2021) · Pulmonary Circulation · doi:10.1177/20458940211055996 · Cited by 18 · see citing works
Lv, P., Gao, S., & Liu, F. (2023) · Development · doi:10.1242/dev.201690 · Cited by 17 · see citing works
Molecular Mechanisms of Iron Metabolism and Overload
Tayal, A., Kaur, J., Sadeghi, P., & Maitta, R. W. (2025) · Biomedicines · doi:10.3390/biomedicines13092067 · Cited by 21 · see citing works
Novel therapies in β‐thalassaemia
Grech, L., Borg, K., & Borg, J. (2021) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.14918 · Cited by 16 · see citing works
Emerging therapies in β-thalassemia: toward a new era in management
Bou‐Fakhredin, R., Tabbikha, R., Daadaa, H., & Taher, A. T. (2020) · Expert Opinion on Emerging Drugs · doi:10.1080/14728214.2020.1752180 · Cited by 15 · see citing works
Emergent treatments for β-thalassemia and orphan drug legislations
Costa, E., Cappellini, M. D., Rivella, S., Chilin, A., Alessi, E., Riccaboni, M., Leufkens, H. G. M., & Luzzatto, L. (2022) · Drug Discovery Today · doi:10.1016/j.drudis.2022.103342 · Cited by 15 · see citing works
Management of non‐transfusion‐dependent β‐thalassemia ( NTDT ): The next 5 years
Musallam, K. M., Rivella, S., & Taher, A. T. (2020) · American Journal of Hematology · doi:10.1002/ajh.26055 · Cited by 15 · see citing works
Iron and erythropoiesis: A mutual alliance
Silvestri, L., & Nai, A. (2021) · Seminars in Hematology · doi:10.1053/j.seminhematol.2021.05.002 · Cited by 14 · see citing works
Interpreting Iron Homeostasis in Congenital and Acquired Disorders
Scaramellini, N., Fischer, D. P., Agarvas, A. R., Motta, I., Muckenthaler, M. U., & Mertens, C. (2023) · Pharmaceuticals · doi:10.3390/ph16030329 · Cited by 14 · see citing works
Kalleda, N., Flace, A., Altermatt, P., Ingoglia, G., Doucerain, C., Nyffenegger, N., Dürrenberger, F., & Manolova, V. (2023) · Haematologica · doi:10.3324/haematol.2022.282328 · Cited by 14 · see citing works
Self-citationActivation of Intestinal HIF2α Ameliorates Iron‐Refractory Anemia
Yu, Y., Su, Y., Yang, S., Liu, Y., Lin, Z., Das, N. K., Wu, Q., Zhou, J., Sun, S., Li, X., et al. (2024) · Advanced Science · doi:10.1002/advs.202307022 · Cited by 13 · see citing works
Iron restriction in sickle cell disease: When less is more
Castro, O. L., Franceschi, L. D., Ganz, T., Kanter, J., Kato, G. J., Pasricha, S., Rivella, S., & Wood, J. C. (2024) · American Journal of Hematology · doi:10.1002/ajh.27267 · Cited by 14 · see citing works
Vamifeport: Monography of the First Oral Ferroportin Inhibitor
Pilo, F., & Angelucci, E. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13185524 · Cited by 13 · see citing works
Current Landscape of Hepcidin Therapeutics
Nai, A., Silvestri, L., Asperti, M., & Vinchi, F. (2025) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-92033-2_26 · Cited by 11 · see citing works
The EHA Research Roadmap: Anemias
Iolascon, A., Rivella, S., Anagnou, N. P., Camaschella, C., Swinkels, D. W., Muckenthaler, M. U., Porto, G., Barcellini, W., Andolfo, I., Risitano, A. M., et al. (2021) · HemaSphere · doi:10.1097/hs9.0000000000000607 · Cited by 11 · see citing works
Khan, M. S., Hu, Q., Okeibunor, K., Ma, L., & Bopassa, J. C. (2025) · Frontiers in Physiology · doi:10.3389/fphys.2025.1641323 · Cited by 10 · see citing works
Nyffenegger, N., Flace, A., Varol, A., Altermatt, P., Doucerain, C., Sundström, H., Dürrenberger, F., & Manolova, V. (2024) · HemaSphere · doi:10.1002/hem3.147 · Cited by 10 · see citing works
Self-citationKolnagou, A., Kleanthous, M., & Kontoghiorghes, G. J. (2022) · Frontiers in Bioscience-Elite · doi:10.31083/j.fbe1403018 · Cited by 10 · see citing works
Poirier, M., Pujol‐Giménez, J., Manatschal, C., Bühlmann, S., Embaby, A., Javor, S., Hediger, M. A., & Reymond, J. (2020) · RSC Medicinal Chemistry · doi:10.1039/d0md00085j · Cited by 9 · see citing works
Wake, M., Palin, A., Belot, A., Berger, M., Lorgouilloux, M., Bichon, M., Papworth, J., Bayliss, L., Grimshaw, B., Rynkiewicz, N. K., et al. (2024) · Blood Advances · doi:10.1182/bloodadvances.2023012010 · Cited by 9 · see citing works
Antypiuk, A., Vance, S. Z., Sharma, R., Passos, S., Asperti, M., Navaneethabalakrishnan, S., Dürrenberger, F., Manolova, V., & Vinchi, F. (2024) · Blood · doi:10.1182/blood.2024026135 · Cited by 8 · see citing works
Self-citationAu, T. Y., Benjamin, S., & Wiśniewski, O. W. (2022) · Thalassemia Reports · doi:10.3390/thalassrep12030017 · Cited by 8 · see citing works
Baek, J. H., Shin, H. K., Gao, Y. S., & Buehler, P. W. (2020) · Transfusion · doi:10.1111/trf.15720 · Cited by 8 · see citing works
Kattamis, A., Taher, A. T., Viprakasit, V., Levin, C., Hermosilla, R., Szecsödy, P., Richard, F., Cappellini, M. D., & Porter, J. B. (2025) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-025-04119-y · Cited by 6 · see citing works
Improving Ineffective Erythropoiesis in Thalassemia: A Hope on the Horizon
Madan, U., Bhasin, H., Dewan, P., & Madan, J. (2021) · Cureus · doi:10.7759/cureus.18502 · Cited by 6 · see citing works
Advancing the care of β-thalassaemia patients with novel therapies.
Bou‐Fakhredin, R., Motta, I., & Cappellini, M. D. (2022) · PubMed Central · doi:10.2450/2021.0265-21 · Cited by 6 · see citing works
Cellular and animal models for the investigation of β-thalassemia
Nai, A., Cordero-Sánchez, C., Tanzi, E., Pagani, A., Silvestri, L., & Modica, S. M. D. (2023) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2023.102761 · Cited by 6 · see citing works
Lob, H. E., Singh, N., Mohammadi, K. A., Ivanova, L., Crowell, B., Kim, H. J., Kravets, L., Das, N., Ray, Y., Kim, J. H., et al. (2025) · JCI Insight · doi:10.1172/jci.insight.191813 · Cited by 5 · see citing works
Drug safety in thalassemia: lessons from the present and directions for the future
Grech, L., Sultana, J., Borg, K., & Borg, J. (2021) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2021.1919081 · Cited by 5 · see citing works
Current and Future Therapies for β-Thalassaemia: A Review Article
Giannoni, L., & Angelucci, E. (2021) · EMJ Hematology · doi:10.33590/emjhematol/20-00249 · Cited by 5 · see citing works
Emerging Therapies in β-Thalassemia
Bou‐Fakhredin, R., Kuo, K. H. M., & Taher, A. T. (2023) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2022.12.010 · Cited by 5 · see citing works
Structural and functional characterisation of HepTH1-5 peptide as a potential hepcidin replacement
Azemin, W.-A., Alias, N., Ali, A. M., & Shamsir, M. S. (2021) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2021.2011415 · Cited by 5 · see citing works
In vitro reconstitution of transition metal transporters
Ongey, E. L., & Banerjee, A. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.107589 · Cited by 5 · see citing works
Ferroportin-inhibitor salt: patent evaluation WO2018192973
Kadam, S., Khaitan, M., Banerjee, P., & Mandhare, A. (2021) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2021.1928075 · Cited by 3 · see citing works
Multidimensional repair of jujube pectic oligosaccharides on bone marrow hematopoietic failure
Chen, H., Wang, B., & Li, X. (2026) · Frontiers in Nutrition · doi:10.3389/fnut.2026.1734800 · Cited by 2 · see citing works
Katikaneni, D. S., Arekar, T., Al-Hraki, L., Garcia, G., Reedy, N., Morel, L. M., Manolova, V., & Scindia, Y. M. (2026) · Clinical Immunology · doi:10.1016/j.clim.2026.110699 · Cited by 2 · see citing works
Self-citationHepcidin as a Molecular Hub of Iron Homeostasis: From BMP–SMAD Signaling to Therapeutic Modulation
Duminuco, A., Costa, A. N., Pilo, F., Scarso, S., Giallongo, C., Giallongo, S., Santisi, A., Sbriglione, A., Santocono, L., Caocci, G., et al. (2026) · Biomolecules · doi:10.3390/biom16070947 · Cited by 2 · see citing works
Mitoxantrone ameliorates ineffective erythropoiesis in a β-thalassemia intermedia mouse model
Zhang, H., Liu, R., Fang, Z., Nie, L., Ma, Y., Sun, F., Mei, J., Song, Z., Ginzburg, Y. Z., Liu, J., et al. (2024) · Blood Advances · doi:10.1182/bloodadvances.2024012679 · Cited by 2 · see citing works
IGHG4: innovative diagnostic biomarkers for iron overload in β-thalassemia patients
Liu, Y., Huang, J., & Luo, J. (2024) · Hematology · doi:10.1080/16078454.2024.2433154 · Cited by 2 · see citing works
Structure of human ferroportin bound to hepcidin reveals mechanisms of iron homeostasisPreprint
Billesbølle, C. B., Azumaya, C. M., Kretsch, R. C., Powers, A. S., Gonen, S., Schneider, S., Arvedson, T., Dror, R. O., Cheng, Y., & Manglik, A. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.03.16.993006 · Cited by 2 · see citing works
Antioxidant Molecules in the Human Vitreous Body During Prenatal Eye Development
Panova, I. G., Galbinur, T., & Tatikolov, A. S. (2025) · Antioxidants · doi:10.3390/antiox14091041 · Cited by 1 · see citing works
Iron metabolism and ferroptosis: druggable targets to delay the progression of lupus nephritis
Al-Hraki, L., Morel, L. M., & Scindia, Y. M. (2025) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00229.2025 · Cited by 1 · see citing works
Al-Helo, H., Desai, S. A., Varma, T., Garg, P., & Shahiwala, A. (2026) · In Silico Research in Biomedicine · doi:10.1016/j.insi.2026.100220 · Cited by 1 · see citing works
Lees, J. A., & Han, S. (2022) · Medicinal chemistry reviews · doi:10.1021/mc-2022-vol57.ch20 · Cited by 1 · see citing works
Isn’t it ironic: better RBCs by blocking iron
Parrow, N. L., & Fleming, R. E. (2022) · Blood · doi:10.1182/blood.2022017209 · Cited by 1 · see citing works
Identification and analysis of genetic and chemical modulators of iron metabolism
Hawula, Z. J. (2021) · Queensland University of Technology · doi:10.5204/thesis.eprints.225904
Kostić, M., & Jones, L. H. (2022) · Wiley eBooks · doi:10.1002/9781119774198.ch15
The Progress in Treatment of β-Thalassemia and Research on Animal Models of the Disease
Zhang, S., Dong, Z., Yan, W., Wang, W., Pei, Y., & Zheng, F. (2025) · Applied Sciences · doi:10.3390/app15031661
Noulsri, E., & Lerdwana, S. (2025) · Medical Hypotheses · doi:10.1016/j.mehy.2025.111686
Pharmacologic Inhibition of Erythrocyte Ferroportin Expression Exacerbates Plasmodium Infection
Zeydabadinejad, S., Theis, B. F., Park, J. S., Gohara, A. F., Vijay–Kumar, M., Yeoh, B. S., & Saha, P. (2025) · Microorganisms · doi:10.3390/microorganisms13081859
Wei, R., Qiu, D., & Zeng, X. (2025) · Annals of Hematology · doi:10.1007/s00277-025-06605-6
ROS and Ferroptosis Impact on Inflammation-Mediated Hemochromatosis
Gobinath, M., Roychowdhury, P., Sarkar, P., Maideen, N. M. P., & Chatterjee, S. (2026) · Springer eBooks · doi:10.1007/978-3-032-11752-6_16
Identification and characterization of novel hepcidin mimetics that modulate ferroportin function
Castillo, C., Zaman, R., El-Derany, M. O., Osman, E. E. A., Li, Y., Robida, A. M., Zhao, L., Talukder, I., Kadiyala, P., Shah, R., et al. (2026) · Blood Red Cells & Iron · doi:10.1016/j.brci.2026.100069
Elephant seal cells export iron and form lipid droplets to evade lipid peroxidationPreprint
Allen, K. N., Piotrowski, E. R., Moreno-Santillán, D. D., Li, A. L., Luong, D., Foley, V., del Real, C. T., & Vázquez‐Medina, J. P. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.08.10.744012
Regulation of erythroid development by iron metabolism
Ishfaq, M., & Yien, Y. Y. (2026) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2026.06.005
Costa, A., Pilo, F., & Breccia, M. (2026) · Blood Reviews · doi:10.1016/j.blre.2026.101420
Zainab, F., Hasan, A. H., Abid, M. H., & Abid, M. (2026) · Health Science Reports · doi:10.1002/hsr2.73178
Lucero, M. J., Nozik‐Grayck, E., Hassell, K. L., Irwin, D. C., Buehler, P. W., & Ferguson, S. K. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27188170
2026 Update on Clinical Trials in β‐Thalassemia
Musallam, K. M., Locatelli, F., Algeri, M., Cappellini, M. D., & Taher, A. T. (2026) · American Journal of Hematology · doi:10.1002/ajh.70472
Alburayh, K. A. S., Emara, A. M., & Elgharabawy, R. M. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27198657
Rescuing anxiety by targeting the neuronal-astrocytic iron signaling axis in male mice
Wang, Z., Yang, S., Tan, S., Huang, T., Yang, Q., Fu, J., Liu, Z., Li, B., Wu, Z., Min, J., et al. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02921-z
Interleukin signaling and iron dysregulation in SARS-CoV-2 pathogenesis and therapeutic targeting
Abdel-Wahab, S. I., Abdel-Wahab, T. I., Abdel-Wahab, E. I., & Adel, M. M. (2026) · Discover Immunity. · doi:10.1007/s44368-026-00024-z
- Authors
- Manolova, V., Nyffenegger, N., Flace, A., Altermatt, P., Varol, A., Doucerain, C., Sundstrom, H., & Dürrenberger, F.
- Corresponding author
- Manolova, Vania
- Venue
- Journal of Clinical Investigation
- Published
- 2019-12-09
- Volume
- 130
- Issue
- 1
- Pages
- 491-506
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC6934209
- OpenAlex
- W2982116473
- Cited by
- 98
- References
- 53
- Citations by year
- 2026: 15 · 2025: 12 · 2024: 12 · 2023: 13 · 2022: 12 · 2021: 20 · 2020: 13 · 2019: 1
- FWCI
- 8.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Vifor (International) Ltd. (Employer of the authors., Internal budget)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Keywords
- beta-thalassemia, ineffective erythropoiesis, hepcidin, iron homeostasis, iron overload, oral drug delivery, beta-thalassemia intermedia, myeloid precursors, spleen
- MeSH terms
- Ferroportin, Administration, Oral, Animals, Cell Line, Disease Models, Animal, Dogs, Drug Evaluation, Preclinical, Erythropoiesis, Female, Ferric Compounds, Humans, Iron, Male, Maltose, Mice, Inbred C57BL, Mice, Mutant Strains, beta-Thalassemia, Rats, Sprague-Dawley, Cation Transport Proteins, Mice, Ubiquitination, beta-Globins, Proteolysis, Madin Darby Canine Kidney Cells, Hepcidins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
