Table 1. Pharmacological agents targeting iron metabolism.
Name | Type | Mechanism | Indication | Clinical status | Trial Number | Ref. |
---|---|---|---|---|---|---|
Therapeutics for iron deficiency conditions | ||||||
Iron supplement for oral administration | ||||||
Ferrous sulfate | Iron salt | Refills depleted iron stores | Iron deficiency anemia | Marketed | NCT01904864 | [28–32] |
Ferrous gluconate | Iron salt | Refills depleted iron stores | Iron deficiency anemia | Marketed | NCT01528644 | [28–32] |
Iron supplement for intravenous administration | ||||||
Ferumoxytol | Iron oxide nanoparticle | Refills depleted iron stores | CKD | Marketed | NCT01227616 | [104] |
Ferric carboxymaltose | Iron complex | Refills depleted iron stores | Iron deficiency anemia | Marketed | NCT03523117 | [28–32] |
Sodium ferric gluconate | Macromolecule | Refills depleted iron stores | Iron deficiency anemia | Marketed | NCT00223964 | [28–32] |
Hepcidin downregulation | ||||||
LY3113593 | Ant¡-BMPΘ antibodies | Binds/inhibits BMP6 | CKD | Phase 1 | NCT02144285 | [47] |
Hepcidin capture | ||||||
Anticalin | Binds hepcidin | Binds/inhibits hepcidin | CKD | Phase 1/II |
NCT02754167 (Ph. 1) NCT03325621 (Ph. II) |
[49] |
LY2787106 | Anti-hepcidin antibody | Binds/inhibits hepcidin | Anemia of chronic disease | Phase 1 | NCT01340976 | [48] |
Stimulation of erythropoiesis | ||||||
Luspatercept | Recombinant fusion protein | Ligand trap for TGF-beta superfamily | β-Thalassemia | Phase III | NCT02604433 | [37] |
Sotatercept | Recombinant fusion protein | Ligand trap for TGF-beta superfamily | β-Thalassemia | Phase II | NCT01S71635 | [38] |
Gene therapy | ||||||
OTL-300 | Cells/Lentiviral vector | Cells genetically modified with a vector encoding human β-globin | β-Thalassemia | Marketed | NCT03275051 | [116] |
LentiGlobinR BB305 | Cells/Lentiviral vector | Engineered hematopoietic stem cells with a functional version of human β-globin gene | β-Thalassemia | Phase III | NCT03207009 | [114] |
ST-400, CTX001 | Cells/Vector | Modified patients’ blood stem cells with disrupted BCL11A gene, induction of fetal hemoglobin synthesis | β-Thalassemia | Phase I/ll | CTX001: NCT03655678 ST-400: NCT03432364 |
[111], [112] |
Therapeutics for iron overload conditions | ||||||
Iron absorption | ||||||
Esomeprazole | Small molecule | Proton pump inhibitor | β-Thalassemia | Phase III | NL6659 (Netherlands trial Register) | [76] |
PT-2385 | Small molecule | Inhibits HIF2α-dependent genes | Hemochromatosis | Preclinîcal | NCT03108066 | [77] |
Ebselen | Small molecule | DMT1 inhibitor acting as a mimic of glutathione peroxidase | Alzheimer’s disease | Preclinical | Not listed yet | [91],[92] |
Iron binding | ||||||
Deferoxamine (DFO), | Small molecule | Iron chelation | Secondary | Marketed | NCT00001203 | [69] |
Deferasirox (DFX), | Small molecule | Iron chelation | Hemochromatosis | NCT00171171 | [35] | |
Deferiprone (DFP) | Small molecule | Iron chelation | NCT02189941 | [69] | ||
Triapine | Small molecule | Iron chelation, RR inhibitor | Cancer | Phase II | NCT00293345 | [63] |
Cefiderocol | Small molecule | Antibiotic-siderophore conjugate | Urinary tract infection | Phase II | NCT02321800 | [96] |
Dpc | Small molecule | Iron chelation | Cancer | Phase 1 | NCT02688101 | [63] |
Polymeric DFO | Nanopartîcle | Iron chelation | Hemochromatosis | Preclinical | [69] | |
Hepcidin upreguiotion | ||||||
TMPRSS6-LRX | Antisense DNA oligonucleotide | Inhibition of TMPRSS6 expression | β-Thalassemia | Phase 1 | NCT03165864 | [70] |
SLN124 | GalNAcdouble-stranded siRNA conjugate | Inhibition of TMPRSS6 expression | Hemochromatosis | Phase 1 | NCT04176653 | [71], [72] |
Antî-ERFE 15.1 | Anti-ERFE antibody | Binds/inhibits ERFE | β-Thalassemia | Preclinical | No listed yet | [73] |
Ferroportin downregulotion | ||||||
VIT-2736 | Anti-Fpn antibody | Fpn inhibitor | β-Thalassemia | Phase 1 | NCT04364269 | [75] |
Ferroptosis inducer | ||||||
Sorafenib | Small molecule | Tyrosine kinase inhibitor, Inhibition of Xc-induced glutathione depletion and lipid peroxidation | Cancer | Marketed | [106] | |
Erastîn | Small molecule | Inhibition of Xc-induced glutathione depletion and lipid peroxidation | Cancer | Preclinical | No listed yet | [106] |
RSL3 | Small molecule | GPX4 inhibition, ROS production | Cancer | Preclinical | No listed yet | [104] |
Ferumoxytol | Iron oxide nanoparticle | ROS production | AML | Preclinical | No listed yet | [105] |