Delving into the Latest Updates on Deferitazole magnesium with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Deferitazole, Deferitazole Magnesium (USAN)

+ [6]

Target-

Mechanism

Iron chelating agents

Therapeutic Areas

Congenital DisordersEndocrinology and Metabolic DiseaseHemic and Lymphatic Diseases+ [1]

Active Indication-

Inactive Indication

Beta-ThalassemiaChronic iron overloadHemosiderosis+ [1]

Originator Organization

Shire Development LLC

Active Organization-

Inactive Organization

Shire Plc

FerroKin BioSciences, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC18H25NO7S

InChIKeyAWHIMFSHNAAMBM-GOSISDBHSA-N

CAS Registry945635-15-4

View All Structures (2)

A 48-week, Open-label, 2-arm, Parallel-group, Randomized Exploratory Study to Assess Liver Iron Concentration Measured by FerriScan® (R2) Magnetic Resonance Imaging in B-thalassemia Subjects Administered SPD602 (SSP-004184AQ) or Exjade® (Deferasirox) for Treatment of Chronic Transfusional Iron Overload

The purpose of this open-label study is to assess liver iron concentration using MRI imaging in subjects with beta-thalassemia when administered with either SPD602 or deferasirox for the treatment of chronic transfusional iron overload.

Start Date20 Nov 2014

Sponsor / Collaborator

Shire Plc

NCT02065401 / WithdrawnPhase 1

A Phase 1, Open-label, Randomized, 3-Period, Relative Bioavailability Study Comparing the Pharmacokinetics of Granule and Tablet Formulations of Deferitazole (Disodium Salt) and a Capsule Formulation of Deferitazole (Magnesium Hydroxide Salt), Each Administered as a Single Oral Dose

The purpose of this study is to compare the pharmacokinetic profiles of deferitazole after administration of granule and tablet formulations of a deferitazole disodium salt to a capsule formulation of deferitazole magnesium hydroxide salt (reference formulation) in healthy adult subjects.

Start Date28 Feb 2014

Sponsor / Collaborator

Shire Plc

100 Clinical Results associated with Deferitazole magnesium

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100 Translational Medicine associated with Deferitazole magnesium

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100 Patents (Medical) associated with Deferitazole magnesium

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10

Literatures (Medical) associated with Deferitazole magnesium

01 Jul 2015·Magnetic Resonance ImagingQ4 · MEDICINE

Liver MRI is more precise than liver biopsy for assessing total body iron balance: a comparison of MRI relaxometry with simulated liver biopsy results

Q4 · MEDICINE

Article

Author: Wood, John C ; Neufeld, Ellis J ; Abi-Saab, Walid ; Rienhoff, Hugh ; Zhang, Pinggao

PURPOSELiver biopsy was long considered the reference standard for measuring liver iron concentration. However, its high sampling variability and invasive nature make it poorly suited for serial analyses. To demonstrate the fallibility of liver biopsy, we use serial estimates of iron chelation efficiency (ICE) calculated by R2 and R2* MRI liver iron concentration (LIC) estimates as well as by simulated liver biopsy (over all physically reasonable sampling variability) to compare the robustness of these three techniques.MATERIALS AND METHODSR2, R2*, transfusional volume, and chelator compliance were obtained from 49 participants in a phase II clinical trial of deferitazole over two years. Liver biopsy LIC results were simulated using sampling errors of 0%, 10%, 20%, 30%, 40% and iron assay variability of 12%. LIC estimates by R2, R2*, and simulated biopsy were used to calculate ICE over time. Bland-Altman limits of agreement were compared across observation intervals of 12, 24, and 48 weeks.RESULTSAt 48 week intervals, LIC estimates by R2, R2* and "perfect" liver biopsy had comparable accuracy in predicting ICE; both MRI methods were superior to any physically realizable liver biopsy (sampling error 10% or higher). LIC by R2* demonstrated the most robust ICE estimates at monitoring intervals of 24 and 12 weeks, but this difference did not remain significant at 48 week intervals.CONCLUSIONMRI relaxometry is superior to liver biopsy for serial LIC observations, such as used in the care of tranfusional siderosis patients, and should also be considered the new standard of LIC determination for regulatory purposes. Among relaxometry techniques, LIC estimates by R2* are more robust for tracking changes in iron balance over intermediate time scales (<=24 weeks).

01 Mar 2015·Antimicrobial Agents and ChemotherapyQ2 · MEDICINE

Antimalarial Iron Chelator FBS0701 Blocks Transmission by Plasmodium falciparum Gametocyte Activation Inhibition

Q2 · MEDICINE

Article

Author: Vega-Rodriguez, Joel ; Ferrer, Patricia ; Sullivan, David J. ; Jacobs-Lorena, Marcelo ; Tripathi, Abhai K.

ABSTRACT Reducing the transmission of the malarial parasite by Anopheles mosquitoes using drugs or vaccines remains a main focus in the efforts to control malaria. Iron chelators have been studied as potential antimalarial drugs due to their activities against different stages of the parasite. The iron chelator FBS0701 affects the development of Plasmodium falciparum early gametocytes and lowers blood-stage parasitemia. Here, we tested the effect of FBS0701 on stage V gametocyte infectivity for mosquitoes. The incubation of stage V gametocytes for up to 3 days with increasing concentrations of FBS0701 resulted in a significant dose-related reduction in mosquito infectivity, as measured by the numbers of oocysts per mosquito. The reduction in mosquito infectivity was due to the inhibition of male and female gametocyte activation. The preincubation of FBS0701 with ferric chloride restored gametocyte infectivity, showing that the inhibitory effect of FBS0701 was quenched by iron. Deferoxamine, another iron chelator, also reduced gametocyte infectivity but to a lesser extent. Finally, the simultaneous administration of drug and gametocytes to mosquitoes without previous incubation did not significantly reduce the numbers of oocysts. These results show the importance of gametocyte iron metabolism as a potential target for new transmission-blocking strategies.

06 Jul 2014·Current Medicinal ChemistryQ2 · MEDICINE

Iron Chelating Strategies in Systemic Metal Overload, Neurodegeneration and Cancer

Q2 · MEDICINE

Review

Author: Ostrowska, Malgorzata ; Pyrkosz-Bulska, Monika ; Gumienna-Kontecka, Elzbieta ; Szebesczyk, Agnieszka

Iron is a trace element required for normal performance of cellular processes. Because both the deficiency and excess of this metal are dangerous, its absorption, distribution and accumulation must be tightly regulated. Disturbances of iron homeostasis and an increase in its level may lead to overload and neurodegenerative diseases. Phlebotomy was for a long time the only way of removing excess iron. But since there are many possible disadvantages of this method, chelation therapy seems to be a logical approach to remove toxic levels of iron. In clinical use, there are three drugs: desferrioxamine, deferiprone and deferasirox. FBS0701, a novel oral iron chelator, is under clinical trials with very promising results. Developing novel iron-binding chelators is an urgent matter, not only for systemic iron overload, but also for neurodegenerative disorders, such as Parkinson's disease. Deferiprone is also used in clinical trials in Parkinson's disease. In neurodegenerative disorders the main goal is not only to remove iron from brain tissues, but also its redistribution in system. Few chelators are tested for their potential use in neurodegeneration, such as nonhalogeneted derivatives of clioquinol. Such compounds gave promising results in animal models of neurodegenerative diseases. Drugs of possible use in neurodegeneration must meet certain criteria. Their development includes the improvement in blood brain barrier permeability, low toxicity and the ability to prevent lipid peroxidation. One of the compounds satisfying these requirements is VK28. In rat models it was able to protect neurons in very low doses without significantly changing the iron level in liver or serum. Also iron chelators able to regulate activity of monoamine oxidase were tested. Polyphenols and flavonoids are able to prevent lipid peroxidation and demonstrate neuroprotective activity. While cancer does not involve true iron overload, neoplastic cells have a higher iron requirement and are especially prone to its depletion. It was shown, that desferrioxamine and deferasirox are antiproliferative agents active in several types of cancer. Very potent compounds with possible use as anticancer drugs are thiosemicarbazones. They are able to inhibit ribonucleotide reductase, an enzyme involved in DNA synthesis. Because the relationship between the development of overload / neurodegenerative disorders, or cancer, and iron are very complex, comprehension of the mechanisms involved in the regulation of iron homeostasis is a crucial factor in the development of new pharmacological strategies based on iron chelation. In view of various factors closely involved in pathogenesis of such diseases, designing multifunctional metal-chelators seems to be the most promising approach, but it requires a lot of effort. In this perspective, the review summarizes systemic iron homeostasis, and in brain and cancer cells, iron dysregulation in neurodegenerative disease and possible chelation strategies in the treatment of metal systemic overload, neurodegeneration and cancer.

100 Deals associated with Deferitazole magnesium

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External Link

KEGG	Wiki	ATC	Drug Bank
D10389	-	-	DB13120

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chronic iron overload	Phase 2	TH	Shire Plc	13 Aug 2010
Chronic iron overload	Phase 2	TR	Shire Plc	13 Aug 2010
Chronic iron overload	Phase 2	GB	Shire Plc	13 Aug 2010
Chronic iron overload	Phase 2	IT	Shire Plc	13 Aug 2010
Chronic iron overload	Phase 2	IT	Shire Plc	13 Aug 2010
Chronic iron overload	Phase 2	GB	Shire Plc	13 Aug 2010
Chronic iron overload	Phase 2	TR	Shire Plc	13 Aug 2010
Chronic iron overload	Phase 2	US	Shire Plc	13 Aug 2010
Chronic iron overload	Phase 2	TH	Shire Plc	13 Aug 2010
Chronic iron overload	Phase 2	US	Shire Plc	13 Aug 2010

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01671111 (CTgov)	Phase 2	Iron Overload	30	SPD602, FBS0701+SSP-004184	wivqfubnlu(ffkgcrjkey) = mudwvlzuyj nnexcxefge (ohroyqvfmf, klnqdtmnhb - igwgldizwt) View more	-	06 Aug 2015
NCT01186419 (CTgov)	Phase 2	Beta-Thalassemia \| Chronic iron overload	51	SPD602 (SPD602)	njwagaytvq(zambzsujnq) = pqnbxpkfnj ewanacvlqj (zkerufzral, fhzbkpzriy - tmavevkxis) View more	-	03 Jun 2015
				SPD602 (SPD602 16 mg/kg/d)	wklcovglvx(zavsturjxm) = ijvhowhyqw ckrxywujtq (gvidzmkzjs, tbzopwjtul - dvjwtdqbur) View more
NCT01363908 (CTgov)	Phase 2	Beta-Thalassemia \| Iron Overload	30	SPD602 (6 to <12 Year Old)	jyowvogtiv(tmpcfwcsxx) = bbnytfzuec lapxsaqnpd (eoetirkzay, alurnvumzn - sholnpasni) View more	-	27 May 2015
				SPD602 (12 to <18 Year Old)	jyowvogtiv(tmpcfwcsxx) = dytxwcqcri lapxsaqnpd (eoetirkzay, lycccoekug - aamgpsxqbz) View more
NCT01905540 (CTgov)	Phase 1	-	28	SSP-004184AQ (SSP-004184AQ (Single Dose))	pqydwbviri(desfbmzrao) = htuqzwvtkq sqhczlpdpi (psvigtruad, nkzsjrneox - kbnqshtlzu) View more	-	24 Dec 2014
				SSP-004184SS (SSP-004184SS (Single Dose))	pqydwbviri(desfbmzrao) = amejopvuai sqhczlpdpi (psvigtruad, uaxthxeuzx - vkladndofv) View more
NCT01989169 (CTgov)	Phase 1	-	30	Midazolam (Midazolam)	juymhxtzki(oqqnucizxu) = xkxnftrakp kxtvoxptam (odsvuosqtq, zpxmiaxtlu - goqsgoxglm) View more	-	24 Dec 2014
				Midazolam+SSP-004184SS (SSP-004184SS + Midazolam)	juymhxtzki(oqqnucizxu) = bkohkfaodb kxtvoxptam (odsvuosqtq, tjexrrldxo - uzewfhbnwo) View more
NCT01905553 (CTgov)	Phase 1	-	9	SSP-004184SS (SSP-004184SS (Fed))	nleltyziex(iitaodmjrd) = tbhbmsynyy tukrqhdoco (vtnotifnfc, koqwsfylqk - buegaeixud) View more	-	24 Dec 2014
				SSP-004184SS (SSP-004184SS (Fasted))	nleltyziex(iitaodmjrd) = hkmlmwznas tukrqhdoco (vtnotifnfc, qpvtyhbcme - kcdexjszhh) View more
NCT01979185 (CTgov)	Phase 1	-	30	Simvastatin+SSP-004184SS	eupismjjzs(zeadunjtmj) = msioirfmvn bxjnshlsqv (mvjfirppol, vlfzlalphv - yvehxoajsu) View more	-	24 Dec 2014
NCT01824446 (CTgov)	Phase 1	-	6	SSP-004184	efwmsnwsml(xvhtikbvqw) = zbwleswhzr huixldwakh (wezhmxzgvm, vwltoajqtt - ciprkpsbhc) View more	-	12 May 2014
NCT01716455 (CTgov)	Phase 1	Renal Insufficiency	66	SSP-004184 (SSP-004184 (Mild Renal Impairment))	ipegqmettl(tkjaqsueqs) = hurpklbnpv tfkkmmjwxe (yebtetnfhq, joexlcclga - mxbpvqgiar) View more	-	19 Feb 2014
				SSP-004184 (SSP-004184 (Moderate Renal Impairment))	ipegqmettl(tkjaqsueqs) = orrkuedmro tfkkmmjwxe (yebtetnfhq, gpcoowxpcw - bwfkkdzqkc) View more
NCT01186419 (Pubmed \| Circulation)	Phase 2	Iron Overload	51	FBS0701 14.5 mg/kg/d	(ueuinrpald) = Treatment-related abdominal pain was noted in < 5% of patients oqgsraktkl (szcefidqte ) View more	-	05 Apr 2012
				FBS0701 29 mg/kg/d