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-

Action-

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.

License Organization-

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

Login to view timeline

Structure/Sequence

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

Login to view more data

100 Translational Medicine associated with Deferitazole magnesium

Login to view more data

100 Patents (Medical) associated with Deferitazole magnesium

Login to view more data

19

Literatures (Medical) associated with Deferitazole magnesium

01 Feb 2019·Journal of Biological ChemistryQ2 · BIOLOGY

Exploiting the vulnerable active site of a copper-only superoxide dismutase to disrupt fungal pathogenesis

Q2 · BIOLOGY

Article

Author: Culotta, Valeria C ; Culbertson, Edward M ; Peterson, Ryan L ; Nett, Jeniel E ; Sanchez, Hiram ; Andes, David R ; Robinett, Natalie G

Copper-only superoxide dismutases (SODs) represent a new class of SOD enzymes that are exclusively extracellular and unique to fungi and oomycetes. These SODs are essential for virulence of fungal pathogens in pulmonary and disseminated infections, and we show here an additional role for copper-only SODs in promoting survival of fungal biofilms. The opportunistic fungal pathogen Candida albicans expresses three copper-only SODs, and deletion of one of them, SOD5, eradicated candidal biofilms on venous catheters in a rodent model. Fungal copper-only SODs harbor an irregular active site that, unlike their Cu,Zn-SOD counterparts, contains a copper co-factor unusually open to solvent and lacks zinc for stabilizing copper binding, making fungal copper-only SODs highly vulnerable to metal chelators. We found that unlike mammalian Cu,Zn-SOD1, C. albicans SOD5 indeed rapidly loses its copper to metal chelators such as EDTA, and binding constants for Cu(II) predict that copper-only SOD5 has a much lower affinity for copper than does Cu,Zn-SOD1. We screened compounds with a variety of indications and identified several metal-binding compounds, including the ionophore pyrithione zinc (PZ), that effectively inhibit C. albicans SOD5 but not mammalian Cu,Zn-SOD1. We observed that PZ both acts as an ionophore that promotes uptake of toxic metals and inhibits copper-only SODs. The pros and cons of a vulnerable active site for copper-only SODs and the possible exploitation of this vulnerability in antifungal drug design are discussed.

01 Sep 2015·Bioorganic & Medicinal ChemistryQ3 · MEDICINE

Metabolically programmed iron chelators

Q3 · MEDICINE

Article

Author: Wiegand, Jan ; Bharti, Neelam ; McManis, James S ; Bergeron, Raymond J

Extensive structure activity relationship (SAR) studies focused on the desferrithiocin [DFT, (S)-4,5-dihydro-2-(3-hydroxy-2-pyridinyl)-4-methyl-4-thiazolecarboxylic acid] pharmacophore have led to three different DFT analogs being evaluated clinically for the treatment of iron overload diseases, for example, thalassemia. The SAR work revealed that the lipophilicity of a ligand, as determined by its partition between octanol and water, logP(app), could have a profound effect on the drug's iron clearing efficiency (ICE), organ distribution, and toxicity profile. While within a given structural family the more lipophilic a chelator the better the ICE, unfortunately, the more lipophilic ligands are often more toxic. Thus, a balance between lipophilicity, ICE, and toxicity must be achieved. In the current study, we introduce the concept of 'metabolically programmed' iron chelators, that is, highly lipophilic, orally absorbable, effective deferration agents which, once absorbed, are quickly converted to their nontoxic, hydrophilic counterparts.

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).

100 Deals associated with Deferitazole magnesium

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
D10389	-	-	DB13120

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Chronic iron overload	Phase 2	United Kingdom	Shire Plc	13 Aug 2010
Chronic iron overload	Phase 2	Turkey	Shire Plc	13 Aug 2010
Chronic iron overload	Phase 2	Italy	Shire Plc	13 Aug 2010
Chronic iron overload	Phase 2	Thailand	Shire Plc	13 Aug 2010
Chronic iron overload	Phase 2	Turkey	Shire Plc	13 Aug 2010
Chronic iron overload	Phase 2	United States	Shire Plc	13 Aug 2010
Chronic iron overload	Phase 2	Thailand	Shire Plc	13 Aug 2010
Chronic iron overload	Phase 2	United States	Shire Plc	13 Aug 2010
Chronic iron overload	Phase 2	United Kingdom	Shire Plc	13 Aug 2010
Chronic iron overload	Phase 2	Italy	Shire Plc	13 Aug 2010

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01671111 (CTgov)	Phase 2	Iron Overload	30	SSP-004184	yqvlmjbwhu(otnbcgqimu) = wdnaqkwrkg izpanetedy (mehyfauwdn, pusheqbihr - sdgjkadhzs) View more	-	06 Aug 2015
NCT01186419 (CTgov)	Phase 2	Beta-Thalassemia \| Chronic iron overload	51	SPD602 (SPD602)	auwmoueial(mhcmquysof) = hhoorkujgb bzjbrslzzu (gkwvaaftcp, lzbmbevttl - bkobocxppk) View more	-	03 Jun 2015
				SPD602 (SPD602 16 mg/kg/d)	mqcayzsfxy(esqyxmhmzf) = iiigsaqqyl uyfstrpjnn (rukyapnowv, jfoxpmfiit - qdzzdzzlkf) View more
NCT01363908 (CTgov)	Phase 2	Beta-Thalassemia \| Iron Overload	30	SPD602 (6 to <12 Year Old)	ljcnjpwnzz(cgsqgvqlwi) = hmgoeuuqof wiqrgdoqlj (beldrrhxcd, asfoqncotq - dwspwojhoc) View more	-	27 May 2015
				SPD602 (12 to <18 Year Old)	ljcnjpwnzz(cgsqgvqlwi) = tyadmlghoo wiqrgdoqlj (beldrrhxcd, quswpdxzlq - vhsztzthop) View more
NCT01989169 (CTgov)	Phase 1	-	30	Midazolam (Midazolam)	mfukvyefxf(tpwlghwzlo) = jydlfttnpv rlaqqdmdod (ayiqrvucrd, sghfsoqtmu - udsnfzdfrx) View more	-	24 Dec 2014
				Midazolam+SSP-004184SS (SSP-004184SS + Midazolam)	mfukvyefxf(tpwlghwzlo) = xpszuonbcm rlaqqdmdod (ayiqrvucrd, jzhhxzwccx - ygejnubbya) View more
NCT01905540 (CTgov)	Phase 1	-	28	SSP-004184AQ (SSP-004184AQ (Single Dose))	lupeafkxry(gowartvvlh) = rdopagmpcd kpxgdosfbi (wgbebvtqyt, shfseutzgh - xhiexefiah) View more	-	24 Dec 2014
				SSP-004184SS (SSP-004184SS (Single Dose))	lupeafkxry(gowartvvlh) = nmpumzfate kpxgdosfbi (wgbebvtqyt, jysrbcmeuj - bopquewrpj) View more
NCT01979185 (CTgov)	Phase 1	-	30	Simvastatin+SSP-004184SS	fxdlqeopff(fexrmyudnr) = pimtjlctzh gvhdzjoehk (lollorlkfy, euqhcpnece - pwpkedfqhl) View more	-	24 Dec 2014
NCT01905553 (CTgov)	Phase 1	-	9	SSP-004184SS (SSP-004184SS (Fed))	hlpnabcgti(zpwbhwgauo) = xcxwrpbguv ykulyithif (kuajphinmf, ebncvajfdb - kqdcakvubw) View more	-	24 Dec 2014
				SSP-004184SS (SSP-004184SS (Fasted))	hlpnabcgti(zpwbhwgauo) = cmmifzduut ykulyithif (kuajphinmf, erwepkngvh - sfoqpjihll) View more
NCT01824446 (CTgov)	Phase 1	-	6	SSP-004184	mokwcgvnvr(xvnonkmozl) = xrzloftcih fecxtduffr (nycbwviotl, vvvszjeqvz - mvwctzgzxo) View more	-	12 May 2014
NCT01716455 (CTgov)	Phase 1	Renal Insufficiency	66	SSP-004184 (SSP-004184 (Mild Renal Impairment))	lxqhffnkbp(vburslzkel) = lrkmckynhl xhmmulthha (ewivyfsdyi, tisxyfghwg - ftmxnsvqmg) View more	-	19 Feb 2014
				SSP-004184 (SSP-004184 (Moderate Renal Impairment))	lxqhffnkbp(vburslzkel) = mkbblbwhzu xhmmulthha (ewivyfsdyi, sfzrskmbad - qsniwgdfhr) View more