Sequence: RecName: Full=Thioredoxin reductase 1, cytoplasmic; Short=TR; AltName: Full=Gene associated with retinoic and interferon-induced mortality 12 protein; Short=GRIM-12; Short=Gene associated with retinoic and IFN-induced mortality 12 protein; AltName: Full=KM-102-derived reductase-like factor; AltName: Full=Thioredoxin reductase TR1 Description ..    Thioredoxin reductase 1, cytoplasmic Protein Family: Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain Comment ..    Confidence: Multiple direct protein targets may be assigned Gene Name: GRIM12;KDRF;TXNRD1 Pref Name: Thioredoxin reductase Description: Thioredoxin reductase 1, cytoplasmic Synonyms: Gene associated with retinoic and IFN-induced mortality 12 protein;Gene associated with retinoic and interferon-induced mortality 12 protein;GRIM-12;KM-102-derived reductase-like factor;Thioredoxin reductase 1; cytoplasmic;Thioredoxin reductase TR1 Db Source: SWISS-PROT Db Version: 2012_01 ChEMBL target type: Target is a group of closely related proteins Relationship Type: Direct protein target assigned Target Class L1: Enzyme Target Classification: enzyme Gene:TXNRD1     Related Protein 3D Structures

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Title: Synthesis of 5-nitro-2-furancarbohydrazides and their cis-diamminedichloroplatinum complexes as bitopic and irreversible human thioredoxin reductase inhibitors.

Abstract: The human selenoprotein thioredoxin reductase is involved in antioxidant defense and DNA synthesis. As increased thioredoxin reductase levels are associated with drug sensitivity to cisplatin and drug resistance in tumor cells, this enzyme represents a promising target for the development of cytostatic agents. To optimize the potential of the widely used cisplatin to inhibit the human thioredoxin reductase and therefore to overcome cisplatin resistance, we developed and synthesized four cis-diamminedichloroplatinum complexes of the lead 5-nitro-2-furancarbohydrazide 8 selected from high-throughput screening. Detailed kinetics revealed that the isolated fragments, 5-nitro-2-furancarbohydrazide and cisplatin itself, bind with micromolar affinities at two different subsites of the human enzyme. By tethering both fragments four nitrofuran-based cis-diamminedichloroplatinum complexes 13a-c and 20 were synthesized and identified as bi-ligand irreversible inhibitors of the human enzyme with nanomolar affinities. Studies with mutant enzymes clearly demonstrate the penultimate selenocysteine residue as the prime target of the synthesized cis-diamminedichloroplatinum complexes.
(PMID: 16250662)

Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

ChEMBL Assay Type: Binding

ChEMBL Assay Data Source: Scientific Literature

ChEMBL Target ID: 104858

ChEMBL target type: Target is a group of closely related proteins