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509880 IDH2 Inhibitor, R140Q Somatic Mutant-Specific, AGI-6780 - CAS 1432660-47-3 - Calbiochem

A cell-permeable inhibitor of isocitrate dehydrogenase 2 R140Q mutant-containing dimers. Has minimal effect on wild type dimer-catalyzed alpha-KG production.

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Synonyme: Isocitrate Dehydrogenase 2 R140 Somatic Mutant Inhibitor, AGI6780

Primary Target: (IDH2) R140Q mutants
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509880
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Übersicht

Replacement Information

Key Spec Table

CAS #Empirical Formula
1432660-47-3C₂₁H₁₈F₃N₃O₃S₂

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5098800001
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      Description
      OverviewA cell-permeable urea sulfonamide that inhibits the activity of Isocitrate Dehydrogenase 2 (IDH2) R140Q mutant-containing dimers in an α-ketoglutarate/α-KG-non-competitive and NADPH-uncompetitive manner by stabilizing the mutant dimers in an inactive conformation via a high-affinity allosteric interaction at the dimer interface with a slow-binding kinetic (kon = 5.8 x 104/M/min; koff = 8.3 x 10-3/min), while displaying much reduced potency against wt IDH2 dimer-catalyzed α-KG production and little or no activity toward wt IDH1 or R132H IDH2 mutant. Selectively inhibits 2-HG production in IDH2 R140Q, but not R132H, mutant-expressing U87 cultures (IC50 in 48 h = 11 nM vs. >100 µM). AGI-6780 treatment (5 µM) of primary bone marrow cultures from AML patients with R140Q mutation is shown to reactivate the differentiation of immature AML blasts without cytotoxicity.
      Catalogue Number509880
      Brand Family Calbiochem®
      SynonymsIsocitrate Dehydrogenase 2 R140 Somatic Mutant Inhibitor, AGI6780
      References
      ReferencesWang, F., et al. 2013. Science 340, 622.
      Product Information
      CAS number1432660-47-3
      FormOff-white powder
      Hill FormulaC₂₁H₁₈F₃N₃O₃S₂
      Chemical formulaC₂₁H₁₈F₃N₃O₃S₂
      ReversibleY
      Structure formula ImageStructure formula Image
      Quality LevelMQ100
      Applications
      Biological Information
      Primary Target(IDH2) R140Q mutants
      Primary Target IC<sub>50</sub>4 nM/16 h & 120 nM/1 h against R140Q-wt heterodimer
      Purity≥95% by HPLC
      Physicochemical Information
      Cell permeableY
      Dimensions
      Materials Information
      Toxicological Information
      Safety Information according to GHS
      Safety Information
      Product Usage Statements
      Storage and Shipping Information
      Ship Code Ambient Temperature Only
      Toxicity Standard Handling
      Storage +2°C to +8°C
      Protect from Light Protect from light
      Do not freeze Ok to freeze
      Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
      Packaging Information
      Packaged under inert gas Packaged under inert gas
      Transport Information
      Supplemental Information
      Specifications
      Global Trade Item Number
      Bestellnummer GTIN
      5098800001 04055977241112

      Documentation

      IDH2 Inhibitor, R140Q Somatic Mutant-Specific, AGI-6780 - CAS 1432660-47-3 - Calbiochem SDB

      Titel

      Sicherheitsdatenblatt (SDB) 

      Literatur

      Übersicht
      Wang, F., et al. 2013. Science 340, 622.
      Datenblatt

      Note that this data sheet is not lot-specific and is representative of the current specifications for this product. Please consult the vial label and the certificate of analysis for information on specific lots. Also note that shipping conditions may differ from storage conditions.

      Revision29-April-2014 JSW
      SynonymsIsocitrate Dehydrogenase 2 R140 Somatic Mutant Inhibitor, AGI6780
      DescriptionA cell-permeable ureido-benzenesulfonamide that inhibits α-ketoglutarate (α-KG)-to-(R)-2-hydroxyglutarate (2-HG) conversion catalyzed by Isocitrate Dehydrogenase-2 (IDH2) R140Q mutant-containing dimers (IC50/preincubation time = 4 nM/16 h & 120 nM/1 h against R140Q-wt heterodimer; 23 nM/16 h & 170 nM/1 h against R140Q homodimer) in a substrate-non-competitive and NADPH-uncompetitive manner by targeting the dimer interface via a high affinity allosteric interaction with a slow-binding kinetic (kon = 5.8 x 104/M/min; koff = 8.3 x 10-3/min) and stabilizing the mutant dimers in an inactive conformation, while displaying much reduced potency against wt IDH2 dimer-catalyzed α-KG production (IC50/preincubation time = 190 nM/16 h & 2.7 µM/1 h) and little or no activity toward LDHA, 3PGDH, GDH, G6PDH, R132H mutant or wt IDH1. Selectively inhibits 2-HG production in R140Q IDH2-expressing U87 glioblastoma & TF-1 erythroleukemia, but not R132H-expressing U87 cultures (IC50 in 48 h = 11 nM, 18 nM, and >100 µM, respectively) and sensitizes R140Q IDH2-expressing TF-1 to EPO-induced erythroid differentiation. Likewise, inhibition of 2-HG production in primary bone marrow cultures from AML patients with R140Q mutation (complete inhibition with 5 µM AGI-6780) is shown to reactivate the differentiation of immature AML blasts without cytotoxicity. IDH1 Inhibitor, R132 Somatic Mutant-Specific, AGI-5198 (Cat. No. 410972) is also available.
      FormOff-white powder
      Intert gas (Yes/No) Packaged under inert gas
      CAS number1432660-47-3
      Chemical formulaC₂₁H₁₈F₃N₃O₃S₂
      Structure formulaStructure formula
      Purity≥95% by HPLC
      SolubilityDMSO (100 mg/ml)
      Storage Protect from light
      +2°C to +8°C
      Do Not Freeze Ok to freeze
      Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
      Toxicity Standard Handling
      ReferencesWang, F., et al. 2013. Science 340, 622.