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

509880
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      Overview

      Replacement Information

      Key Specifications Table

      Empirical FormulaCAS #
      C₂₁H₁₈F₃N₃O₃S₂ 1432660-47-3

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      5.09880.0001
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          Glass bottle 10 mg
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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
          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

          Documentation

          SDS

          Title

          Safety Data Sheet (SDS) 

          References

          Reference overview
          Wang, F., et al. 2013. Science 340, 622.
          Data Sheet

          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 +2°C to +8°C
          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.
          Toxicity Standard Handling
          ReferencesWang, F., et al. 2013. Science 340, 622.