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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.

MSDS (material safety data sheet) or SDS, CoA and CoQ, dossiers, brochures and other available documents.

Synonyms: Isocitrate Dehydrogenase 2 R140 Somatic Mutant Inhibitor, AGI6780

Primary Target: (IDH2) R140Q mutants
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Overview

Replacement Information

Key Spec Table

CAS #Empirical Formula
1432660-47-3C₂₁H₁₈F₃N₃O₃S₂

Products

Catalogue NumberPackaging Qty/Pack
5.09880.0001 Glass bottle 10 mg
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
Catalogue Number GTIN
5.09880.0001 04055977241112

Documentation

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