AGI-5198

Catalog No.S7185 Synonyms: IDH-C35

For research use only.

AGI-5198 (IDH-C35) is the first highly potent and selective inhibitor of IDH1 R132H/R132C mutants with IC50 of 0.07 μM/0.16 μM.

AGI-5198 Chemical Structure

CAS No. 1355326-35-0

Selleck's AGI-5198 has been cited by 9 Publications

1 Customer Review

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Biological Activity

Description AGI-5198 (IDH-C35) is the first highly potent and selective inhibitor of IDH1 R132H/R132C mutants with IC50 of 0.07 μM/0.16 μM.
Targets
R132H-IDH1 [1]
(Cell-free assay)
R132C-IDH1 [1]
70 nM 0.16 μM
In vitro

AGI-5198, potently inhibits mutant IDH1 (R132H-IDH1 and R132C-IDH1), but not wildtype IDH1 (IC50 > 100 μM) or any of IDH2 isoforms (R140Q, R172K, wildtype) (IC50 > 100 μM). AGI-5198, has been shown to have anti-tumor efficacy in the TS603 glioma cell line and to block R-2HG production in a dose-dependent manner. Under conditions of near-complete R-2HG inhibition, AGI-5198 induced demethylation of histone H3K9me3 and expression of genes associated with gliogenic differentiation. Blockade of mIDH1 impaired the growth of IDH1-mutant—but not IDH1–wild-type—glioma cells without appreciable changes in genome-wide DNA methylation. [1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human U87 cells M4nQ[mZ2dmO2aX;uJIF{e2G7 NGrFR5Y1QCCq NWnadG5sUW6qaXLpeIlwdiCxZjDJSGgyKFJzM{LIJI12fGGwdDDlfJBz\XO|ZXSgbY4hcHWvYX6gWVg4KGOnbHzzJIF{e2W|c3XkJIF{KGmwaHnibZRqd25ib3[gNk1pgWS{b4j5[4x2fGG{YYTlJJBzd2S3Y4Tpc44h[W[2ZYKgOFghcHK|IHL5JGxEN02VIHHuZYx6e2m|LDDJR|UxRTBwMEeg{txO NXTrOlhNOjR7MECzPFk>
human HT1080 cells MUHGeY5kfGmxbjDhd5NigQ>? MUS0PEBp NXfpOmxRUW6qaXLpeIlwdiCxZjDJSGgyKFJzM{LDJI12fGGwdDDveoVz\XiycnXzd4VlKGmwIHj1cYFvKEiWMUC4NEBk\WyuczDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oIEKtbJllem:6eXfseZRiemG2ZTDwdo9lfWO2aX;uJIFnfGW{IES4JIhzeyCkeTDMR{9OWyCjbnHsfZNqeyxiSVO1NF0xNjR6IN88US=> MVuyOFkxODN6OR?=
In vivo In R132H-IDH1 glioma xenografts, AGI-5198 (450 mg/kg/day) causes 50-60% growth inhibition over a treatment period of three weeks with no affect in the growth of IDH1 wild-type glioma xenografts. Tumors from AGI-5198-treated mice shows reduced staining with an antibody against the Ki-67 protein. But cleaved caspase-3 shows no differences between tumors from vehicle and AGI-5198–treated mice. [1]

Protocol (from reference)

Kinase Assay:

[1]

  • IDH enzyme activity:

    Compound is prepared as 10 mM stock in DMSO and diluted to 50X final concentration in DMSO, for a 50 μL reaction mixture. IDH enzyme activity converting alpha-ketogluta rate to 2-hydroxyglutarate is measured using a NADPH depletion assay. In the assay the remaining cofactor is measured at the end of the reaction with the addition of a catalytic excess of diaphorase and resazurin, to generate a fluorescent signal in proportion to the amount of NADPH remaining. IDH enzyme activity in the direction of isocitrate to alpha-ketoglutarate conversion is measured by direct coupling of the NADPH production to conversion of resazurin to resorufin by diaphorase. In both cases, resorufin is measured fluorometrically at Ex544 Em 590.

Cell Research:

[1]

  • Cell lines: TS603
  • Concentrations: 0, 23.4, 93.8, 375, 3000 nM
  • Incubation Time: --
  • Method:

    soft-agar colony formation

Animal Research:

[1]

  • Animal Models: IDH1 mutant glioma xenografts
  • Dosages: 150 mg/kg, 450 mg/kg per day
  • Administration: gavage

Solubility (25°C)

In vitro

DMSO 24 mg/mL
(51.88 mM)
Ethanol 14 mg/mL
(30.26 mM)
Water Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
0.5% methylcellulose+0.2% Tween 80
For best results, use promptly after mixing.

30 mg/mL

Chemical Information

Molecular Weight 462.56
Formula

C27H31FN4O2

CAS No. 1355326-35-0
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1=CC=CC=C1C(C(=O)NC2CCCCC2)N(C3=CC(=CC=C3)F)C(=O)CN4C=CN=C4C

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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