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AGI-5198 Dehydrogenase inhibitor

Name: AGI-5198
Brand: Selleck Chemicals
SKU: S7185
Availability: InStock
Rating: 5 (15 reviews)

Cat.No.S7185

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.

Chemical Structure

Molecular Weight: 462.56

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.94%

99.94

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Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Incubation Time	Activity Description
human U87 cells	Function assay	48 h	Inhibition of IDH1 R132H mutant expressed in human U87 cells assessed as inhibition of 2-hydroxyglutarate production after 48 hrs by LC/MS analysis, IC50=0.07 μM
human HT1080 cells	Function assay	48 h	Inhibition of IDH1 R132C mutant overexpressed in human HT1080 cells assessed as inhibition of 2-hydroxyglutarate production after 48 hrs by LC/MS analysis, IC50=0.48 μM
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	462.56	Formula	C₂₇H₃₁FN₄O₂	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1355326-35-0	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	IDH-C35			Smiles	CC1=CC=CC=C1C(C(=O)NC2CCCCC2)N(C3=CC(=CC=C3)F)C(=O)CN4C=CN=C4C

Solubility

In vitro
Batch:

DMSO : 24 mg/mL (51.88 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 14 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	0.5% methylcellulose 1 0.2% Tween 80 Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	10.000mg/ml (21.62mM)	Taking the 1 mL working solution as an example, take 10 mg of this product, add it to 1 ml of 0.5% methylcellulose+0.2% Tween 80 clear solution, and mix evenly to make it a uniform suspension. The mixed solution should be used immediately for optimal results.

In vivo Formulation Calculator (Clear solution)

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

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

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.

Mechanism of Action

Targets/IC₅₀/Ki	R132H-IDH1 ^[1] (Cell-free assay) 70 nM R132C-IDH1 ^[1] 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). This compound 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, it 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]
Kinase Assay	IDH enzyme activity
Kinase Assay	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.
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 this compound-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 this chemical–treated mice. ^[1]
References	[1] https://pubmed.ncbi.nlm.nih.gov/23558169/

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