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AGI-5198

In stock
Catalog No.
A4339
IDH1 inhibitor against R132 mutant,selective and cell-permeable
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$130.00
In stock
Evaluation Sample
$28.00
In stock
5mg
$120.00
In stock
25mg
$380.00
In stock

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Email: [email protected]

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AGI-5198 is a selective R132H-IDH1 inhibitor which is identified through a high-throughput screen blocked, in a dose-dependent manner, the ability of the mutant enzyme (mIDH1) to produce R-2-hydroxyglutarate (R-2HG). It is also induced the expression of zinc finger and BTB domain–containing protein 16 (ZBTB16), known as promyelocytic leukemia zinc finger (PLZF), a transcriptional repressor protein which is located on chromosome 11q23 and has been shown to promote glial differentiation in the central nervous system. AGI-5198 is also able to induce the expression of genes and cell markers associated with glial-specific differentiation in glioma cell, the expression of differentiation-associated genes, reduce H3K9 trimethylaytion, and cause tumor growth inhibition.

Reference

Dan Rohle, Janeta Popovici-Muller, Nicolaos Palaskas, Sevin Turcan, Christian Grommes, Carl Campos, Jennifer Tsoi, Owen Clark, Barbara Oldrini, Evangelia Komisopoulou, Kaiko Kunii, Alicia Pedraza, Stefanie Schalm, Lee Silverman, Alexandra Miller, Fang Wang, Hua Yang, Yue Chen, Andrew Kernytsky, Marc K. Rosenblum, Wei Liu, Scott A. Biller, Shinsan M. Su, Cameron W. Brennan, Timothy A. Chan, Thomas G. Graeber, Katharine E. Yen, Ingo K. Mellinghoff. An Inhibitor of Mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells. Science 340, 626 (2013)

Francine E Garrett-Bakelman, Ari M Melnick. Differentiation therapy for IDH1/2 mutant malignancies. Cell Research (2013) 23:975–977.

Product Citation

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt462.56
Cas No.1355326-35-0
FormulaC27H31FN4O2
SynonymsAGI5198, AGI 5198
Solubility≥23.15 mg/mL in DMSO, ≥18.17 mg/mL in EtOH with ultrasonic and warming, <2.3 mg/mL in H2O
Chemical NameN-cyclohexyl-2-(3-fluoro-N-[2-(2-methylimidazol-1-yl)acetyl]anilino)-2-(2-methylphenyl)acetamide
SDFDownload SDF
Canonical SMILESCC1=CC=CC=C1C(C(=O)NC2CCCCC2)N(C3=CC(=CC=C3)F)C(=O)CN4C=CN=C4C
Shipping ConditionEvaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

Protocol

Cell experiment [1]:

Cell lines

TS603 glioma cells with an endogenous heterozygous R132H-IDH1 mutation

Preparation method

The solubility of this compound in DMSO is >23.2mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

20-3000 nM; 2 days

Applications

In R132H-IDH1 mutant TS603 glioma cells, AGI-5198 inhibited R-2HG production and impaired soft-agar colony formation of IDH1-mutant TS603 glioma cells.

Animal experiment [1]:

Animal models

mice with established R132H-IDH1 glioma xenografts

Dosage form

450 mg/kg; orally administered; 3 weeks of daily treatment

Application

In mice with established R132H-IDH1 glioma xenografts, AGI-5198 (450 mg/kg) caused 50 to 60% growth inhibition. AGI-5198 was tolerated well with no signs of toxicity. The growth-inhibitory effects of AGI-5198 were primarily due to impaired tumor cell proliferation rather than induction of apoptotic cell death.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Dan Rohle, Janeta Popovici-Muller, Nicolaos Palaskas, Sevin Turcan, Christian Grommes, Carl Campos, Jennifer Tsoi, Owen Clark, Barbara Oldrini, Evangelia Komisopoulou, Kaiko Kunii, Alicia Pedraza, Stefanie Schalm, Lee Silverman, Alexandra Miller, Fang Wang, Hua Yang, Yue Chen, Andrew Kernytsky, Marc K. Rosenblum, Wei Liu, Scott A. Biller, Shinsan M. Su, Cameron W. Brennan, Timothy A. Chan, Thomas G. Graeber, Katharine E. Yen, Ingo K. Mellinghoff. An Inhibitor of Mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells. Science 340, 626 (2013).

Biological Activity

Description AGI-5198 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 R132C-IDH1        
IC50 0.07 μM 0.16 μM        

Quality Control

Chemical structure

AGI-5198

Related Biological Data

AGI-5198

Related Biological Data

AGI-5198