AGI-5198|IDH1 inhibitor against R132 mutant,selective and cell-permeable|CAS# 1355326-35-0

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Size	Price	Stock
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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Nature.
2017 Jan 19;541(7637):417-420.

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2016 Aug 5;353(6299)594-8

Nature Biotechnology.
2017 Jun;35(6):569-576

Cell.
2017 Jul 13;170(2):312-323

Cell.
2017 Apr 6;169(2):286-300.

Cell.
2015 Aug 27;162(5):987-1002.

Cell.
2015 Feb 12;160(4):729-44.

Nature Medicine.
2017 Apr;23(4):493-500.

Cancer Cell.
2017 Aug 14;32(2):253-267.e5.

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2017 May 8;31(5):635-652.e6.

Immunity.
2016 Jan 19;44(1):88-102

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2015 May;17(5):627-38.

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2017 Jun;18(6):654-664.

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2016 Sep;26(9):1007-20.

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2016 Feb 1;7:10492.

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2015 Jun 30;112(26):E3365-73.

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2015 Jul 28;112(30):9412-7.

Autophagy.
2016 Jul 2;12(7):1129-52.

Cancer Res canres.
2946.2015.

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2016 Jan 14;5. pii: e12203.

Nucleic Acids Res.
2016 Feb 18;44(3):e2.

EMBO Rep.
2015 Sep;16(9):1114-30.

Oncogene.
2016 Mar 21.

Cell Rep.
2015 Sep 29;12(12):1986-96.

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Quality Control

Quality Control & MSDS

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Purity = 98.08%

Chemical structure

Related Biological Data

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

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).

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Chemical Properties

Cas No.	1355326-35-0	SDF	Download SDF
Synonyms	AGI5198, AGI 5198
Chemical Name	N-cyclohexyl-2-(3-fluoro-N-[2-(2-methylimidazol-1-yl)acetyl]anilino)-2-(2-methylphenyl)acetamide
Canonical SMILES	CC1=CC=CC=C1C(C(=O)NC2CCCCC2)N(C3=CC(=CC=C3)F)C(=O)CN4C=CN=C4C
Formula	C₂₇H₃₁FN₄O₂	M.Wt	462.56
Solubility	>23.2mg/mL in DMSO	Storage	Store at -20°C
General tips	For 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.
Shipping Condition	Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request

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Background

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.