AGI-5198 (Synonyms: IDH-C35)

Name: AGI-5198
Brand: MedChemExpress
SKU: HY-18082
Rating: 5.0 (18 reviews)

Cat. No.: HY-18082 Purity: 98.57%: FAQs
Data Sheet SDS COA Handling Instructions

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AGI-5198 (IDH-C35) is a potent and selective mutant IDH1^R132H inhibitor with an IC₅₀ of 0.07 μM.

For research use only. We do not sell to patients.

AGI-5198 Chemical Structure

CAS No. : 1355326-35-0

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Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 73	In-stock	Estimated Time of Arrival: December 31
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10 mM * 1 mL in DMSO	USD 73	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	USD 42	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 66	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 99	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 165	In-stock	Estimated Time of Arrival: December 31
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Customer Review

Based on 18 publication(s) in Google Scholar

15 Publications Citing Use of MCE AGI-5198

: AGI-5198 purchased from MedChemExpress. Usage Cited in: Cancer Res. 2018 Nov 15;78(22):6386-6398. [Abstract]; IDH1^R132H-mediated epigenetic silencing of TSGs is inhibited by cyclin F.

: AGI-5198 purchased from MedChemExpress. Usage Cited in: FASEB J. 2018 Jun 7:fj201800547R. [Abstract]; Representative photomicrographs of cells that are plated on glass coverslips in the presence or absence of 1μM AGI-5198, treated with 5 or 10μM Cisplatin for 1 h, and fixed after 30 min. γ-H2AX is stained immunocytochemically (red) to demonstrate DNA DSBs and with DAPI (blue) to demonstrate DNA nucleus content.

: AGI-5198 purchased from MedChemExpress. Usage Cited in: J Neurooncol. 2018 Jun;138(2):241-250. [Abstract]; LN18 IDH1 R132H cells are either treated with vehicle (DMSO) or 1 μM AG-5198 for the indicated number of days. Cells are harvested and Fn14, PAR-4 and GAPDH levels are evaluated by Western blot analysis.

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IDH1 IDH2

Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

AGI-5198 (IDH-C35) is a potent and selective mutant IDH1^R132H inhibitor with an IC₅₀ of 0.07 μM.

IC₅₀ & Target

IDH1

Cellular Effect

Cell Line	Type	Value	Description	References
A549	EC₅₀	> 50 μM Compound: 1, AGI-5198	Cytotoxicity against human A549 cells assessed as growth inhibition after 48 to 96 hrs by MTT assay Cytotoxicity against human A549 cells assessed as growth inhibition after 48 to 96 hrs by MTT assay	[PMID: 26280302]
HT-1080	IC₅₀	< 0.25 μM Compound: 1; AGI-5198	Inhibition of IDH1 R132H mutant in human HT-1080 cells assessed as suppression of 2-HG production incubated for 48 hrs by LC-MS analysis Inhibition of IDH1 R132H mutant in human HT-1080 cells assessed as suppression of 2-HG production incubated for 48 hrs by LC-MS analysis	[PMID: 29847930]
HT-1080	GI₅₀	> 20 μM Compound: 35	Growth inhibition of human HT1080 cells after 72 hrs by CellTiter-Glo assay Growth inhibition of human HT1080 cells after 72 hrs by CellTiter-Glo assay	[PMID: 24900389]
HT-1080	EC₅₀	> 50 μM Compound: 1, AGI-5198	Cytotoxicity against human HT1080 cells assessed as growth inhibition after 48 to 96 hrs by MTT assay Cytotoxicity against human HT1080 cells assessed as growth inhibition after 48 to 96 hrs by MTT assay	[PMID: 26280302]
HT-1080	IC₅₀	0.48 μM Compound: 35	Inhibition of IDH1 R132C mutant overexpressed in human HT1080 cells assessed as inhibition of 2-hydroxyglutarate production after 48 hrs by LC/MS analysis Inhibition of IDH1 R132C mutant overexpressed in human HT1080 cells assessed as inhibition of 2-hydroxyglutarate production after 48 hrs by LC/MS analysis	[PMID: 24900389]
MCF7	EC₅₀	> 50 μM Compound: 1, AGI-5198	Cytotoxicity against human MCF7 cells assessed as growth inhibition after 48 to 96 hrs by MTT assay Cytotoxicity against human MCF7 cells assessed as growth inhibition after 48 to 96 hrs by MTT assay	[PMID: 26280302]
U-87MG ATCC	GI₅₀	> 20 μM Compound: 35	Growth inhibition of human U87 cells after 72 hrs by CellTiter-Glo assay Growth inhibition of human U87 cells after 72 hrs by CellTiter-Glo assay	[PMID: 24900389]
U-87MG ATCC	IC₅₀	0.07 μM Compound: 35	Inhibition of IDH1 R132H mutant expressed in human U87 cells assessed as inhibition of 2-hydroxyglutarate production after 48 hrs by LC/MS analysis Inhibition of IDH1 R132H mutant expressed in human U87 cells assessed as inhibition of 2-hydroxyglutarate production after 48 hrs by LC/MS analysis	[PMID: 24900389]
U-87MG ATCC	IC₅₀	20.1 μM Compound: AGI-5198	Antiproliferative activity against human U87 cells by MTT assay Antiproliferative activity against human U87 cells by MTT assay	[PMID: 30108937]
WI-38	EC₅₀	> 50 μM Compound: 1	Inhibition of cell proliferation of human WI38 cells by CCK8 assay Inhibition of cell proliferation of human WI38 cells by CCK8 assay	[PMID: 25271760]
WI-38	EC₅₀	> 50 μM Compound: 1, AGI-5198	Cytotoxicity against human WI38 cells assessed as growth inhibition after 48 to 96 hrs by MTT assay Cytotoxicity against human WI38 cells assessed as growth inhibition after 48 to 96 hrs by MTT assay	[PMID: 26280302]

In Vitro

Measurements of R-2HG concentrations in pellets of TS603 glioma cells demonstrates dose-dependent inhibition of the mutant IDH1 enzyme by AGI-5198. AGI-5198 does not impair colony formation of two patient-derived glioma lines that express only the wild-type IDH1 allele (TS676 and TS516)^[1]. Cancer cells heterozygous for the IDH1(R132H) mutation exhibits less IDH-mediated production of NADPH, such that after exposure to ionizing radiation (IR), there are higher levels of reactive oxygen species, DNA double-strand breaks, and cell death compared with IDH1 wild-type cells. These effects are reversed by the IDH1(R132H) inhibitor AGI-5198^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

AGI-5198 (450 mg/kg, p.o.) causes 50 to 60% growth inhibition of the tumor growth from human glioma xenografts. Tumors from AGI-5198- treated mice show reduced staining with an antibody against the Ki-67 protein. AGI-5198 does not affect the growth of IDH1 wild-type glioma xenografts^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Molecular Weight

462.56

Formula

C₂₇H₃₁FN₄O₂

CAS No.

1355326-35-0

Appearance

Solid

Color

White to off-white

SMILES

FC1=CC=CC(N(C(C2=CC=CC=C2C)C(NC3CCCCC3)=O)C(CN4C=CN=C4C)=O)=C1

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Solvent & Solubility

In Vitro:

DMF : ≥ 50 mg/mL (108.09 mM)

DMSO : 20.83 mg/mL (45.03 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.1619 mL	10.8094 mL	21.6188 mL
5 mM	0.4324 mL	2.1619 mL	4.3238 mL
10 mM	0.2162 mL	1.0809 mL	2.1619 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.08 mg/mL (4.50 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.08 mg/mL (4.50 mM); Suspended solution; Need ultrasonic

This protocol yields a suspended solution of 2.08 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.08 mg/mL (4.50 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

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(per animal)

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μL

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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Purity & Documentation

Purity: 99.65%

Select Batch:

Data Sheet (282 KB) SDS (420 KB)

COA (253 KB) HNMR (206 KB) LCMS (241 KB)

Handling Instructions (2659 KB)

References

[1]. Rohle D, et al. An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science. 2013 May 3;340(6132):626-30. [Content Brief]

[2]. Molenaar RJ, et al. Radioprotection of IDH1-Mutated Cancer Cells by the IDH1-Mutant Inhibitor AGI-5198. Cancer Res. 2015 Nov 15;75(22):4790-802. [Content Brief]

Kinase Assay ^[1]	Inhibitory potency against the IDH2 R140Q and IDH2 R172K enzymes is determined in an endpoint assay in which the amount of NADPH remaining at the end of the reaction is measured by the addition of a large excess of diaphorase and resazurin. IDH2 R140Q is diluted to 0.25 μg/mL in 40 μL 1X Assay Buffer (150 mM NaCl, 50 mM potassium phosphate pH 7.5, 10 mM MgCl₂, 10% glycerol, 2 mM B-ME, 0.03% BSA) and incubated for 16 hours at 25°C in the presence of 1 μL of compound in DMSO. The reaction is started with the addition of 10 μL of Substrate Mix (20 μM NADPH, 8 μM alpha-ketoglutarate, in 1X Assay Buffer) and incubated for 1 hour at 25°C. Then, remaining NADPH is measured by the addition of 25 μL of Detection Mix (36 μg/mL diaphorase, 18 μM resazurin in 1X Assay buffer), incubated for 5 minutes at 25°C, and read as described above. IDH2 R172K is assayed as for IDH2 R140Q with the following modifications: 1.25 μg/mL of protein is used, the Substrate Mix contained 50 μM NADPH and 6.4 μM alpha-ketoglutarate, and the compound is incubated for 1 hour before starting the reaction. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay ^[1]	TS603 cells are grown in medium containing either AGI-5198 (1.5μM) or DMSO vehicle control. One week prior to harvest cells are ransferred to differentiation medium (DMEM F12; 15 mM HEPES; 0.06% glucose; B27 without vitamin A; N2; Insulin/transferrin; 1% FBS) containing freshly added retinoic acid (1μM). ChIP of non-crosslinked cells is then carried out using established ChIP methods. 350 μg of lysate is immunoprecipitated-using anti-H3K9Me3, H3K27me3 or Rabbit Control IgG. After washing, ChIP DNA is eluted from protein G beads and analyzed by RT-PCR using SYBR green. Relative occupancy is calculated using the standard curve method and fold enrichment versus IgG. Enrichment in AGI- 5198-treated cells is normalized to vehicle control. Means and standard deviation are calculated from 4 technical replicates. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[1]	SCID mice are injected subcutaneously with 10⁶ glioma cells, which are suspended in 100 μL of a 50:50 mixture of growth media and Matrigel. Once tumors have reached a measurable size, mice are randomized into the indicated treatment groups. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References	[1]. Rohle D, et al. An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science. 2013 May 3;340(6132):626-30. [Content Brief] [2]. Molenaar RJ, et al. Radioprotection of IDH1-Mutated Cancer Cells by the IDH1-Mutant Inhibitor AGI-5198. Cancer Res. 2015 Nov 15;75(22):4790-802. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO / DMF	1 mM	2.1619 mL	10.8094 mL	21.6188 mL	54.0470 mL
	5 mM	0.4324 mL	2.1619 mL	4.3238 mL	10.8094 mL
	10 mM	0.2162 mL	1.0809 mL	2.1619 mL	5.4047 mL
	15 mM	0.1441 mL	0.7206 mL	1.4413 mL	3.6031 mL
	20 mM	0.1081 mL	0.5405 mL	1.0809 mL	2.7024 mL
	25 mM	0.0865 mL	0.4324 mL	0.8648 mL	2.1619 mL
	30 mM	0.0721 mL	0.3603 mL	0.7206 mL	1.8016 mL
	40 mM	0.0540 mL	0.2702 mL	0.5405 mL	1.3512 mL
DMF	50 mM	0.0432 mL	0.2162 mL	0.4324 mL	1.0809 mL
	60 mM	0.0360 mL	0.1802 mL	0.3603 mL	0.9008 mL
	80 mM	0.0270 mL	0.1351 mL	0.2702 mL	0.6756 mL
	100 mM	0.0216 mL	0.1081 mL	0.2162 mL	0.5405 mL

AGI-5198 Related Classifications

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Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

AGI-51981355326-35-0IDH-C35AGI5198AGI 5198Isocitrate Dehydrogenase (IDH)Inhibitorinhibitorinhibit

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AGI-5198 (Synonyms: IDH-C35)

Customer Review

AGI-5198 Related Antibodies

15 Publications Citing Use of MCE AGI-5198

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Complete Stock Solution Preparation Table

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