AGI-6780 (Synonyms: AGI 6780;AGI6780) |
Catalog No.GC14757
One-Click Copy Product Info
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AGI-6780 is an orally active, potent and selective mutant isocitrate dehydrogenase 2 (IDH2R140Q) inhibitor (IC₅₀=23±1.7nM).
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1432660-47-3
Sample solution is provided at 25 µL, 10mM.
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AGI-6780 is an orally active, potent and selective mutant isocitrate dehydrogenase 2 (IDH2R140Q) inhibitor (IC₅₀=23±1.7nM). AGI-6780 allosterically binds at the IDH2 dimer interface to noncompetitively inhibit the substrate and uncompetitively inhibit the NADPH cofactor, thereby blocking the gain-of-function activity of mutant IDH2 (especially R140Q). AGI-6780 can be used in research related to acute myeloid leukemia (AML) and other IDH2 mutation-associated tumors (e.g., low-grade gliomas)[1-4].
In vitro, AGI-6780 (2-4µM) had been applied to treat K562 cells and imatinib/adriamycin-resistant K562 cells for 48h. AGI-6780 had shown little effect on the basal survival of K562 cells. AGI-6780 had reduced the IC₅₀ of resistant K562 cells to imatinib or adriamycin[5]. AGI-6780 (5µM) had been used to treat multiple myeloma cell lines, mantle cell lymphoma and Burkitt lymphoma cell lines for 96h. AGI-6780 had impaired tricarboxylic acid cycle activity and mitochondrial ATP production in these cells, promoted cell cycle arrest at G0/G1 phase accompanied by cyclin downregulation, PARP-1 cleavage, and caspase-3/7/9 activation, thereby enhancing tumor cell death[6].
In vivo, AGI-6780 (60mg/kg; single injection) had been intraperitoneally administered to C57BL/6J mice, followed 30min later by an intraperitoneal glucose load (1.5g/kg) for an intraperitoneal glucose tolerance test. AGI-6780 had achieved a plasma drug concentration of approximately 15µM maintained between 30 and 90min, had abolished the normal insulin secretory response to glucose stimulation, and had significantly reduced circulating glucagon levels[7]. AGI-6780 (25mg/kg/day and 50mg/kg/day) had been intraperitoneally injected into BALB/c nude mice bearing orthotopic xenografts of MDA-MB-231 triple-negative breast cancer (starting when tumor diameter reached approximately 5-6mm) for 6 consecutive weeks. AGI-6780 had inhibited tumor growth in a dose-dependent manner[8].
References:
[1] Chen Y, Feng X, Yin X, et al. Prognostic and immunological role of RHEBL1 in pan-cancer: a target for survival and immunotherapy. Discov Oncol. 2025 May 14;16(1):766.
[2] Kim J, DeBerardinis RJ. Cancer. Silencing a metabolic oncogene. Science. 2013 May 3;340(6132):558-9.
[3] Chen J, Yang J, Sun X, et al. Allosteric inhibitor remotely modulates the conformation of the orthestric pockets in mutant IDH2/R140Q. Sci Rep. 2017 Nov 28;7(1):16458.
[4] Li J, He Y, Tan Z, et al. Wild-type IDH2 promotes the Warburg effect and tumor growth through HIF1α in lung cancer. Theranostics. 2018 Jul 16;8(15):4050-4061.
[5] Liu W, Sun Y, Ge W, et al. DIA-Based Proteomics Identifies IDH2 as a Targetable Regulator of Acquired Drug Resistance in Chronic Myeloid Leukemia. Mol Cell Proteomics. 2022 Feb;21(2):100187.
[6] Bergaggio E, Riganti C, Garaffo G, et al. IDH2 inhibition enhances proteasome inhibitor responsiveness in hematological malignancies. Blood. 2019 Jan 10;133(2):156-167.
[7] Zhang GF, Jensen MV, Gray SM, et al. Reductive TCA cycle metabolism fuels glutamine- and glucose-stimulated insulin secretion. Cell Metab. 2021 Apr 6;33(4):804-817.e5.
[8] Li JJ, Yu T, Zeng P, et al. Wild-type IDH2 is a therapeutic target for triple-negative breast cancer. Nat Commun. 2024 Apr 24;15(1):3445.
| Cell experiment [1]: | |
Cell lines | K562 cells (human chronic myeloid leukemia cell line) and derivative K562 cells with acquired resistance to imatinib (IMA) or adriamycin (ADR) |
Preparation Method | Cells were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin at 37°C with 5% CO2. Cells were treated with AGI-6780 at 2 or 4μM alone or in combination with IMA or ADR for 48 hours. |
Reaction Conditions | 2 or 4μM; 48h |
Applications | AGI-6780 did not affect the survival of parental K562 cells but significantly increased the sensitivity of resistant K562 cells to IMA and ADR, as evidenced by reduced IC50 values and synergistic effects observed in Bliss independence model. |
| Animal experiment [2]: | |
Animal models | Healthy young male C57BL/6J mice |
Preparation Method | Mice were intraperitoneally injected with the IDH2 inhibitor AGI-6780 at 60mg/kg, and plasma AGI-6780 levels were measured by LC–MS/MS at multiple time points over 90min to define exposure; in the functional experiment, AGI-6780 was administered i.p. 30min before an intraperitoneal glucose bolus (1.5g glucose/kg), with blood sampled before AGI-6780 injection (−30min), just before glucose (0min), and post-bolus for plasma glucose, insulin, and glucagon measurements. |
Dosage form | 60mg/kg; i.p.; single injection |
Applications | At exposures achieving plasma AGI-6780 concentrations peaking at ~15μM (30–90min post-injection), AGI-6780 abolished the normal glucose-stimulated insulin secretion (GSIS) rise seen in vehicle (DMSO)-treated mice, and significantly lowered circulating glucagon after the glucose bolus, such that overall blood glucose excursions remained comparable to vehicle controls despite the blunted insulin secretory response. |
References: | |
| Cas No. | 1432660-47-3 | SDF | |
| Synonyms | AGI 6780;AGI6780 | ||
| Chemical Name | 1-[5-(cyclopropylsulfamoyl)-2-thiophen-3-ylphenyl]-3-[3-(trifluoromethyl)phenyl]urea | ||
| Canonical SMILES | C1CC1NS(=O)(=O)C2=CC(=C(C=C2)C3=CSC=C3)NC(=O)NC4=CC=CC(=C4)C(F)(F)F | ||
| Formula | C21H18F3N3O3S2 | M.Wt | 481.51 |
| Solubility | ≥ 22.25 mg/mL in DMSO, ≥ 100.8 mg/mL in EtOH | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0768 mL | 10.384 mL | 20.768 mL |
| 5 mM | 415.4 μL | 2.0768 mL | 4.1536 mL |
| 10 mM | 207.7 μL | 1.0384 mL | 2.0768 mL |
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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 saline, 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.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)