| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IDH1 <100 nM (IC50)
Isocitrate dehydrogenase 1 (IDH1). |
|---|---|
| ln Vitro |
IDH1 Inhibitor 7 (Compound 88) is an IDH1 inhibitor with an IC50 of less than 100 nM. It is a selective inhibitor of IDH1, with lower activity against other IDH isoforms and metabolic enzymes. By inhibiting IDH1, it reduces the conversion of alpha-ketoglutarate to 2-hydroxyglutarate (2-HG), a competitive inhibitor of alpha-KG-dependent dioxygenases, thereby blocking the aberrant epigenetic changes and cellular differentiation block caused by mutant IDH1.
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| Enzyme Assay |
The standard IDH1 biochemical assay is used. Recombinant human IDH1 (either wild-type or R132H mutant) is incubated with the compound, the substrate isocitrate, and the cofactor NADP+. After incubation at 37degC, the reaction is stopped. The production of NADPH is measured by fluorescence (ex: 340 nm, em: 460 nm) or by a colorimetric method at 340 nm. Alternatively, the formation of 2-HG is quantified by LC-MS/MS for more sensitive detection. IC50 values are calculated.
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| Cell Assay |
IDH1 Inhibitor 7 is tested in IDH1-mutant cancer cell lines (e.g., HT1080 fibrosarcoma, U87MG glioblastoma, or TF-1 erythroleukemia). Cells are treated with varying concentrations for 48-72 hours. The reduction of intracellular 2-HG levels is measured by LC-MS/MS as the primary pharmacodynamic endpoint. Cell proliferation is assessed by CellTiter-Glo or MTT assays. Induction of cellular differentiation is assessed by flow cytometry for cell surface markers.
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| Animal Protocol |
In vivo studies are performed in mouse xenograft models of IDH1-mutant cancer. Immunocompromised mice are implanted with IDH1-mutant tumor cells. The compound is administered orally at various dose levels (e.g., 25, 50, 100 mg/kg) daily for 2-4 weeks. Tumors are collected to measure 2-HG reduction by LC-MS. Tumor growth inhibition, animal survival, and histopathological analysis of tumors are evaluated.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic data are not publicly available. However, as a small molecule (MW 459.47 g/mol) with good potency, its oral bioavailability, plasma half-life, and tissue distribution (particularly brain penetration, as IDH1 mutations occur in gliomas) would be characterized in standard preclinical PK studies using rodents.
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| Toxicity/Toxicokinetics |
No detailed toxicology data are publicly available. As an IDH1 inhibitor, potential on-target toxicities could arise from inhibition of wild-type IDH1 in normal tissues, affecting the TCA cycle and cellular redox balance. Standard preclinical toxicity studies in two species would be required for drug development. This compound is for research only.
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| References | |
| Additional Infomation |
IDH1 Inhibitor 7 is a research chemical, not an approved drug. It is a highly potent IDH1 inhibitor with an IC50 of less than 100 nM. This compound is useful for studying the metabolic pathways involved in cancer, particularly in tumors with IDH1 mutations. It is structurally related to the deuterated version IDH1 Inhibitor 7-d2, which is used as an internal standard for LC-MS/MS-based bioanalysis of this and related IDH1 inhibitors.
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| Molecular Formula |
C22H24F3N7O
|
|---|---|
| Molecular Weight |
459.467473983765
|
| Exact Mass |
459.199
|
| CAS # |
2135309-56-5
|
| Related CAS # |
IDH1 Inhibitor 7-d2;2135309-51-0
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| PubChem CID |
130469630
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| Appearance |
White to off-white solid powder
|
| LogP |
3.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
33
|
| Complexity |
671
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
C1(=O)N(C2C=CN=C(N[C@H](C3=CN(C4=CC=C(C(F)(F)F)C=C4)C=N3)C)N=2)[C@@H](C(C)C)CN1
|
| InChi Key |
LVRDYDOHWFEBQG-KBXCAEBGSA-N
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| InChi Code |
InChI=1S/C22H24F3N7O/c1-13(2)18-10-27-21(33)32(18)19-8-9-26-20(30-19)29-14(3)17-11-31(12-28-17)16-6-4-15(5-7-16)22(23,24)25/h4-9,11-14,18H,10H2,1-3H3,(H,27,33)(H,26,29,30)/t14-,18+/m0/s1
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| Chemical Name |
(5S)-5-propan-2-yl-1-[2-[[(1S)-1-[1-[4-(trifluoromethyl)phenyl]imidazol-4-yl]ethyl]amino]pyrimidin-4-yl]imidazolidin-2-one
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~100 mg/mL (~217.6 mM; with ultrasonication)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.44 mM) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (5.44 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: 2.5 mg/mL (5.44 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1764 mL | 10.8821 mL | 21.7642 mL | |
| 5 mM | 0.4353 mL | 2.1764 mL | 4.3528 mL | |
| 10 mM | 0.2176 mL | 1.0882 mL | 2.1764 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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