| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
IDH1 Inhibitor 1 targets mutant isocitrate dehydrogenase 1 (IDH1), an enzyme that catalyzes the conversion of isocitrate to alpha-ketoglutarate. Mutant IDH1 (such as R132H and R132C) produces the oncometabolite 2-hydroxyglutarate (2-HG), which contributes to tumorigenesis. By selectively inhibiting mutant IDH1, the compound reduces 2-HG production and inhibits tumor growth.
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| ln Vitro |
HCT116-IDH1R132H/+ cells are inhibited by IDH1 Inhibitor 1 (Compound 19) with an IC50 of 0.039 μM [1].
In vitro, IDH1 Inhibitor 1 is a potent and selective mutant IDH1 inhibitor with IC₅0 values of 0.021 microM for IDH1R132H, 0.045 microM for IDH1R132C, and 2.52 microM for IDH1WT. Its high potency against mutant IDH1 and selectivity over wild-type IDH1 make it a valuable tool for studying IDH1 mutant biology and for developing targeted cancer therapies. The compound has anticancer activity. |
| ln Vivo |
In preclinical xenograft tumor models, 2-hydroxyglutarate (2-HG) synthesis is inhibited by IDH1 Inhibitor 1 (Compound 19). In order to assess the in vivo reduction of 2-HG synthesis, IDH1 Inhibitor 1 was also examined in a mechanistic xenograft tumor model derived from mouse patients that was IDH1 mutant, HCT116-IDH1R132H/+. At 150 mg/kg orally administered orally, IDH1 inhibitor 1 suppresses the formation of new 2-HG [1].
In vivo, IDH1 Inhibitor 1 is orally bioavailable and brain-penetrant, making it suitable for studying IDH1 mutant tumors, including brain tumors. Its oral bioavailability supports administration via oral gavage in animal studies. The compound's brain penetration enables evaluation of efficacy in intracranial tumor models. Further in vivo studies are needed to fully characterize its efficacy and safety profile. |
| Enzyme Assay |
For in vitro enzyme assays, IDH1 Inhibitor 1 is evaluated using IDH1 enzymatic activity assays. The compound is incubated with recombinant IDH1 enzyme (wild-type or mutant) and substrate at various concentrations. IDH1 activity is quantified by measuring the conversion of isocitrate to alpha-ketoglutarate or the production of 2-HG using spectrophotometric, fluorometric, or LC-MS methods. IC₅0 values are determined from dose-response curves.
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| Cell Assay |
For in vitro cellular experiments, IDH1 Inhibitor 1 is tested in cancer cell lines harboring IDH1 mutations. Cells are cultured in appropriate media and treated with various concentrations of the compound. 2-HG levels in cell lysates or supernatants are measured by LC-MS. Cell viability, proliferation, and differentiation are assessed using standard assays. The compound's effects on IDH1 mutant-dependent gene expression and epigenetic changes are evaluated.
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| Animal Protocol |
For in vivo animal experiments, IDH1 Inhibitor 1 can be administered to tumor-bearing mice via oral gavage. Xenograft models using IDH1 mutant cancer cell lines, including intracranial models, are commonly used. Typical dosing regimens may range from 1 to 50 mg/kg. Tumor volume is measured regularly, and tumor growth inhibition is calculated. 2-HG levels in tumors and plasma are measured as pharmacodynamic markers.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of IDH1 Inhibitor 1 include oral bioavailability and brain penetration. As a small molecule with a molecular weight of 450.39, it has favorable properties for central nervous system penetration. Detailed parameters such as Cₘₐₓ, Tₘₐₓ, AUC, half-life, and clearance would need to be determined through comprehensive PK studies. The compound's metabolism and excretion pathways remain to be fully characterized.
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| Toxicity/Toxicokinetics |
Toxicological data for IDH1 Inhibitor 1 are limited, as it is primarily a research tool. As a mutant IDH1 inhibitor, its toxicity would depend on the importance of IDH1 for normal cellular metabolism. Comprehensive toxicology studies including acute and repeated-dose toxicity, genotoxicity, and cardiotoxicity assessments would be needed for further development. Appropriate safety precautions should be taken when handling this compound.
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| References | |
| Additional Infomation |
IDH1 Inhibitor 1 is a research compound used to study IDH1 mutant biology and develop targeted cancer therapies. No clinical trials or regulatory approvals have been reported for this compound as a therapeutic agent. It is available from various chemical suppliers for research purposes only. The compound is a potent, orally bioavailable, brain-penetrant, and selective mutant IDH1 inhibitor.
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| Molecular Formula |
C20H18F4N6O2
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|---|---|
| Molecular Weight |
450.389537334442
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| Exact Mass |
450.142
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| CAS # |
2234285-81-3
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| PubChem CID |
137333448
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| Appearance |
White to off-white solid powder
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| LogP |
3.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
32
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| Complexity |
648
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| Defined Atom Stereocenter Count |
2
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| SMILES |
FC[C@H]1COC(N1C1C=CN=C(N=1)N[C@@H](C)C1=CN(C=N1)C1C=CC(C(F)(F)F)=CC=1)=O
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| InChi Key |
ULTZLMKTFYRMFK-WFASDCNBSA-N
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| InChi Code |
InChI=1S/C20H18F4N6O2/c1-12(16-9-29(11-26-16)14-4-2-13(3-5-14)20(22,23)24)27-18-25-7-6-17(28-18)30-15(8-21)10-32-19(30)31/h2-7,9,11-12,15H,8,10H2,1H3,(H,25,27,28)/t12-,15-/m0/s1
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| Chemical Name |
(4R)-4-(fluoromethyl)-3-[2-[[(1S)-1-[1-[4-(trifluoromethyl)phenyl]imidazol-4-yl]ethyl]amino]pyrimidin-4-yl]-1,3-oxazolidin-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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 (~222.03 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.55 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to 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 (5.55 mM) (saturation unknown) 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. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.55 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2203 mL | 11.1015 mL | 22.2030 mL | |
| 5 mM | 0.4441 mL | 2.2203 mL | 4.4406 mL | |
| 10 mM | 0.2220 mL | 1.1101 mL | 2.2203 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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