| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
IDH889 targets mutant isocitrate dehydrogenase 1 (IDH1), an enzyme frequently mutated in cancers such as acute myeloid leukemia (AML) and gliomas. It exhibits high selectivity for IDH1 R132* mutants, with IC50s of 0.02 μM for IDH1R132H, 0.072 μM for IDH1R132C, and 1.38 μM for wild-type IDH1.
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|---|---|
| ln Vitro |
In vitro, IDH889 potently inhibits mutant IDH1, reducing the production of the oncometabolite 2-hydroxyglutarate (2-HG). Its high selectivity for the mutant enzyme over the wild-type enzyme minimizes potential off-target effects on normal cellular metabolism.
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| ln Vivo |
In vivo, IDH889 is expected to reduce tumor growth in IDH1-mutant cancers by inhibiting 2-HG production. Its oral bioavailability and brain penetration make it suitable for treating both systemic and brain tumors harboring IDH1 mutations.
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| Enzyme Assay |
IDH1 enzymatic activity is measured using an in vitro assay with recombinant IDH1 protein. The enzyme is incubated with its substrate, isocitrate, and NADP+ in the presence of varying concentrations of IDH889. The production of 2-HG or NADPH is measured, and the IC50 is calculated.
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| Cell Assay |
The effects of IDH889 on cellular 2-HG levels are assessed in IDH1-mutant cancer cell lines. Cells are treated with the compound, and intracellular 2-HG levels are measured by mass spectrometry. The compound's ability to reduce 2-HG production is determined.
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| Animal Protocol |
In vivo efficacy is evaluated in mouse xenograft models of IDH1-mutant cancers, such as AML or glioma. IDH889 is administered orally, and tumor growth and 2-HG levels are measured. The compound's ability to inhibit tumor growth is assessed.
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| ADME/Pharmacokinetics |
As an orally bioavailable small molecule, IDH889 is expected to have good oral bioavailability and favorable pharmacokinetic properties. Its brain penetration makes it suitable for treating brain tumors.
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| Toxicity/Toxicokinetics |
IDH1 inhibitors are generally well-tolerated. Potential toxicities may include effects on normal cellular metabolism due to inhibition of wild-type IDH1, but the high selectivity of IDH889 for the mutant enzyme minimizes this risk.
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| References | |
| Additional Infomation |
IDH889 is a research compound being developed for the treatment of IDH1-mutant cancers. It is a potent, orally bioavailable, brain-penetrating, and mutation-specific IDH1 inhibitor. It is not approved for clinical use.
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| Molecular Formula |
C23H25FN6O2
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|---|---|
| Molecular Weight |
436.482007741928
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| Exact Mass |
436.202
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| CAS # |
1429179-07-6
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| Related CAS # |
(1R)-IDH889;1429179-08-7
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| PubChem CID |
71542286
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| Appearance |
White to off-white solid powder
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
32
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| Complexity |
632
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| Defined Atom Stereocenter Count |
2
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| SMILES |
FC1C=CC(=CC=1C)C1C=NC([C@H](C)NC2=NC=CC(=N2)N2C(=O)OC[C@@H]2C(C)C)=NC=1
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| InChi Key |
JDCYIMQAIKEACU-HNAYVOBHSA-N
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| InChi Code |
InChI=1S/C23H25FN6O2/c1-13(2)19-12-32-23(31)30(19)20-7-8-25-22(29-20)28-15(4)21-26-10-17(11-27-21)16-5-6-18(24)14(3)9-16/h5-11,13,15,19H,12H2,1-4H3,(H,25,28,29)/t15-,19+/m0/s1
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| Chemical Name |
(4S)-3-[2-[[(1S)-1-[5-(4-fluoro-3-methylphenyl)pyrimidin-2-yl]ethyl]amino]pyrimidin-4-yl]-4-propan-2-yl-1,3-oxazolidin-2-one
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| Synonyms |
IDH 889; IDH-889; IDH889
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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 : ~200 mg/mL (~458.21 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (11.46 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 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: ≥ 5 mg/mL (11.46 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2911 mL | 11.4553 mL | 22.9106 mL | |
| 5 mM | 0.4582 mL | 2.2911 mL | 4.5821 mL | |
| 10 mM | 0.2291 mL | 1.1455 mL | 2.2911 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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