| 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
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| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (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.
Products are for research use only; We do not sell to patients
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