| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| Other Sizes |
| Targets |
IDH1
Wild-type isocitrate dehydrogenase 1 (WT IDH1); also inhibits mutant R132H IDH1 (weaker). |
|---|---|
| ln Vitro |
(R,R)-GSK321 dose-dependently reduces reductive glutaminolysis (0.1–3 μM; 5 hours; A-498 cells)[1].
(R,R)-GSK321 (WT IDH1 Inhibitor 2) inhibits wild-type IDH1 with an IC50 of 120 nM. It is an isomer of GSK321 and exhibits wild-type cross-reactivity, meaning it can inhibit both WT and mutant IDH1. It is used to study the consequences of inhibiting the normal WT IDH1 enzyme, which is critical for cellular metabolism and redox balance. |
| Enzyme Assay |
The standard IDH1 biochemical assay is used. Recombinant human wild-type IDH1 enzyme is incubated with (R,R)-GSK321, the substrate isocitrate, and the cofactor NADP+. After reaction, the production of NADPH is monitored fluorometrically or by measuring the formation of 2-hydroxyglutarate (2-HG) by LC-MS/MS. IC50 values are calculated from dose-response curves. The WT and R132H mutant enzymes are tested in parallel.
|
| Cell Assay |
To study the effect on wild-type IDH1, non-mutant cell lines (e.g., HEK293 or HCT116) are treated with (R,R)-GSK321. Key cellular readouts include: changes in the NADPH/NADP+ ratio (via colorimetric assays), alterations in alpha-ketoglutarate and 2-HG levels (by LC-MS), effects on cellular reactive oxygen species (ROS) levels (by DCFH-DA staining), and impacts on cell proliferation and survival in normoxia vs. hypoxia.
|
| Animal Protocol |
In vivo studies are conducted in immunocompetent mice to understand the role of WT IDH1 in normal physiology. Mice are administered (R,R)-GSK321 intraperitoneally or orally. Tissues (e.g., liver, kidney, brain) are harvested to measure changes in metabolite levels (NADPH, 2-HG, GSH/GSSG ratio), oxidative stress markers, and histopathology. This helps elucidate the consequences of WT IDH1 inhibition in a whole-animal context.
|
| ADME/Pharmacokinetics |
Detailed pharmacokinetic data are not publicly available. As a small molecule with a molecular weight of 501.55 g/mol, its oral bioavailability and half-life would need to be characterized. Its tissue distribution, particularly to organs with high metabolic activity (liver, kidney) and the brain, would be important for interpreting in vivo results.
|
| Toxicity/Toxicokinetics |
No dedicated toxicology data are available for this research chemical. Inhibiting wild-type IDH1 could have significant consequences given its role in the TCA cycle, lipid metabolism, and cellular redox balance. Potential toxicities might include metabolic disturbances, oxidative stress, and liver or kidney dysfunction. This compound is for research only.
|
| References | |
| Additional Infomation |
(R,R)-GSK321 is a research chemical, not an approved drug. This compound is the (R,R)-enantiomer of GSK321 and is also known as wild-type IDH1 inhibitor 2. It is a useful tool for studying the biology of wild-type IDH1 and for understanding the potential off-target effects of mutant-selective IDH1 inhibitors. It helps researchers distinguish between the effects of on-target mutant IDH1 inhibition and effects due to cross-inhibition of the wild-type enzyme.
|
| Molecular Formula |
C28H28FN5O3
|
|---|---|
| Molecular Weight |
501.55
|
| Exact Mass |
501.217
|
| CAS # |
1816272-19-1
|
| Related CAS # |
(S,S)-GSK321;1816272-20-4;(S,R)-GSK321;1816272-18-0
|
| PubChem CID |
134693801
|
| Appearance |
White to off-white solid powder
|
| LogP |
3.1
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
37
|
| Complexity |
809
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
C1N(C(C2=CC=CN2)=O)C[C@@H](C)C2N(CC3=CC=C(F)C=C3)N=C(C(NC3=CC=CC([C@H](O)C)=C3)=O)C1=2
|
| InChi Key |
IVFDDVKCCBDPQZ-QZTJIDSGSA-N
|
| InChi Code |
InChI=1S/C28H28FN5O3/c1-17-14-33(28(37)24-7-4-12-30-24)16-23-25(27(36)31-22-6-3-5-20(13-22)18(2)35)32-34(26(17)23)15-19-8-10-21(29)11-9-19/h3-13,17-18,30,35H,14-16H2,1-2H3,(H,31,36)/t17-,18-/m1/s1
|
| Chemical Name |
(7R)-1-[(4-fluorophenyl)methyl]-N-[3-[(1R)-1-hydroxyethyl]phenyl]-7-methyl-5-(1H-pyrrole-2-carbonyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO: 250 mg/mL (498.45 mM)
|
|---|---|
| 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 | 1.9938 mL | 9.9691 mL | 19.9382 mL | |
| 5 mM | 0.3988 mL | 1.9938 mL | 3.9876 mL | |
| 10 mM | 0.1994 mL | 0.9969 mL | 1.9938 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
Copyright 2020 InvivoChem LLC | All Rights Reserved
