| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Mutant isocitrate dehydrogenase 1 (IDH1).
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| ln Vitro |
(S,S)-GSK321, as the active enantiomer, is a potent inhibitor of mutant IDH1 enzymes. GSK321 (likely the racemic or active mixture) inhibits mutant IDH1, blocks lipid synthesis, prevents cell proliferation in OPA1-deficient MEFs, and prevents cytosolic glutamine reductive carboxylation. It is used in research on leukemia. The (S,S)-enantiomer is believed to be the eutomer (more active enantiomer).
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| Enzyme Assay |
The IDH1 mutant inhibition assay uses the purified recombinant IDH1 R132H mutant enzyme. The assay buffer contains IDH1, the compound, substrate (isocitrate), and cofactor (NADP+). After incubation, the reaction is stopped, and the product (NADPH or 2-HG) is quantified by fluorescence or LC-MS/MS. IC50 values are calculated. The (S,S)-enantiomer should show greater potency than the (R,R)-enantiomer.
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| Cell Assay |
The activity of (S,S)-GSK321 can be assessed in IDH1-mutant cancer cell lines (e.g., HT1080 fibrosarcoma). Cells are treated with the compound for 24-72 hours. The primary endpoint is the reduction of the oncometabolite 2-hydroxyglutarate (2-HG), measured by LC-MS/MS. Effects on cell proliferation (MTT assay) and differentiation (flow cytometry for differentiation markers) are also evaluated.
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| Animal Protocol |
In vivo studies are conducted in mouse xenograft models of IDH1-mutant tumors. Mice are implanted with IDH1-mutant cancer cells and treated orally with (S,S)-GSK321. Tumor tissue is collected to measure 2-HG reduction, and tumor growth is monitored. The compound also shows activity in models of IDH1-dependent leukemia, where it may reduce leukemic blast counts and improve survival.
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| ADME/Pharmacokinetics |
Detailed PK data are not publicly available. As a small molecule with molecular weight ~501.55 g/mol, it is expected to have favorable oral bioavailability. Its absorption, distribution, metabolism, and excretion would be characterized in standard preclinical PK studies. The (S,S)-enantiomer may have different PK properties compared to the racemic mixture.
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| Toxicity/Toxicokinetics |
No detailed toxicology data are available for this specific enantiomer. As an IDH1 inhibitor, potential toxicities could be related to on-mechanism effects in normal cells or off-target kinase inhibition. Standard preclinical safety studies would be required for development, including in vitro safety pharmacology (hERG, CYP inhibition) and repeat-dose toxicity studies in rodents.
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| References | |
| Additional Infomation |
(S,S)-GSK321 is a research chemical, not an approved drug. This compound is the active (S,S)-enantiomer of the IDH1 inhibitor GSK321. It is structurally related to GSK864 (an IDH1 mutant inhibitor) and WT IDH1 Inhibitor 2. This compound is a valuable tool for studying the stereospecific requirements of IDH1 inhibition and for understanding the role of mutant IDH1 in cancer metabolism.
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| Molecular Formula |
C28H28FN5O3
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|---|---|
| Molecular Weight |
501.55202960968
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| Exact Mass |
501.217
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| CAS # |
1816272-20-4
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| Related CAS # |
(R,R)-GSK321;1816272-19-1;(S,R)-GSK321;1816272-18-0
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| PubChem CID |
165437226
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.1
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
37
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| Complexity |
809
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| Defined Atom Stereocenter Count |
2
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| 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
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| InChi Key |
IVFDDVKCCBDPQZ-ROUUACIJSA-N
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| 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-/m0/s1
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| Chemical Name |
(7S)-1-[(4-fluorophenyl)methyl]-N-[3-[(1S)-1-hydroxyethyl]phenyl]-7-methyl-5-(1H-pyrrole-2-carbonyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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: 150 mg/mL (299.07 mM)
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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 | 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.
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