Physicochemical Properties
| Molecular Formula | C28H28FN5O3 |
| Molecular Weight | 501.5520 |
| Exact Mass | 501.217 |
| CAS # | 1816331-63-1 |
| Related CAS # | (S,R)-GSK321;1816272-18-0 |
| PubChem CID | 91864709 |
| Appearance | Off-white to light brown 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 | FC1C([H])=C([H])C(=C([H])C=1[H])C([H])([H])N1C2=C(C(C(N([H])C3=C([H])C([H])=C([H])C([C@]([H])(C([H])([H])[H])O[H])=C3[H])=O)=N1)C([H])([H])N(C(C1=C([H])C([H])=C([H])N1[H])=O)C([H])([H])[C@@]2([H])C([H])([H])[H] |
| InChi Key | IVFDDVKCCBDPQZ-MSOLQXFVSA-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-[(1S)-1-hydroxyethyl]phenyl]-7-methyl-5-(1H-pyrrole-2-carbonyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-3-carboxamide |
| Synonyms | GSK-321.; GSK 321; GSK321 |
| 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 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) |
Biological Activity
| ln Vitro | GSK321 has IC50 values of 4.6 nM, 3.8 nM, and 2.9 nM for R132H, R132C, and R132G, respectively, indicating that it is strongly suppressive to mutant IDH1 enzyme [1]. H3K9me2 levels are dramatically decreased by GSK321 (0, 0.5, 5 μM; 48 hours) [1]. GSK321 inhibits the growth of primary IDH1 mutant AML cells and decreases intracellular 2-HG [1]. GSK321 has inhibitory effect towards mutant IDH1, surmounting the typical differentiation barriers of AML cells and promoting myeloid differentiation of IDH1 mutant cells to the extent of leukemic blasts and stem cell-like cells [1]. In IDH1 mutant AML cells, GSK321 results in genome-wide DNA cytosine hypomethylation [1]. |
| Cell Assay |
Western Blot analysis [1] Cell Types: HT-1080 Cell Tested Concentrations: 0, 0.5, 5 μM Incubation Duration: 48 h Experimental Results: diminished histone H3K9 dimethylation (H3K9me2). Cell proliferation assay[1] Cell Types: IDH1 mutant AML cells Tested Concentrations: 3 μM Incubation Duration: 15 days Experimental Results: There was an initial significant increase in cell number (2-fold to 15-fold) in IDH1 mutant AML cells. Cell cycle analysis[1] Cell Types: IDH1 Mutant AML Cell Tested Concentrations: Incubation Duration: 7 Days Experimental Results: A reproducible and significant reduction in quiescent (G0) phase cells was observed in R132G IDH1 and R132C IDH1 AML cells. |
| References |
[1]. New IDH1 mutant inhibitors for treatment of acute myeloid leukemia. Nat Chem Biol. 2015 Nov;11(11):878-86. [2]. Discovery and Optimization of Allosteric Inhibitors of Mutant Isocitrate Dehydrogenase 1 (R132H IDH1) Displaying Activity in Human Acute Myeloid Leukemia Cells. J Med Chem. 2016 Dec 22;59(24):11120-11137. |
Solubility Data
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (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 |