CTP Synthetase-IN-1 (compound 27) is a first-in-class and orally bioactive pan-inhibitor of cytidine 5'-triphosphate synthetase (CTPS) with anti-inflammatory effects. Its IC50 values for human CTPS1/2 inhibition are 32 nM and 18 nM, respectively. In the process of de novo pyrimidine synthesis, CTPS1/2 are essential enzymes. A high-throughput screening of 240K compounds led to the discovery of CTP Synthetase-IN-1, which in a well-researched animal model of inflammation, demonstrated notable pharmacological responses at a dose of 10 mg/kg BID.
Physicochemical Properties
| Molecular Formula | C20H19F3N6O3S2 |
| Molecular Weight | 512.528471231461 |
| Exact Mass | 512.091 |
| CAS # | 2338811-71-3 |
| PubChem CID | 138674003 |
| Appearance | White to off-white solid powder |
| LogP | 2.2 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 12 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 34 |
| Complexity | 850 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | C(C1=CN=CC(C2=CN=C(NC(=O)C(C3=CSC(NS(C4CC4)(=O)=O)=N3)(C)C)C=C2)=N1)(F)(F)F |
| InChi Key | CZIDGRDZSFIUHX-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C20H19F3N6O3S2/c1-19(2,15-10-33-18(27-15)29-34(31,32)12-4-5-12)17(30)28-16-6-3-11(7-25-16)13-8-24-9-14(26-13)20(21,22)23/h3,6-10,12H,4-5H2,1-2H3,(H,27,29)(H,25,28,30) |
| Chemical Name | 2-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]-2-methyl-N-[5-[6-(trifluoromethyl)pyrazin-2-yl]pyridin-2-yl]propanamide |
| Synonyms | CTP Synthetase-IN-1 |
| 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) |
Biological Activity
| Targets | human CTPS1 ( IC50 = 32 nM ); human CTPS2 ( IC50 = 18 nM ) |
| ln Vitro | CTP Synthetase-IN-1 (compound 27) has IC50 values of 27 nM, 23 nM, 26 nM, and 33 nM, respectively, and inhibits rat CTPS1, rat CTPS2, mouse CTPS1, and mouse CTPS2[1]. |
| ln Vivo | CTP Synthetase-IN-1 (compound 27; 10-50 mg/kg; p.o; twice daily; for 18 days) exhibits noteworthy pharmacological responses in collagen-induced arthritis (CIA) model[1]. |
| Animal Protocol |
Mouse collagen-induced arthritis (CIA) model 10 mg/kg and 50 mg/kg p.o; twice daily; for 18 days |
| References |
[1]. Discovery and Optimization of Potent and Orally Available CTP Synthetase Inhibitors for Use in Treatment of Diseases Driven by Aberrant Immune Cell Proliferation. J Med Chem. 2022 Dec 22;65(24):16640-16650. |
Solubility Data
| 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 |
| 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 | 1.9511 mL | 9.7555 mL | 19.5111 mL | |
| 5 mM | 0.3902 mL | 1.9511 mL | 3.9022 mL | |
| 10 mM | 0.1951 mL | 0.9756 mL | 1.9511 mL |