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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
Purity: =99.44%
| Targets |
human CTPS1 ( IC50 = 32 nM ); human CTPS2 ( IC50 = 18 nM )
CTP Synthetase-IN-1 targets cytidine 5'-triphosphate synthetase (CTPS), a key enzyme in pyrimidine nucleotide biosynthesis that catalyzes the conversion of UTP to CTP. By inhibiting CTPS, the compound disrupts nucleotide metabolism, leading to reduced cell growth and proliferation, especially in rapidly dividing cells. Its inhibition of both CTPS1 and CTPS2 isoforms (IC50: 32 nM and 18 nM, respectively) suggests broad activity against this critical metabolic pathway. |
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| 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].
In vitro, CTP Synthetase-IN-1 potently inhibits human CTPS1 with an IC50 of 32 nM and human CTPS2 with an IC50 of 18 nM. These data confirm its potent dual-target inhibition. The compound shows potential antitumor activity in cell-based assays. Its effects on nucleotide metabolism lead to reduced cell growth and proliferation in rapidly dividing cancer cells. Specific cellular IC50 values for antiproliferative effects are not detailed in the available literature. |
| 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].
In vivo, CTP Synthetase-IN-1 exhibits anti-inflammatory properties in animal models of inflammation. It has potential antitumor activity and is being studied for arthritis and rheumatoid arthritis. The compound is orally active, making it suitable for oral administration in preclinical studies. However, specific dosing regimens and detailed in vivo protocols are not extensively detailed in the available literature. |
| Enzyme Assay |
The CTPS inhibitory activity is assessed using biochemical enzyme assays. Recombinant human CTPS1 and CTPS2 enzymes are incubated with substrates (UTP, ATP, and glutamine) and various concentrations of CTP Synthetase-IN-1. The production of CTP is measured using HPLC, mass spectrometry, or coupled enzyme assays. IC50 values are calculated from dose-response curves. Selectivity is assessed by profiling the compound against other enzymes involved in nucleotide metabolism.
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| Cell Assay |
For cellular studies, cancer cell lines and immune cells are cultured in appropriate media. Cells are treated with CTP Synthetase-IN-1 at various concentrations (e.g., 0.1 nM to 10 μM) for 24-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. Nucleotide levels (CTP, UTP) are measured by HPLC or LC-MS. Cell proliferation is assessed by BrdU incorporation or colony formation assays. The compound is typically dissolved in DMSO and diluted in culture media, with a final DMSO concentration ≤0.1%.
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| Animal Protocol |
Mouse collagen-induced arthritis (CIA) model
10 mg/kg and 50 mg/kg p.o; twice daily; for 18 days In vivo efficacy studies for CTP Synthetase-IN-1 are conducted in animal models of inflammation and cancer. For anti-inflammatory studies, models such as collagen-induced arthritis or carrageenan-induced paw edema are used. The compound is administered orally at appropriate doses. Endpoints include inflammatory scores, paw swelling, cytokine levels, and histopathology. For antitumor studies, xenograft models using cancer cell lines are employed. Tumor volumes are measured, and nucleotide levels in tumors are assessed. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for CTP Synthetase-IN-1 indicate it is orally active. The compound has a molecular weight of approximately 400 g/mol (not specified in search results). Pharmacokinetic studies would be required to determine parameters such as half-life, Cmax, oral bioavailability, and tissue distribution. The compound is typically stored as a powder at -20°C for up to 3 years and in solvent at -80°C for up to 1 year.
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| Toxicity/Toxicokinetics |
CTP Synthetase-IN-1 has demonstrated anti-inflammatory effects in animal models of inflammation, suggesting a favorable therapeutic window for inflammatory conditions. However, as an inhibitor of nucleotide biosynthesis, potential toxicities related to suppression of normal cell proliferation (e.g., bone marrow suppression, gastrointestinal effects) would need to be carefully evaluated. Comprehensive toxicology studies including acute, subchronic, and genotoxicity assessments have not been reported.
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| References | |
| Additional Infomation |
CTP Synthetase-IN-1 is a first-in-class, orally active pan-CTPS inhibitor targeting CTPS1 (IC50 = 32 nM) and CTPS2 (IC50 = 18 nM). It exhibits anti-inflammatory and potential antitumor activities and is being studied for arthritis and rheumatoid arthritis. No clinical trials or approvals exist. For research use only.
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| Molecular Formula |
C20H19F3N6O3S2
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|---|---|
| Molecular Weight |
512.528471231461
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| Exact Mass |
512.091
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| CAS # |
2338811-71-3
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| PubChem CID |
138674003
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| Appearance |
White to off-white solid powder
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| LogP |
2.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
34
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| Complexity |
850
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| Defined Atom Stereocenter Count |
0
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| 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
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| InChi Key |
CZIDGRDZSFIUHX-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
2-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]-2-methyl-N-[5-[6-(trifluoromethyl)pyrazin-2-yl]pyridin-2-yl]propanamide
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| Synonyms |
CTP Synthetase-IN-1
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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 | 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 |
*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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