| Size | Price | Stock | Qty |
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| 2mg |
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| 5mg | |||
| 10mg | |||
| Other Sizes |
| Targets |
The primary target of NTRC-0066-0 is threonine tyrosine kinase (TTK/Mps1). It acts as a selective and potent inhibitor of TTK with an IC50 of 0.6-0.9 nM. By inhibiting TTK, it disrupts the mitotic checkpoint, leading to chromosome missegregation and ultimately cell death in cancer cells. Its high selectivity minimizes off-target effects, making it a valuable tool for studying TTK-mediated signaling in tumorigenesis.
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| ln Vitro |
The TTK target dwell time of NTRC 0066-0 has low inertia and relative inertia, which can reduce the inertia of several Manhattan systems. Its effects range from those of traditional chemotherapy medications like doxorubicin. With IC50 values ranging from 11 to 290 nM at day 5, NTRC 0066-0 suppresses the proliferation of cartilage lineages originating from various sources of tumor tissue in TTK enzyme experiments with subnanomolar effects [1].
In vitro, NTRC-0066-0 shows very potent anti-proliferative activity on a broad panel of human cancer cell lines, with IC50 values ranging from 18 to 897 nM. It has subnanomolar potency in TTK enzyme assays and inhibits the proliferation of cancer cell lines from diverse tumor tissue origins with IC50 values from 11 to 290 nM at a 5-day incubation time. It also has a relatively long target residence time on TTK. |
| ln Vivo |
In a mouse xenograft model of the human triple-negative breast cancer (TNBC) cell line MDA-MB-231, NTRC 0066-0 suppresses tumor growth [1].
In vivo, NTRC-0066-0 inhibits tumor growth in mouse xenograft models of human triple-negative breast cancer (TNBC) using the MDA-MB-231 cell line. It increases survival in a murine breast cancer model and delays tumor relapse when combined with docetaxel. The compound is orally available and demonstrates efficacy in cancer models. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for NTRC-0066-0 typically involve kinase activity assays using purified TTK enzyme. The compound's inhibitory activity is measured by monitoring the phosphorylation of a substrate peptide or protein in the presence of ATP. IC50 values are determined from dose-response curves, and selectivity is assessed by profiling against a panel of 276 kinases. Radioactive or fluorescence-based detection methods are commonly employed in these assays.
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| Cell Assay |
In vitro cellular assays for NTRC-0066-0 use human cancer cell lines from various tumor tissues. Cells are treated with the compound for 5 days, and proliferation is measured using standard assays such as CellTiter-Glo or MTT. Anti-proliferative activity is quantified by IC50 values. The compound's effects on chromosome segregation can be visualized by microscopy following staining of DNA and mitotic markers.
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| Animal Protocol |
In vivo animal studies for NTRC-0066-0 are conducted in mouse xenograft models, particularly using the MDA-MB-231 human triple-negative breast cancer cell line. Mice are orally administered the compound, and tumor growth is monitored over time. The compound's efficacy is assessed by measuring tumor volume reduction and survival rates. Combination studies with docetaxel are also performed to evaluate potential synergistic effects.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of NTRC-0066-0 indicate it is orally available. It has a molecular weight of 565.72 and a molecular formula of C33H39N7O2. The compound is soluble in DMSO at 10 mM. For in vivo administration, it can be formulated in suitable vehicles for oral gavage. Standard PK parameters such as bioavailability, half-life, and clearance would be determined in preclinical studies.
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| Toxicity/Toxicokinetics |
Toxicological information for NTRC-0066-0 is derived from preclinical studies in animal models. At efficacious doses, the compound has shown acceptable tolerability. As with other potent kinase inhibitors, potential on-target and off-target toxicities are carefully monitored during development. Comprehensive toxicology studies would be required to advance the compound into clinical trials, given its role in disrupting mitotic processes.
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| References |
[1]. Uitdehaag JCM, et al. Target Residence Time-Guided Optimization on TTK Kinase Results in Inhibitors with Potent Anti-Proliferative Activity. J Mol Biol. 2017;429(14):2211-2230.
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| Additional Infomation |
NTRC-0066-0 is a research compound primarily used for cancer research, specifically targeting TTK/Mps1. It is not yet approved for clinical use. The compound is valued for its high selectivity and potent anti-proliferative activity in various cancer cell lines. It is available from multiple research chemical suppliers for preclinical studies.
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| Molecular Formula |
C33H39N7O2
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|---|---|
| Molecular Weight |
565.708466768265
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| Exact Mass |
565.316
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| CAS # |
1817791-73-3
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| PubChem CID |
122632882
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| Appearance |
White to yellow solid powder
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| LogP |
5.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
42
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| Complexity |
873
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
HGEIUFJVGHMGRR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C33H39N7O2/c1-5-22-8-7-9-23(6-2)30(22)36-32(41)26-14-15-40-28(26)13-10-24-21-34-33(37-31(24)40)35-27-12-11-25(20-29(27)42-4)39-18-16-38(3)17-19-39/h7-9,11-12,14-15,20-21H,5-6,10,13,16-19H2,1-4H3,(H,36,41)(H,34,35,37)
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| Chemical Name |
N-(2,6-diethylphenyl)-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5,6-dihydropyrimido[4,5-e]indolizine-7-carboxamide
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| Synonyms |
NTRC0066-0; NTRC 0066-0; NTRC-0066-0
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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) |
DMSO : ~20.83 mg/mL (~36.82 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 | 1.7677 mL | 8.8385 mL | 17.6769 mL | |
| 5 mM | 0.3535 mL | 1.7677 mL | 3.5354 mL | |
| 10 mM | 0.1768 mL | 0.8838 mL | 1.7677 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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