Synonym
NTRC-0066-0; NTRC 0066-0; NTRC0066-0; NTRC-00660; NTRC 00660; NTRC00660
IUPAC/Chemical Name
8-[2-Methoxy-4-(4-methyl-piperazin-1-yl)-phenylamino]-4,5-dihydro-7,9,9b-triaza-cyclopenta[a]naphthalene-3-carboxylic acid (2,6-diethyl-phenyl)-amide
InChi Key
HGEIUFJVGHMGRR-UHFFFAOYSA-N
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)
SMILES Code
O=C(C(C=C1)=C2N1C3=NC(NC4=CC=C(N5CCN(C)CC5)C=C4OC)=NC=C3CC2)NC6=C(CC)C=CC=C6CC
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Inhibition of the spindle assembly checkpoint kinase TTK enhances the efficacy of docetaxel in a triple-negative breast cancer model.
Biological target:
NTRC 0066-0 is a selective threonine tyrosine kinase (TTK) inhibitor (IC50=0.9 nM).
In vitro activity:
This study shows that treatment of tumor cells with the selective small molecule TTK inhibitor NTRC 0066-0 overrides the mitotic checkpoint, irrespective of cell line sensitivity. In stable aneuploid cells NTRC 0066-0 induced acute CIN, whereas in cells with high levels of pre-existing CIN there was only a small additional fraction of cells mis-segregating their chromosomes.
Reference: Ann Transl Med. 2022 Dec;10(24):1352. https://pubmed.ncbi.nlm.nih.gov/28415765/
In vivo activity:
In cell lines and in mice, NTRC 0066-0 inhibits the phosphorylation of a TTK substrate and induces chromosome missegregation. NTRC 0066-0 inhibits tumor growth in MDA-MB-231 xenografts as a single agent after oral application.
Reference: Ann Oncol. 2015 Oct;26(10):2180-92. https://pubmed.ncbi.nlm.nih.gov/26153498/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
20.8 |
36.82 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
565.72
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Cui CH, Wu Q, Zhou HM, He H, Wang Y, Tang Z, Zhang Y, Wang X, Xiao J, Zhang H. High tyrosine threonine kinase expression predicts a poor prognosis: a potential therapeutic target for endometrial carcinoma. Ann Transl Med. 2022 Dec;10(24):1352. doi: 10.21037/atm-22-5783. PMID: 36660721; PMCID: PMC9843307.
2. Libouban MAA, de Roos JADM, Uitdehaag JCM, Willemsen-Seegers N, Mainardi S, Dylus J, de Man J, Tops B, Meijerink JPP, Storchová Z, Buijsman RC, Medema RH, Zaman GJR. Stable aneuploid tumors cells are more sensitive to TTK inhibition than chromosomally unstable cell lines. Oncotarget. 2017 Jun 13;8(24):38309-38325. doi: 10.18632/oncotarget.16213. PMID: 28415765; PMCID: PMC5503534.
3. Maia AR, de Man J, Boon U, Janssen A, Song JY, Omerzu M, Sterrenburg JG, Prinsen MB, Willemsen-Seegers N, de Roos JA, van Doornmalen AM, Uitdehaag JC, Kops GJ, Jonkers J, Buijsman RC, Zaman GJ, Medema RH. Inhibition of the spindle assembly checkpoint kinase TTK enhances the efficacy of docetaxel in a triple-negative breast cancer model. Ann Oncol. 2015 Oct;26(10):2180-92. doi: 10.1093/annonc/mdv293. Epub 2015 Jul 7. PMID: 26153498.
In vitro protocol:
1. Cui CH, Wu Q, Zhou HM, He H, Wang Y, Tang Z, Zhang Y, Wang X, Xiao J, Zhang H. High tyrosine threonine kinase expression predicts a poor prognosis: a potential therapeutic target for endometrial carcinoma. Ann Transl Med. 2022 Dec;10(24):1352. doi: 10.21037/atm-22-5783. PMID: 36660721; PMCID: PMC9843307.
2. Libouban MAA, de Roos JADM, Uitdehaag JCM, Willemsen-Seegers N, Mainardi S, Dylus J, de Man J, Tops B, Meijerink JPP, Storchová Z, Buijsman RC, Medema RH, Zaman GJR. Stable aneuploid tumors cells are more sensitive to TTK inhibition than chromosomally unstable cell lines. Oncotarget. 2017 Jun 13;8(24):38309-38325. doi: 10.18632/oncotarget.16213. PMID: 28415765; PMCID: PMC5503534.
In vivo protocol:
1. Maia AR, de Man J, Boon U, Janssen A, Song JY, Omerzu M, Sterrenburg JG, Prinsen MB, Willemsen-Seegers N, de Roos JA, van Doornmalen AM, Uitdehaag JC, Kops GJ, Jonkers J, Buijsman RC, Zaman GJ, Medema RH. Inhibition of the spindle assembly checkpoint kinase TTK enhances the efficacy of docetaxel in a triple-negative breast cancer model. Ann Oncol. 2015 Oct;26(10):2180-92. doi: 10.1093/annonc/mdv293. Epub 2015 Jul 7. PMID: 26153498.
1: Zaman GJR, de Roos JADM, Libouban MAA, Prinsen MBW, de Man J, Buijsman RC, Uitdehaag JCM. TTK inhibitors as a targeted therapy for CTNNB1 (β-catenin) mutant cancers. Mol Cancer Ther. 2017 Jul 27. pii: molcanther.0342.2017. doi: 10.1158/1535-7163.MCT-17-0342. [Epub ahead of print] PubMed PMID: 28751540.
2: Uitdehaag JCM, de Man J, Willemsen-Seegers N, Prinsen MBW, Libouban MAA, Sterrenburg JG, de Wit JJP, de Vetter JRF, de Roos JADM, Buijsman RC, Zaman GJR. Target Residence Time-Guided Optimization on TTK Kinase Results in Inhibitors with Potent Anti-Proliferative Activity. J Mol Biol. 2017 Jul 7;429(14):2211-2230. doi: 10.1016/j.jmb.2017.05.014. Epub 2017 May 21. PubMed PMID: 28539250.
3: Libouban MAA, de Roos JADM, Uitdehaag JCM, Willemsen-Seegers N, Mainardi S, Dylus J, de Man J, Tops B, Meijerink JPP, Storchová Z, Buijsman RC, Medema RH, Zaman GJR. Stable aneuploid tumors cells are more sensitive to TTK inhibition than chromosomally unstable cell lines. Oncotarget. 2017 Jun 13;8(24):38309-38325. doi: 10.18632/oncotarget.16213. PubMed PMID: 28415765; PubMed Central PMCID: PMC5503534.
4: Maia AR, de Man J, Boon U, Janssen A, Song JY, Omerzu M, Sterrenburg JG, Prinsen MB, Willemsen-Seegers N, de Roos JA, van Doornmalen AM, Uitdehaag JC, Kops GJ, Jonkers J, Buijsman RC, Zaman GJ, Medema RH. Inhibition of the spindle assembly checkpoint kinase TTK enhances the efficacy of docetaxel in a triple-negative breast cancer model. Ann Oncol. 2015 Oct;26(10):2180-92. doi: 10.1093/annonc/mdv293. Epub 2015 Jul 7. PubMed PMID: 26153498.
