NTRC-0066-0 | NTRC-00660 | CAS#1817791-73-3 | TTK inhibitor

NTRC-0066-0
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 407828

CAS#: 1817791-73-3

Description: NTRC-0066-0 is a a highly potent and selective small molecule inhibitor of TTK. 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. The combination of NTRC 0066-0 with a therapeutic dose of docetaxel resulted in doubling of mouse survival and extended tumor remission, without toxicity.

Chemical Structure

NTRC-0066-0

CAS# 1817791-73-3

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 407828
Name: NTRC-0066-0
CAS#: 1817791-73-3
Chemical Formula: C33H39N7O2
Exact Mass: 565.32
Molecular Weight: 565.722
Elemental Analysis: C, 70.06; H, 6.95; N, 17.33; O, 5.66

Price and Availability

Size	Price	Availability
5mg	USD 450	2 Weeks
10mg	USD 750	2 Weeks
25mg	USD 1250	2 Weeks
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

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

Appearance: Solid powder

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.

Product Data:

Product Data

Instruction:

View handling instruction

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/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMSO	20.8	36.82

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.

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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.

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