NCB-0846 | CAS#1792999-26-8

MedKoo Cat#: 526464 | Name: NCB-0846

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

NCB-0846 is the first orally available small-molecule TNIK inhibitor, having anti-Wnt activity and suppressing Wnt-driven intestinal tumorigenesis, also inhibiting FLT3, JAK3, PDGFRa, TRKA, CDK2/CycA2, and HGK.

Chemical Structure

NCB-0846

CAS#1792999-26-8

Theoretical Analysis

MedKoo Cat#: 526464

Name: NCB-0846

CAS#: 1792999-26-8

Chemical Formula: C21H21N5O2

Exact Mass: 375.1695

Molecular Weight: 375.43

Elemental Analysis: C, 67.18; H, 5.64; N, 18.65; O, 8.52

Price and Availability

Size	Price	Availability
5mg	USD 285.00	2 Weeks
10mg	USD 500.00	2 Weeks
25mg	USD 960.00	2 Weeks

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Related CAS #

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Synonym

NCB-0846

IUPAC/Chemical Name

cis-4-(2-(3H-Benzo[d]imidazol-5-ylamino)quinazolin-8-yloxy)cyclohexanol

InChi Key

FYWRWBSYRGSWIQ-IYBDPMFKSA-N

InChi Code

InChI=1S/C21H21N5O2/c27-15-5-7-16(8-6-15)28-19-3-1-2-13-11-22-21(26-20(13)19)25-14-4-9-17-18(10-14)24-12-23-17/h1-4,9-12,15-16,27H,5-8H2,(H,23,24)(H,22,25,26)/t15-,16+

SMILES Code

O[C@H]1CC[C@@H](OC2=CC=CC3=CN=C(NC4=CC=C5N=CNC5=C4)N=C23)CC1

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

Product Data

Product Data

Instruction

View handling instruction

Biological target:

NCB-0846 is an orally available TNIK inhibitor with an IC50 of 21 nM.

In vitro activity:

To validate the clinical relevance of these findings, this study characterized expression of TNIK and TNIK phosphorylated at serine 764 (pS764) in a localized prostate cancer patient cohort and showed that nuclear enrichment of TNIK (pS764) was significantly positively correlated with ERG expression. Moreover, TNIK protein levels were dependent upon ERG expression in VCaP cells and primary cells established from a prostate cancer patient-derived xenograft. Furthermore, reduction of TNIK expression and activity by silencing TNIK expression or using the TNIK inhibitor NCB-0846 reduced cell viability, colony formation and anchorage independent growth. Reference: Neoplasia. 2019 Apr;21(4):389-400. https://pubmed.ncbi.nlm.nih.gov/30901730/

In vivo activity:

The effect of NCB-0846 on Wnt-driven tumorigenesis was then investigated in Apcmin/+ mice. NCB-0846 dose dependently reduced the multiplicity and dimensions of tumours that developed in the small intestine (Fig. 3g). Reference: Nat Commun. 2016 Aug 26;7:12586. https://pubmed.ncbi.nlm.nih.gov/27562646/

	Solvent	mg/mL	mM
Solubility
	DMF	1.0	2.66
	DMSO	17.5	46.61

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 375.43 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. Sekita T, Yamada T, Kobayashi E, Yoshida A, Hirozane T, Kawai A, Uno Y, Moriyama H, Sawa M, Nagakawa Y, Tsuchida A, Matsumoto M, Nakamura M, Nakayama R, Masuda M. Feasibility of Targeting Traf2-and-Nck-Interacting Kinase in Synovial Sarcoma. Cancers (Basel). 2020 May 16;12(5):1258. doi: 10.3390/cancers12051258. PMID: 32429395; PMCID: PMC7281028. 2. Lee RS, Zhang L, Berger A, Lawrence MG, Song J, Niranjan B, Davies RG, Lister NL, Sandhu SK, Rubin MA, Risbridger GP, Taylor RA, Rickman DS, Horvath LG, Daly RJ. Characterization of the ERG-regulated Kinome in Prostate Cancer Identifies TNIK as a Potential Therapeutic Target. Neoplasia. 2019 Apr;21(4):389-400. doi: 10.1016/j.neo.2019.02.005. Epub 2019 Mar 20. PMID: 30901730; PMCID: PMC6426874. 3. Sugano T, Masuda M, Takeshita F, Motoi N, Hirozane T, Goto N, Kashimoto S, Uno Y, Moriyama H, Sawa M, Nagakawa Y, Tsuchida A, Seike M, Gemma A, Yamada T. Pharmacological blockage of transforming growth factor-β signalling by a Traf2- and Nck-interacting kinase inhibitor, NCB-0846. Br J Cancer. 2021 Jan;124(1):228-236. doi: 10.1038/s41416-020-01162-3. Epub 2020 Nov 27. PMID: 33244122; PMCID: PMC7782820. 4. Masuda M, Uno Y, Ohbayashi N, Ohata H, Mimata A, Kukimoto-Niino M, Moriyama H, Kashimoto S, Inoue T, Goto N, Okamoto K, Shirouzu M, Sawa M, Yamada T. TNIK inhibition abrogates colorectal cancer stemness. Nat Commun. 2016 Aug 26;7:12586. doi: 10.1038/ncomms12586. PMID: 27562646; PMCID: PMC5007443.

In vitro protocol:

In vivo protocol:

1. Sugano T, Masuda M, Takeshita F, Motoi N, Hirozane T, Goto N, Kashimoto S, Uno Y, Moriyama H, Sawa M, Nagakawa Y, Tsuchida A, Seike M, Gemma A, Yamada T. Pharmacological blockage of transforming growth factor-β signalling by a Traf2- and Nck-interacting kinase inhibitor, NCB-0846. Br J Cancer. 2021 Jan;124(1):228-236. doi: 10.1038/s41416-020-01162-3. Epub 2020 Nov 27. PMID: 33244122; PMCID: PMC7782820. 2. Masuda M, Uno Y, Ohbayashi N, Ohata H, Mimata A, Kukimoto-Niino M, Moriyama H, Kashimoto S, Inoue T, Goto N, Okamoto K, Shirouzu M, Sawa M, Yamada T. TNIK inhibition abrogates colorectal cancer stemness. Nat Commun. 2016 Aug 26;7:12586. doi: 10.1038/ncomms12586. PMID: 27562646; PMCID: PMC5007443.

1: Yamada T, Masuda M. Emergence of TNIK inhibitors in cancer therapeutics. Cancer Sci. 2017 May;108(5):818-823. doi: 10.1111/cas.13203. Epub 2017 Apr 24. Review. PubMed PMID: 28208209; PubMed Central PMCID: PMC5448614. 2: Masuda M, Uno Y, Ohbayashi N, Ohata H, Mimata A, Kukimoto-Niino M, Moriyama H, Kashimoto S, Inoue T, Goto N, Okamoto K, Shirouzu M, Sawa M, Yamada T. TNIK inhibition abrogates colorectal cancer stemness. Nat Commun. 2016 Aug 26;7:12586. doi: 10.1038/ncomms12586. PubMed PMID: 27562646; PubMed Central PMCID: PMC5007443.