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Tankyrase Inhibitors (TNKS) 22 (Synonyms: TNKS 22;TNKS22;TNKS-22)

Catalog No.GC15041

Tankyrase inhibitor

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Tankyrase Inhibitors (TNKS) 22 Chemical Structure

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5mg
$148.00
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10mg
$239.00
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50mg
$715.00
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100mg
$1,082.00
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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment [1]:

Cell lines

SW480-TBC cell lines

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Reaction Conditions

24 h; IC50=3.7nM

Applications

Tankyrase Inhibitors (TNKS) 22, lead-optimized phenyloxadiazole compounds, has a good enzymatic potency and cellular potency with IC50 value of 3.7 nM in the SW480-TBC cellular assay. The compound demonstrated excellent potencies in TNKS2 autoparsylation assay and the two additional functional cellular assays.

Animal experiment [1]:

Animal models

Athymic nude mice.

Dosage form

10 and 50 mg/kg; q.d.; oral taken

Applications

Tankyrase Inhibitors (TNKS) 22 was evaluated for Wnt-pathway specific pharmacological activity in mouse tumor pharmacodynamic (PD) models. Upon once daily oral administration (at 10 and 50 mg/kg) to mice (n=4) bearing human DLD-1 tumors for 3 days, both compounds exhibited statistically significant, dose-dependent axin2 accumulation (2.7-to 3.5-fold) and inhibition of STF (51−58%) at day 3 (24 h after the last dose) .

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Hua Z, Bregman H, Buchanan J L, et al. Development of Novel Dual Binders as Potent, Selective, and Orally Bioavailable Tankyrase Inhibitors[J]. Journal of medicinal chemistry, 2013, 56(24): 10003-10015.

Background

Tankyrase Inhibitors (TNKS) 22 is a potent, selective and orally bioavailable inhibitor of tankyrase with IC50 value of 0.1nM [1].

Tankyrase 1 and tankyrase 2 are members of PARP family. They can use NAD+ as substrates to transfer ADP-ribose polymers onto tagert proteins. The tankyrase are found to bind to PARSylate axin proteins which are the negative regulator of Wnt pathway. It makes tankyrase to be targets in treatment for adenomatous polyposis coli. Tankyrase inhibitors 22 is an optimization of the previous hit compound inhibitor 8 with improved potency and selectivity. It has excellent effects in both tankyrase assay and cellular assay (total β-catenin degradation assay in SW480 cells) with IC50 values of 0.1nM and 3.7nM, respectively. In addition, it is found to be a dual binder with both the nicotinamide pocket and the induced pocket of the enzymes [1].

In the in vivo studies in rodents, tankyrase inhibitors 22 is found to potently inhibit TNKS2 autoparsylation with IC50 value of 4.1nM. It also causes stabilization and accumulation of axin protein in SW480 cells with EC50 value of 3.9nM. In DLD-1 cells with truncated APC, the inhibitor inhibits the STF reporter transcription with IC50 value of 0.6nM suggesting its downstream inhibitory activity on Wnt-associated transcription [1].

References:
[1] Hua Z, Bregman H, Buchanan J L, et al. Development of Novel Dual Binders as Potent, Selective, and Orally Bioavailable Tankyrase Inhibitors. Journal of medicinal chemistry, 2013, 56(24): 10003-10015.

Chemical Properties

Cas No. SDF
Synonyms TNKS 22;TNKS22;TNKS-22
Chemical Name 3-((4-oxo-3,4-dihydroquinazolin-2-yl)thio)-N-((1r,4r)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)cyclohexyl)propanamide
Canonical SMILES O=C1NC(SCCC(N[C@H]2CC[C@H](C3=NN=C(C4=CC=CC=C4)O3)CC2)=O)=NC5=CC=CC=C51
Formula C25H25N5O3S M.Wt 475.56
Solubility <4.76mg/mL in DMSO Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
1 mg 5 mg 10 mg
1 mM 2.1028 mL 10.5139 mL 21.0278 mL
5 mM 0.4206 mL 2.1028 mL 4.2056 mL
10 mM 0.2103 mL 1.0514 mL 2.1028 mL
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
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Reviews

Review for Tankyrase Inhibitors (TNKS) 22

Average Rating: 5 ★★★★★ (Based on Reviews and 34 reference(s) in Google Scholar.)

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