Tankyrase Inhibitors (TNKS) 22
TNKS 22 (TNKS-IN-22, CAS 1507362-00-6) is a small-molecule inhibitor targeting tankyrase 1 and tankyrase 2 enzymes of the poly(ADP-ribose) polymerase (PARP) family. It is designed to inhibit tankyrase enzymatic activity.
TNKS 22 regulates the Wnt signaling pathway through inhibition of TNKS-mediated poly-ADP-ribosylation of Axin, leading to reduced β-catenin levels. In cell-based studies, TNKS 22 demonstrates potent inhibition with an IC50 of 0.1 nM for TNKS enzymatic activity, 3.7 nM in SW480 cells for β-catenin reduction, 4.1 nM for TNKS2 autoparsylation in vivo, and 0.6 nM for Wnt pathway suppression in APC-deficient (DLD-1) cells.
TNKS 22 is utilized in investigating Wnt signaling and potential therapeutic strategies related to intestinal proliferative disorders.
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.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 475.56 |
| Cas No. | 1507362-00-6 |
| Formula | C25H25N5O3S |
| Synonyms | TNKS 22; TNKS22; TNKS-22 |
| Solubility | insoluble in H2O; insoluble in DMSO; ≥3.07 mg/mL in EtOH with gentle warming |
| 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 |
| SDF | Download SDF |
| Canonical SMILES | O=C(CCSC(N1)=Nc(cccc2)c2C1=O)N[C@H](CC1)CC[C@@H]1c1nnc(-c2ccccc2)[o]1 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
SW480-TBC cell lines |
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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. |
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Reaction Conditions |
24 h; IC50=3.7nM |
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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]: | |
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Animal models |
Athymic nude mice. |
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Dosage form |
10 and 50 mg/kg; q.d.; oral taken |
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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) . |
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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. |
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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. | |
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