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Purity: ≥98%
WIKI4 (WIKI 4; WIKI-4) is a novel and potent Tankyrase inhibitor with potential anticancer activity. It inhibits Tankyrase2 (TNKS2) in the Wnt/β-catenin signaling pathway with an IC50 of 15 nM.
| Targets |
WIKI4 is a selective inhibitor of tankyrase 1 (TNKS1) and tankyrase 2 (TNKS2) (TNKS1 IC50 = 49 nM; TNKS2 IC50 = 45 nM) [2]
WIKI4 shows no significant inhibition of other poly(ADP-ribose) polymerases (PARP1, PARP2: IC50 > 10 μM) [2] |
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| ln Vitro |
In comparison to the DMSO control, WIKI4 (100 nM, 1 μM; 6 days) reduces the proliferation of DLD1 cells in media with low serum. The expression of genes targeted by β-catenin and the cell's reaction to Wnt/β-catenin signaling are suppressed by WIKI4 [1]. The steady-state abundance of AXIN1 and AXIN2 is dramatically increased by WIKI4 (1 μM; 2 hours, 4 hours, 6 or 24 hours; DLD1 cells) [1].
In recombinant TNKS1/TNKS2 enzyme assays, WIKI4 dose-dependently inhibits ADP-ribosylation activity, with 70% inhibition of TNKS1 and 72% inhibition of TNKS2 at 200 nM. It blocks TNKS-mediated AXIN degradation, thereby suppressing canonical Wnt/β-catenin signaling [2] - In HEK293 cells transfected with Wnt-responsive luciferase reporter plasmid, WIKI4 (5 μM) reduces Wnt3a-induced luciferase activity by 80% after 24 hours. It downregulates Wnt target genes (AXIN2, LEF1) at mRNA level by 63% and 59% respectively [2] - In human mesenchymal stem cells (hMSCs), WIKI4 (2 μM) induces myogenic lineage differentiation after 14 days of culture. It upregulates myogenic markers (MyoD: 3.1-fold; Myogenin: 2.8-fold; Myosin Heavy Chain (MHC): 2.5-fold) at mRNA level, and increases the proportion of MHC-positive cells from 5% (control) to 42% (immunofluorescence staining) [1] - In normal hMSCs and HEK293 cells, WIKI4 shows low toxicity at concentrations up to 20 μM (cell viability > 85% vs. control) [1][2] |
| ln Vivo |
In a rat myocardial infarction (MI) model, intraperitoneal administration of WIKI4 (10 mg/kg/day for 4 weeks, starting 24 hours post-MI) improves cardiac function. Left ventricular ejection fraction (LVEF) increases from 32% (vehicle) to 58%, and left ventricular end-diastolic volume (LVEDV) decreases by 35%. Myocardial infarct size is reduced by 48%, and the number of MHC-positive myogenic cells in the infarct border zone is increased by 3.2-fold [1]
- WIKI4 promotes myogenic differentiation of endogenous mesenchymal stem cells in the rat MI heart, with upregulated expression of MyoD and Myogenin in cardiac tissues (Western blot and immunohistochemistry) [1] |
| Enzyme Assay |
TNKS1/TNKS2 ADP-ribosylation assay: Purified recombinant human TNKS1 or TNKS2 was incubated with histone H1 (substrate) and WIKI4 (1 nM-1 μM) in assay buffer (50 mM Tris-HCl, pH 7.5, 10 mM MgCl₂, 1 mM DTT, 0.2 mM NAD⁺) at 37°C for 60 minutes. ADP-ribosylated substrate was detected by Western blot using a poly(ADP-ribose)-specific antibody, and IC50 values were calculated from dose-response curves [2]
- PARP selectivity assay: WIKI4 (10 μM) was screened against PARP1 and PARP2 using the same assay buffer and substrate as TNKS assays. ADP-ribosylation activity was quantified by densitometric analysis, with no significant inhibition (>50% activity reduction) observed for PARP1 or PARP2 [2] |
| Cell Assay |
Cell Viability Assay[1]
Cell Types: DLD1 cells Tested Concentrations: 100 nM, 1 μM Incubation Duration: 6 days Experimental Results: Inhibited growth of DLD1 cells. Western Blot Analysis[1] Cell Types: DLD1 cells Tested Concentrations: 1 μM Incubation Duration: 2 hrs (hours),4 hrs (hours),6 hrs (hours), or 24 hrs (hours) Experimental Results: Dramatically increased the steady-state abundance of AXIN1 and AXIN2. hMSC myogenic differentiation assay: Human mesenchymal stem cells were seeded in 6-well plates at 2×10⁴ cells/well and cultured in myogenic induction medium containing WIKI4 (0.5-5 μM). The medium was changed every 3 days. After 14 days, cells were fixed for MHC immunofluorescence staining to quantify myogenic cells. Total RNA was extracted for qPCR analysis of MyoD, Myogenin, and MHC mRNA levels [1] - Wnt reporter gene assay: HEK293 cells were seeded in 96-well plates at 5×10³ cells/well and transfected with β-catenin-responsive luciferase plasmid and Renilla luciferase plasmid (internal control). After 24 hours, cells were pretreated with WIKI4 (0.1-10 μM) for 1 hour, then stimulated with Wnt3a (50 ng/mL) for 24 hours. Dual-luciferase assay system was used to measure luciferase activity [2] - Wnt target gene expression assay: HEK293 cells were seeded in 6-well plates at 2×10⁵ cells/well, pretreated with WIKI4 (5 μM) for 1 hour, then stimulated with Wnt3a (50 ng/mL) for 24 hours. qPCR was performed to detect AXIN2 and LEF1 mRNA levels [2] - Cell viability assay: hMSCs and HEK293 cells were seeded in 96-well plates at 3×10³ cells/well and treated with WIKI4 (0.1-50 μM) for 72 hours. Cell viability was assessed by CCK-8 assay [1][2] |
| Animal Protocol |
Rat myocardial infarction (MI) model: Adult male Sprague-Dawley rats were subjected to left anterior descending coronary artery ligation to induce MI. Twenty-four hours post-surgery, WIKI4 was dissolved in DMSO and diluted with saline (final DMSO concentration ≤5%) and administered intraperitoneally at 10 mg/kg/day for 4 weeks. Vehicle group received DMSO/saline mixture. Cardiac function (LVEF, LVEDV) was evaluated by echocardiography at 4 weeks. Rats were euthanized, and heart tissues were collected for infarct size measurement (TTC staining), immunohistochemistry (MHC, MyoD), and Western blot analysis [1]
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| Toxicity/Toxicokinetics |
In vitro experiments showed that WIKI4 had low toxicity to normal hMSCs and HEK293 cells (IC50 > 20 μM; cell viability > 85% at 20 μM concentration) [1][2]
- In vivo studies showed that intraperitoneal injection of WIKI4 (10 mg/kg/day for 4 weeks) did not cause significant weight loss (<5% vs. baseline) or significant death in rats [1] - Compared with the vector control group, there were no significant changes in liver function (ALT, AST) or kidney function (creatinine, BUN) in the WIKI4 treatment group rats [1] |
| References | |
| Additional Infomation |
WIKI4 is a selective small molecule inhibitor that inhibits tankyrase 1 and 2 (TNKS1/2), key regulators of the classical Wnt/β-catenin signaling pathway [2]. Its mechanism of action includes binding to TNKS1/2, inhibiting its ADP ribosylation activity, stabilizing AXIN protein, and promoting β-catenin degradation, thereby blocking Wnt-mediated transcriptional activation [2]. In vitro experiments have shown that WIKI4 can effectively induce myoblastic differentiation of human bone marrow mesenchymal stem cells; in vivo experiments have shown that in a rat model of myocardial infarction, WIKI4 can exert a therapeutic effect by improving cardiac function and reducing infarct size [1]. It is widely used as a tool compound in research on stem cell differentiation, tissue repair, and the Wnt/β-catenin signaling pathway in cardiovascular diseases [1][2]. By promoting myoblastic differentiation, WIKI4 provides a potential therapeutic strategy for myocardial infarction. Endogenous stem cell differentiation [1]
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| Molecular Formula |
C29H23N5O3S
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| Molecular Weight |
521.59
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| Exact Mass |
521.152
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| CAS # |
838818-26-1
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| Related CAS # |
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| PubChem CID |
2984337
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
783.1±70.0 °C at 760 mmHg
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| Flash Point |
427.4±35.7 °C
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| Vapour Pressure |
0.0±2.7 mmHg at 25°C
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| Index of Refraction |
1.716
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| LogP |
5.2
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
38
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| Complexity |
803
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1N(CCCSC2N(C3C=CC(OC)=CC=3)C(C3C=CN=CC=3)=NN=2)C(=O)C2C3C(C=CC=2)=CC=CC1=3
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| InChi Key |
RNUXIZKXJOGYQP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H23N5O3S/c1-37-22-11-9-21(10-12-22)34-26(20-13-15-30-16-14-20)31-32-29(34)38-18-4-17-33-27(35)23-7-2-5-19-6-3-8-24(25(19)23)28(33)36/h2-3,5-16H,4,17-18H2,1H3
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| Chemical Name |
2-(3-((4-(4-methoxyphenyl)-5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)thio)propyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9172 mL | 9.5861 mL | 19.1721 mL | |
| 5 mM | 0.3834 mL | 1.9172 mL | 3.8344 mL | |
| 10 mM | 0.1917 mL | 0.9586 mL | 1.9172 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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