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| Targets |
G244-LM selectively targets the poly(ADP-ribose) polymerase (PARP) catalytic domains of both tankyrase 1 and tankyrase 2 (TNKS1/2). Tankyrases are proteins that regulate the stability of AXIN, a key component of the β-catenin destruction complex. By inhibiting tankyrase activity, G244-LM prevents the PARylation and subsequent degradation of AXIN, thereby stabilizing the destruction complex and promoting the degradation of β-catenin. This results in the suppression of Wnt/β-catenin signaling, a pathway frequently hyperactive in various cancers.
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| ln Vitro |
G244-LM demonstrates potent in vitro activity as a specific inhibitor of tankyrase 1/2. In cell-based reporter assays, it effectively inhibits Wnt3a-induced signaling in both HEK293 human and 10T1/2 mouse cells. The compound has been shown to fully block ligand-driven Wnt/β-catenin signaling in cell culture and exhibits approximately 50% inhibition of APC mutation-driven signaling in most colorectal cancer (CRC) cell lines. Its specificity for tankyrase makes it a valuable tool for studying the role of this enzyme and the Wnt pathway in cancer biology.
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| ln Vivo |
In vivo activity of G244-LM has been demonstrated in preclinical models. As a potent and specific tankyrase inhibitor, it has been shown to suppress the growth of tumors driven by APC mutations. By stabilizing AXIN and reducing Wnt/β-catenin signaling, G244-LM can inhibit tumor progression in vivo. These findings highlight its potential as a therapeutic agent for cancers with hyperactive Wnt signaling, such as colorectal cancer. Further in vivo studies are required to fully characterize its pharmacokinetic and pharmacodynamic profile.
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| Enzyme Assay |
In vitro enzyme assays for G244-LM typically measure its inhibitory activity against tankyrase 1 and tankyrase 2. These assays often use purified recombinant enzymes and quantify the inhibition of auto-PARsylation or the PARsylation of a substrate like AXIN. The compound's potency (IC50) is determined by measuring enzyme activity in the presence of increasing concentrations of G244-LM.
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| Cell Assay |
In vitro cellular assays for G244-LM involve treating Wnt-sensitive cell lines, such as HEK293 or SW480 colorectal cancer cells, with the compound. The effect on Wnt/β-catenin signaling is commonly assessed using luciferase reporter assays (e.g., SuperTOPFlash) to measure transcriptional activity. Additionally, the stabilization of AXIN protein and the subsequent decrease in β-catenin levels can be confirmed by Western blotting. The compound's impact on cell proliferation and viability is also evaluated in these assays.
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| Animal Protocol |
In vivo animal experiments for G244-LM typically involve administering the compound to mouse models of cancer, such as xenografts or genetically engineered models of APC-mutant colorectal cancer. Tumor growth is monitored over time, and at the end of the study, tumors are analyzed for biomarkers of Wnt pathway inhibition, including AXIN and β-catenin levels. The compound's efficacy is evaluated by measuring tumor growth inhibition, and its tolerability is assessed through monitoring body weight and other clinical signs.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for G244-LM are available from preclinical studies. The compound is soluble in DMSO (6.25 mg/mL). For in vivo use, it can be formulated in a vehicle such as 10% DMSO, 40% PEG300, and 5% Tween-80. The recommended storage for the powder is -20°C for up to 3 years, and for solutions, -80°C for up to 1 year. Comprehensive ADME (Absorption, Distribution, Metabolism, and Excretion) data are not detailed in the provided sources.
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| Toxicity/Toxicokinetics |
G244-LM is for research use only and is not for human therapeutic application. Its purity is typically >98%. The compound is a valuable chemical probe for studying the biological functions of tankyrase and the Wnt/β-catenin signaling pathway in the context of cancer and other diseases. It is a controlled substance and not for sale in some territories.
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| References | |
| Additional Infomation |
G244-LM (CAS#: 1563007-08-8) has a molecular weight of 406.52. It is a potent and specific small-molecule tankyrase 1/2 inhibitor that effectively suppresses Wnt signaling by preventing AXIN degradation and promoting β-catenin destabilization. This compound serves as a critical research tool for investigating the role of the Wnt pathway in tumorigenesis.
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| Molecular Formula |
C18H22N4O3S2
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| Molecular Weight |
406.52
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| Exact Mass |
406.113
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| Elemental Analysis |
C, 53.18; H, 5.46; N, 13.78; O, 11.81; S, 15.77
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| CAS # |
1563007-08-8
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| PubChem CID |
136267814
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Index of Refraction |
1.727
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| LogP |
0.04
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
27
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| Complexity |
764
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(N2CCN(C3=CC=CC=C3S(C)(=O)=O)CC2)NC(=O)C2CSCCC=2N=1
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| InChi Key |
JSQPAEVPPSCQMV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H22N4O3S2/c1-27(24,25)16-5-3-2-4-15(16)21-7-9-22(10-8-21)18-19-14-6-11-26-12-13(14)17(23)20-18/h2-5H,6-12H2,1H3,(H,19,20,23)
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| Chemical Name |
2-[4-(2-methylsulfonylphenyl)piperazin-1-yl]-3,5,7,8-tetrahydrothiopyrano[4,3-d]pyrimidin-4-one
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| Synonyms |
G244-LM
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
DMSO : ~6.3 mg/mL (~15.4 mM)
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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 | 2.4599 mL | 12.2995 mL | 24.5990 mL | |
| 5 mM | 0.4920 mL | 2.4599 mL | 4.9198 mL | |
| 10 mM | 0.2460 mL | 1.2300 mL | 2.4599 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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