| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
WRN ( IC50 = 0.06 µM )
Werner syndrome RecQ helicase-IN-3 targets Werner syndrome RecQ DNA helicase (WRN). WRN is a DNA helicase and exonuclease that plays a critical role in maintaining genomic integrity. The compound selectively inhibits WRN helicase activity. It blocks WRN's ATPase/helicase activity. |
|---|---|
| ln Vitro |
RecQ helicase-IN-3 (example 96) for Werner syndrome exhibits anti-proliferative action at GI50s of >10 µM for DLD1 WRN-KO cells and 0.06 for SW48 cells, respectively, during 8–20 days [1].
Werner syndrome RecQ helicase-IN-3 shows antiproliferative activity in cancer cell lines. It inhibits WRN with an IC50 of 0.06 μM. The compound induces replication stress, DNA damage accumulation, and cell cycle arrest, suppressing tumor cell proliferation. |
| ln Vivo |
Mice treated daily for 22 days with 120 mg/kg of Werner syndrome RecQ helicase-IN-3 exhibit antitumor action [1].
Mice treated daily for 22 days with 120 mg/kg of Werner syndrome RecQ helicase-IN-3 exhibit antitumor action. This demonstrates the compound's in vivo efficacy in suppressing tumor growth. Further studies are needed to fully characterize its efficacy in various cancer models. |
| Enzyme Assay |
In vitro enzyme assays measure WRN helicase inhibition using recombinant WRN enzyme. IC50 values are determined by assessing helicase or ATPase activity in the presence of varying concentrations of the inhibitor. Antiproliferative activity is assessed in cell lines.
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: SW48, DLD1 WRN-KO cells Tested Concentrations: 0-10 µM Incubation Duration: 8-20 days Experimental Results: demonstrated antiproliferative activity with GI50s of 0.06, >10 µM for SW48, DLD1 WRN-KO cells, respectively. Cell-based assays measure antiproliferative activity in cancer cell lines. Cell cycle analysis and DNA damage markers are assessed to confirm the mechanism of action. The compound's ability to induce replication stress and cell cycle arrest is evaluated. |
| Animal Protocol |
Animal/Disease Models: Female Crl:NU(NCr)-Foxn1nu -Homozygous nude mice (SW48 xenografts cells)[1]
Doses: 120 mg/kg Route of Administration: Po ; daily for 22 days Experimental Results: Inhibited tumor growth. In vivo efficacy is evaluated in mice treated daily for 22 days with 120 mg/kg of Werner syndrome RecQ helicase-IN-3. Antitumor activity is assessed by measuring tumor growth inhibition. The compound is orally active. |
| ADME/Pharmacokinetics |
Werner syndrome RecQ helicase-IN-3 is orally active. In mice, it is administered at 120 mg/kg daily for 22 days. The compound shows good oral bioavailability and antitumor activity. Further pharmacokinetic studies are needed to fully characterize its ADME properties.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data for Werner syndrome RecQ helicase-IN-3 are limited. As a WRN inhibitor, it may have on-target effects related to DNA replication stress. Standard laboratory safety precautions should be followed. Further toxicological studies are needed for comprehensive safety assessment.
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| References | |
| Additional Infomation |
Werner syndrome RecQ helicase-IN-3 is a potent and orally active WRN inhibitor with an IC50 of 0.06 μM. It shows antiproliferative and anticancer activity by blocking WRN's helicase activity, disrupting DNA replication and repair, and causing cell cycle arrest. The compound is a valuable research tool for studying WRN biology and has potential therapeutic applications in cancers with WRN dependency.
|
| Molecular Formula |
C31H30CLF3N8O5
|
|---|---|
| Molecular Weight |
687.068715572357
|
| Exact Mass |
686.2
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| CAS # |
2869954-98-1
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| PubChem CID |
166140846
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| Appearance |
White to off-white solid powder
|
| LogP |
4.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
7
|
| Heavy Atom Count |
48
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| Complexity |
1290
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
C12=NC(C3=CCOCC3)=NN1C(=O)C(N1CCN(C(C3=NC=CC=C3O)=O)CC1)=C(CC)N2CC(NC1=CC=C(C(F)(F)F)C=C1Cl)=O
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| InChi Key |
JXPFVKAENGSGMB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C31H30ClF3N8O5/c1-2-22-26(40-10-12-41(13-11-40)28(46)25-23(44)4-3-9-36-25)29(47)43-30(38-27(39-43)18-7-14-48-15-8-18)42(22)17-24(45)37-21-6-5-19(16-20(21)32)31(33,34)35/h3-7,9,16,44H,2,8,10-15,17H2,1H3,(H,37,45)
|
| Chemical Name |
-[2-chloro-4-(trifluoromethyl)phenyl]-2-[2-(3,6-dihydro-2H-pyran-4-yl)-5-ethyl-6-[4-(3-hydroxypyridine-2-carbonyl)piperazin-1-yl]-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4-yl]acetamide
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| Synonyms |
Werner syndrome RecQ helicase-IN-3
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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 |
| 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 : ~62.5 mg/mL (~91 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.03 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.03 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.03 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4555 mL | 7.2773 mL | 14.5546 mL | |
| 5 mM | 0.2911 mL | 1.4555 mL | 2.9109 mL | |
| 10 mM | 0.1455 mL | 0.7277 mL | 1.4555 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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