| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
WRN helicase (Werner syndrome RecQ helicase). It also suppresses WRN ATPase activity in a dose-dependent manner. It shows no significant inhibition against other helicases such as BLM, FANCJ, ChlR1, RecQ, and UvrD.
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| ln Vitro |
In HeLa cells, NSC 617145 (0.75-3 μM; 24-72 hours) exhibits WRN-specific maximum suppression of growth (98%) at the lowest concentration[1]. Protease-induced WRN binding to chromatin and proteasomal breakdown is induced by NSC 617145 (0.75 μM; 6 hours)[1]. NSC 617145 (0.125 μM) functions in concert with extremely low concentrations of Mitomycin C in FA-D2-/-cells to suppress proliferation in a way that is dependent on WRN and to cause chromosomal aberrations and double-strand breaks (DSB). In mitomycin C-treated FA-deficient cells exposed to NSC 617145, there is an increased build-up of Rad51 foci and DNA-PKcs pS2056 foci. This suggests that WRN helicase inhibition inhibits the processing of Rad51-mediated recombination products and triggers NHEJ[1]. Adult T-cell leukemia cells transformed by the human T-cell leukemia virus type 1 (HTLV-1) undergo cell cycle arrest and death when exposed to NSC 617145[2].
In HeLa cells, NSC 617145 (0.75-3 µM; 24-72 hours) shows maximal inhibition of proliferation (98%) at the lowest concentration in a WRN-specific manner. At 0.75 µM for 6 hours, it induces WRN binding to chromatin and proteasomal degradation. In FA-D2-/- cells, it acts synergistically with very low concentrations of Mitomycin C to inhibit proliferation in a WRN-dependent manner and induce double-strand breaks and chromosomal abnormalities. It also induces cell cycle arrest and apoptosis in HTLV-1-transformed adult T-cell leukemia cells. |
| ln Vivo |
In vivo activity data for NSC 617145 is not extensively detailed in standard reference sources. As a WRN helicase inhibitor, it is expected to exhibit antitumor efficacy in xenograft models, particularly when combined with DNA-damaging agents such as Mitomycin C, based on its mechanism of action.
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| Enzyme Assay |
In vitro enzyme assays typically involve measuring the inhibition of WRN helicase activity using a fluorescence-based or gel-based DNA unwinding assay with recombinant WRN protein and a labeled DNA substrate, with IC50 values calculated from dose-response curves. ATPase activity is measured using a malachite green phosphate detection assay.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: HeLa cells Tested Concentrations: 0.75 μM, 1 μM, 1.5 μM, 2 μM, 3 μM Incubation Duration: 24 hrs (hours), 48 hrs (hours), 72 hrs (hours) Experimental Results: Inhibited cell proliferation in a WRN-specific manner. Western Blot Analysis[1] Cell Types: HeLa cells Tested Concentrations: 0.75 μM Incubation Duration: 6 hrs (hours) Experimental Results: Caused WRN to become degraded by a proteasome-mediated pathway. In vitro cell viability is assessed using standard assays such as MTT or CellTiter-Glo in HeLa or FA-D2-/- cells treated with various concentrations of the compound for 24-72 hours. WRN protein degradation and chromatin binding are analyzed by Western blotting after treatment. Synergy with Mitomycin C is evaluated via combination index analysis. |
| Animal Protocol |
In vivo efficacy studies are typically conducted in mouse xenograft models using tumor-bearing immunodeficient mice. Compound is formulated in a suitable vehicle such as 5% DMSO, 40% PEG300, 5% Tween 80, and 50% ddH2O. Tumor volume and body weight are monitored, followed by histopathological and biochemical analyses of tumor tissues.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of NSC 617145 are not extensively detailed in standard references. Based on its physicochemical properties (MW 400.04, LogP estimated ~2-3), it is expected to have moderate oral bioavailability. Typical in vivo formulations use a clear solution with 5% DMSO, 40% PEG300, 5% Tween 80, and 50% ddH2O for administration.
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| Toxicity/Toxicokinetics |
Detailed toxicological profiles of NSC 617145 are not extensively reported in the literature. As a research compound targeting DNA damage repair pathways, it may exhibit cytotoxicity at higher concentrations. In vivo studies have reported no significant effect on body weight at efficacious doses in mouse xenograft models, suggesting a manageable safety profile under experimental conditions.
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| References |
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| Additional Infomation |
NSC 617145 is a research-grade WRN helicase inhibitor used primarily in preclinical studies to explore DNA repair mechanisms and anticancer strategies. It acts synergistically with mitomycin C to inhibit proliferation in a WRN-dependent manner. It is not approved for clinical use and is available only for research purposes. Its molecular formula is C13H10Cl4N2O4 and its molecular weight is 400.04.
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| Molecular Formula |
C13H10CL4N2O4
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|---|---|
| Molecular Weight |
400.04
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| Exact Mass |
397.939
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| Elemental Analysis |
C, 39.03; H, 2.52; Cl, 35.45; N, 7.00; O, 16.00
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| CAS # |
203115-63-3
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| PubChem CID |
357621
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| Appearance |
Light yellow to brown solid powder
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| LogP |
2.004
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
23
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| Complexity |
605
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1=C(C(N(C1=O)CC(C)(C)CN1C(C(=C(C1=O)Cl)Cl)=O)=O)Cl
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| InChi Key |
PCOXPBOKDABARQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H10Cl4N2O4/c1-13(2,3-18-9(20)5(14)6(15)10(18)21)4-19-11(22)7(16)8(17)12(19)23/h3-4H2,1-2H3
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| Chemical Name |
3,4-dichloro-1-[3-(3,4-dichloro-2,5-dioxopyrrol-1-yl)-2,2-dimethylpropyl]pyrrole-2,5-dione
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| Synonyms |
NSC 617145; NSC-617145; NSC617145
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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 : ~10 mg/mL (~25 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (4.17 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 16.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4998 mL | 12.4988 mL | 24.9975 mL | |
| 5 mM | 0.5000 mL | 2.4998 mL | 4.9995 mL | |
| 10 mM | 0.2500 mL | 1.2499 mL | 2.4998 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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