WC-2
WC-2 is an ATP-competitive covalent WRN helicase inhibitor with IC50 values of 252 nM and 250 nM. WC-2 binds covalently to Cys727 of WRN helicase and maintains conformational complementarity with this protein. WC-2 induces p21 transcription as part of the DNA damage response, and selectively reduces the viability of MSI-H cancer cells. WC-2 can be used in the research of MSI-H tumors.
For research use only. We do not sell to patients.
- CAS No.: 3112500-81-6
- Formula: C21H21F3N2O4S
- Molecular Weight:454.46
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Biological Activity
Description
IC50 & Target
[1]|
p21 |
WRN helicase 250-252 nM (IC50) |
In Vitro
WC-2 (11-point 3-fold serial dilutions; 30 min preincubation, 30 min reaction) inhibits full-length WRN helicase ATPase activity (100 μM ATP) with an IC50 of 250 nM[1].
WC-2 inhibits full-length WRN helicase activity with an apparent kinet/Ki value of 1593 M-1s-1[1].
WC-2 (10-point 3-fold serial dilutions; 48 h) induces p21 expression in HCT116 MSI-H colon carcinoma cells with an unbound AC50 of 31 nM[1].
WC-2 (10-point 3-fold serial dilutions; 7 days) selectively inhibits viability of HCT116 MSI-H colon carcinoma cells with an unbound IC50 of 3 nM, while sparing HT29 MSS colon carcinoma cells[1].
WC-2 (1 μM; up to 1185 min) shows very low reactivity with GSH in pH 7.4 buffer, with a half-life of >2400 min[1].
WC-2 (5 μM; up to 240 min) is highly stable in human plasma, with a half-life of >480 min[1].
WC-2 (5 μM; up to 240 min) is highly stable in human whole blood, with a half-life of >480 min[1].
WC-2 (10 μM) exhibits favorable cell penetration in the Caco-2 monolayer system, with an A to B Papp of 3.0 × 10-6 cm/s and an efflux ratio of 1[1].
WC-2 does not significantly inhibit hERG channels, with an IC50 > 10 μM[1].
WC-2 has excellent metabolic stability in human and rat liver microsomes, with intrinsic clearance < 10 μL/min/mg (human) and < 18 μL/min/mg (rat)[1].
WC-2 has favorable metabolic stability in human, rat, and dog hepatocytes, with intrinsic clearance values of 6.3, 18.9, and 25.0 μL/min/106 cells respectively[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:HCT116 (MSI-H colon carcinoma) cells, HT29 (MSS colon carcinoma) cells
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Concentration:10-point 3-fold serial dilutions
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Incubation Time:7 days
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Result:Inhibited viability of HCT116 MSI-H cells with an unbound IC50 of 3 nM and total IC50 of 38 nM.
Showed no antiproliferative activity against HT29 MSS cells (IC50 > 3000 nM).
Parmacokinetics
In Vivo
WC-2 (0.1 mg/kg; i.v.; single dose) exhibits favorable pharmacokinetic properties in male beagle dogs, including an 18.9 h in vivo half-life[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley (male)[1]
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Dosage:0.5 mg/kg (i.v.); 2.5 mg/kg (p.o.)
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Administration:i.v.; single dose; p.o.; single dose
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Result:Achieved a total clearance of 11 mL/min/kg.
Achieved an in vivo half-life of 7.2 h.
Achieved a volume of distribution at steady state of 4.7 L/kg.
Achieved an oral bioavailability of 62%.
Achieved an oral AUC0-last of 2233 hr·ng/mL.
Achieved an oral Cmax of 133 ng/mL.
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Animal Model:Beagle (male)[1]
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Dosage:0.1 mg/kg
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Administration:i.v.; single dose
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Result:Achieved a total clearance of 4.1 mL/min/kg.
Achieved an in vivo half-life of 18.9 h.
Achieved a volume of distribution at steady state of 5.0 L/kg.
Chemical Information
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CAS No. 3112500-81-6
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Molecular Weight 454.46
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Formula C21H21F3N2O4S
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SMILES
O=C(N[C@@H](C1CC1)/C=C(F)/S(C)(=O)=O)C2=CC=C(C(C)(F)F)C(OC3=CC=CC=C3)=N2
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Genotoxicity/Mutagenicity Study
The bacterial reverse mutation assay detects point mutations that restore amino-acid prototrophy in auxotrophic Salmonella typhimurium or Escherichia coli tester strains; after exposure to a test article, mutagenic activity is read out as an increased number of revertant colonies on minimal agar compared with the vehicle control. The assay uses tester strains with different mutation targets so that base-substitution and frameshift mutagens can be detected, and testing is performed with and without exogenous mammalian metabolic activation because some chemicals require biotransformation to become mutagenic.
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Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
WC-2 Related Classifications
HY-189009 Related Classifications
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