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.
All DNA/RNA Synthesis Isoforms
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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.
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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.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)