CW-10201
CW-10201 is a KRASG12D and KRASG12V PROTAC degrader with DC50 values of 4.0 nM. CW-10201 induces ubiquitination and degradation of KRASG12D and KRASG12V. CW-10201 mildly inhibits pERK1/2. CW-10201 does not induce degradation of IKZF1 and GSPT1. CW-10201 exhibits anticancer activity against pancreatic cancer and colorectal cancer. CW-10201 can be used for research on pancreatic cancer and colorectal cancer.
(Pink: KRas G12D and KRas G12V ligand (HY-189349); Blue: Cereblon ligand (HY-189348); Black: linker).
Para uso exclusivo en investigación. No vendemos a pacientes.
- Fòrmula: C56H62F3N9O7
- Peso molecular:1030.14
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Actividad biológica
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Actividad biológica
Descripciòn
IC50 & Target
[1]|
KRas G12D 4.0 nM (DC50) |
KRas G12V 4.0 nM (DC50) |
ERK1 |
ERK2 |
Cereblon |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| SW1990 | IC50 |
1.7 nM
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Antiproliferative activity against human SW1990 cells assessed as inhibition of cell growth incubated for 6 days by CellTiter-Glo 3D assay.
Antiproliferative activity against human SW1990 cells assessed as inhibition of cell growth incubated for 6 days by CellTiter-Glo 3D assay.
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42720481 |
| SW-620 | IC50 |
3.9 nM
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Antiproliferative activity against human SW620 cells assessed as inhibition of cell growth incubated for 6 days by CellTiter-Glo 3D assay.
Antiproliferative activity against human SW620 cells assessed as inhibition of cell growth incubated for 6 days by CellTiter-Glo 3D assay.
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42720481 |
In Vitro
CW-10201 (24-48 h) is a potent degrader of both KRASG12D and KRASG12V mutant proteins (DC50 = 4.0 nM for both) in HEK293 and SW620 cell lines, while showing no activity against the CRBN neo-substrates IKZF1 and GSPT1[1].
CW-10201 (6 days) exhibits potent antiproliferative activity against SW1990 and SW620 cancer cell lines with IC50 values of 1.7 nM and 3.9 nM, respectively[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:SW1990 (KRAS G12D mutant) and SW620 (KRAS G12V mutant)
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Concentration:Serially diluted
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Incubation Time:6 days
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Result:Inhibited cell growth with IC50 values of 1.7 nM in SW1990 cells and 3.9 nM in SW620 cells.
Was 3- and 5-times more potent than its corresponding KRAS inhibitor compound 30 in SW1990 and SW620 cell lines, respectively.
Parmacokinetics
| Species | Dose | Route | T1/2 | Cmax | AUC0-t | Vss | CL |
|---|---|---|---|---|---|---|---|
| Mice[1] | 2.0 mg/kg | i.v. | 7.7 h | 836 ng/mL | 2557 ng·h/mL | 5.7 L/kg | 740 mL/h/kg |
In Vivo
CW-10201 (30 mg/kg; i.v.; single dose) reduces KRASG12V protein levels by approximately 50% for up to 48 h and inhibits pERK1/2 by 70% at 6 and 24 h in the SW620 xenograft tumor mouse model[1].
CW-10201 (30-60 mg/kg; i.v.; weekly) achieves 51% and 67% tumor regression, respectively, in SW1990 KRASG12D xenograft model mice without obvious toxicity[1].
CW-10201 (30 mg/kg; i.v.; twice weekly; 4 weeks) achieves 73-74% tumor growth inhibition in the SW620 KRASG12V xenograft mouse model with minimal toxicity[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:CB.17 SCID (female, 90-110 mm3 tumor)[1]
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Dosage:60 mg/kg
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Administration:i.v.; single dose
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Result:Reduced KRASG12D protein levels by >80% at 24, 48, and 96 h and by 74% at 168 h in tumor tissue.
Achieved plasma concentrations of 559 ng/mL at 24 h and <100 ng/mL at 48, 96, and 168 h.
Attained tumor concentrations of 2628 ng/g at 24 h, 1875 ng/g at 48 h, 1400 ng/g at 96 h, and 965 ng/g at 168 h.
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Animal Model:CB.17 SCID (female, 90-110 mm3 tumor)[1]
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Dosage:30 mg/kg
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Administration:i.v.; single dose
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Result:Reduced KRASG12V protein levels by approximately 50% at 6, 24, and 48 h, modestly by 20% at 96 h, and had no effect at 168 h.
Reduced pERK1/2 levels by 70% at 6 and 24 h and by 50% at 48 h.
Achieved plasma concentrations of 1482 ng/mL at 6 h, 129.7 ng/mL at 24 h, 38.7 ng/mL at 48 h, 7.0 ng/mL at 96 h, and 3.9 ng/mL at 168 h.
Achieved tumor concentrations of 2606 ng/g at 6 h, 520.5 ng/g at 24 h, 150.8 ng/g at 48 h, and BLQ at 96 and 168 h.
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Animal Model:CB.17 SCID (female, 220-250 mm3 tumor)[1]
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Dosage:30-60 mg/kg
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Administration:i.v.; weekly
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Result:Achieved 51% tumor regression in the 30 mg/kg group after the second dose.
Achieved 67% tumor regression in the 60 mg/kg group after the second dose.
No significant weight loss or other signs of toxicity observed at doses up to 60 mg/kg.
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Animal Model:CB.17 SCID (female, 90-110 mm3 tumor)[1]
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Dosage:30 mg/kg
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Administration:i.v.; twice weekly; 4 weeks
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Result:Achieved a tumor growth inhibition (TGI) of 73-74% on day 36.
Well tolerated with minimal weight loss.
Chemical Information
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Peso molecular 1030.14
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Fòrmula C56H62F3N9O7
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SMILES
O=C(C(N(C(N(C)C1=C2)=O)C1=CC3=C2C4(CCN(CC5(F)CCN(CC6(COC7=NC(N(CCC8)C[C@]98CCO9)=C(C=NC(C%10=C%11C(CC)=C(F)C=CC%11=CC(O)=C%10)=C%12F)C%12=N7)CC6)CC5)CC4)CO3)CC%13)NC%13=O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
CW-10201 Related Classifications
HY-189305 Related Classifications
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