YN14-H
YN14-H is a potent mutant KRASG12C PROTAC degrader. The DC50 values of YN14-H in NCI-H358 and MIA PaCa-2 cells are 28.9 nM and 18.1 nM, respectively, with corresponding IC50 values of 42 nM and 21 nM. YN14-H degrades KRASG12C in a ubiquitin-proteasome system-dependent manner, thereby significantly inducing apoptosis and inhibiting cell migration. YN14-H can be used for targeting tumors with KRASG12C mutations (such as non-small cell lung cancer, pancreatic cancer, etc.).
(Pink: KRas G12C ligand (HY-173252); Blue: VHL ligand (HY-125905); Black: linker).
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- Fòrmula: C65H78F3N11O8S
- Peso molecular:1230.44
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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KRAS(G12C) 28.9 nM (DC50, NCI-H358) |
KRAS(G12C) 18.1 nM (DC50, MIA PaCa-2) |
YN14-H (500 ns) promotes the formation of more stable interactions in the KRASG12C-VHL ternary complex, which is evidenced by a binding free energy of -158.12 kJ/mol and the presence of 10 stable hydrogen-bond interactions between the two proteins[1].
YN14-H (0.01 nM-1 μM) induces the formation of the KRASG12C-VHL ternary complex with high affinity, with a dissociation constant Kd of 18.8 nM[1].
YN14-H (0-5 μM) potently induces the KRASG12C-VHL protein-protein interaction, which is validated by a strong relative AlphaScreen luminescent signal[1].
YN14-H (1 μM; 8 h) most effectively promotes the interaction between endogenous KRASG12C and VHL in NCI-H358 cells[1].
YN14-H (1 nM-10 μM; 72 h) potently degrades KRASG12C protein in NCI-H358 and MIA PaCa-2 cells, with a DC50 of 28.9 nmol/L in the former and 18.1 nmol/L in the latter, and achieves a maximal degradation rate of over 95% in both cell types[1].
YN14-H (0-10 μM; 72 h) potently inhibits the proliferation of NCI-H358 (IC50 = 0.042 μmol/L) and MIA PaCa-2 (IC50 = 0.021 μmol/L) cells, whereas it exhibits no cytotoxicity in non-KRASG12C cells even at concentrations up to 10 μmol/L[1].
YN14-H (0.01-1 μM; 48 h) potently inhibits the levels of phosphorylated AKT and ERK in a concentration-dependent manner in NCI-H358 and MIA PaCa-2 cells[1].
YN14-H (100 nM; 12 h) potently inhibits the migratory capacity of NCI-H358 and MIA PaCa-2 cells[1].
YN14-H (100 nM; 48 h) induces apoptosis in 35.19% of NCI-H358 cells and 55.19% of MIA PaCa-2 cells, and its efficacy is superior to that of other tested degraders[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:NCI-H358 and MIA PaCa-2
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Concentration:1 nM, 3.3 nM, 10 nM, 33 nM, 100 nM, 330 nM, 1 μM, 3.3 μM, 10 μM
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Incubation Time:72 h
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Result:Significantly degraded the KRASG12C protein in a concentration-dependent manner, with a maximum degradation rate exceeding 98%.
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Cell Line:NCI-H358 and MIA PaCa-2
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Concentration:0.01, 0.1, 1 μM
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Incubation Time:48 h
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Result:Significantly inhibited the phosphorylation of downstream signaling molecules AKT and ERK in a concentration-dependent manner.
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Cell Line:NCI-H358 and MIA PaCa-2
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Concentration:100 nM
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Incubation Time:48 h
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Result:Significantly induced apoptosis in both tumor cell lines, demonstrating superior pro-apoptotic ability compared to other tested compounds.
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Cell Line:NCI-H358 and MIA PaCa-2
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Concentration:100 nM
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Incubation Time:12 h
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Result:Significantly inhibited the migration and wound closure of tumor cells.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude (male, xenograft model with 5 x 106 NCI-H358 cells)[1]
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Dosage:10 mg/kg; 30 mg/kg
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Administration:i.p.; once daily; 20 days
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Result:Achieved a tumor growth inhibition (TGI) rate of 88.68% at 10 mg/kg at 14 days post-treatment.
Induced marked tumor regression with a TGI of 95.4% at 30 mg/kg at 14 days post-treatment.
Reduced tumor volume to approximately 500 mm3 in the 10 mg/kg group by day 20.
Caused complete tumor regression in the 30 mg/kg group by day 20.
Reduced KRASG12C protein levels in tumor tissue to a greater extent than YN14 at matching doses.
Reduced the percentage of Ki67-positive and CD31-positive tumor cells with greater potency than YN14 at matching doses.
Increased the percentage of cleaved caspase 3-positive tumor cells with greater potency than YN14 at matching doses.
Showed no obvious body weight loss or toxic signs during treatment.
Chemical Information
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Peso molecular 1230.44
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Fòrmula C65H78F3N11O8S
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SMILES
O=C([C@H]1N(C([C@@H](NC(C2(F)CC2)=O)C(C)(C)C)=O)C[C@H](O)C1)NCC3=CC=C(C4=C(C)N=CS4)C=C3OCCCN5CCC(COC6=CC=CC(F)=C6C7=C(F)C=C(C(N8[C@@H](C)CN(C(C=C)=O)CC8)=N9)C(N(C%10=C(C)C=CN=C%10C(C)C)C9=O)=N7)CC5
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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)
YN14-H Related Classifications
HY-173250 Related Classifications
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