YF135
YF135 is an efficient and reversible-covalent KRASG12C PROTAC. YF135 is designed and synthesized by tethering KRAS G12C inhibitor 48 (compound 6d) as the ligand, and basing on the scaffold of MRTX849 linkage VHL ligand. YF135 significantly induces the degradation of KRASG12C in a reversible manner and decreases phospho-ERK level through the E3 ligase VHL mediated proteasome pathway.
(Pink: KRas G12C ligand (HY-146061); Blue: VHL ligand (HY-125845); Black: linker).
For research use only. We do not sell to patients.
- CAS No.: 2913177-53-2
- Formula: C63H75ClN12O7S
- Molecular Weight:1179.86
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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
- Purity & Documentation
- References
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Biological Activity
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KRas G12C |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| NCI-H23 | IC50 |
243.9 nM
Compound: YF135
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Antiproliferative activity against human NCI-H23 cells harboring KRAS G12C mutant measured after 72 hrs by CCK-8 assay
Antiproliferative activity against human NCI-H23 cells harboring KRAS G12C mutant measured after 72 hrs by CCK-8 assay
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[PMID: 35007863] |
| NCI-H358 | IC50 |
153.9 nM
Compound: YF135
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Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C mutant measured after 72 hrs by CCK-8 assay
Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C mutant measured after 72 hrs by CCK-8 assay
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[PMID: 35007863] |
YF135 inhibits the proliferation of H358 and H23 cells with IC50 values of 153.9 and 243.9 nM, respectively[1].
YF135 obviously decreases the protein level of KRASG12C and phospho-ERK in H358 and H23 cells in a time (3 μM, 0-36 h) and dose (0-10 μM, 24 h) dependent manner, while the washout by fresh medium significantly rescues such effects[1].
YF135 induces degradation of KRASG12C through the E3 ligase VHL mediated proteasome pathway. YF135 covalently bind to KRASG12C and VHL ligase to form a ternary complex[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:lung cancer cell lines H358, H23 and A549 [1]
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Concentration:0, 0.3, 1, 3, 10 μM
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Incubation Time:0, 12, 24, 36 h
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Result:Obviously decreased the protein level of KRASG12C and phospho-ERK in a time (3 μM, 0-36 h) and dose (0-10 μM, 24 h) dependent manner, with DC50 values of 3.61, 1.68 μM in H358 cells, respectively, and 4.53, 1.44 μM in H23 cells, respectively.
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Cell Line:lung cancer cell lines H358, H23 and A549 [1]
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Concentration:3 μM
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Incubation Time:24 h
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Result:Induced the significant degradation on KRASG12C and decreased the level of phospho-ERK, while the washout by fresh medium significantly rescued such effects.
Chemical Information
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CAS No. 2913177-53-2
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Molecular Weight 1179.86
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Formula C63H75ClN12O7S
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SMILES
CC1=C(SC=N1)C2=CC=C(C=C2)CNC([C@@H]3C[C@H](CN3C([C@H](C(C)(C)C)NC(CCOCCCN4CCC[C@H]4COC5=NC6=C(C(N7CCN([C@H](C7)CC#N)C(/C(C#N)=C/C8CC8)=O)=N5)CCN(C6)C9=CC=CC%10=C9C(Cl)=CC=C%10)=O)=O)O)=O
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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)
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