CH091138
CH091138 is a potent and selective KRASG12D PROTAC degrader with DC50s of 148.3 nM in HeLa cells and 469.8 nM in AsPC-1 cells. CH091138 selectively degrades exogenous and endogenous KRASG12D but not KRASWT or other KRAS mutants (G12C/G12S/G12V), depending on the VHL-mediated ubiquitin-proteasome system. CH091138 exhibits potent anti-tumor activity and induces cancer cell apoptosis. CH091138 can be used for the studies of pancreatic cancer and colon cancer. (Pink: KRASG12D ligand (HY-175144); Blue: VHL E3 ligase ligand (HY-138678); Black: Linker; VHL E3 ligase ligand + Linker (HY-136006B)).
(Pink: KRas G12D ligand (HY-175144); Blue: VHL ligand (HY-138678); Black: linker).
For research use only. We do not sell to patients.
- Formula: C59H69FN10O6S
- Molecular Weight:1065.31
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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 |
KRas G12D |
KRas G12V |
NEP108 3.8 μM (DC50) |
VHL |
CH091138 (0-30 μM, 24 h) blocks KRAS downstream signaling in cells harboring KRASG12D in AsPC1 cells[1].
CH091138 (0.01-100 μM, 3 days) exhibits a GI50 of 0.75 μM in KRASG12D mutant AsPC1 cells[1].
CH091138 (1-30 μM, 24 h) suppresses migration and invasion of AsPC-1[1].
CH091138 (1-10 μM, 24 h-21 d) is capable of suppressing colony formation and induces apoptosis of AsPC-1[1].
CH091138 (0-100 μM, 5 days) suppresses the growth of patient-derived organoids (PDOs) harboring KRASG12D more strongly than those with wild-type KRAS[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:AsPC1-cells
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Concentration:0, 10, 30 μM
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Incubation Time:24 h
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Result:Effectively inhibited KRAS-dependent downstream pathways p-AKT, p-MEK and p-ERK1/2 levels.
Had no effect on other KRAS mutant cells.
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Cell Line:Human-derived organoids (PDOs) with wild-type KRAS (COL-032-T and COL-047-T) and KRASG12D mutation (COL-018-T and COL-049-T)
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Concentration:0, 16.7 and 50 μM
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Incubation Time:5 days
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Result:Exhibited an IC50 of 12.62-33.13 μM for KRASG12D PDO.
Exhibited an IC50 > 50 μM for KRASWT PDO.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Xenograft model bearing AsPC-1 cells established in five-week-old female Balb/C nude mice[1]
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Dosage:60 mg/kg
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Administration:Intraperitoneal injection (i.p.) once every three days for 29 days
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Result:Achieved 61.8 % tumor growth inhibition.
Significantly decreased the average tumor weight and size.
Caused a decrease in KRAS level by up to 76.04 %.
Chemical Information
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Molecular Weight 1065.31
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Formula C59H69FN10O6S
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SMILES
OC1=CC(C=CC=C2C#C)=C2C(C3=C(F)C(N=C(OC[C@@H]4CCCN4CCCCCCC(N[C@H](C(N5[C@H](C(NCC6=CC=C(C7=C(C)N=CS7)C=C6)=O)C[C@@H](O)C5)=O)C(C)(C)C)=O)N=C8N9C[C@H]%10N[C@H](CC%10)C9)=C8C=N3)=C1
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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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