AM-8719
AM-8719 is an orally active, blood-brain barrier-penetrant KRASG12C inhibitor. AM-8719 binds covalently to KRASG12C, inhibits SOS1-catalyzed GDP/GTP exchange, and suppresses downstream ERK phosphorylation. AM-8719 exhibits antiproliferative activity against KRASG12C tumor cells. AM-8719 can be used for the research of KRASG12C-positive cancers.
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- CAS No.: 3034975-33-9
- Formule: C31H40F3N7O3
- Masse moléculaire:615.69
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
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Activité biologique
Description
IC50 & Target
[1]|
KRAS(G12C) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MIA PaCa-2 | IC50 |
0.157 μM
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Inhibition of ERK1/2 phosphorylation in MIA PaCa-2 (KRAS G12C) cells assessed by p-ERK1/2 MSD immunoassay after 2 h incubation.
Inhibition of ERK1/2 phosphorylation in MIA PaCa-2 (KRAS G12C) cells assessed by p-ERK1/2 MSD immunoassay after 2 h incubation.
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42593915 |
| MIA PaCa-2 | IC50 |
0.082 μM
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Reduction of cell viability in MIA PaCa-2 (KRAS G12C) cells assessed by CellTiter-Glo luminescence viability assay after 72 h incubation.
Reduction of cell viability in MIA PaCa-2 (KRAS G12C) cells assessed by CellTiter-Glo luminescence viability assay after 72 h incubation.
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42593915 |
In Vitro
AM-8719 (compound 27) potently inhibits SOS1-catalyzed GDP/GTP exchange in purified KRASG12C/c-RAF Ras-binding domain protein, with an IC50 of 0.034 μM; it also inhibits ERK1/2 phosphorylation in MIA PaCa-2 (KRASG12C) cells, with an IC50 of 0.157 μM[1].
AM‑8719 (1 μM) exhibits a Pgp efflux ratio of 3 in MDCK‑hMDR1 cells[1].
AM-8719 covalently alkylates KRASG12C with a kinact/Ki value of 1123 M-1s-1; its passive permeability in MDCK cells expressing hMDR1 is 13 μcm/s[1].
AM-8719 (incubated for 72 h) reduces the viability of MIA PaCa-2 cells harboring the KRASG12C mutation, with an IC50 value of 0.082 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
| Species | Dose | Route | CL | Vss | T1/2 | Bioavailability | F |
|---|---|---|---|---|---|---|---|
| Mice[1] | 1 mg/kg | i.v. | 0.3 L/h/kg | 0.64 L/kg | 2.4 h | / | / |
| Rat[1] | 1 mg/kg | i.v. | 2.9 L/h/kg | 5.0 L/kg | 3.1 h | / | / |
| Dog[1] | 0.5 mg/kg | i.v. | 1.3 L/h/kg | 2.8 L/kg | 3.5 h | / | / |
| Rat[1] | 5 mg/kg | p.o. | / | / | / | / | 78 % |
| Mice[1] | 5 mg/kg | p.o. | / | / | / | 53 % | / |
| Dog[1] | 2 mg/kg | p.o. | / | / | / | 33 % | / |
In Vivo
AM-8719 (30 mg/kg; p.o.; single administration) exhibits favorable central nervous system penetration in healthy mice and rats, with unbound brain-to-plasma concentration ratios of 0.2 and 0.1, respectively[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 3034975-33-9
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Masse moléculaire 615.69
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Formule C31H40F3N7O3
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SMILES
COC1(COC1)C2=NC=CC(C)=C2C(CC3)CCN3C4=CC(N5C[C@H]([C@H]5C)N(CC6)CCN6C(C=C)=O)=NC(C(F)(F)F)=N4
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
AM-8719 Related Classifications
HY-187998 Related Classifications
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