| 包装 | 价格(元) |
| 10mM (in 1mL DMSO) | 电议 |
| 5mg | 电议 |
| 10mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
Cell lines | NCI-H358 and MIA PaCa-2 cell line |
Preparation Method | The phosphorylation of ERK was evaluated by treating cells with different concentrations of AMG-510 for 2 hours. |
Reaction Conditions | 10-4-102uM AMG-510 for 2h |
Applications | In two KRASG12C cell lines, NCI-H358 and MIA PaCa-2, AMG-510 almost completely inhibited p-ERK (IC50 ≈ 0.03 μM) after a 2h treatment and was 20-fold more potent than ARS-1620. |
Animal models | Mice bearing MIA PaCa-2 T2 or CT-26 KRASG12C |
Preparation Method | tumours were treated orally with a single dose of vehicle or with the indicated doses of AMG-510 . Tumours were collected 2 h later or over time as indicated and levels of p-ERK were measured. |
Dosage form | 0.3-100mg/kg AMG-510 for 2-4h |
Applications | In KRAS G12C tumor models, AMG-510 inhibited P-ERK in a dose-dependent manner at 2 h after treatment. |
| 产品描述 | AMG-510 is the first KRAS G12C inhibitor in clinical development and leads to the regression of KRAS G12C tumors[1,3]. AMG-510 did not inhibit wild-type KRAS. AMG-510 irreversibly inhibits KRAS G12C by locking it in an inactive GDP-bound state[4].Amg-510 (Sotorasib) selectively reduced the viability of cell lines containing KRAS p.G12C mutation and showed antitumor activity. In cellular assays, AMG-510 covalently modifies KRAS G12C and inhibits KRAS G12C signaling AMG-510 binds to the KRASG12C cysteine residue to lock the protein in its inactive form, inhibiting cell proliferation and promoting apoptosis[5].In two KRASG12C cell lines, NCI-H358 and MIA PaCa-2, AMG-510 almost completely inhibited p-ERK (IC50 ≈ 0.03 μM) after a 2h treatment and was 20-fold more potent than ARS-1620,AMG 510 also potently impaired cellular viability in both NCI-H358 and MIA PaCa-2 (IC50 ≈ 0.006 μM and 0.009 μM respectively[2]. Disrupting EFR3A or PI4KA reduces phosphatidylinositol-4-phosphate, phosphatidylserine, and KRAS levels at the plasma membrane, as well as oncogenic signaling and tumorigenesis, phenotypes rescued by tethering PI4KA to the plasma membrane.A selective PI4KA inhibitor augments the antineoplastic activity of the KRASG12C inhibitor AMG-510 [5]. In KRAS G12C tumor models, AMG-510 inhibited P-ERK in a dose-dependent manner at 2 h after treatment[2]. When evaluating toxicity, one preclinical study demonstrated that rats receiving 960mg sotorasib daily developed renal toxicity with necrosis and degeneration of kidney tubules, primarily at the proximal tubule[7]. References: |
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