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AMG-510 racemate

Catalog No.GC19546

Sotorasib (AMG-510) racemate is the racemate of Sotorasib (AMG-510). AMG-510 is a potent, orally bioavailable, and selective KRAS G12C covalent inhibitor with anti-tumor activity.

Products are for research use only. Not for human use. We do not sell to patients.

AMG-510 racemate Chemical Structure

Cas No.: 2252403-56-6

Size Price Stock Qty
10mM (in 1mL DMSO)
$60.00
In stock
5mg
$49.00
In stock
10mg
$81.00
In stock
50mg
$315.00
In stock
100mg
$495.00
In stock

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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment [1]:

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 -102 uM 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 experiment [2]:

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.

References:

[1]. Canon J, Rex K, et,al. The clinical KRAS(G12C) inhibitor AMG-510 drives anti-tumour immunity. Nature. 2019 Nov;575(7781):217-223. doi: 10.1038/s41586-019-1694-1. Epub 2019 Oct 30. PMID: 31666701.

Background

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:
[1]: DOI: 10.1200/JCO.2019.37.15_suppl.3003 Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019) 3003-3003.Published online May 26, 2019.
[2]: Canon J, Rex K,et,al. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature. 2019 Nov;575(7781):217-223. doi: 10.1038/s41586-019-1694-1. Epub 2019 Oct 30. PMID: 31666701.
[3]: Barbacid M. ras genes. Annu Rev Biochem. 1987;56:779-827. doi: 10.1146/annurev.bi.56.070187.004023. PMID: 3304147.
[4]: Lanman BA, Allen JR,et,al. Discovery of a Covalent Inhibitor of KRASG12C (AMG 510) for the Treatment of Solid Tumors. J Med Chem. 2020 Jan 9;63(1):52-65. doi: 10.1021/acs.jmedchem.9b01180. Epub 2019 Dec 24. PMID: 31820981.
[5]: Adhikari H, Kattan WE,et,al. Oncogenic KRAS is dependent upon an EFR3A-PI4KA signaling axis for potent tumorigenic activity. Nat Commun. 2021 Sep 9;12(1):5248. doi: 10.1038/s41467-021-25523-5. PMID: 34504076; PMCID: PMC8429657.
[6]: AMG 510 Shows Activity beyond NSCLC. Cancer Discov. 2020 Aug;10(8):1084-1085. doi: 10.1158/2159-8290.CD-NB2020-061. Epub 2020 Jun 15. PMID: 32540954.
[7]: Werner JA, Davies R,et,al. Mercapturate pathway metabolites of sotorasib, a covalent inhibitor of KRASG12C, are associated with renal toxicity in the Sprague Dawley rat. Toxicol Appl Pharmacol. 2021 Jul 15;423:115578. doi: 10.1016/j.taap.2021.115578. Epub 2021 May 15. PMID: 34004237.

Chemical Properties

Cas No. 2252403-56-6 SDF
Canonical SMILES O=C(C=C)N1C[C@H](C)N(C2=NC(N(C3=C(C)C=CN=C3C(C)C)C4=C2C=C(F)C(C5=C(O)C=CC=C5F)=N4)=O)CC1
Formula C₃₀H₃₀F₂N₆O₃ M.Wt 560.59
Solubility 50 mg/ml in DMSO (Need ultrasonic); Insoluble in Water Storage Store at -20°C, stored under nitrogen
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 1.7838 mL 8.9192 mL 17.8383 mL
5 mM 0.3568 mL 1.7838 mL 3.5677 mL
10 mM 0.1784 mL 0.8919 mL 1.7838 mL
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Average Rating: 5 ★★★★★ (Based on Reviews and 39 reference(s) in Google Scholar.)

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