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.
Cas No.: 2252403-56-6
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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. |
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.
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. |
Prepare stock solution | |||
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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
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