AMG-510 racemate |
Catalog No.GC19546
One-Click Copy Product Info
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AMG-510 is the first KRAS G12C inhibitor in clinical development and leads to the regression of KRAS G12C tumors.
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.
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AMG-510 racemate is a covalent inhibitor of KRAS G12C. AMG-510 racemate selectively and irreversibly binds to cysteine residue 12 of mutant KRAS G12C protein. This binding locks KRAS in an inactive GDP-bound state. AMG-510 racemate thereby blocks downstream RAF-MEK-ERK signaling pathway. AMG-510 racemate suppresses tumor cell proliferation and induces apoptosis. AMG-510 racemate can be used for research on KRAS G12C-mutant non-small cell lung cancer and colorectal cancer[1-3].
In vitro, treatment of NCI-H358 cells with 25-50nM AMG-510 racemate for 24-72 hours reduced mRNA expression levels of CDK4, CDK6, Cyclin D1 and β-catenin[4].
In vivo, oral administration of 10-100mg/kg AMG-510 racemate to athymic nude mice subcutaneously implanted with MIA PaCa-2 T2 cells for 2 weeks inhibited tumor growth and caused tumor regression. AMG-510 racemate reduced ERK phosphorylation levels in tumor tissues[5].
References:
[1] Pantsar T. KRAS(G12C)-AMG 510 interaction dynamics revealed by all-atom molecular dynamics simulations. Sci Rep. 2020 Jul 20;10(1):11992.
[2] Xia Y, Ji X, Jang IS, et al. Genetic and pharmacological interrogation of cancer vulnerability using a multiplexed cell line screening platform. Commun Biol. 2021 Jul 2;4:834.
[3] Jiang Y, Zhou K, Wei X, et al. RAC1 directly phosphorylates both PKM2 and FBP1 to promote radioresistance in hepatocellular carcinoma. Mol Ther. 2026 Feb;34(2):1201-1214.
[4] Khan HY, Nagasaka M, Nagasaka M, et al. Anticancer Efficacy of KRASG12C Inhibitors Is Potentiated by PAK4 Inhibitor KPT9274 in Preclinical Models of KRASG12C-Mutant Pancreatic and Lung Cancers. Mol Cancer Ther. 2023 Dec;22(12):1422-33.
[5] Lanman BA, Allen JR, Allen JG, et al. Discovery of a Covalent Inhibitor of KRASG12C Treatment of Solid Tumors. J Med Chem. 2020;63(1):52-65.
| Cell experiment [1]: | |
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Cell lines |
MIA PaCa-2 cells (human pancreatic ductal adenocarcinoma cell line), NCI-H358 cells (human non-small cell lung cancer cell line) |
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Preparation Method |
MIA PaCa-2 and NCI-H358 cells were maintained in DMEM or RPMI1640 supplemented with 10% FBS at 37°C, 5% CO2. Cells were treated with AMG-510 racemate at 50nM for 24 hours or 25nM for 72 hours. After treatment, MTT assay, RT-qPCR and Western blot were performed. |
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Reaction Conditions |
25-50nM; 24-72h |
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Applications |
AMG-510 racemate reduced CDK4, CDK6, Cyclin D1 and β-catenin mRNA levels in NCI-H358 cells. AMG-510 racemate reduced MIA PaCa-2 and NCI-H358 cell viability in MTT assay. |
| Animal experiment [2]: | |
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Animal models |
Athymic nude mice subcutaneously implanted with MIA PaCa-2 T2 human tumor cells (homozygous KRAS p.G12C) |
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Preparation Method |
Mice were orally administered AMG-510 racemate ((R)-38) once daily at 10-100mg/kg for 2 weeks. Serum and tumor samples were collected 2h postdosing for PK/PD analysis, and tumor volumes were measured during the dosing period. |
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Dosage form |
10-100mg/kg; p.o.; 2 weeks |
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Applications |
AMG-510 racemate suppressed tumor growth and elicited tumor regression. AMG-510 racemate reduced ERK phosphorylation in tumor tissue. |
References: [1] Brismar J, Ozand PT. CT and MR of the brain in disorders of the propionate and methylmalonate metabolism. AJNR Am J Neuroradiol. 1994 Sep;15(8):1459-73. [2] Lanman BA, Allen JR, Allen JG, et al. Discovery of a Covalent Inhibitor of KRASG12C Treatment of Solid Tumors. J Med Chem. 2020;63(1):52-65. | |
| 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 |
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7838 mL | 8.9192 mL | 17.8383 mL |
| 5 mM | 356.8 μL | 1.7838 mL | 3.5677 mL |
| 10 mM | 178.4 μL | 891.9 μL | 1.7838 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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 saline, 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.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 39 reference(s) in Google Scholar.)