ARS-853
Based on 5 publication(s) in Google Scholar
ARS-853 is a cell-active, selective, covalent KRAS G12C inhibitor with an IC50 of 2.5 μM. ARS-853 inhibits mutant KRAS-driven signaling by binding to the GDP-bound oncoprotein and preventing activation.
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- Purity: 98.39%
- CAS No.: 1629268-00-3
- 화학식: C22H29ClN4O3
- 분자량:432.94
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보관:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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Biological Activity
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Chemical Information
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용액&용해도
- Protocol
- 순도&문서
- References
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Help & FAQs
Publications Citing Use of MedChemExpress (MCE) ARS-853
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Biological Activity
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KRAS(G12C) 2.5 μM (IC50) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A549 | IC50 |
35.2 μM
Compound: ARS-853
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Antiproliferative activity against human A549 cells harboring homozygous KRAS G12S mutant assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
Antiproliferative activity against human A549 cells harboring homozygous KRAS G12S mutant assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
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[PMID: 36842271] |
| BXPC-3 | IC50 |
36.8 μM
Compound: ARS-853
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Antiproliferative activity against human BXPC-3 cells harboring wild type KRAS assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
Antiproliferative activity against human BXPC-3 cells harboring wild type KRAS assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
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[PMID: 36842271] |
| LCLC-103H cell line | IC50 |
41.5 μM
Compound: ARS-853
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Antiproliferative activity against human LCLC-103H cells harboring wild type KRAS assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
Antiproliferative activity against human LCLC-103H cells harboring wild type KRAS assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
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[PMID: 36842271] |
| MIA PaCa-2 | IC50 |
5.8 μM
Compound: ARS-853
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Antiproliferative activity against human MIA PaCa-2 cells harboring homozygous KRAS G12C mutant assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
Antiproliferative activity against human MIA PaCa-2 cells harboring homozygous KRAS G12C mutant assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
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[PMID: 36842271] |
| MRC5 | IC50 |
75.3 μM
Compound: ARS-853
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Cytotoxicity against human MRC5 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
Cytotoxicity against human MRC5 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
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[PMID: 36842271] |
| NCI-H1792 | IC50 |
27.9 μM
Compound: ARS-853
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Antiproliferative activity against human NCI-H1792 cells harboring heterozygous KRAS G12C mutant assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
Antiproliferative activity against human NCI-H1792 cells harboring heterozygous KRAS G12C mutant assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
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[PMID: 36842271] |
| NCI-H358 | IC50 |
6.9 μM
Compound: ARS-853
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Antiproliferative activity against human NCI-H358 cells harboring heterozygous KRAS G12C mutant assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
Antiproliferative activity against human NCI-H358 cells harboring heterozygous KRAS G12C mutant assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
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[PMID: 36842271] |
| PANC-1 | IC50 |
58.2 μM
Compound: ARS-853
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Antiproliferative activity against human PANC-1 cells harboring heterozygous KRAS G12D mutant assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
Antiproliferative activity against human PANC-1 cells harboring heterozygous KRAS G12D mutant assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
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[PMID: 36842271] |
| SW1573 | IC50 |
25.9 μM
Compound: ARS-853
|
Antiproliferative activity against human SW1573 cells harboring homozygous KRAS G12C mutant assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
Antiproliferative activity against human SW1573 cells harboring homozygous KRAS G12C mutant assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
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[PMID: 36842271] |
| SW480 | IC50 |
27.8 μM
Compound: ARS-853
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Antiproliferative activity against human SW480 cells harboring homozygous KRAS G12V mutant assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
Antiproliferative activity against human SW480 cells harboring homozygous KRAS G12V mutant assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
|
[PMID: 36842271] |
ARS853 is designed to bind KRASG12C with high affinity. Treatment of KRASG12C-mutant lung cancer cells with ARS853 reduces the level of GTP-bound KRAS by more than 95% (10 μM). ARS853 inhibits proliferation with an inhibitory concentration 50% (IC50) of 2.5 μM, which is similar to its IC50 for target inhibition. ARS853 (10 μM) inhibits effector signaling and cell proliferation to varying degrees in six KRASG12C mutant lung cancer cell lines, but not in non-KRASG12C models. Similarly, it completely suppresses the effects of exogenous KRASG12C expression on KRAS-GTP levels, KRAS-BRAF interaction, and ERK signaling. ARS-853 treatment also induces apoptosis in four KRASG12C mutant cell lines. ARS853 selectively reduces KRAS-GTP levels and RAS-effector signaling in KRASG12C-mutant cells, while inhibiting their proliferation and inducing cell death[1]. ARS-853 inhibits mutant KRAS-driven signaling by binding to the GDP-bound oncoprotein and preventing activation[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 1629268-00-3
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Appearance Solid
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분자량 432.94
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화학식 C22H29ClN4O3
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Color White to off-white
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SMILES
ClC1=C(C2(C)CC2)C=C(NCC(N3CCN(C4CN(C(C=C)=O)C4)CC3)=O)C(O)=C1
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (5)
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Journal Impact Factor
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Most Recent
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Cancer Discov
D3S-001, a KRAS G12C inhibitor with rapid target engagement kinetics, overcomes nucleotide cycling and demonstrates robust preclinical and clinical activities. [Abstract]2024 May 8. PMID: 38717075 -
Cancer Discov
Combined Proteomic and Genetic Interaction Mapping Reveals New RAS Effector Pathways and Susceptibilities. [Abstract]2020 Dec;10(12):1950-1967. PMID: 32727735 -
Cell Chem Biol
2026 Feb 11:S2451-9456(26)00027-9. PMID: 41679298 -
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용액&용해도
DMSO : 25 mg/mL (57.74 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.77 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (5.77 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocol
Purified KRAS (1 μM) is incubated EDTA (10 mM) and GDP (1 mM) or GTPγS (1 mM) at room temperature for 1 h followed by addition of MgCl2 (1 mM) to terminate the reaction. ARS853 (1 μM) is then added and the mixture is incubated for another hour at room temperature. HEK293 cells expressing various KRAS mutants are treated with ARS853. Proteins are extracted using a buffer containing 9M urea, 10 mM DTT and 50 mM ammonium bicarbonate, pH 8, heated to 65°C for 15 min and alkylated using 50 mM iodoacetamide at 37°C for 30 min. The samples are desalted by gel filtration in Zeba spin desalting plates followed by addition of sequencing-grade trypsin to a concentration of 10 μg/ml, and incubation for one hour at 37°C. Heavy isotopic standards (25 fmol) of the KRASG12C target peptide and KRAS normalization peptide are added to the samples followed by desalting in Strata-X polymeric reverse phase plates. LC-MS/MS analysis is performed in a Q Exactive quadrupole orbitrap mass spectrometer under standard condition. The amount of KRASG12C bound by the drug is determined by the ratio of the modified G12C peptide to that of the heavy isotopic standards[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
순도&문서
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Data Sheet (274 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
References
[1]. Lito P, et al. Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism. Science. 2016 Feb 5;351(6273):604-8. [Content Brief]
[2]. Patricelli MP, et al. Selective Inhibition of Oncogenic KRAS Output with Small Molecules Targeting the Inactive State. Cancer Discov. 2016 Mar;6(3):316-29. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.3098 mL | 11.5489 mL | 23.0979 mL | 57.7447 mL |
| 5 mM | 0.4620 mL | 2.3098 mL | 4.6196 mL | 11.5489 mL | |
| 10 mM | 0.2310 mL | 1.1549 mL | 2.3098 mL | 5.7745 mL | |
| 15 mM | 0.1540 mL | 0.7699 mL | 1.5399 mL | 3.8496 mL | |
| 20 mM | 0.1155 mL | 0.5774 mL | 1.1549 mL | 2.8872 mL | |
| 25 mM | 0.0924 mL | 0.4620 mL | 0.9239 mL | 2.3098 mL | |
| 30 mM | 0.0770 mL | 0.3850 mL | 0.7699 mL | 1.9248 mL | |
| 40 mM | 0.0577 mL | 0.2887 mL | 0.5774 mL | 1.4436 mL | |
| 50 mM | 0.0462 mL | 0.2310 mL | 0.4620 mL | 1.1549 mL |
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