ARS-853

Catalog No.S8156 Batch:S815603

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Technical Data

Formula

C22H29ClN4O3
Molecular Weight 432.94 CAS No. 1629268-00-3
Solubility (25°C)* In vitro DMSO 86 mg/mL (198.64 mM)
Ethanol 7 mg/mL (16.16 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
4.3mg/ml Taking the 1 mL working solution as an example, add 50 μL of 86 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
Clear solution
5% DMSO 95% Corn oil
0.71mg/ml Taking the 1 mL working solution as an example, add 50 μL of 14.2 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description ARS-853 is a selective, covalent KRAS(G12C) inhibitor that inhibits mutant KRAS-driven signaling by binding to the GDP-bound oncoprotein and preventing activation. ARS-853 also induces apoptosis.
Targets
K-Ras(G12C) [2]
(in H358 cells)
2.5 μM
In vitro ARS-853 treatment of KRASG12C cells led to a dose-dependent and nearly complete inhibition of CRAF-RBD (RBD)-mediated pulldown of KRAS from lysates, with an IC50 of approximately 1 μmol/L. Treatment of H358 cells by ARS-853 resulted in a significant loss of KRAS–CRAF interactions. Consistent with an inactive state of KRASG12C once bound to ARS-853, downstream signaling through both MAPK (including pMEK, pERK, and pRSK) and PI3K signaling (pAKT) pathways was inhibited by ARS-853 in H358 and other KRASG12C cell lines. The inhibition of RAF-RBD pulldown and KRAS downstream signaling was sustained over a period of 72 hours, accompanied by G1 cell-cycle arrest, loss of Cyclin D1 and Rb expression, and an increase in the cell-cycle inhibitor p27 KIP1. In addition, hallmarks of apoptosis, including cleaved PARP and increases in sub-diploid DNA, were observed in H358 cells following treatment with ARS-853. No effects on RAF-RBD binding or downstream signaling were observed in A549 cells (KRASG12S), and the inhibitory effects of ARS-853 in H358 cells could be rescued by ectopic expression of KRASG12V. KRASG12C is the most potent covalent target of ARS-853 across more than 2,700 cellular proteins and consistently find that this compound exerts no effects on cellular signaling or growth in non-KRASG12C cells at concentrations up to 10-fold higher than its KRASG12C potency. ARS-853 reacts only with the inactive (GDP-bound), but the not the active (GTP-bound), state of KRAS[1]. ARS853 reduced KRAS-GTP levels and ERK phosphorylation in human embryonic kidney 293 (HEK293) or H358 cells engineered to express KRASG12C but not in those expressing KRASG12C/A59G. ARS853 traps KRASG12C in a GDP-bound conformation by lowering its affinity for nucleotide exchange factors[2].

Protocol (from reference)

Cell Assay:

[2]
  • Cell lines

    H358 (G12C) cells

  • Concentrations

    0.05, 0.1, 0.5, 1, 5, 10, 50 μM

  • Incubation Time

    5 h

  • Method

    KRASG12C mutant cells (H358) were treated with ARS853 for 5 hours. The effect on the level of active, or GTP-bound, KRAS was determined by a RAS-binding domain pull-down (RBD:PD) assay and immunoblotting with a KRAS-specific antibody. 

Selleck's ARS-853 has been cited by 5 publications

Real-time monitoring of the reaction of KRAS G12C mutant specific covalent inhibitor by in vitro and in-cell NMR spectroscopy [ Sci Rep, 2023, 10.1038/s41598-023-46623-w] PubMed: 37935773
HDLBP promotes hepatocellular carcinoma proliferation and sorafenib resistance by suppressing Trim71-dependent RAF1 degradation [ Cell Mol Gastroenterol Hepatol, 2022, S2352-345X(22)00216-8] PubMed: 36244648
Profiling oncogenic KRAS mutant drugs with a cell-based Lumit p-ERK immunoassay [ SLAS Discov, 2022, S2472-5552(22)12517-7] PubMed: 35288294
Investigation of KRAS Dependency Bypass and Functional Characterization of All Possible KRAS Missense Variants [ ProQuest, 2020, N/A] PubMed: None
Coxsackievirus Type B3 Is a Potent Oncolytic Virus against KRAS-Mutant Lung Adenocarcinoma. [ Mol Ther Oncolytics, 2019, 14:266-278] PubMed: 31463367

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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