ARS-1620

Catalog No.S8707 Batch:S870707

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Technical Data

Formula

C21H17ClF2N4O2
Molecular Weight 430.84 CAS No. 1698055-85-4
Solubility (25°C)* In vitro DMSO 86 mg/mL (199.61 mM)
Ethanol 86 mg/mL (199.61 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 86 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. 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-1620 is a potent, orally bioavailable covalent inhibitor of KRASG12C and could achieve rapid and sustained in vivo target occupancy to induce tumor regression.
Targets
K-Ras(G12C) [1]
In vitro

ARS-1620 covalently inhibits KRAS (G12C) activity with high potency and atropisomeric selectivity in p.G12C mutant cancer cells. ARS-1620 rapidly engaged G12C in a concentration- and time- dependent manner consistent with its covalent mechanism of inhibition. Across a panel of cell lines harboring the mutant allele, ARS-1620 exhibited a half maximal G12C target engagement (TE50) at ~0.3 μM and near complete engagement at 3.0 μM after 2 hr of treatment. RS-1620 inhibits RAS-GTP and the phosphorylation of MEK, ERK, RSK, S6, and AKT in a dose-dependent and selective manner in H358 (p.G12C) but not in negative control lung cancer cell lines lacking p.G12C (A549, H460, and H441). ARS-1620 elicits sub-micromolar allele-specific potency (IC50 = 0.3 μM; IC90 = 1 μM). The activity of ARS-1620 is specific to the G12C allele and mediated by the covalent modification of Cys-12[1].
In vivo

ARS-1620 exhibits excellent oral bioavailability (F > 60%) in mice. In MIA-PaCa2 xenografts (p.G12C), ARS-1620 significantly inhibits tumor growth (p < 0.001) in a dose-dependent manner with marked regression at a dose of 200 mg/kg, given once daily. Xenografts of H441 (p.G12V) lack a response at all doses tested and the R-atropisomer of ARS-1620 lacks activity in both models. ARS-1620 selectively induces tumor regression in patient-derived tumor models (harboring KRAS p.G12C)[1].

Protocol (from reference)

Cell Assay:

[1]
  • Cell lines

    H358 cells

  • Concentrations

    4 μM

  • Incubation Time

    4 h

  • Method

    Cells are maintained in a humidified incubator at 37 C with 5% CO2, and grown in RPMI 1640 or DMEM supplemented with 10% FBS and 50 IU ml-1 penicillin/streptomycin.
Animal Study:

[1]
  • Animal Models

    6- to 8-week-old male BALB/c mice

  • Dosages

    2 and 10 mg/kg

  • Administration

    intravenous (IV) bolus or oral gavage administration

Selleck's ARS-1620 has been cited by 14 publications

Hedgehog signalling is involved in acquired resistance to KRASG12C inhibitors in lung cancer cells [ Cell Death Dis, 2024, 15(1):56] PubMed: 38225225
Multiscale Analysis and Validation of Effective Drug Combinations Targeting Driver KRAS Mutations in Non-Small Cell Lung Cancer [ Int J Mol Sci, 2023, 24(2)997] PubMed: 36674513
Creating MHC-restricted neoantigens with covalent inhibitors that can be targeted by immune therapy [ Cancer Discov, 2022, CD-22-1074] PubMed: 36250888
KRASG12C-independent feedback activation of wild-type RAS constrains KRASG12C inhibitor efficacy [ Cell Rep, 2022, 39(12):110993] PubMed: 35732135
Development of a biotin-streptavidin-enhanced enzyme-linked immunosorbent assay (BA-ELISA) for high-throughput screening of KRASG12C inhibitors [ SLAS Discov, 2022, 27(2):107-113] PubMed: 35058184
Clinical Acquired Resistance to KRASG12C Inhibition through a Novel KRAS Switch-II Pocket Mutation and Polyclonal Alterations Converging on RAS-MAPK Reactivation [ Cancer Discov, 2021, 11(8):1913-1922] PubMed: 33824136
Selective and noncovalent targeting of RAS mutants for inhibition and degradation [ Nat Commun, 2021, 12(1):2656] PubMed: 33976200
SHP2 inhibition diminishes KRASG12C cycling and promotes tumor microenvironment remodeling [ J Exp Med, 2021, 218(1)e20201414] PubMed: 33045063
B2M gene expression shapes the immune landscape of lung adenocarcinoma and determines the response to immunotherapy [ Immunology, 2021, 164(3):507-523] PubMed: 34115389
RAS-Driven Macropinocytosis of Albumin or Dextran Reveals Mutation-Specific Target Engagement of RAS p.G12C Inhibitor ARS-1620 by NIR-Fluorescence Imaging [ Mol Imaging Biol, 2021, 10.1007/s11307-021-01689-8] PubMed: 34905147

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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.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.