ARS-1620

Catalog No.S8707

For research use only.

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.

ARS-1620 Chemical Structure

CAS No. 1698055-85-4

Selleck's ARS-1620 has been cited by 9 Publications

Purity & Quality Control

Choose Selective Ras Inhibitors

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].

Assay
Methods Test Index PMID
Western blot RAS-GTP / RAS / pERK / p-S6 / p-AKT / Cleaved-PARP 29373830
Growth inhibition assay Cell viability 29373830
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 Research:

[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 Research:

[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

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 430.84
Formula

C21H17ClF2N4O2

CAS No. 1698055-85-4
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C=CC(=O)N1CCN(CC1)C2=NC=NC3=C(C(=C(C=C32)Cl)C4=C(C=CC=C4F)O)F

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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