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ARS1620

ARS1620 is a covalent inhibitor of K-RAS<sup>G12C</sup> (IC50 = 10 μM). ARS1620 (200 mg/kg) induces tumor regression in a MIA-PaCa2, but not an H441, mouse xenograft model. It also decreases tumor volume in patient-derived xenograft (PDX) mouse models expressing K-RAS<sup>G12C</sup>, but not K-RAS<sup>G12D</sup> or wild-type K-RAS.
1698055-85-4
Item No.
TX01EHFI
CAS No.
1698055-85-4
Molecular Formula
C21H17ClF2N4O2S
Molecular Weight
462.90008639999985
Pricing ＆ Availability
Pack Size Purity Price(USD) Availability Quantity
1mg 99% $23.00 in stock
5mg 99% $53.00 in stock
10mg 99% $78.00 in stock
25mg 99% $131.00 in stock
100mg 95% $371.00 in stock
250mg 95% $669.00 in stock
WARNING This product is for research use only. SDS
Technical Information
Item No.:
TX01EHFI
Product Name:
ARS1620
Description:
Synonyms:
ARS1620; ARS-1620
CAS Number:
1698055-85-4
MDL:
MFCD31619312
Molecular Formula:
C21H17ClF2N4O2S
Molecular Weight:
462.90008639999985
SMILES:
C=CC(N1CCN(C2=C3C=C(Cl)[C@]([C@]4=C(O)C=CC=C4F)=C(F)C3=NC=N2)CC1)=O.[S]
IC₅₀ & Target:
KRAS(G12C)
In Vitro:
ARS-1620 is an atropisomeric selective KRASG12C inhibitor with desirable pharmacokinetics. ARS-1620 exhibits complete growth suppression of p.G12C cell lines (IC50=150 nM) with relatively benign effects on control cell lines. It is found that ARS-1620 significantly reduces expression of the gene set in p.G12C mutant cells in a time-dependent manner but not in the p.G12S mutant cells. Following a 5-day treatment period, only a minority of G12C mutant cell lines are sensitive to ARS-1620 under monolayer culture conditions, whereas in 3D-spheroid conditions, ARS-1620 elicits a robust response (p=0.0140). Method(s) not verified, for reference only.
In Vivo:
Following a single oral dose or 5 consecutive daily doses, ARS-1620 yields average peak tumor concentrations of 1.5 μM (50 mg/kg) and 5.5 μM (200 mg/kg), respectively, that enables significant KRASG12C target occupancy (&gt;=70% G12C-TE at 200 mg/kg) for &gt;24 hr. In MIAPaCa2 xenografts (p.G12C), ARS-1620 significantly inhibits tumor growth (p. Method(s) not verified, for reference only.
Kinase Assay:
5×104 cells are seeded into 24 well ULA-plates and allowed to rest overnight. Cells are then treated with DMSO or ARS-1620. After 2 days of treatment, apoptosis and cell death is measured by staining with annexinV-APC and prodidium iodide or by 70% ethanol fixation followed by FxCycle Violet staining to measure DNA content (cell cycle) and percentage of sub-diploid events by flow cytometry.Method(s) not verified, for reference only., 5×104 cells are seeded into 24 well ULA-plates and allowed to rest overnight. Cells are then treated with DMSO or ARS-1620. After 2 days of treatment, apoptosis and cell death is measured by staining with annexinV-APC and prodidium iodide or by 70% ethanol fixation followed by FxCycle Violet staining to measure DNA content (cell cycle) and percentage of sub-diploid events by flow cytometry[1].*Method(s) not verified, for reference only.
Animal Administration:
For pharmacokinetic (PK) studies 6- to 8-week-old male BALB/c mice are used. To determine oral bioavailability, mice are treated with ARS-1620 by a single intravenous (IV) bolus or oral gavage administration at the doses of 2 and 10 mg/kg, respectively. ARS-1620 concentration in plasma is quantified by LC-MS/MS-based methods. Pharmacokinetic parameters are estimated from mean plasma concentration-time profiles. The area under the curve (AUC) is calculated from time versus concentration data using the linear trapezoidal rule. The oral bioavailability is calculated as the ratio of AUC for ARS-1620 from oral and IV dosage. The calculation is normalized by relative doses.Method(s) not verified, for reference only., For pharmacokinetic (PK) studies 6- to 8-week-old male BALB/c mice are used. To determine oral bioavailability, mice are treated with ARS-1620 by a single intravenous (IV) bolus or oral gavage administration at the doses of 2 and 10 mg/kg, respectively. ARS-1620 concentration in plasma is quantified by LC-MS/MS-based methods. Pharmacokinetic parameters are estimated from mean plasma concentration-time profiles. The area under the curve (AUC) is calculated from time versus concentration data using the linear trapezoidal rule. The oral bioavailability is calculated as the ratio of AUC for ARS-1620 from oral and IV dosage. The calculation is normalized by relative doses[1].*Method(s) not verified, for reference only.
Solubility:
DMSO: soluble
Shipping Condition:
Room temperature in continental US; may vary elsewhere.
References & Citations:
[1]. Janes MR, et al. Targeting KRAS Mutant Cancers with a Covalent G12C-Specific Inhibitor. Cell. 2018 Jan 25;172(3):578-589.e17.