ARS-1620

A covalent inhibitor of K-RASG12C

此产品仅用于科学研究，我们不为任何个人用途提供产品和服务

库存: 现货

可选规格

包装

价格

促销价

数量
5mg

￥2287.00

1830.00

- +
10mg

￥3612.00

2890.00

- +
25mg

￥5712.00

4570.00

- +
50mg

￥9175.00

7340.00

- +
100mg

￥13350.00

10680.00

- +
200mg

￥25887.00

20710.00

- +

已选 0 种 0 瓶

金额: ￥0.00

首页收藏

Background

ARS1620 is a covalent inhibitor of K-RAS^G12C (IC₅₀ = <3 μM).¹ It selectively inhibits growth of H358, MIA-PaCa2, and LU65 cancer cells that express K-RAS^G12C (IC₅₀s = 150 nM) over H441, A549, and HCT116 cells expressing wild-type K-RAS (IC₅₀s = >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^G12C, but not K-RAS^G12D or wild-type K-RAS.

1.Janes, M.R., Zhang, J., Li, L.-S., et al.Targeting KRAS mutant cancer cells with a covalent G12C-specific inhibitorCell172(3)578-589(2018)

Protocol

Cell experiment:

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].

Animal experiment:

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].

参考文献:

[1]. Janes MR, et al. Targeting KRAS Mutant Cancers with a Covalent G12C-Specific Inhibitor. Cell. 2018 Jan 25;172(3):578-589.e17.