ARS-1620
目录号 : GC34055
A covalent inhibitor of K-RASG12C
Cas No.:1698055-85-4
Sample solution is provided at 25 µL, 10mM.
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ARS1620 is a covalent inhibitor of K-RASG12C (IC50 = <3 μM).1 It selectively inhibits growth of H358, MIA-PaCa2, and LU65 cancer cells that express K-RASG12C (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-RASG12C, but not K-RASG12D 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)
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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]. |
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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]. |
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References: [1]. Janes MR, et al. Targeting KRAS Mutant Cancers with a Covalent G12C-Specific Inhibitor. Cell. 2018 Jan 25;172(3):578-589.e17. |
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| Cas No. | 1698055-85-4 | SDF | |
| Canonical SMILES | C=CC(N1CCN(C2=C3C=C(Cl)[C@@]([C@@]4=C(O)C=CC=C4F)=C(F)C3=NC=N2)CC1)=O.[S] | ||
| 分子式 | C21H17ClF2N4O2 | 分子量 | 430.84 |
| 溶解度 | DMSO : ≥ 53 mg/mL (123.02 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.321 mL | 11.6052 mL | 23.2105 mL |
| 5 mM | 0.4642 mL | 2.321 mL | 4.6421 mL |
| 10 mM | 0.2321 mL | 1.1605 mL | 2.321 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet