Vps34-IN-2
目录号 : GC32932
Vps34-IN-2是一种新型的，有效且有选择性的Vps34抑制剂，在Vps34酶促测定和GFP-FYVE细胞测定中的IC50值分别为2和82nM。
Cas No.:1523404-29-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | Cells are cultured in RPMI-1640 medium with 10% fetal bovine serum. Cells are lysed by sonication in a detergent containing lysis buffer and cleared by centrifugation, and the resulting supernatant is collected for compound treatment. Final protein concentration of lysates is 4 mg/mL. An amount of 5 μL of Vps34-IN-2 (Compound 31) is added from 100× stock solutions in DMSO to 445 μL of lysate in duplicate. An amount of 5 μL of DMSO is added to 445 μL of lysate in quadruplicate for controls. After 15 min incubation, 5 μL of a 100× aqueous solution of the ATP probe I is added to each sample (final concentration of ATP probe I is 0.5 μM). After 5 min, 50 μL of a 10× aqueous solution of the ATP probe II is added to each sample (final concentration of ATP probe II is 20 μM). All samples are then incubated for an additional 10 min[1]. |
Animal experiment: | For PK/PD studies, 3×106 H1299-GFP-FYVE tumor cells with 50% Matrigel are subcutaneously injected on the dorsal side of SCID mice, one tumor per mouse. When xenografted tumors reach a range of ~200 to 400 mm3, mice are treated with vehicle (98% PEG200/2% PS80) or a single dose of Vps34-IN-2 (compound 31) at 100 and 50 mg/kg via oral gavage. Three mice treated with vehicle alone and three mice treated with Vps34-IN-2 are sacrificed at each time point; tumor tissues are harvested for immunohistochemistry (IHC) analysis and plasma samples are collected to determine the concentration of Vps34-IN-2[1]. |
References: [1]. Pasquier B, et al. Discovery of (2S)-8-[(3R)-3-methylmorpholin-4-yl]-1-(3-methyl-2-oxobutyl)-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido[1,2-a]pyrimidin-6-one: a novel potent and selective inhibitor of Vps34 for the treatment of solid tumors. J Med Chem. 2015 Jan 8;58(1):376-400. | |
Vps34-IN-2 is a novel, potent and selective inhibitor of Vps34 with IC50s of 2 and 82 nM on the Vps34 enzymatic assay and the GFP-FYVE cellular assay, respectively.
Vps34-IN-2 (Compound 31) displays IC50s of 2 and 82 nM on the Vps34 enzymatic assay and the GFP-FYVE cellular assay, respectively. Vps34-IN-2 exhibits selectivity against mTOR (IC50>10 μM) and class I PI3Ks (IC50 values of 2.7, 4.5, 2.5, and >10 μM on PI3K α, β, δ, γ isoforms, respectively)[1].
After administration by the intravenous (iv) route, Vps34-IN-2 (Compound 31) concentrations are quantifiable up to 6, 8, and 24 h (last sampling time) depending on animals. After oral administration (po), Vps34-IN-2 is rapidly absorbed with maximal plasma concentrations observed at 0.5 h and a bioavailability of 85%. Slight rebounds of concentrations are observed at 4 and 8 h after oral dosing with no obvious explanation. After iv injection of Vps34-IN-2 at 3 mg/kg, plasma clearance is found moderate (i.e., 2.3 L/h/kg), corresponding to 44% of hepatic blood flow in this species, volume of distribution at steady state is moderate, and terminal elimination half-life is short[1].
[1]. Pasquier B, et al. Discovery of (2S)-8-[(3R)-3-methylmorpholin-4-yl]-1-(3-methyl-2-oxobutyl)-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido[1,2-a]pyrimidin-6-one: a novel potent and selective inhibitor of Vps34 for the treatment of solid tumors. J Med Chem. 2015 Jan 8;58(1):376-400.
| Cas No. | 1523404-29-6 | SDF | |
| Canonical SMILES | O=C1C=C(N2[C@H](C)COCC2)N=C3N(CC(C(C)C)=O)[C@H](C(F)(F)F)CCN31 | ||
| 分子式 | C18H25F3N4O3 | 分子量 | 402.41 |
| 溶解度 | Ethanol: 50 mg/mL (124.25 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 | 2.485 mL | 12.4251 mL | 24.8503 mL |
| 5 mM | 0.497 mL | 2.485 mL | 4.9701 mL |
| 10 mM | 0.2485 mL | 1.2425 mL | 2.485 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。