Omapatrilat (BMS-186716)
(Synonyms: BMS-186716) 目录号 : GC34019
An ACE and NEP inhibitor
Cas No.:167305-00-2
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Omapatrilat is an orally bioavailable angiotensin-converting enzyme (ACE) and neprilysin (NEP) inhibitior (IC50s = 1.7 and 5.3 nM, respectively, for the human enzymes).1 It inhibits the pressor response induced by angiotensin I in normotensive rats (ED50 = 0.07 ?mol/kg) and lowers mean arterial pressure (MAP) in sodium-depleted spontaneously hypertensive rats when administered at a dose of 30 ?mol/kg.2 Omapatrilat lowers MAP in rats when co-administered with bradykinin .3 It also increases tracheal plasma extravasation in a rat model of upper airway angioedema in a dose-dependent manner.4
1.Sulpizio, A.C., Pullen, M.A., Edwards, R.M., et al.Mechanism of vasopeptidase inhibitor-induced plasma extravasation: Comparison of omapatrilat and the novel neutral endopeptidase 24.11/angiotensin-converting enzyme inhibitor GW796406J. Pharmacol. Exp. Ther.315(3)1306-1313(2005) 2.Robl, J.A., Sun, C.-Q., Stevenson, J., et al.Dual metalloprotease inhibitors: Mercaptoacetyl-based fused heterocyclic dipeptide mimetics as inhibitors of angiotensin-converting enzyme and neutral endopeptidaseJ. Med. Chem.40(11)1570-1577(1997) 3.Fryer, R.M., Segreti, J., Banfor, P.N., et al.Effect of bradykinin metabolism inhibitors on evoked hypotension in rats: Rank efficacy of enzymes associated with bradykinin-mediated angioedemaBr. J. Pharmacol.153(5)947-955(2008) 4.Murray McKinnell, R., Fatheree, P., Choi, S.-K., et al.Discovery of TD-0212, an orally active dual pharmacology AT1 antagonist and neprilysin inhibitor (ARNI)ACS Med. Chem. Lett.10(1)86-91(2018)
|
Kinase experiment: |
Omapatrilat is dissolved in 100% DMSO at 10 mM and diluted to 1% DMSO. NEP, NEP2, ACE and APP assays are performed at pH 7.4. The reaction buffer for NEP and NEP2 contained 50 mM HEPES, 140 mM NaCl, 10 mM KCl, 0.01% BSA. The buffer for ACE contained 100 mM Tris-HCl, 50 mM NaCl, 10 μM ZnCl2, and the buffer for APP contained 100 mM HEPES and 0.01% BSA. Assays are performed in 100 μL volume in black 96-well round-bottom plates at room temperature. Reactions are continuously monitored with excitation and emission wavelengths appropriate for each respective substrate. Enzyme velocity is determined from the linear part of the reaction[1]. |
|
Animal experiment: |
Rats: Sprague Dawley rats are weighed and then gavaged with vehicle (5% arabic gum) or omapatrilat (0.1, 1, 10 mg/kg) (n 5 6 rats/group). Rats are killed by decapitation at 1 h after gavage. Trunk blood is collected into prechilled tubes containing EDTA/aprotinin for the measurement of PRA and into prechilled heparin tubes for the measurement ofplasma ACE[4]. Rabbits: Omapatrilat is dissolved in drinking water. Rabbits are divided into 2 groups with 1% cholesterol diet, placebo-treated group and omapatrilat-treated group, and administrated (12 mg/Kg/day omapatrilat) once daily for 8 weeks. To demonstrate the acute effect of omapatrilat, urine is collected after omapatrilat or placebo administration for 24 hours at day 1, and urine volume, cGMP and ANP levels are assessed[3]. |
|
References: [1]. Fryer RM, et al. Effect of bradykinin metabolism inhibitors on evoked hypotension in rats: rank efficacy ofenzymes associated with bradykinin-mediated angioedema.Br J Pharmacol. 2008 Mar;153(5):947-55. |
|
| Cas No. | 167305-00-2 | SDF | |
| 别名 | BMS-186716 | ||
| Canonical SMILES | O=C([C@@H]1CCC[C@](N21)([H])SCC[C@H](NC([C@@H](S)CC3=CC=CC=C3)=O)C2=O)O | ||
| 分子式 | C19H24N2O4S2 | 分子量 | 408.53 |
| 溶解度 | DMSO : ≥ 31 mg/mL (75.88 mM) | 储存条件 | Store at -20°C, protect from light, stored under nitrogen |
| 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.4478 mL | 12.239 mL | 24.478 mL |
| 5 mM | 0.4896 mL | 2.4478 mL | 4.8956 mL |
| 10 mM | 0.2448 mL | 1.2239 mL | 2.4478 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: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet