BPTU
(Synonyms: BMS-646786) 目录号 : GC19081
A P2Y1 receptor antagonist
Cas No.:870544-59-5
Sample solution is provided at 25 µL, 10mM.
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BPTU is a novel P2Y1 allosteric antagonist.
BPTU blocks the supramaximal fast inhibitory junction potentials (fIJP) in a concentration-dependent manner both in the rat and mouse colon (P<0.0001 for both). The EC50 of BPTU is approximately 0.3 uM and 0.06 uM for the rat and mouse colon, respectively. In the rat colon, addition of the P2Y agonist ADPβS at 10 uM significantly reduces spontaneous contractions to a 43.2±13.4% (N=5) (P=0.0002), and this reduction is blocked by 15 min incubation with BPTU at a concentration of 3 uM (93.3±5.1%). Similar results are obtained in the murine colon where ADPβS at 10 uM reduces the area under the curve (AUC) of contractions to a 15.8±5.1% (N=4) (P<0.0001) and its effect is reversed with BPTU at 3 uM (82.7±3.6%). Addition of MRS2365, a selective P2Y1 agonist, at a concentration of 5 uM significantly reduces spontaneous contractions to a 21.2±4.8% (N=5) (P=0.0002) in the murine colon, and this reduction is blocked by 15 min incubation with BPTU at a concentration of 3 uM (93.1±3.8%). The blockage of the MRS2365-induced response by BPTU at 3 uM also occurs in control conditions (N=5) (10.2±5.5% vs. 86.7±5.0%)[1].
Uptake of BPTU from the peritoneal cavity is relatively rapid. Blood boron levels are maximal within 1 h after administration. After only 1 h, a boron tumor-to-blood ratio above 1 is found for BPTU in pigmented tumors, which is indicative of drug retention. This is not seen in the non-pigmented tumor variant, in which tumor boron levels closely follow blood levels. Up to 24 h, Borocaptate sodium (BSH) exhibits no selective retention in either tumor, but achieves higher maximum tumor boron concentrations than BPTU as a result of the administration of higher amounts of boron. During the tissue distribution phase, liver-to-kidney boron concentration ratios range from 2 to 4 for BSH and from 0.5 to 1 for BPTU[2].
References:
[1]. Maé N, et al. BPTU, an allosteric antagonist of P2Y1 receptor, blocks nerve mediated inhibitory neuromuscular responses in the gastrointestinal tract of rodents. Neuropharmacology. 2016 Nov;110(Pt A):376-385.
[2]. Verrijk R, et al. Pharmacokinetics in melanoma-bearing mice of 5-dihydroxyboryl-6-propyl-2-thiouracil (BPTU), a candidate compound for boron neutron capture therapy. Br J Cancer. 1994 Apr;69(4):641-7.
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Cell experiment: |
Electrophysiological experiments are performed with colonic rat and mouse strips. Inhibitory junction potentials (IJP) are elicited by electrical field stimulation (EFS) using two silver chloride plates placed 1.5 cm apart perpendicular to the longitudinal axis of the preparation. The protocol consists of single pulse trains of EFS (0.4 ms pulse duration) at increasing voltages (8, 12, 16, 20, 24, 28, 32, 36, 40 V). The voltage responsible for the supramaximal response is used to elicit single pulses during incubation with BPTU at increasing concentrations (1×10-8 M, 1×10-7 M, 3×10-7 M, 1×10-6 M and 3×10-6 M). Another train of single pulses at increasing voltages is elicited after the highest dose of BPTU. The amplitude of the IJP (mV) is measured considering it as the difference between the maximal hyperpolarization and the resting membrane potential (RMP)[1]. |
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Animal experiment: |
Mice are given BPTU intraperitoneally at doses of 3.15 mg of boron per kg body weight. Injection volumes range from 0.25 to 0.5 mL for both intravenous and intraperitoneal administrations. Six mice are not given any drug to allow measurement of boron background levels. Animals are killed with carbon dioxide 0.2, 0.4, 1, 2, 4, 24 and 48 h after drug administration and samples are taken from tumor, blood, skin, muscle, brain, kidneys and liver. Tumor tissue from mice bearing B16.013 tumor is checked by eye for the absence of pigmentation. BPTU is also given in a multiple dose scheme. Every 2 h 0.4 to 0.5 mL of the above-mentioned BPTU solution is given intraperitoneally (4×3.15 mg/kg boron). Twenty-four hours after the last administration, the animals are sacrificed and samples are taken[2]. |
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References: [1]. Ma é N, et al. BPTU, an allosteric antagonist of P2Y1 receptor, blocks nerve mediated inhibitory neuromuscular responses in the gastrointestinal tract of rodents. Neuropharmacology. 2016 Nov;110(Pt A):376-385. |
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| Cas No. | 870544-59-5 | SDF | |
| 别名 | BMS-646786 | ||
| Canonical SMILES | O=C(NC1=CC=C(OC(F)(F)F)C=C1)NC2=CC=CN=C2OC3=CC=CC=C3C(C)(C)C | ||
| 分子式 | C23H22F3N3O3 | 分子量 | 445.43 |
| 溶解度 | DMSO : ≥ 33.3 mg/mL (74.76 mM);Water : < 0.1 mg/mL (insoluble) | 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 | 2.245 mL | 11.2251 mL | 22.4502 mL |
| 5 mM | 0.449 mL | 2.245 mL | 4.49 mL |
| 10 mM | 0.2245 mL | 1.1225 mL | 2.245 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。
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Quality Control & SDS
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet