BPTU-BMS-646786-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBPTUCat. No.: HY-13831CAS No.: 870544-59-5Synonyms: BMS-646786分式: CHFNO分量: 445.43作靶点: P2Y Receptor作通路: GPCR/G Protein储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 33.3 mg/mL (74.76 mM)H2O

2、 : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.61 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (5.61 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 BPTU种新型的 P2Y1 变构拮抗剂。IC50 & Target P2Y1 1体外研究 BPTU blocks the su

3、pramaximal fast inhibitory junction potentials (fIJP) in a concentration-dependent mannerboth in the rat and mouse colon (P50 of BPTU is approximately 0.3 M and 0.06 M for the rat and mousecolon, respectively. In the rat colon, addition of the P2Y agonist ADPS at 10 M significantly reducesspontaneou

4、s contractions to a 43.213.4% (N=5) (P=0.0002), and this reduction is blocked by 15 minincubation with BPTU at a concentration of 3 M (93.35.1%). Similar results are obtained in the murinecolon where ADPS at 10 M reduces the area under the curve (AUC) of contractions to a 15.85.1% (N=4)(P 1.体内研究 Upt

5、ake of BPTU from the peritoneal cavity is relatively rapid. Blood boron levels are maximal within 1 h afteradministration. 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 var

6、iant, in which tumorboron levels closely follow blood levels. Up to 24 h, Borocaptate sodium (BSH) exhibits no selective retentionin either tumor, but achieves higher maximum tumor boron concentrations than BPTU as a result of theadministration of higher amounts of boron. During the tissue distribut

7、ion phase, liver-to-kidney boronconcentration ratios range from 2 to 4 for BSH and from 0.5 to 1 for BPTU 2.PROTOCOLCell Assay 1 Electrophysiological experiments are performed with colonic rat and mouse strips. Inhibitory junctionpotentials (IJP) are elicited by electrical field stimulation (EFS) us

8、ing two silver chloride plates placed 1.5 cmapart perpendicular to the longitudinal axis of the preparation. The protocol consists of single pulse trains ofEFS (0.4 ms pulse duration) at increasing voltages (8, 12, 16, 20, 24, 28, 32, 36, 40 V). The voltageresponsible for the supramaximal response i

9、s used to elicit single pulses during incubation with BPTU atincreasing concentrations (110-8 M, 110-7 M, 310-7 M, 110-6 M and 310-6 M). Another train of singlepulses at increasing voltages is elicited after the highest dose of BPTU. The amplitude of the IJP (mV) ismeasured considering it as the dif

10、ference between the maximal hyperpolarization and the resting membranepotential (RMP) 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice are given BPTU intraperitoneally at doses of 3.15 mg of boron per kg body weight. Injection volumesAdmini

11、stration 2 range from 0.25 to 0.5 mL for both intravenous and intraperitoneal administrations. Six mice are not givenany 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 tum

12、or, blood, skin, muscle, brain,kidneys and liver. Tumor tissue from mice bearing B16.013 tumor is checked by eye for the absence of2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEpigmentation. BPTU is also given in a multiple dose scheme. Every 2 h 0.4 to 0.5 mL of the above-mentionedBPTU solution

13、is given intraperitoneally (43.15 mg/kg boron). Twenty-four hours after the lastadministration, the animals are sacrificed and samples are taken 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Ma? N, et al. BPTU, an allosteric antagonist

14、of P2Y1 receptor, blocks nerve mediated inhibitory neuromuscular responses in thegastrointestinal 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 compoundfor boron neutron capture therapy. Br J Cancer. 1994 Apr;6