Diaveridine-EGIS-5645-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEDiaveridineCat. No.: HY-B1902CAS No.: 5355-16-8Synonyms: EGIS-5645分式: CHNO分量: 260.29作靶點(diǎn): Antifolate; Bacterial作通路: Cell Cycle/DNA Damage; Anti-infection儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體

2、外實(shí)驗(yàn) DMSO : 32 mg/mL (122.94 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 3.8419 mL 19.2093 mL 38.4187 mL5 mM 0.7684 mL 3.8419 mL 7.6837 mL10 mM 0.3842 mL 1.9209 mL 3.8419 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Diaveridine (EGIS-5645)氫葉酸還原酶 (DHF

3、R) 的抑制劑，對(duì)于野型 DHFR 的 Ki 值為 11.5nM，Diaveridine 也 種抗菌劑。IC50 & Target Ki: 11.5 nM (DHFR) 1Bacterial 21/2 Master of Small Molecules 您邊的抑制劑師www.MedChemE體外研究 Diaveridine is a dihydrofolate reductase (DHFR) inhibitor with a Ki of 11.5 nM for the wild type DHFR andalso an antibacterial agent 1. Treatments wi

4、th Diaveridine for 90 min have a strong bactericidal effect on S.typhimurium TA1535, and no bacterial growth is observed at 10g/mL or more. Without metabolic activation,treatment with Diaveridine for 48 h, but not 24 h, causes a dose-dependent, significant increase in thefrequency of aberrant metaph

5、ases. At 100 g/mL, 60% of the metaphases contain chromosome aberrations2.體內(nèi)研究 The sperm abnormality of the Diaveridine (DVD) treatment groups at all dose levels (Diaveridine, 128 to 512mg/kg) shows no significant differences compare with the negative control group. There are no significantdifference

6、s of micronucleus between the negative control group and the Diaveridine treatment groups(Diaveridine, 128 to 512 mg/kg). The chromosome aberration of the Diaveridine treatment groups at all doselevels and the negative control group are significantly lower than those in the positive control group tr

7、eatedwith cyclophosphamide (P 3.PROTOCOLCell Assay 2 Cells are cultured at 37C in a humidified atmosphere of 5% CO2 in air. The growth medium is Eagles MEMsupplemented with 10% fetal bovine serum. In the experiment without metabolic activation, the cells aretreated for 24 or 48 h continuously withou

8、t a medium change. In the experiment with metabolic activation, thecells are pulse treated with test compounds (including Diaveridine) at varying doses for 6 h and incubated for18 h in fresh culture medium. Breakage type chromatid aberrations, exchange type chromatid aberrations,breakage type chromo

9、some aberrations, and exchange type chromosome aberrations are scored. Gaps arealso counted. Mitotic index is determined from scoring 2000 cells 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal 3Fifty male ICR mice, weighing 25 to 35 g, are assi

10、gned to five groups randomly with 10 mice in each group.Administration Mice in the experiment groups receive Diaveridine (DVD) via IG at ed 128 mg/kg (low doses), 256 mg/kg(medium doses), and 512 mg/kg (high doses) body weight for 5 consecutive days, respectively. Mice innegative and positive contro

11、l groups receive IG 1% CMC-Na solvent and 40 mg/kg body weight ofcyclophosphamide, respectively. The testing groups are administered 0.2 mL/10 g Diaveridine (mixed with1% of CMC-Na, to obtain the concentration of 2 mg/mL.) body weight, once a day, for 5 days. The behavioralchanges are recorded on th

12、e daily basis 3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Sirichaiwat C et al. Target guided synthesis of 5-benzyl-2,4-diamonopyrimidines: their antimalarial activities and binding affinities to wildtype and mutant dihydrofolate reduc

13、tases from Plasmodium falciparum. J Med Chem 47:345-54 (2004).2. Ono T, et al. The genotoxicity of diaveridine and trimethoprim. Environ Toxicol Pharmacol. 1997 Sep;3(4):297-306.3. Wang J, et al. Acute, mutagenicity, teratogenicity and subchronic oral toxicity studies of diaveridine in rodents. Environ ToxicolPharmacol. 2015 Sep;40(2):660-70.McePdfHeight2/2 Master of Small Molecules 您邊的抑制劑師ww