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Diflunisal

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Chemical Structure| 22494-42-4 同义名 : MK-647;5-(2,4-Difluorophenyl)salicylic Acid;Dflunisal;Fluodonil;Fluniget;Flovacil;Dolobis;Dolobid
CAS号 : 22494-42-4
货号 : A193875
分子式 : C13H8F2O3
纯度 : 98%
分子量 : 250.2
MDL号 : MFCD00057834
存储条件：

粉末 Keep in dark place,Sealed in dry,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(199.84 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • COX
描述 Diflunisal, a nonsteroidal anti-inflammatory agent, stabilizes transthyretin tetramers and prevents amyloid fibril formation in vitro. Among patients with familial amyloid polyneuropathy, the use of diflunisal compared with placebo for 2 years reduced the rate of progression of neurological impairment and preserved quality of life[3]. Diflunisal exhibits activity after oral administration with potency about 25 times greater than that of aspirin, about 3 times that of glafenine and twice that of zomepirac. Repeated administration of large doses produced neither tolerance nor sensitization to the analgesic action of diflunisal[4]. Administration of increasing doses of diflunisal to rats shows that the effect of the dose on the pharmacokinetics of diflunisal is quite complicated. The CLp is reduced considerably when the dose increases from 3 to 10 mg/kg and then remains relatively constant over the dose range of 10 to 60 mg/kg. Diflunisal has been shown to be highly bound to rat plasma protein and dependent on concentration. The fraction of unbound diflunisal is increased about 10-fold over the concentration range of 5 to 300 μg/mL[5]. Diflunisal, an aspirin-like nonsteroidal anti-inflammatory drug (NSAID), specifically inhibits in vitro and in vivo the chemotactic activity of HMGB1 at nanomolar concentrations, at least in part by binding directly to both HMGB1 and CXCL12 and disrupting their heterocomplex[6].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

4.00mL

0.80mL

0.40mL

19.98mL

4.00mL

2.00mL

39.97mL

7.99mL

4.00mL
参考文献

[1]Shirakawa K, Wang L, Man N, et al. Salicylate, diflunisal and their metabolites inhibit CBP/p300 and exhibit anticancer activity. Elife. 2016 May 31;5. pii: e11156.

[2]Cappon GD, Cook JC, Hurtt ME. Relationship between cyclooxygenase 1 and 2 selective inhibitors and fetal development when administered to rats and rabbits during the sensitive periods for heart development and midline closure. Birth Defects Res B Dev Reprod Toxicol. 2003 Feb;68(1):47-56.

[3]Berk JL, Suhr OB, Obici L, et al. Repurposing diflunisal for familial amyloid polyneuropathy: a randomized clinical trial. JAMA. 2013;310(24):2658-2667

[4]Winter CA, Kling PJ, Tocco DJ, Tanabe K. Analgesic activity of diflunisal [MK-647; 5-(2,4-difluorophenyl)salicylic acid] in rats with hyperalgesia induced by Freund's adjuvant. J Pharmacol Exp Ther. 1979;211(3):678-685

[5]Lin JH, Hooke KF, Yeh KC, Duggan DE. Dose-dependent pharmacokinetics of diflunisal in rats: dual effects of protein binding and metabolism. J Pharmacol Exp Ther. 1985;235(2):402-406

[6]De Leo F, Quilici G, Tirone M, et al. Diflunisal targets the HMGB1/CXCL12 heterocomplex and blocks immune cell recruitment. EMBO Rep. 2019;20(10):e47788