Diflunisal | CAS#22494-42-4 | Non-Steroidal Anti-Inflammatory

MedKoo Cat#: 317613 | Name: Diflunisal

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Diflunisal is a salicylic acid derivative with analgesic and anti-inflammatory activity. It was developed by Merck Sharp & Dohme in 1971 after showing promise in a research project studying more potent chemical analogs of aspirin. It was first sold under the brand name Dolobid, marketed by Merck & Co., but generic versions are now widely available. It is classed as a non-steroidal anti-inflammatory drug (NSAID).

Chemical Structure

Diflunisal

CAS#22494-42-4

Theoretical Analysis

MedKoo Cat#: 317613

Name: Diflunisal

CAS#: 22494-42-4

Chemical Formula: C13H8F2O3

Exact Mass: 250.0442

Molecular Weight: 250.20

Elemental Analysis: C, 62.41; H, 3.22; F, 15.19; O, 19.18

Price and Availability

Size	Price	Availability
1g	USD 250.00	2 Weeks
5g	USD 450.00	2 Weeks
10g	USD 650.00	2 Weeks
25g	USD 950.00	2 Weeks

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Related CAS #

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Synonym

MK-647; MK647; MK 647; Dolobid; Dolobis; Flovacil; Fluniget; Fluodonil; Dflunisal;

IUPAC/Chemical Name

2',4'-difluoro-4-hydroxy-[1,1'-biphenyl]-3-carboxylic acid

InChi Key

HUPFGZXOMWLGNK-UHFFFAOYSA-N

InChi Code

InChI=1S/C13H8F2O3/c14-8-2-3-9(11(15)6-8)7-1-4-12(16)10(5-7)13(17)18/h1-6,16H,(H,17,18)

SMILES Code

O=C(C1=CC(C2=CC=C(F)C=C2F)=CC=C1O)O

Appearance

White to off-white solid powder.

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Diflunisal (MK-647) is a salicylate derivative with nonsteroidal anti-inflammatory and uricosuric properties and is also a Cyclooxygenase (COX) Inhibitor.

In vitro activity:

Migration of mouse 3T3 fibroblasts toward HMGB1 were used as cellular readout, and it was found that DFL halved the number of migrating cells (IC50) already at a concentration below 10 nM, the lowest documented IC50 so far for HMGB1 inhibitors. NMR titration experiments of DFL into 0.1 mM 15N‐labeled CXCL12 clearly demonstrated an interaction between CXCL12 and DFL in fast exchange regime, with an apparent Kd of 800 ± 102 μM, in agreement with the millimolar affinity measured by MST (Kd = 2.6 ± 1.2 mM; Fig EV2A–C). The extent of dimer formation was assessed by monitoring CXCL12 chemical shift changes as a function of CXCL12 concentration, in the absence and in the presence of 1 mM DFL. The dimerization constants were 5.6 ± 0.4 and 2.1 ± 0.8 mM, respectively (Appendix Fig S5D), corresponding to an increase in dimer content from 3 to 8% for a 0.1 mM CXCL12 solution upon the addition of 1 mM DFL. DFL also significantly reduced the migration of 3T3 fibroblasts toward the preformed HMGB1/CXCL12 heterocomplex (Fig 2E). Reference: EMBO Rep. 2019 Oct 4;20(10):e47788. https://pubmed.ncbi.nlm.nih.gov/31418171/

In vivo activity:

The in vivo ability of DFL to inhibit the migration of inflammatory cells into injured muscle, which also depends on the HMGB1/CXCL12 heterocomplex was tested. Muscle injury was induced by a single dose of cardiotoxin in the tibialis anterior muscle of C57Bl/6 wild‐type mice, and the infiltration of leukocytes (CD45+ cells) in injured muscle was assessed 6 h later 32. DFL significantly decreased the recruitment of CD45+ cells into the injured muscle compared to vehicle‐treated mice (Fig 4C). These findings clarify the mode of action of diflunisal and open the way to the rational design of functionally specific anti-inflammatory drugs. Reference: EMBO Rep. 2019 Oct 4;20(10):e47788. https://pubmed.ncbi.nlm.nih.gov/31418171/

	Solvent	mg/mL	mM
Solubility
	DMSO	63.0	251.80
	Ethanol	23.0	91.93

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 250.20 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Duret G, Pereira FA, Raphael RM. Diflunisal inhibits prestin by chloride-dependent mechanism. PLoS One. 2017 Aug 17;12(8):e0183046. doi: 10.1371/journal.pone.0183046. PMID: 28817613; PMCID: PMC5560734. 2. De Leo F, Quilici G, Tirone M, De Marchis F, Mannella V, Zucchelli C, Preti A, Gori A, Casalgrandi M, Mezzapelle R, Bianchi ME, Musco G. Diflunisal targets the HMGB1/CXCL12 heterocomplex and blocks immune cell recruitment. EMBO Rep. 2019 Oct 4;20(10):e47788. doi: 10.15252/embr.201947788. Epub 2019 Aug 14. PMID: 31418171; PMCID: PMC6776901. 3. 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 Dec;211(3):678-85. PMID: 512931.

In vitro protocol:

In vivo protocol:

1. De Leo F, Quilici G, Tirone M, De Marchis F, Mannella V, Zucchelli C, Preti A, Gori A, Casalgrandi M, Mezzapelle R, Bianchi ME, Musco G. Diflunisal targets the HMGB1/CXCL12 heterocomplex and blocks immune cell recruitment. EMBO Rep. 2019 Oct 4;20(10):e47788. doi: 10.15252/embr.201947788. Epub 2019 Aug 14. PMID: 31418171; PMCID: PMC6776901. 2. 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 Dec;211(3):678-85. PMID: 512931.

1: Snetkov P, Morozkina S, Olekhnovich R, Uspenskaya M. Diflunisal Targeted Delivery Systems: A Review. Materials (Basel). 2021 Nov 6;14(21):6687. doi: 10.3390/ma14216687. PMID: 34772213; PMCID: PMC8588122. 2: Ibrahim M, Saint Croix GR, Lacy S, Fattouh M, Barillas-Lara MI, Behrooz L, Mechanic O. The use of diflunisal for transthyretin cardiac amyloidosis: a review. Heart Fail Rev. 2022 Mar;27(2):517-524. doi: 10.1007/s10741-021-10143-4. Epub 2021 Jul 16. PMID: 34272629. 3: Rubin J, Maurer MS. Cardiac Amyloidosis: Overlooked, Underappreciated, and Treatable. Annu Rev Med. 2020 Jan 27;71:203-219. doi: 10.1146/annurev- med-052918-020140. PMID: 31986086. 4: Azanza Perea JR, Honorato Pérez JM, Cuena Boy R. Diflunisal [Diflunisal]. Rev Med Univ Navarra. 1982 Dec;26(4):253-4. Spanish. PMID: 7182898. 5: Brogden RN, Heel RC, Pakes GE, Speight TM, Avery GS. Diflunisal: a review of its pharmacological properties and therapeutic use in pain and musculoskeletal strains and sprains and pain in osteoarthritis. Drugs. 1980 Feb;19(2):84-106. doi: 10.2165/00003495-198019020-00002. PMID: 6988202. 6: McLean CA, Begley CG, Harris RA. Diflunisal-induced neutropenia. Aust N Z J Med. 1986 Dec;16(6):811-2. doi: 10.1111/j.1445-5994.1986.tb00046.x. PMID: 3471201. 7: Ford CA, Spoonmore TJ, Gupta MK, Duvall CL, Guelcher SA, Cassat JE. Diflunisal-loaded poly(propylene sulfide) nanoparticles decrease S. aureus- mediated bone destruction during osteomyelitis. J Orthop Res. 2021 Feb;39(2):426-437. doi: 10.1002/jor.24948. Epub 2020 Dec 20. PMID: 33300149; PMCID: PMC7855846. 8: Wasey JO, Derry S, Moore RA, McQuay HJ. Single dose oral diflunisal for acute postoperative pain in adults. Cochrane Database Syst Rev. 2010 Apr 14;2010(4):CD007440. doi: 10.1002/14651858.CD007440.pub2. PMID: 20393958; PMCID: PMC4164831. 9: Lawton GM, Chapman PJ. Diflunisal--a long-acting non-steroidal anti- inflammatory drug. A review of its pharmacology and effectiveness in management of postoperative dental pain. Aust Dent J. 1993 Aug;38(4):265-71. doi: 10.1111/j.1834-7819.1993.tb05494.x. PMID: 8216032. 10: Nedkova-Hristova V, Baliellas C, González-Costello J, Lladó L, González- Vilatarsana E, Vélez-Santamaría V, Casasnovas C. Treatment With Diflunisal in Domino Liver Transplant Recipients With Acquired Amyloid Neuropathy. Transpl Int. 2022 Apr 13;35:10454. doi: 10.3389/ti.2022.10454. PMID: 35497887; PMCID: PMC9044119. 11: Yang Y, Borel T, de Azambuja F, Johnson D, Sorrentino JP, Udokwu C, Davis I, Liu A, Altman RA. Diflunisal Derivatives as Modulators of ACMS Decarboxylase Targeting the Tryptophan-Kynurenine Pathway. J Med Chem. 2021 Jan 14;64(1):797-811. doi: 10.1021/acs.jmedchem.0c01762. Epub 2020 Dec 28. PMID: 33369426; PMCID: PMC7856275. 12: Duret G, Pereira FA, Raphael RM. Diflunisal inhibits prestin by chloride- dependent mechanism. PLoS One. 2017 Aug 17;12(8):e0183046. doi: 10.1371/journal.pone.0183046. PMID: 28817613; PMCID: PMC5560734. 13: Sekijima Y. Transthyretin (ATTR) amyloidosis: clinical spectrum, molecular pathogenesis and disease-modifying treatments. J Neurol Neurosurg Psychiatry. 2015 Sep;86(9):1036-43. doi: 10.1136/jnnp-2014-308724. Epub 2015 Jan 20. PMID: 25604431. 14: Fishel B, Weiss S, Yaron M. Diflunisal in rheumatoid arthritis. Inflammation. 1981 Sep;5(3):253-61. doi: 10.1007/BF00914448. PMID: 7028626. 15: Siddiqi OK, Mints YY, Berk JL, Connors L, Doros G, Gopal DM, Kataria S, Lohrmann G, Pipilas AR, Ruberg FL. Diflunisal treatment is associated with improved survival for patients with early stage wild-type transthyretin (ATTR) amyloid cardiomyopathy: the Boston University Amyloidosis Center experience. Amyloid. 2022 Jun;29(2):71-78. doi: 10.1080/13506129.2021.2000388. Epub 2022 Jan 27. PMID: 35083944; PMCID: PMC9258521. 16: Ikram A, Donnelly JP, Sperry BW, Samaras C, Valent J, Hanna M. Diflunisal tolerability in transthyretin cardiac amyloidosis: a single center's experience. Amyloid. 2018 Sep;25(3):197-202. doi: 10.1080/13506129.2018.1519507. Epub 2018 Nov 2. PMID: 30388377. 17: Davies RO. Review of the animal and clinical pharmacology of diflunisal. Pharmacotherapy. 1983 Mar-Apr;3(2 Pt 2):9S-22S. PMID: 6344042. 18: Castaño A, Helmke S, Alvarez J, Delisle S, Maurer MS. Diflunisal for ATTR cardiac amyloidosis. Congest Heart Fail. 2012 Nov-Dec;18(6):315-9. doi: 10.1111/j.1751-7133.2012.00303.x. Epub 2012 Jul 2. PMID: 22747647; PMCID: PMC3727153. 19: De Leo F, Quilici G, Tirone M, De Marchis F, Mannella V, Zucchelli C, Preti A, Gori A, Casalgrandi M, Mezzapelle R, Bianchi ME, Musco G. Diflunisal targets the HMGB1/CXCL12 heterocomplex and blocks immune cell recruitment. EMBO Rep. 2019 Oct 4;20(10):e47788. doi: 10.15252/embr.201947788. Epub 2019 Aug 14. PMID: 31418171; PMCID: PMC6776901. 20: Abe DO , Eskandari A , Suntharalingam K . Diflunisal-adjoined cobalt(iii)-polypyridyl complexes as anti-cancer stem cell agents. Dalton Trans. 2018 Oct 9;47(39):13761-13765. doi: 10.1039/c8dt03448f. PMID: 30225483.