Diflapolin | CAS#724453-98-9 | FLAP inhibitor

MedKoo Cat#: 471026 | Name: Diflapolin

Description:

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

Diflapolin is a potent dual soluble epoxide hydrolase (sEH)/5-lipoxygenase-activating protein (FLAP) inhibitor. It inhibits formation of the 5-lipoxygenase (5-LO) products leukotriene B4 (LTB4) and 5-HpETE in isolated human monocytes and neutrophils (IC50s = 30 and 170 nM, respectively) and inhibits the epoxide hydrolase activity of sEH with an IC50 value of 20 nM in a cell-free assay.

Chemical Structure

Diflapolin

CAS#724453-98-9

Theoretical Analysis

MedKoo Cat#: 471026

Name: Diflapolin

CAS#: 724453-98-9

Chemical Formula: C22H17Cl2N3O2S

Exact Mass: 457.0419

Molecular Weight: 458.36

Elemental Analysis: C, 57.65; H, 3.74; Cl, 15.47; N, 9.17; O, 6.98; S, 6.99

Price and Availability

Size	Price	Availability
25mg	USD 350.00	2 Weeks
50mg	USD 550.00	2 Weeks
100mg	USD 950.00	2 Weeks
200mg	USD 1,550.00	2 Weeks
500mg	USD 2,650.00	2 Weeks
1g	USD 3,650.00	2 Weeks
2g	USD 5,950.00	2 Weeks

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Related CAS #

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Synonym

Diflapolin

IUPAC/Chemical Name

1-(4-(benzo[d]thiazol-2-ylmethoxy)-2-methylphenyl)-3-(3,4-dichlorophenyl)urea

InChi Key

FGXLEECGXSDIMM-UHFFFAOYSA-N

InChi Code

InChI=1S/C22H17Cl2N3O2S/c1-13-10-15(29-12-21-26-19-4-2-3-5-20(19)30-21)7-9-18(13)27-22(28)25-14-6-8-16(23)17(24)11-14/h2-11H,12H2,1H3,(H2,25,27,28)

SMILES Code

O=C(NC1=CC=C(Cl)C(Cl)=C1)NC2=CC=C(OCC3=NC4=CC=CC=C4S3)C=C2C

Appearance

Solid powder

Purity

>97% (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

Shelf Life

>3 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:

Diflapolin is a highly active dual 5-lipoxygenase-activating protein (FLAP)/soluble epoxide hydrolase (sEH) inhibitor with marked anti-inflammatory efficacy and high target selectivity that inhibits 5-LOX product formation in intact human monocytes and neutrophils with IC50s of 30 and 170 nM, respectively.

In vitro activity:

To confirm the hypothesis that diflapolin acts as FLAP inhibitor, the suppression of 5-LOX product formation in stably transfected HEK293 cells that either express 5-LOX plus FLAP or 5-LOX alone was studied. Diflapolin strongly inhibited 5-LOX product formation in intact HEK293 cells expressing both 5-LOX and FLAP, whereas in HEK293 cells deficient in FLAP, 5-LOX product formation was hardly impaired by diflapolin (Fig. 1e). Together, these data show that diflapolin inhibits 5-LOX product formation only when FLAP is operative supporting FLAP as target of diflapolin. Reference: Sci Rep. 2017 Aug 24;7(1):9398. https://pubmed.ncbi.nlm.nih.gov/28839250/

In vivo activity:

The anti-inflammatory effectiveness of diflapolin was next investigated in the zymosan-induced peritonitis mouse model39 that is strongly related to the pathophysiological activities of LTs. Diflapolin pre-treatment (1, 3 and 10 mg/kg, i.p. 30 min before zymosan injection) induced a significant reduction of LTC4 and LTB4 peritoneal levels, starting from the dose of 1 mg/kg (Fig. 5a and b) and comparable to the effect of MK886 (1 mg/kg, i.p. 30 min before zymosan). Since LTB4 is a major chemoattractant for leukocytes, diflapolin and MK886 caused concomitant block of leukocyte recruitment, which was dose-dependent for diflapolin (Fig. 5c). Accordingly, at the dose of 10 mg/kg, diflapolin inhibited the activity of MPO, a typical marker protein for neutrophils to 52.8 ± 12.2% (mean ± SEM) vs. vehicle control and reduced vascular permeability to 55.7 ± 14.4% (mean ± SEM) vs. vehicle control (Table 1), compared to inhibitory effects of MK886 (1 and 3 mg/kg) to 58.5 ± 10.6% and 48.6 ± 3.2%, respectively. Reference: Sci Rep. 2017 Aug 24;7(1):9398. https://pubmed.ncbi.nlm.nih.gov/28839250/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	42.0	91.63

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 458.36 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. Garscha U, Romp E, Pace S, Rossi A, Temml V, Schuster D, König S, Gerstmeier J, Liening S, Werner M, Atze H, Wittmann S, Weinigel C, Rummler S, Scriba GK, Sautebin L, Werz O. Pharmacological profile and efficiency in vivo of diflapolin, the first dual inhibitor of 5-lipoxygenase-activating protein and soluble epoxide hydrolase. Sci Rep. 2017 Aug 24;7(1):9398. doi: 10.1038/s41598017-09795-w. PMID: 28839250; PMCID: PMC5571211.

In vitro protocol:

In vivo protocol:

1: Vieider L, Zoeller E, Romp E, Schoenthaler M, Hernández-Olmos V, Temml V, Hasenoehrl T, Schuster D, Werz O, Garscha U, Matuszczak B. Synthesis and structure-activity relationships for some novel diflapolin derivatives with benzimidazole subunit. J Enzyme Inhib Med Chem. 2022 Dec;37(1):1752-1764. doi: 10.1080/14756366.2022.2087645. PMID: 36124840; PMCID: PMC9518245. 2: Grune C, Kretzer C, Zergiebel S, Kattner S, Thamm J, Hoeppener S, Werz O, Fischer D. Encapsulation of the Anti-inflammatory Dual FLAP/sEH Inhibitor Diflapolin Improves the Efficiency in Human Whole Blood. J Pharm Sci. 2022 Jun;111(6):1843-1850. doi: 10.1016/j.xphs.2021.10.030. Epub 2021 Oct 29. PMID: 34756868. 3: Schoenthaler M, Waltl L, Hasenoehrl T, Seher D, Lutz A, Aulinger L, Temml V, König S, Siller A, Braun DE, Garscha U, Werz O, Schuster D, Schennach H, Koeberle A, Matuszczak B. Novel thiazolopyridine derivatives of diflapolin as dual sEH/FLAP inhibitors with improved solubility. Bioorg Chem. 2023 Oct;139:106685. doi: 10.1016/j.bioorg.2023.106685. Epub 2023 Jun 28. PMID: 37418786. 4: Garscha U, Romp E, Pace S, Rossi A, Temml V, Schuster D, König S, Gerstmeier J, Liening S, Werner M, Atze H, Wittmann S, Weinigel C, Rummler S, Scriba GK, Sautebin L, Werz O. Pharmacological profile and efficiency in vivo of diflapolin, the first dual inhibitor of 5-lipoxygenase-activating protein and soluble epoxide hydrolase. Sci Rep. 2017 Aug 24;7(1):9398. doi: 10.1038/s41598-017-09795-w. PMID: 28839250; PMCID: PMC5571211. 5: Vieider L, Romp E, Temml V, Fischer J, Kretzer C, Schoenthaler M, Taha A, Hernández-Olmos V, Sturm S, Schuster D, Werz O, Garscha U, Matuszczak B. Synthesis, Biological Evaluation and Structure-Activity Relationships of Diflapolin Analogues as Dual sEH/FLAP Inhibitors. ACS Med Chem Lett. 2018 Nov 29;10(1):62-66. doi: 10.1021/acsmedchemlett.8b00415. PMID: 30655948; PMCID: PMC6331193.

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TK-129

MedKoo CAT#: 208483

CAS#: unknown