Paquinimod
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MedKoo CAT#: 319595

CAS#: 248282-01-1

Description: Paquinimod, also known as ABR‑215757, is a S100A9 inhibitor preventing S100A9 binding to TLR-4. Paquinimod reduces pathology in experimental collagenase-induced osteoarthritis. Paquinimod treatment of collagenase-induced OA (CIOA) resulted in significantly reduced synovial thickening (57%), osteophyte size at the medial femur (66%) and cruciate ligaments (67%) and cartilage damage at the medial tibia (47%) and femur (75%; n=7, untreated n=6). Paquinimod reduces leukocyte recruitment during sterile inflammation. Paquinimod also reduced priming of proinflammatory effector CD4(+) T cells.

Chemical Structure

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Paquinimod
CAS# 248282-01-1
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 319595
Name: Paquinimod
CAS#: 248282-01-1
Chemical Formula: C21H22N2O3
Exact Mass: 350.16
Molecular Weight: 350.420
Elemental Analysis: C, 71.98; H, 6.33; N, 7.99; O, 13.70

Price and Availability

Size Price Availability Quantity
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1350 Ready to ship
500mg USD 2650 Ready to ship
1g USD 3850 Ready to ship
2g USD 6250 Ready to ship
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Synonym: ABR‑215757; ABR 215757; ABR215757; Paquinimod.

IUPAC/Chemical Name: N,5-diethyl-4-hydroxy-1-methyl-2-oxo-N-phenyl-1,2-dihydroquinoline-3-carboxamide

InChi Key: DIKSYHCCYVYKRO-UHFFFAOYSA-N

InChi Code: InChI=1S/C21H22N2O3/c1-4-14-10-9-13-16-17(14)19(24)18(20(25)22(16)3)21(26)23(5-2)15-11-7-6-8-12-15/h6-13,24H,4-5H2,1-3H3

SMILES Code: O=C(C1=C(O)C2=C(N(C)C1=O)C=CC=C2CC)N(CC)C3=CC=CC=C3

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:

Biological target: Paquinimod (ABR 25757) is a specific inhibitor of S100A8/S100A9.
In vitro activity: The purporse of this study was to investigate the role of damage-associated molecular patterns (DAMPs) in recurrent experimental autoimmune uveitis (EAU). Paquinimod (PA) is a drug that is an S100 inhibitor and blocks the binding of S100A8/A9. S100A8, an important DMAP member is a small-sized 10-kDa molecule and preferentially exists as a heterodimer or heterotetramer with S100A9, known as calprotectin (S100A8/A9). These molecules are highly expressed on bone marrow-derived myeloid cells, specifically neutrophils and monocytes, and on endothelial cells. To examine whether the reduced proliferation of lymphocytes was a direct effect of the S100A8/9 inhibitor on T cells or an indirect effect on T cells via APCs, crossover tests were performed in which T cell proliferation was measured using all four combinations of responder T cells and APCs isolated on day 16 from the two sets. APCs were incubated in vitro with recombinant S100A8. As shown in Figure 5, T cells from PA-treated tEAU rats did not respond to increasing doses of R16 in the presence of APCs from either PA-treated or control tEAU rats, whereas T cells from control tEAU rats reacted well in the presence of APCs from control tEAU rats, but not PA-treated tEAU rats, indicating that dysfunction of both T cells and APCs contributed to the T cell hyporesponsiveness in PA-treated mice. This data demonstrate a link between local expression of DAMPs and autoimmune responses, and suggest that complete S100A8/A9 blockade may be a new therapeutic target in recurrent autoimmune uveitis. Reference: Invest Ophthalmol Vis Sci. 2018 Mar 1;59(3):1332-1342. https://pubmed.ncbi.nlm.nih.gov/29625456/
In vivo activity: Paquinimod was orally administered to 6-week-old C57BL/6 mice sensitized and challenged with ovalbumin (OVA)/complete Freund's adjuvant (CFA) and OVA. Lung inflammation and remodeling were evaluated using bronchoalveolar lavage (BAL) and histologic findings including goblet cell count. S100A9, caspase-1, IL-1β, MPO, IL-17, IFN-γ, and TNF-α were measured in lung lysates using western blotting. Paquinimod restored the enhancement of airway resistance and the increases in numbers of neutrophils and macrophages of BAL fluids and those of goblet cells in OVA/CFA mice toward the levels of sham-treated mice in a dose-dependent manner (0.1, 1, 10, and 25 mg/kg/day, p.o.). These data indicate that paquinimod effectively inhibits neutrophilic inflammation and remodeling in the murine model of neutrophilic asthma, possibly via downregulation of IL-17, IFN-γ, and IL-1β. Reference: Can Respir J . 2021 Mar 15;2021:8896108. https://pubmed.ncbi.nlm.nih.gov/33791048/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 15.0 42.80

Preparing Stock Solutions

The following data is based on the product molecular weight 350.42 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.

Recalculate based on batch purity %
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. Yun J, Xiao T, Zhou L, Beuerman RW, Li J, Zhao Y, Hadayer A, Zhang X, Sun D, Kaplan HJ, Shao H. Local S100A8 Levels Correlate With Recurrence of Experimental Autoimmune Uveitis and Promote Pathogenic T Cell Activity. Invest Ophthalmol Vis Sci. 2018 Mar 1;59(3):1332-1342. doi: 10.1167/iovs.17-23127. PMID: 29625456; PMCID: PMC5846334. 2. Tahvili S, Törngren M, Holmberg D, Leanderson T, Ivars F. Paquinimod prevents development of diabetes in the non-obese diabetic (NOD) mouse. PLoS One. 2018 May 9;13(5):e0196598. doi: 10.1371/journal.pone.0196598. PMID: 29742113; PMCID: PMC5942776. 3. Lee JU, Park JS, Jun JA, Kim MK, Chang HS, Baek DG, Song HJ, Kim MS, Park CS. Inhibitory Effect of Paquinimod on a Murine Model of Neutrophilic Asthma Induced by Ovalbumin with Complete Freund's Adjuvant. Can Respir J. 2021 Mar 15;2021:8896108. doi: 10.1155/2021/8896108. PMID: 33791048; PMCID: PMC7984926.
In vitro protocol: 1. Yun J, Xiao T, Zhou L, Beuerman RW, Li J, Zhao Y, Hadayer A, Zhang X, Sun D, Kaplan HJ, Shao H. Local S100A8 Levels Correlate With Recurrence of Experimental Autoimmune Uveitis and Promote Pathogenic T Cell Activity. Invest Ophthalmol Vis Sci. 2018 Mar 1;59(3):1332-1342. doi: 10.1167/iovs.17-23127. PMID: 29625456; PMCID: PMC5846334.
In vivo protocol: 1.Tahvili S, Törngren M, Holmberg D, Leanderson T, Ivars F. Paquinimod prevents development of diabetes in the non-obese diabetic (NOD) mouse. PLoS One. 2018 May 9;13(5):e0196598. doi: 10.1371/journal.pone.0196598. PMID: 29742113; PMCID: PMC5942776. 2. Lee JU, Park JS, Jun JA, Kim MK, Chang HS, Baek DG, Song HJ, Kim MS, Park CS. Inhibitory Effect of Paquinimod on a Murine Model of Neutrophilic Asthma Induced by Ovalbumin with Complete Freund's Adjuvant. Can Respir J. 2021 Mar 15;2021:8896108. doi: 10.1155/2021/8896108. PMID: 33791048; PMCID: PMC7984926.

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1: Schelbergen RF, Geven EJ, van den Bosch MH, Eriksson H, Leanderson T, Vogl T, Roth J, van de Loo FA, Koenders MI, van der Kraan PM, van den Berg WB, Blom AB, van Lent PL. Prophylactic treatment with S100A9 inhibitor paquinimod reduces pathology in experimental collagenase-induced osteoarthritis. Ann Rheum Dis. 2015 Dec;74(12):2254-8. doi: 10.1136/annrheumdis-2014-206517. Epub 2015 May 12. PubMed PMID: 25969431.

2: Wache C, Klein M, Ostergaard C, Angele B, Häcker H, Pfister HW, Pruenster M, Sperandio M, Leanderson T, Roth J, Vogl T, Koedel U. Myeloid-related protein 14 promotes inflammation and injury in meningitis. J Infect Dis. 2015 Jul 15;212(2):247-57. doi: 10.1093/infdis/jiv028. Epub 2015 Jan 20. PubMed PMID: 25605866.

3: Deronic A, Helmersson S, Leanderson T, Ivars F. The quinoline-3-carboxamide paquinimod (ABR-215757) reduces leukocyte recruitment during sterile inflammation: leukocyte- and context-specific effects. Int Immunopharmacol. 2014 Feb;18(2):290-7. doi: 10.1016/j.intimp.2013.12.008. Epub 2013 Dec 23. PubMed PMID: 24370393.

4: Helmersson S, Sundstedt A, Deronic A, Leanderson T, Ivars F. Amelioration of experimental autoimmune encephalomyelitis by the quinoline-3-carboxamide paquinimod: reduced priming of proinflammatory effector CD4(+) T cells. Am J Pathol. 2013 May;182(5):1671-80. doi: 10.1016/j.ajpath.2013.01.032. Epub 2013 Mar 16. PubMed PMID: 23506849.

5: Yan L, Bjork P, Butuc R, Gawdzik J, Earley J, Kim G, Hofmann Bowman MA. Beneficial effects of quinoline-3-carboxamide (ABR-215757) on atherosclerotic plaque morphology in S100A12 transgenic ApoE null mice. Atherosclerosis. 2013 May;228(1):69-79. doi: 10.1016/j.atherosclerosis.2013.02.023. Epub 2013 Feb 28. PubMed PMID: 23497784; PubMed Central PMCID: PMC3640742.

6: Bengtsson AA, Sturfelt G, Lood C, Rönnblom L, van Vollenhoven RF, Axelsson B, Sparre B, Tuvesson H, Ohman MW, Leanderson T. Pharmacokinetics, tolerability, and preliminary efficacy of paquinimod (ABR-215757), a new quinoline-3-carboxamide derivative: studies in lupus-prone mice and a multicenter, randomized, double-blind, placebo-controlled, repeat-dose, dose-ranging study in patients with systemic lupus erythematosus. Arthritis Rheum. 2012 May;64(5):1579-88. doi: 10.1002/art.33493. PubMed PMID: 22131101.