Apafant | WEB-2086 | CAS#105219-56-5 | PAF receptor antagonist

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

MedKoo CAT#: 326905

CAS#: 105219-56-5

Description: Apafant, also known as DE-081; WEB-2086; WEB-2086BS, is a platelet activating factor (PAF) inhibitor potentially for the treatment of asthma and allergic rhinitis (AR). Apafant blocks eosinophil activation and is effective in the chronic phase of experimental allergic conjunctivitis in guinea pigs. Apafant suppresses the early and late airway responses in guinea pigs: a comparison with antiasthmatic drugs.

Chemical Structure

Apafant

CAS# 105219-56-5

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 326905
Name: Apafant
CAS#: 105219-56-5
Chemical Formula: C22H22ClN5O2S
Exact Mass: 455.12
Molecular Weight: 455.961
Elemental Analysis: C, 57.95; H, 4.86; Cl, 7.77; N, 15.36; O, 7.02; S, 7.03

Price and Availability

Size	Price	Availability	Quantity
1mg	USD 160
5mg	USD 240
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: DE-081; WEB-2086; WEB2086; WEB2086; WEB-2086BS; Apafant.

IUPAC/Chemical Name: 4-(3-(4-(o-Chlorophenyl)-9-methyl-6H-thieno(3,2-f)-s-triazolo(4,3-a)(1,4)diazepin-2-yl)propionyl)morpholine

InChi Key: JGPJQFOROWSRRS-UHFFFAOYSA-N

InChi Code: InChI=1S/C22H22ClN5O2S/c1-14-25-26-19-13-24-21(16-4-2-3-5-18(16)23)17-12-15(31-22(17)28(14)19)6-7-20(29)27-8-10-30-11-9-27/h2-5,12H,6-11,13H2,1H3

SMILES Code: O=C(N1CCOCC1)CCC(S2)=CC3=C2N4C(CN=C3C5=CC=CC=C5Cl)=NN=C4C

Appearance: 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

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:

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Biological target:	Apafant (WEB 2086) inhibits PAF binding to human PAF receptors with a Ki of 9.9 nM.
In vitro activity:	WEB-2086 decreased S. pneumoniae adhesion to CSE-treated BEAS-2B cells back to control levels at a concentration of 100 nM (P=0.0058) (Figure 4A–C). WEB-2086 at 10 μM, but not at lower concentrations, also reduced adhesion of the reference strain of NTHi to CSE-treated cells to control levels (P<0.0001) (Figure 4D). Adhesion of the clinical strain of NTHi to CSE-treated BEAS-2B cells was reduced to control levels by WEB-2086 at a concentration of 1 μM (Figure 4E). WEB-2086 was nontoxic to epithelial cells at the highest concentration tested, that is, IC50 >10 μM. Reference: Int J Chron Obstruct Pulmon Dis. 2016; 11: 1647–1655. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965220/
In vivo activity:	PAF dose-dependently induced oxidative stress that was blocked by WEB-2086 (100 μM) or N-acetylcysteine (10 mM) (Fig. 2A). The concentrations of PAF, WEB-2086, and N-acetylcysteine used in these studies were not toxic to peritoneal macrophages as shown by the LDH cytotoxicity assay (data not shown). In addition, WEB-2086 (10 μM, 100 μM, and 1000 μM) dose-dependently inhibited H2O2-induced oxidative stress in mouse macrophages (Fig. 2B). This result indicates that PAF causes oxidative stress and that the PAF-R antagonist WEB-2086 also has antioxidant properties. Reference: Free Radic Biol Med. 2019 Nov 1;143:275-287. https://pubmed.ncbi.nlm.nih.gov/31442556/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMSO	34.1	74.72
	DMF	14.3	31.36
	Ethanol	25.3	55.49
	PBS (pH 7.2)	0.3	0.55

Preparing Stock Solutions

The following data is based on the product molecular weight 455.96 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. Shukla SD, Fairbairn RL, Gell DA, Latham RD, Sohal SS, Walters EH, O'Toole RF. An antagonist of the platelet-activating factor receptor inhibits adherence of both nontypeable Haemophilus influenzae and Streptococcus pneumoniae to cultured human bronchial epithelial cells exposed to cigarette smoke. Int J Chron Obstruct Pulmon Dis. 2016 Jul 25;11:1647-55. doi: 10.2147/COPD.S108698. PMID: 27524890; PMCID: PMC4965220. 2. Machado EM, Azambuja P, Garcia ES. WEB 2086, a platelet-activating factor antagonist, inhibits prophenoloxidase-activating system and hemocyte microaggregation reactions induced by Trypanosoma rangeli infection in Rhodnius prolixus hemolymph. J Insect Physiol. 2006 Jul;52(7):685-92. doi: 10.1016/j.jinsphys.2006.03.008. Epub 2006 Apr 5. PMID: 16777137. 3. Abhilasha KV, Sumanth MS, Chaithra VH, Jacob SP, Thyagarajan A, Sahu RP, Rajaiah R, Prabhu KS, Kemparaju K, Travers JB, Chen CH, Marathe GK. p38 MAP-kinase inhibitor protects against platelet-activating factor-induced death in mice. Free Radic Biol Med. 2019 Nov 1;143:275-287. doi: 10.1016/j.freeradbiomed.2019.08.019. Epub 2019 Aug 20. PMID: 31442556. 4. Gao T, Yu Y, Cong Q, Wang Y, Sun M, Yao L, Xu C, Jiang W. Human mesenchymal stem cells in the tumour microenvironment promote ovarian cancer progression: the role of platelet-activating factor. BMC Cancer. 2018 Oct 19;18(1):999. doi: 10.1186/s12885-018-4918-0. PMID: 30340558; PMCID: PMC6241787.
In vitro protocol:	1. Shukla SD, Fairbairn RL, Gell DA, Latham RD, Sohal SS, Walters EH, O'Toole RF. An antagonist of the platelet-activating factor receptor inhibits adherence of both nontypeable Haemophilus influenzae and Streptococcus pneumoniae to cultured human bronchial epithelial cells exposed to cigarette smoke. Int J Chron Obstruct Pulmon Dis. 2016 Jul 25;11:1647-55. doi: 10.2147/COPD.S108698. PMID: 27524890; PMCID: PMC4965220. 2. Machado EM, Azambuja P, Garcia ES. WEB 2086, a platelet-activating factor antagonist, inhibits prophenoloxidase-activating system and hemocyte microaggregation reactions induced by Trypanosoma rangeli infection in Rhodnius prolixus hemolymph. J Insect Physiol. 2006 Jul;52(7):685-92. doi: 10.1016/j.jinsphys.2006.03.008. Epub 2006 Apr 5. PMID: 16777137.
In vivo protocol:	1. Abhilasha KV, Sumanth MS, Chaithra VH, Jacob SP, Thyagarajan A, Sahu RP, Rajaiah R, Prabhu KS, Kemparaju K, Travers JB, Chen CH, Marathe GK. p38 MAP-kinase inhibitor protects against platelet-activating factor-induced death in mice. Free Radic Biol Med. 2019 Nov 1;143:275-287. doi: 10.1016/j.freeradbiomed.2019.08.019. Epub 2019 Aug 20. PMID: 31442556. 2. Gao T, Yu Y, Cong Q, Wang Y, Sun M, Yao L, Xu C, Jiang W. Human mesenchymal stem cells in the tumour microenvironment promote ovarian cancer progression: the role of platelet-activating factor. BMC Cancer. 2018 Oct 19;18(1):999. doi: 10.1186/s12885-018-4918-0. PMID: 30340558; PMCID: PMC6241787.

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1: Ikegami K, Hata H, Fuchigami J, Tanaka K, Kohjimoto Y, Uchida S, Tasaka K. Apafant (a PAF receptor antagonist) suppresses the early and late airway responses in guinea pigs: a comparison with antiasthmatic drugs. Eur J Pharmacol. 1997 Jun 5;328(1):75-81. doi: 10.1016/s0014-2999(97)83031-2. PMID: 9203572.

2: Kato M, Imoto K, Miyake H, Oda T, Miyaji S, Nakamura M. Apafant, a potent platelet-activating factor antagonist, blocks eosinophil activation and is effective in the chronic phase of experimental allergic conjunctivitis in guinea pigs. J Pharmacol Sci. 2004 Aug;95(4):435-42. doi: 10.1254/jphs.fp0040265. Epub 2004 Jul 31. PMID: 15286429.

3: Akagi M, Nishioka E, Kanoh R, Tachibana M, Fukuishi N. Inhibitor effect of apafant on bronchopulmonary responses to platelet activating factor and to antigen in rats. Arzneimittelforschung. 1997 Dec;47(12):1364-9. PMID: 9450165.

4: Leusch A, Volz A, Müller G, Wagner A, Sauer A, Greischel A, Roth W. Altered drug disposition of the platelet activating factor antagonist apafant in mdr1a knockout mice. Eur J Pharm Sci. 2002 Aug;16(3):119-28. doi: 10.1016/s0928-0987(02)00088-x. PMID: 12128165.

5: Ring PC, Seldon PM, Barnes PJ, Giembycz MA. Pharmacological characterization of a receptor for platelet-activating factor on guinea pig peritoneal macrophages using [3H]apafant, a selective and competitive platelet-activating factor antagonist: evidence that the noncompetitive behavior of apafant in functional studies relates to slow kinetics of dissociation. Mol Pharmacol. 1993 Feb;43(2):302-12. PMID: 8381515.

6: Kato M, Kurose T, Oda T, Miyaji S. The role of platelet activating factor and the efficacy of apafant ophthalmic solution in experimental allergic conjunctivitis. J Ocul Pharmacol Ther. 2003 Aug;19(4):315-24. doi: 10.1089/108076803322279372. PMID: 12964956.

7: Sugimoto Y, Mihara T, Hayakawa T, Nakayama Y, Kishida H, Kamei C. Effect of Apafant on bronchial hyperresponsiveness and down-regulation of beta- adrenoceptors induced by endotoxin in guinea pigs. Arzneimittelforschung. 1997 Jul;47(7):837-41. PMID: 9272241.

8: Fuchs H, Kishimoto W, Gansser D, Tanswell P, Ishiguro N. Brain penetration of WEB 2086 (Apafant) and dantrolene in Mdr1a (P-glycoprotein) and Bcrp knockout rats. Drug Metab Dispos. 2014 Oct;42(10):1761-5. doi: 10.1124/dmd.114.058545. Epub 2014 Jul 22. PMID: 25053619.

9: Bielenberg GW, Wagener G, Beck T. Infarct reduction by the platelet activating factor antagonist apafant in rats. Stroke. 1992 Jan;23(1):98-103. doi: 10.1161/01.str.23.1.98. PMID: 1731428.

10: Balsa D, Merlos M, Giral M, Ferrando R, García-Rafanell J, Forn J. Characterization of [3H]apafant binding to PAF receptor on rabbit platelet membranes: a comparison of a microplate filtration system and a standard method. J Pharmacol Toxicol Methods. 1996 Sep;36(1):53-62. doi: 10.1016/1056-8719(96)00074-3. PMID: 8872920.

11: Martin J. Platelet-activating factor. Lancet. 1988 Dec 24-31;2(8626-8627):1486. doi: 10.1016/s0140-6736(88)90956-7. PMID: 2904593.

12: Brecht HM, Adamus WS, Heuer HO, Birke FW, Kempe ER. Pharmacodynamics, pharmacokinetics and safety profile of the new platelet-activating factor antagonist apafant in man. Arzneimittelforschung. 1991 Jan;41(1):51-9. PMID: 1646613.

13: Nabe T, Yamamura H, Kohno S. Eosinophil chemotaxis induced by several biologically active substances and the effects of apafant on it in vitro. Arzneimittelforschung. 1997 Oct;47(10):1112-6. PMID: 9368704.

14: Sugimoto Y, Nakayama Y, Kishida H, Hayakawa T, Fujiwara R, Kamei C. Effects of apafant on PAF-induced downregulation of beta-adrenoceptors in guinea pigs. Methods Find Exp Clin Pharmacol. 1997 Oct;19(8):547-52. PMID: 9442478.

15: Caplan MS, Sun XM, Hsueh W. Hypoxia, PAF, and necrotizing enterocolitis. Lipids. 1991 Dec;26(12):1340-3. doi: 10.1007/BF02536562. PMID: 1819729.

16: Giudice A, Herbert JM, Maffrand JP, Manara L, Manzoni L, Le Fur G. Prevention of platelet-activating factor-induced gastrointestinal lesions in rats by the new specific antagonist N-(2-dimethylaminoethyl)-N-(3-pyridinylmethyl)[4-(2,4,6-triisopropylphe nyl) thiazol-2yl]amine. Arzneimittelforschung. 1996 Apr;46(4):407-12. PMID: 8740089.

17: Shimizu T, Honda Z, Nakamura M, Bito H, Izumi T. Platelet-activating factor receptor and signal transduction. Biochem Pharmacol. 1992 Sep 25;44(6):1001-8. doi: 10.1016/0006-2952(92)90360-u. PMID: 1329754.

18: Chung KF, Barnes PJ. Role for platelet-activating factor in asthma. Lipids. 1991 Dec;26(12):1277-9. doi: 10.1007/BF02536547. PMID: 1819715.

19: Du ZY, Li XY. Effects of ginkgolides on interleukin-1, tumor necrosis factor-alpha and nitric oxide production by rat microglia stimulated with lipopolysaccharides in vitro. Arzneimittelforschung. 1998 Dec;48(12):1126-30. PMID: 9893925.

20: Heuer HO. Involvement of platelet-activating factor (PAF) in septic shock and priming as indicated by the effect of hetrazepinoic PAF antagonists. Lipids. 1991 Dec;26(12):1369-73. doi: 10.1007/BF02536569. PMID: 1819735.

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