SC 57461ALTA4 hydrolase inhibitor,potent and selective CAS# 423169-68-0 |
Quality Control & MSDS
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| Cas No. | 423169-68-0 | SDF | Download SDF |
| PubChem ID | 9820433 | Appearance | Powder |
| Formula | C20H26ClNO3 | M.Wt | 363.88 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | Soluble to 25 mM in water and to 100 mM in DMSO | ||
| Chemical Name | 3-[3-(4-benzylphenoxy)propyl-methylamino]propanoic acid;hydrochloride | ||
| SMILES | CN(CCCOC1=CC=C(C=C1)CC2=CC=CC=C2)CCC(=O)O.Cl | ||
| Standard InChIKey | SBBJJLDNKNNWFJ-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C20H25NO3.ClH/c1-21(14-12-20(22)23)13-5-15-24-19-10-8-18(9-11-19)16-17-6-3-2-4-7-17;/h2-4,6-11H,5,12-16H2,1H3,(H,22,23);1H | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | Potent and selective inhibitor of LTA4 hydrolase. Does not inhibit other enzymes of the arachidonic acid cascade including COX-1, COX-2, LTC4 synthase and 5-lipoxygenase. Potently inhibits LTB4 production in whole blood (IC50 = 49 nM). Orally active. |
SC 57461A Dilution Calculator
SC 57461A Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.7482 mL | 13.7408 mL | 27.4816 mL | 54.9632 mL | 68.704 mL |
| 5 mM | 0.5496 mL | 2.7482 mL | 5.4963 mL | 10.9926 mL | 13.7408 mL |
| 10 mM | 0.2748 mL | 1.3741 mL | 2.7482 mL | 5.4963 mL | 6.8704 mL |
| 50 mM | 0.055 mL | 0.2748 mL | 0.5496 mL | 1.0993 mL | 1.3741 mL |
| 100 mM | 0.0275 mL | 0.1374 mL | 0.2748 mL | 0.5496 mL | 0.687 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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SC-57461A is a selective inhibitor of human recombinant LTB4 with IC50 value of 49 nM [1].
LTB4 (leukotriene B (4)) is a leukotriene and plays an important role in inflammation. LTB4 functions through interacting with the specific cell-surface receptors BLTR1 and BLTR2 [2].
SC-57461A is a potent LTB4 inhibitor and has a more potent activity than the reported LTA4 inhibitor RP64966. When tested with PMN cells, administration of SC-57461A significantly inhibited the synthesis of LT that induced by fMLP and PAF by acting on LTB4-BLTR1 interaction [3].
In fasted CD rat model of calcium ionophore A23187-induced eicosanoid production, oral administration of SC-57461A showed effective inhibition on LTB4 with ED50 value of 0.3-1.0 mg/kg. When tested with AA-induced edema on the ear, oral administration of SC-57461A resulted in markedly inhibition of edema at doses of 0.8, 4 and 20 mg/kg [1].
It is also been reported that SC-57461A inhibited LTB4A with Ki values of 23 nM and 27 nM for epoxide hydrolase and aminopeptidase, respectively [1].
References:
[1]. Kachur, J.F., et al., Pharmacological characterization of SC-57461A (3-[methyl[3-[4-(phenylmethyl)phenoxy]propyl]amino]propanoic acid HCl), a potent and selective inhibitor of leukotriene A(4) hydrolase II: in vivo studies. J Pharmacol Exp Ther, 2002. 300(2): p. 583-7.
[2]. Filgueiras, L.R., et al., Leukotriene B4-mediated sterile inflammation promotes susceptibility to sepsis in a mouse model of type 1 diabetes. Sci Signal, 2015. 8(361): p. ra10.
[3]. Grenier, S., et al., Arachidonic acid activates phospholipase D in human neutrophils; essential role of endogenous leukotriene B4 and inhibition by adenosine A2A receptor engagement. J Leukoc Biol, 2003. 73(4): p. 530-9.
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Pharmacological characterization of SC-57461A (3-[methyl[3-[4-(phenylmethyl)phenoxy]propyl]amino]propanoic acid HCl), a potent and selective inhibitor of leukotriene A(4) hydrolase I: in vitro studies.[Pubmed:11805219]
J Pharmacol Exp Ther. 2002 Feb;300(2):577-82.
Leukotriene (LT) B(4) is an inflammatory mediator that has been implicated in the pathogenesis of various diseases, including inflammatory bowel disease and psoriasis. As the rate-limiting step for LTB(4) production, LTA(4) hydrolase represents an attractive target for therapeutic agents that interfere with LTB(4) production. In the present study we evaluated a chemically novel compound designated SC-57461A (3-[methyl[3-[4-(phenylmethyl)phenoxy]propyl]amino]propanoic acid HCl) as an inhibitor of LTA(4) hydrolase. Pharmacological comparisons are made to its free acid SC-57461. SC-57461A is a potent competitive inhibitor of recombinant human LTA(4) hydrolase when either LTA(4) (IC(50) = 2.5 nM, K(i) = 23 nM) or peptide substrates (IC(50) = 27 nM) are used. In human whole blood, the IC(50) for calcium ionophore-induced LTB(4) production was 49 nM, indicative of good cell penetration. Whole blood production of the cyclooxygenase metabolite thromboxane B(2) was not affected. SC-57461A was also active in several other species, including mouse, rat, dog, and rhesus monkey. The data indicate that SC-57461A is a potent and selective inhibitor of LTA(4) hydrolase.
Pharmacological characterization of SC-57461A (3-[methyl[3-[4-(phenylmethyl)phenoxy]propyl]amino]propanoic acid HCl), a potent and selective inhibitor of leukotriene A(4) hydrolase II: in vivo studies.[Pubmed:11805220]
J Pharmacol Exp Ther. 2002 Feb;300(2):583-7.
Leukotriene (LT) A(4) hydrolase is a dual function enzyme that is essential for the conversion of LTA(4) to LTB(4) and also possesses an aminopeptidase activity. SC-57461A (3-[methyl[3-[4-phenylmethyl)phenoxy]propyl]amino]propanoic acid HCl) is a potent inhibitor of human recombinant LTA(4) hydrolase (epoxide hydrolase and aminopeptidase activities, K(i) values = 23 and 27 nM, respectively) as well as calcium ionophore-induced LTB(4) production in human whole blood (IC(50) = 49 nM). In the present study, we investigated its action in several animal models. Oral activity was evident from the ability of the compound to inhibit mouse ex vivo calcium ionophore-stimulated blood LTB(4) production with ED(50) values at 1.0 and 3.0 h of 0.2 and 0.8 mg/kg, respectively. A single oral dose of 10 mg/kg SC-57461A blocked mouse ex vivo LTB(4) production 67% at 18 h and 44% at 24 h, suggesting a long pharmacodynamic half-life. In a rat model of ionophore-induced peritoneal eicosanoid production, SC-57461 inhibited LTB(4) production in a dose-dependent manner (ED(50) = 0.3-1 mg/kg) without affecting LTC(4) or 6-keto-prostaglandin F(1alpha) production. Oral pretreatment with SC-57461 in a rat reversed passive dermal Arthus model blocked LTB(4) production with an ED(90) value of 3 to 10 mg/kg, demonstrating good penetration of drug into skin. Plasma level of intact SC-57461 (3 h after oral gavage dosing with 3 mg/kg) was 0.4 microg/ml, which corresponds to >80% inhibition of dermal LTB(4) production. Oral or topical pretreatment with SC-57461A 1 h before challenge with arachidonic acid blocked ear edema in the mouse. SC-57461A is a competitive, selective, and orally active inhibitor of LTA(4) hydrolase in vivo, making it useful to explore the contribution of LTB(4) to a number of inflammatory diseases.
Pyrrolidine and piperidine analogues of SC-57461A as potent, orally active inhibitors of leukotriene A(4) hydrolase.[Pubmed:12419366]
Bioorg Med Chem Lett. 2002 Dec 2;12(23):3383-6.
The synthesis and biological evaluation of a series of functionalized pyrrolidine- and piperidine-containing analogues of our lead LTA(4) hydrolase inhibitor, SC-57461A, is described. A number of compounds showed excellent potency in our in vitro screens and several demonstrated good oral activity in a mouse ex vivo assay. These efforts led to the identification of SC-56938 (14) as a potent, orally active inhibitor of LTA(4) hydrolase.
Synthesis of potent leukotriene A(4) hydrolase inhibitors. Identification of 3-[methyl[3-[4-(phenylmethyl)phenoxy]propyl]amino]propanoic acid.[Pubmed:12139459]
J Med Chem. 2002 Aug 1;45(16):3482-90.
Leukotriene B(4) (LTB(4)) is a potent, proinflammatory mediator involved in the pathogenesis of a number of diseases including inflammatory bowel disease, psoriasis, rheumatoid arthritis, and asthma. The enzyme LTA(4) hydrolase represents an attractive target for pharmacological intervention in these disease states, since the action of this enzyme is the rate-limiting step in the production of LTB(4). Our previous efforts focused on the exploration of a series of analogues related to screening hit SC-22716 (1, 1-[2-(4-phenylphenoxy)ethyl]pyrrolidine) and resulted in the identification of potent, orally active inhibitors such as 2. Additional structure-activity relationship studies around this structural class resulted in the identification of a series of alpha-, beta-, and gamma-amino acid analogues that are potent inhibitors of the LTA(4) hydrolase enzyme and demonstrated good oral activity in a mouse ex vivo whole blood LTB(4) production assay. The efforts leading to the identification of clinical candidate SC-57461A (8d, 3-[methyl[3-[4-(phenylmethyl)phenoxy]propyl]amino]propanoic acid) are described.
