Disease relevance of SC 41930

• Mucin purified from additional animals with hapten-induced colitis but treated with the oral leukotriene B4-receptor antagonist SC-41930 showed intermediate inhibition of RDEC-1 binding (35.6% +/- 14.3%) [1].
• We evaluated the efficacy of 7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-3,4-dihydro-8-propyl -2H-1-benzopyran-2-carboxylic acid (SC-41930), a potent, orally active leukotriene B4 receptor antagonist, in a model of inflammatory bowel disease [2].
• Compounds such as SC-41930 may well have utility for treating human psoriasis [3].
• The PMA-induced skin inflammation model also was assessed histologically and revealed acanthosis, edema, PMNL infiltration, and rete ridge prominence as long as 96 h after a single application that was completely inhibited by SC-41930 topical coapplication [4].
• SC-41930 also very significantly protected rats against pulmonary oxygen toxicity, but had only marginally significant effects on pulmonary protection in mice [5].

High impact information on SC 41930

• Both lipoxygenase inhibitors, as well as leukotriene B4 antagonist (SC-41930) significantly attenuated the reperfusion-induced infiltration of granulocytes [6].
• However, shear rate-dependent leukocyte adhesion was largely prevented by pretreatment with either a leukotriene B4 receptor antagonist (SC-41930) or a leukotriene synthesis inhibitor (L663,536) [7].
• However, it could be partly blocked by treating HUVEC with an LTB4 receptor antagonist (SC-41930) [8].
• LY293111 was 300 times more potent than SC-41930 in blocking LTB4-induced CD11b up-regulation on isolated neutrophils [9].
• SC-41930 inhibited human neutrophil (PMN) superoxide generation maximally stimulated by f-Met-Leu-Phe (IC50 4 microM) and C5a (IC50 approximately 12 microM) [10].

Biological context of SC 41930

• SC-50605 was found to be significantly more potent than SC-41930 in LTB4 receptor binding, chemotaxis, and degranulation assays [11].
• Moreover, postreceptor stimulation of superoxide production by NaF (a G protein activator), but not by phorbol myristate acetate, was significantly inhibited by SC-41930, indicating that SC-41930 may act via attenuation of a G protein-mediated signal transduction [10].

Anatomical context of SC 41930

• The SC-41930-treated tissues were less edematous and had fewer neutrophils within the subepithelial space [2].
• SC-41930 inhibits neutrophil infiltration of the cavine dermis induced by 12(R)-hydroxyeicosatetraenoic acid [3].
• In this study, anti-inflammatory effects of SC-41930 were investigated in a guinea pig model of OM induced by middle ear (ME) inoculation of killed Staphylococcus aureus [12].

Associations of SC 41930 with other chemical compounds

• When coinjected intradermally (400 micrograms/site), SC-41930 inhibited A23187-stimulated increases in LTB4 levels in guinea pig skin [10].
• The chemotactic activity of SC-45694 was blocked by the LTB4 receptor antagonists SC-41930 and LY-255283 [13].
• The two LTD4 receptor antagonists (MK-571 and ICI-204,219) significantly reduced the permeability changes induced by indomethacin, while the two LTB4 antagonists (SC-41930 and LY-255,283) were without significant effect [14].

Gene context of SC 41930

• The LTB4 receptor antagonist, SC-41930, inhibited the inflammatory response to TPA but had little effect on that initiated by AA [15].
• Effect of the leukotriene B4 receptor antagonist SC-41930 on colonic inflammation in rat, guinea pig and rabbit [2].
• SC-41930 inhibited human synovial phospholipase A2 (IC50 72 microM), A23187-stimulated 5-hydroxy-eicosatetranoic acid production in human PMN (IC50 8.5 microM), and rat peritoneal leukotriene A4 hydrolase (IC50 20 microM), but not ram seminal vesical cyclooxygenase [10].
• Furthermore when mice were pretreated (-30 min) with SC-41930 (1 mg/kg) orally, the trafficking of granulocytes was inhibited (p less than .01) as assessed by dermal MPO levels [16].
• At concentrations up to 100 microM, SC-41930 alone exhibited no effect on neutrophil migration, but dose-dependently inhibited neutrophil chemotaxis induced by leukotriene B4 (LTB4) in a modified Boyden chamber [17].

Analytical, diagnostic and therapeutic context of SC 41930

• Myeloperoxidase activity in the SC-41930-treated group was found to be significantly lower than that in the control group [12].
• SC-41930 (20 mg/kg) given orally to guinea pigs with intradermal injections of 1 microgram C5a significantly (p less than 0.001) reduced dermal MPO content [18].
• SC-41930, 7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)propoxy]-3,4- dihydro-8-propyl-2H-1-benzopyran-2-carboxylic acid, is a selective, orally active, LTB4 receptor antagonist currently in clinical trials for psoriasis and ulcerative colitis [19].

References