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SB-408124

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Chemical Structure| 288150-92-5 同义名 : -
CAS号 : 288150-92-5
货号 : A714872
分子式 : C19H18F2N4O
纯度 : 98%
分子量 : 356.369
MDL号 : MFCD06411575
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(140.3 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • OX1 receptor

    OX1 (membrane), Ki:27 nM

    OX1 (whole cell), Ki:57 nM
描述 Orexins (A and B) are hypothalamic peptides that interact with OX1 and OX2 receptors and are involved in the sleep/wake cycle. OX1 receptors are highly expressed in colon cancer tumours and colonic cancer cell lines where orexins induce apoptosis and inhibit tumour growth in preclinical animal models[3]. Injection of exogenous orexin-A specifically improved the inflammatory symptoms in the two colitis murine models. Conversely, injection of inactive orexin-A analog, OxB7-28 or OX1R specific antagonist SB-408124 did not have anti-inflammatory effect. Moreover, treatment with orexin-A in DSS-colitis induced OX1R-/- knockout mice did not have any protective effect. The orexin-A anti-inflammatory effect was due to the decreased expression of pro-inflammatory cytokines in immune cells and specifically in T-cells isolated from colonic mucosa[4].SB-408124 is a non-peptide OX1 receptor antagonist with Kis of 57 nM and 27 nM in whole cell and membrane, respectively. SB-408124 exhibits 50-fold selectivity over OX2 receptor[5]. SB-408124 (30 μg/10 μl; i.c.v.; male Wistar rats) decreases Orexin-A induced water intake in Wistar rats[6].In isolated rat cardiomyocytes, only orexin-B (OR-B) caused an increase in contractile shortening, independent of diastolic or systolic calcium levels. A specific orexin receptor-2 (OX2R) agonist ([Ala11, d-Leu15]-Orexin B) exerted similar effects as OR-B, whereas a specific orexin receptor-1 (OX1R) antagonist (SB-408124) did not alter the responsiveness of OR-B[7].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.81mL

0.56mL

0.28mL

14.03mL

2.81mL

1.40mL

28.06mL

5.61mL

2.81mL
参考文献

[1]Morairty SR, Revel FG, et al. Dual hypocretin receptor antagonism is more effective for sleep promotion than antagonism of either receptor alone. PLoS One. 2012;7(7):e39131.

[2]Melis MR, Sanna F, et al. Neuroendocrine regulatory peptide-1 and neuroendocrine regulatory peptide-2 influence differentially feeding and penile erection in male rats: sites of action in the brain. Regul Pept. 2012 Aug 20;177(1-3):46-52.

[3] Pascal Nicole,et al. Crucial role of the orexin-B C-terminus in the induction of OX1 receptor-mediated apoptosis: analysis by alanine scanning, molecular modelling and site-directed mutagenesis. Br J Pharmacol. 2015 Nov;172(21):5211-23.

[4] N Messal,et al. Ectopic expression of OX1R in ulcerative colitis mediates anti-inflammatory effect of orexin-A. Biochim Biophys Acta Mol Basis Dis. 2018 Nov;1864(11):3618-3628.

[5] Langmead CJ, et al. Characterisation of the binding of [3H]-SB-674042, a novel nonpeptide antagonist, to the human orexin-1 receptor. Br J Pharmacol. 2004;141(2):340-346.

[6] Kis GK, et al. The osmotically and histamine-induced enhancement of the plasma vasopressin level is diminished by intracerebroventricularly administered orexin in rats. Pflugers Arch. 2012;463(4):531-536.

[7]Vanlata H Patel,et al. Functional cardiac orexin receptors: role of orexin-B/orexin 2 receptor in myocardial protection. Clin Sci (Lond). 2018 Dec 13;132(24):2547-2564.