Astressin
目录号 : GC16218
Astressin是一种有效的非选择性的促肾上腺皮质激素释放因子（CRF）拮抗剂，对CRF结合蛋白具有低亲和力，而对克隆的垂体受体具有高亲和力（Ki=2nM）。
Cas No.:170809-51-5
Sample solution is provided at 25 µL, 10mM.
Astressin is an effective non-selective corticotropin-releasing factor (CRF) antagonist, with a low affinity for CRF binding proteins and a high affinity for cloned pituitary receptors (Ki = 2nM) [1]. Astressin can block CRF-induced release of adrenocorticotropic hormone (ACTH) [2]. Astressin can be used as a neuroprotective agent and has an anxiolytic effect [3].
In vitro, treatment with Astressin (200nM; 24h) significantly reduced the secretion of cytokines IL-8 and TNF-α in human HTR-8/SVneo cells co-cultured with corticotropin-releasing hormone (CRH) and lipopolysaccharide (LPS) [4]. Astressin (1, 10, and 100nM; 72h) could increase estrogen (E2) induced proliferation of MCF7 cells in a concentration-dependent manner and reversed the proliferation inhibition of CRH on cells [5].
In vivo, treatment with Astressin (25μg in 4μl saline; intracerebroventricular injection; 30min before and 10min after seizure) effectively protected the neuronal function of rats with excitotoxic epilepsy induced by kainic acid and significantly reduced the damage of hippocampal cells in rats [6]. Treatment with Astressin (5μg/mouse; intraperitoneally; 5 days) could reverse the depigmentation phenotype of CRF overexpressing (OE) alopecia mice, induce pigmentation and hair regrowth, and restored 50–90% hair coverage within 2–4 weeks [7].
References:
[1] Gulyas J, Rivier C, Perrin M, et al. Potent, structurally constrained agonists and competitive antagonists of corticotropin-releasing factor. Proc Natl Acad Sci U S A. 1995;92(23):10575-10579.
[2] Smith S M, Vaughan J M, Donaldson C J, et al. Cocaine-and amphetamine-regulated transcript activates the hypothalamic-pituitary-adrenal axis through a corticotropin-releasing factor receptor-dependent mechanism[J]. Endocrinology, 2004, 145(11): 5202-5209.
[3] Spina M G, Basso A M, Zorrilla E P, et al. Behavioral effects of central administration of the novel CRF antagonist astressin in rats[J]. Neuropsychopharmacology, 2000, 22(3): 230-239.
[4] Wang W, Nan X, Ji P, Dow KE. Corticotropin releasing hormone modulates endotoxin-induced inflammatory cytokine expression in human trophoblast cells. Placenta. 2007;28(10):1032-1038.
[5] Graziani G, Tentori L, Muzi A, et al. Evidence that corticotropin-releasing hormone inhibits cell growth of human breast cancer cells via the activation of CRH-R1 receptor subtype. Mol Cell Endocrinol. 2007;264(1-2):44-49.
[6] Maecker H, Desai A, Dash R, Rivier J, Vale W, Sapolsky R. Astressin, a novel and potent CRF antagonist, is neuroprotective in the hippocampus when administered after a seizure. Brain Res. 1997;744(1):166-170.
[7] Wang L, Million M, Rivier J, et al. CRF receptor antagonist astressin-B reverses and prevents alopecia in CRF over-expressing mice[J]. PLoS One, 2011, 6(2): e16377.
Astressin是一种有效的非选择性的促肾上腺皮质激素释放因子（CRF）拮抗剂，对CRF结合蛋白具有低亲和力，而对克隆的垂体受体具有高亲和力（Ki=2nM） [1]。Astressin可以阻断CRF诱导的促肾上腺皮质激素（ACTH）释放 [2]。Astressin可作为神经保护剂，且具有缓解焦虑作用 [3]。
在体外，Astressin（200nM; 24h）处理显著减少了促肾上腺皮质激素释放激素（CRH）和脂多糖（LPS）共培养的人类HTR-8/SVneo细胞中细胞因子IL-8和TNF-α的分泌 [4]。Astressin（1, 10, and 100nM; 72h）能够以浓度依赖性方式增加雌二醇（E2）诱导的MCF7细胞增殖，并逆转了CRH对细胞的增殖抑制 [5]。
在体内，Astressin（25μg in 4μl saline; 脑室内注射; 癫痫发作前30min和发作后10min）治疗有效保护了Kainic acid诱导的兴奋性毒性癫痫发作大鼠的神经元功能，并显著减少了大鼠海马细胞的损伤 [6]。Astressin（5µg/mouse; i.p.; 5 days）治疗可逆转CRF过度表达（OE）脱毛小鼠的脱发现象，诱导色素沉着和毛发再生，在2–4周恢复了50–90%的毛发覆盖率 [7]。
| Cell experiment [1]: | |
Cell lines | Human HTR-8/SVneo cells |
Preparation Method | The HTR-8/SVneo cells were cultured in RPMI 1640 supplemented with 5% heat-inactivated fetal bovine serum, 2% penicillin/streptomycin and 2mM glutamine in a 95% air, 5% CO2 humidified atmosphere at 37°C. The culture medium was changed every 24h until the cells were grown to confluence. Cultured cells were stimulated with lipopolysaccharide (LPS) at different concentrations for 24h. The cells were co-treated with either 100nM corticotropin releasing hormone (CRH), 200nM Astressin or CRH plus Astressin for 24h. Cell culture supernatants were collected and assayed by ELISA and normalised to cell protein. |
Reaction Conditions | 200nM; 24h |
Applications | The treatment with Astressin significantly reduced the secretion of cytokines IL-8 and TNF-α in human HTR-8/SVneo cells co-cultured with corticotropin-releasing hormone (CRH) and lipopolysaccharide (LPS). |
| Animal experiment [2]: | |
Animal models | Sprague–Dawley rats |
Preparation Method | Subjects were male Sprague–Dawley rats (275–325g) housed on a 12:12 light:dark cycle and fed and watered ad libitum. For focal Kainic acid (KA) injection into the dorsal hippocampus, rats were anesthetized with a ketamine/rompun cocktail, placed in a stereotaxic head holder, and the skull exposed along the midline. KA (0.035μg in a volume of 1μl) was injected unilaterally into dorsal hippocampus (stereotaxic coordinates: AP=−3.0 from lambda, ML=2.1; DV=4.0mm). The animals treated with KA exhibited epileptic seizures within the first hour after the injection. Astressin (25μg in 4μl saline) or vehicle control (4μl saline) were administered by injection via an indwelling guide cannula into the lateral ventricle (coordinates: AP=4.1 from bregma, ML=3.0; DV=2.0) over a 2min period at indicated times with respect to the KA administration. Three days post KA administration rats were perfused with 4% paraformaldehyde. Coronal brain sections (30μm) were stained with Cresyl violet and damage was quantified by measuring the length and width of the lesion in each hippocampal cell field with a calibrated ocular grid at ×40 magnification. Areas of damage within successive sections were then integrated into a measure of total volume of damage. |
Dosage form | 25μg in 4μl saline; 30 minutes before and 10 minutes after the seizure; intraventricular injection |
Applications | Astressin treatment effectively protected the neuronal function of rats with excitotoxic epilepsy induced by kainic acid and significantly reduced the damage to hippocampal cells in the rats. |
References: | |
| Cas No. | 170809-51-5 | SDF | |
| Canonical SMILES | CCCC[C@@](/N=C(O)/[C@](/N=C(O)/[C@](/N=C(O)/[C@](/N=C(O)/[C@](/N=C(O)/[C@](/N=C(O)/[C@](/N=C(O)/[C@](/N=C(O)/[C@](/N=C(O)/[C@@](N)([H])CC1=CC=CC=C1)([H])CC2=CN=CN2)([H])CC(C)C)([H])CC(C)C)([H])CCCNC(N)=N)([H])CCC(O)=O)([H])C(C)C)([H])CC(C)C)([H])CCC(O)=O) | ||
| 分子式 | C161H269N49O42 | 分子量 | 3563.2 |
| 溶解度 | Soluble to 1 mg/ml in 10% Acetic acid / sterile water | 储存条件 | Store at -20°C,away from moisture and light, under nitrogen |
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