Corticotropin-releasing factor (human) (acetate)
(Synonyms: Human CRF acetate; Human corticotropin-releasing factor acetate) 目录号 : GC60724
Corticotropin-releasingfactorhumanacetate(HumanCRFacetate)能够刺激垂体前叶的促肾上腺皮质激素的合成和分泌。
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Corticotropin-releasing factor human acetate (Human CRF acetate) stimulates the synthesis and secretion of adrenocorticotropin in the anterior pituitary.
CRF increases excitability of type II dlBNST neurons through activation of the AC-cAMP-PKA pathway, thereby causing pain-induced aversive responses[1].
In rats injected with CRF (1 nmol/side), the time spent in the drug-paired compartment during the test session (314±22 s) is significantly shorter than time spent in that compartment during the preconditioning session (520±18 s)[1].
[1]. Kaneko T et al. Activation of adenylate cyclase-cyclic AMP-protein kinase A signaling by corticotropin-releasing factorwithin the dorsolateral bed nucleus of the stria terminalis is involved in pain-induced aversion. Eur J Neurosci. 2016 Sep 30. [2]. Tenk J et al. Acute central effects of corticotropin-releasing factor (CRF) on energy balance: Effects of age and gender. Peptides. 2016 Nov;85:63-72.
| Cas No. | SDF | ||
| 别名 | Human CRF acetate; Human corticotropin-releasing factor acetate | ||
| 分子式 | C210H348N60O65S2 | 分子量 | 4817.5 |
| 溶解度 | 储存条件 | Store at -20°C | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 0.2076 mL | 1.0379 mL | 2.0758 mL |
| 5 mM | 0.0415 mL | 0.2076 mL | 0.4152 mL |
| 10 mM | 0.0208 mL | 0.1038 mL | 0.2076 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Corticotropin releasing factor decidualizes human endometrial stromal cells in vitro. Interaction with progestin
J Steroid Biochem Mol Biol 1995 Sep;54(5-6):251-5.PMID:7577707DOI:10.1016/0960-0760(95)00142-m.
Decidualization of endometrial cells is a hormone-dependent process of differentiation which occurs during the menstrual cycle and pregnancy. Recent in vitro studies have revealed that cAMP and its generators induce decidualization of stromal cells isolated from proliferative endometrium and that progestins enhance the effect of cAMP. Since corticotropin releasing factor (CRF) generates cAMP and prostaglandins in other organs, in the present study the effect of CRF, a hypothalamic factor also produced by decidua and fetal membranes, on in vitro decidualization of endometrial stromal cells was evaluated. The addition of CRF to a culture medium of stromal cells induced in vitro decidualization, as indicated by morphologic changes from elongated fibroblast-like cells into larger and round cells and by the release of prolactin in the medium. The effect of CRF on stromal cells and on prolactin release was significantly augmented by the coincubation in the presence of medroxyprogesterone acetate. This observation indicates CRF as a novel factor of decidualization and confirms that progestins act as enhancers of the expression of decidual products.
Corticorelin acetate, a synthetic corticotropin-releasing factor with preclinical antitumor activity, alone and with bevacizumab, against human solid tumor models
Cancer Chemother Pharmacol 2011 Jun;67(6):1415-22.PMID:20809121DOI:10.1007/s00280-010-1437-3.
Purpose: Corticorelin acetate (CrA) is a synthetic form of corticotropin-releasing factor undergoing clinical trials in the treatment of peritumoral brain edema (PBE). We sought to investigate preclinically its potential as an antitumor agent against human solid tumors and to assess its ability to enhance the therapeutic activity of bevacizumab (BEV) in these same models. Methods: The in vivo efficacy of CrA as a single agent and in combination with the antiangiogenic agent, BEV, was examined in two preclinical human tumor models, the MX-1 breast and Colo-205 colon carcinomas. These models were selected based on their known sensitivity to BEV and were tumor types in which BEV has been approved for clinical use. The corneal micropocket assay was also performed to assess the antiangiogenic activity of CrA relative to BEV. The exposure level of CrA in the mouse using a typical preclinical regimen was measured so as to compare it to reported clinical exposure levels. Results: CrA was active as a single agent in the MX-1 breast carcinoma, but did not exhibit statistically significant activity as a single agent in the Colo-205 colon carcinoma under the doses and schedules used in the study. When BEV, which was active or near active in both the MX-1 and Colo-205 models, was administered concomitantly with CrA, therapeutic outcomes were observed that were significantly better than those obtained using either monotherapy. These therapeutic potentiations using CrA plus BEV were obtained in the absence of any observable increase in toxicities. CrA was active in the corneal micropocket assay, producing a substantial (>70%) inhibition of neovascularization. A representative CrA regimen in mice produced an exposure within eightfold of human exposure determined at one-half the current clinical dose. Conclusions: The application of CrA for the treatment of PBE likely involves its activity as an antiangiogenic agent, which may be one possible mechanism to explain its observed preclinical antitumor activity. That activity, as well as its ability to provide an enhanced therapeutic outcome when given in conjunction with BEV in the absence of increased toxicity, supports the use of CrA clinically as other than a replacement therapy for dexamethasone in PBE.
Corticorelin acetate, a synthetic corticotropin-releasing factor with preclinical antitumor activity, alone and with bevacizumab, against human brain tumor models
Anticancer Res 2010 Dec;30(12):5037-42.PMID:21187487doi
Background: Corticorelin acetate (CrA) is a synthetic form of corticotropin-releasing factor that is currently undergoing clinical trials in the treatment of peritumoral brain edema (PBE). This study preclinically investigated its potential as an antitumor agent against human brain tumor xenografts. Materials and methods: The in vivo efficacy of CrA as a single agent and in combination with the antiangiogenic agent, bevacizumab, was examined in three different patient-derived human brain tumor xenografts implanted orthotopically (intracranially) or subcutaneously in athymic mice. Results: CrA significantly increased the lifespan of mice implanted orthotopically with two different pediatric brain tumor xenograft models. In one of these tumor models, the combination of CrA with bevacizumab produced a therapeutic outcome superior to that found using either of the two agents alone. Conclusion: The application of CrA for the treatment of PBE likely involves its activity as an anti-angiogenic agent, which may be one possible mechanism to explain its observed preclinical antitumor activity against orthotopic human brain tumor models. Additional studies to investigate other possible mechanisms of action are underway.
Comparison of corticotropin-releasing factor, dexamethasone, and temozolomide: treatment efficacy and toxicity in U87 and C6 intracranial gliomas
Clin Cancer Res 2011 May 15;17(10):3282-92.PMID:21385926DOI:10.1158/1078-0432.CCR-10-3203.
PURPOSE/EXPERIMENTAL DESIGN: Treatment of cerebral tumors and peritumoral brain edema remains a clinical challenge and is associated with high morbidity and mortality. Dexamethasone is an effective drug for treating brain edema, but it is associated with well-documented side effects. Corticorelin acetate (Xerecept) or human corticotrophin-releasing factor (hCRF) is a comparatively new drug and has been evaluated in two orthotopic glioma models (U87 and C6), by a direct comparison with dexamethasone and temozolomide. Results: In vitro combination therapy and monotherapy showed a variable response in 6 different glioma cell lines. In vivo studies showed a dose-dependent effect of hCRF (0.03 and 0.1 mg/kg q12h) on survival of U87 intracranial xenograft-bearing animals [median survival: control--41 days (95% CI 25-61); "low-hCRF" 74.5 days (95% CI 41-88); "high-hCRF" >130 days (95% CI not reached)]. Dexamethasone treatment had no effect on survival, but significant toxicity was observed. A survival benefit was observed with temozolomide and temozolomide + hCRF-treated animals but with significant temozolomide toxicity. C6-bearing animals showed no survival benefit, but there were similar treatment toxicities. The difference in hCRF treatment response between U87 and C6 intracranial gliomas can be explained by a difference in receptor expression. RT-PCR identified CRF2r mRNA in U87 xenografts; no CRF receptors were identified in C6 xenografts. Conclusions: hCRF was more effective than either dexamethasone or temozolomide in the treatment of U87 xenografts, and results included improved prognosis with long-term survivors and only mild toxicity. The therapeutic efficacy of hCRF seems to be dependent on tumor hCRF receptor (CRFr) expression. These results support further clinical assessment of the therapeutic efficacy of hCRF and levels of CRFr expression in different human gliomas.
Single-Dose Study of a Corticotropin-Releasing Factor Receptor-1 Antagonist in Women With 21-Hydroxylase Deficiency
J Clin Endocrinol Metab 2016 Mar;101(3):1174-80.PMID:26751191DOI:10.1210/jc.2015-3574.
Context: Treatment of 21-hydroxylase deficiency (21OHD) is difficult to optimize. Normalization of excessive ACTH and adrenal steroid production commonly requires supraphysiologic doses of glucocorticoids. Objectives: We evaluated the safety and tolerability of the selective corticotropin releasing factor type 1 (CRF1) receptor antagonist NBI-77860 in women with classic 21OHD and tested the hypothesis that CRF1 receptor blockade decreases early-morning ACTH and 17α-hydroxyprogesterone (17OHP) in these patients. Participants: The study enrolled eight classic 21OHD females, ages 18-58 years, seen at a single tertiary referral university setting. Design: This was a phase Ib, single-blind, placebo-controlled, fixed-sequence, single-dose trial. During three treatment periods separated by 3-week washout intervals, patients sequentially received placebo, NBI-77860 300 mg, and NBI-77860 600 mg at 10 pm; glucocorticoid therapy was withheld for 20 hours. We evaluated ACTH, 17OHP, androstenedione, and testosterone as well as NBI-77860 pharmacokinetics over 24 hours. Results: Dose-dependent reductions of ACTH and/or 17OHP were observed in six of eight subjects. Relative to placebo, NBI-77860 led to an ACTH and 17OHP reduction by a mean of 43% and 0.7% for the 300 mg dose, respectively, and by 41% and 27% for the 600 mg dose, respectively. Both NBI-77860 doses were well tolerated. Conclusion: The meaningful reductions in ACTH and 17OHP following NBI-77860 dosing in 21OHD patients demonstrate target engagement and proof of principle in this disorder. These promising data provide a rationale for additional investigations of CRF1 receptor antagonists added to physiologic doses of hydrocortisone and fludrocortisone acetate for the treatment of classic 21OHD.