Antide (acetate)
(Synonyms: N-((4R,7R,10R,13S,16S,19R)-19-(((S)-1-(((S)-1-((S)-2-((R)-1-氨基-1-氧代丙烷-2-基)氨基甲酰基)吡咯烷-1-基)-6-(异丙基氨基)-1-氧代己基-2-基)氨基)-4-甲基-1-氧代戊烷-2-基)氨基甲酰基)-7-(4-氯苄基)-13-(羟甲基)-4-(萘-2-基甲基)-16-(4-(烟酰胺基)丁基)-2,5,8,11,14,17-六氧代-10-(吡啶-3-基甲基)-3,6,9,12,15,18-六氮杂二十三烷-23-基)烟酰胺乙酸盐) 目录号 : GC46859
A GnRHR antagonist
Cas No.:625092-10-6
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Antide is a third generation gonadotropin-releasing hormone receptor (GnRHR) antagonist.1,2,3,4 It inhibits GnRH-induced secretion of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and gonadotropin in isolated rat pituitary cells when used at concentrations ranging from 0.001 to 1,000 nM but does not induce histamine release in isolated rat mast cells (EC50 = >300 µg/ml).1,3 Antide (250 µg/kg, i.v.) reduces serum LH and FSH levels in orchidectomized cynomolgus monkeys.2 It inhibits ovulation in rats when administered at a dose of 2 µg/animal.3 Antide (10 µg/animal, s.c.) reduces the intensity and duration of catalepsy induced by haloperidol in rats.4
1.Danforth, D.R., Williams, R.F., Gordon, K., et al.Inhibition of pituitary gonadotropin secretion by the gonadotropin-releasing hormone antagonist antide. I. In vitro studies on mechanism of actionEndocrinology128(4)2036-2040(1991) 2.Weinbauer, G.F., and Nieschlag, E.Comparison of the antigonadotropic activity of three GnRH antagonists (Nal-Glu, Antide and Cetrorelix) in a non-human primate model (Macaca fascicularis)Andrologia25(3)141-147(1993) 3.Flouret, G., Arnold, Z.S., Majewski, T., et al.Antiovulatory antagonists of LHRH related to antideJ. Pept. Sci.1(2)89-108(1995) 4.Umathe, S.N., Wanjari, M.M., Manna, S.S.S., et al.A possible participation of gonadotropin-releasing hormone in the neuroleptic and cataleptic effect of haloperidolNeuropeptides43(3)251-257(2009)
| Cas No. | 625092-10-6 | SDF | |
| 别名 | N-((4R,7R,10R,13S,16S,19R)-19-(((S)-1-(((S)-1-((S)-2-((R)-1-氨基-1-氧代丙烷-2-基)氨基甲酰基)吡咯烷-1-基)-6-(异丙基氨基)-1-氧代己基-2-基)氨基)-4-甲基-1-氧代戊烷-2-基)氨基甲酰基)-7-(4-氯苄基)-13-(羟甲基)-4-(萘-2-基甲基)-16-(4-(烟酰胺基)丁基)-2,5,8,11,14,17-六氧代-10-(吡啶-3-基甲基)-3,6,9,12,15,18-六氮杂二十三烷-23-基)烟酰胺乙酸盐 | ||
| Canonical SMILES | ClC(C=C1)=CC=C1C[C@@H](NC([C@H](NC(C)=O)CC2=CC3=C(C=CC=C3)C=C2)=O)C(N[C@H](CC4=CN=CC=C4)C(N[C@@H](CO)C(N[C@@H](CCCCNC(C5=CN=CC=C5)=O)C(N[C@H](CCCCNC(C6=CN=CC=C6)=O)C(N[C@@H](CC(C)C)C(N[C@@H](CCCCNC(C)C)C(N7[C@@H](CCC7)C(N[C@H](C)C(N)=O)=O)=O)=O)=O)=O)=O)=O)=O.O=C(C)O | ||
| 分子式 | C82H108ClN17O14.C2H4O2 | 分子量 | 1651.3 |
| 溶解度 | DMSO: soluble,Ethanol: soluble | 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 0.6056 mL | 3.0279 mL | 6.0558 mL |
| 5 mM | 0.1211 mL | 0.6056 mL | 1.2112 mL |
| 10 mM | 0.0606 mL | 0.3028 mL | 0.6056 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。
Gonadotropin-releasing hormone antagonist Antide inhibits apoptosis of preovulatory follicle cells in rat ovary
Biol Reprod 2005 Mar;72(3):659-66.PMID:15564600DOI:10.1095/biolreprod.104.034454.
Analogs of GnRH, including agonists (GnRH-a) and antagonists (GnRH-ant), have been widely used to inhibit gonadotropin pituitary release. Aside from the effect of GnRH analogs on the pituitary-gonadal axis, studies have shown that GnRH has extrapituitary effects, particularly on rat and human ovaries. In the present study, we evaluated the direct in vivo effects of the GnRH-a, leuprolide acetate (LA), or the GnRH-ant, Antide (Ant), either singly or together, on ovarian follicular development in prepubertal eCG-treated rats. LA significantly decreased ovarian weight, whereas Ant increased ovarian weight compared with controls; however, coinjection of both compounds had no effect. In addition, LA increased the number of preantral follicles (PFs) and atretic follicles, and decreased the number of early antral follicles (EAFs) and preovulatory follicles (POFs). Coinjection of Ant interfered with this LA effect. Ant alone increased the number of POFs compared with that of controls. Analysis of apoptosis has shown that LA increases the percentage of apoptotic cells in PFs, EAFs, and POFs; however, Ant prevented this effect. In addition, Ant alone decreased the percentage of apoptotic cells in EAFs and POFs. Data have shown that Ant per se inhibited BAX translocation from cytosol to mitochondria and retained cytochrome C in the mitochondria, whereas LA induced cytochrome C release. We conclude that Ant inhibits apoptosis in preovulatory follicles through a decrease of BAX translocation to mitochondria, suggesting that GnRH may act as a physiological intraovarian modulator factor that is able to interfere with follicular development through an increase in apoptotic events mediated by an imbalance among the BCL-2 family members.
Apoptosis of bovine granulosa cells: Intracellular pathways and differentiation
Acta Histochem 2017 Jun;119(5):462-470.PMID:28506467DOI:10.1016/j.acthis.2017.04.010.
Follicular atresia in granulosa and theca cells occurs by apoptosis through weak hormonal stimulation. We have previously proposed an in vitro model to study this process by inducing apoptosis in BGC-1, a bovine granulosa cell line, and in primary cultures from ovaries with or without corpus luteum (CPGB+ and CPGB-, respectively), with different doses of gonadotropin releasing hormone (GnRH) analogs (leuprolide acetate (LA) as agonist and Antide as antagonist). BGC-1 represent immature granulosa cells, whereas CPGB represent different degrees of luteinization. Our aim was to evaluate the intracellular pathways involved in the GnRH regulation of apoptosis in BGC-1. Treatment with LA 100nM but not with Antide led to an increase in BAX over BCL-2 expression, showing antagonism of Antide. All treatments inhibited phospholipase-D (PLD) activity compared to control, implying agonist behavior of Antide. Progesterone in vitro production and 3β-hydroxysteroid dehydrogenase (3β-HSD) expression revealed different degrees of luteinization: BGC-1 were immature, whereas CPGB+ were less differentiated than CPGB-. We concluded that LA-induced apoptosis in BGC-1 occurs by activation of the mitochondrial pathway and by inhibition of PLD activity and that Antide might work both as an antagonist of the intrinsic pathway and as an agonist of the extrinsic protection pathway by inhibiting PLD activity.
Effect of GnRH analogues on apoptosis and expression of Bcl-2, Bax, Fas and FasL proteins in endometrial epithelial cell cultures from patients with endometriosis and controls
Hum Reprod 2007 Mar;22(3):644-53.PMID:17092985DOI:10.1093/humrep/del423.
Background: Our purpose was to evaluate the effect of the GnRH agonist (GnRHa), leuprolide acetate (LA), and the GnRH antagonist (GnRHant), Antide, on apoptosis and expression of apoptosis-related proteins in endometrial epithelial cell (EEC) cultures from patients with endometriosis and controls (infertile women without endometriosis). Methods: Biopsy specimens of eutopic endometrium were obtained from 22 patients with endometriosis and from 14 women that served as controls. Apoptosis was examined in EEC after incubation with LA and Antide. Bax, Bcl-2, Fas and FasL expression was evaluated after exposure to LA, Antide or a combination of both. The percentage of apoptotic cells (%ApC) was assessed by the acridine orange-ethidium bromide technique, and protein expression was evaluated by western blot and immunocytochemistry. Results: LA 100 and 1000 ng/ml increased the %ApC in EEC from patients with endometriosis (both P < 0.05) and controls (p < 0.05 and P < 0.01, respectively). Antide 10(-5) M increased the %ApC in EEC from patients with endometriosis and controls (P < 0.01). In EEC from women with endometriosis, Bax expression increased after treatment with LA, Antide and LA + Antide (P < 0.05, P < 0.001 and P < 0.001), whereas Bcl-2 expression decreased after exposure to LA and Antide (P < 0.001 and P < 0.01). FasL expression increased after LA, Antide and LA + Antide treatments (P < 0.01, P < 0.001 and P < 0.01). No significant changes were observed on Fas expression. Conclusions: GnRH analogues enhanced apoptosis in EEC, and this was accompanied by an increase in expression of the pro-apoptotic proteins Bax and FasL and a decrease in expression of the anti-apoptotic protein Bcl-2.
In vivo evaluation of an oral drug delivery system for peptides based on S-protected thiolated chitosan
J Control Release 2012 Jun 28;160(3):477-85.PMID:22542699DOI:10.1016/j.jconrel.2012.04.020.
The aim of the present study was the development and evaluation in vitro as well as in vivo of an oral delivery system based on a novel type of thiolated chitosan, so-called S-protected thiolated chitosan, for the peptide drug Antide. The sulfhydryl ligand thioglycolic acid (TGA) was covalently attached to chitosan (CS) in the first step of modification. In the second step, these thiol groups of thiolated chitosan were protected by disulfide bond formation with the thiolated aromatic residue 6-mercaptonicotinamide (6-MNA). Absorptive transport studies of Antide were evaluated ex vivo using rat intestinal mucosa. Matrix tablets of each polymer sample were prepared and their effect on the absorption of Antide evaluated in vivo in male Sprague-Dawley rats. In addition, tablets were examined in terms of their disintegration, swelling and drug release behavior. The resulting S-protected thiomer (TGA-MNA) exhibited 840μmol of covalently linked 6-MNA per gram thiomer. Based on the implementation of this hydrophobic ligand on the thiolated backbone, the disintegration behavior was reduced greatly and a controlled release of the peptide could be achieved. Furthermore, permeation studies with TGA-MNA on rat intestine revealed a 4.5-fold enhanced absorptive transport of the peptide in comparison to Antide in solution. Additional in vivo studies confirmed the potential of this novel conjugate. Oral administration of Antide in solution led to only very small detectable quantities in plasma with an absolute and relative bioavailability (BA) of 0.003 and 0.03%, only. In contrast, with Antide incorporated in TGA-MNA matrix tablets an absolute and relative BA of 1.4 and 10.9% could be reached, resulting in a 421-fold increased area under the plasma concentration time curve (AUC) compared to the Antide solution. According to these results, S-protected thiolated chitosan as oral drug delivery system might be a valuable tool for improving the bioavailability of peptides.
Regulation of ovarian angiogenesis and apoptosis by GnRH-I analogs
Mol Reprod Dev 2008 Apr;75(4):623-31.PMID:17874466DOI:10.1002/mrd.20806.
An adequate vascular supply is important to provide endocrine and paracrine signals during follicular development. We evaluated the direct in vivo effects of both the GnRH-agonist Leuprolide acetate (LA) and the GnRH-antagonist Antide (Ant) on the expression of VEGF-A and ANPT-1 and their receptors in ovarian follicles from prepubertal eCG-treated rats. We also examined whether the changes observed in apoptosis by GnRH-I analogs have an effect on the caspase cascade. LA significantly decreased the levels of VEGF-A, its receptor Flk-1, and ANPT-1 when compared to controls, while the co-injection of Ant interfered with this effect. No changes were observed in the levels of Tie-2 after treatment with these analogs. When we measured the follicular content of caspase-3 protein, we observed that LA significantly increased the level of the active form. The co-injection of Ant interfered with this effect and Ant alone significantly decreased caspase-3 cleavage. IHC analyses corroborated these data. Notably, while LA increased caspase-3 activity levels, Ant decreased them when compared to controls. In follicles obtained from LA-treated rats, cleavage of PARP (a substrate of caspase-3) from the intact 113-kDa protein showed a significant enhancement in an 85-kDa fragment. The co-injection of Ant interfered with this effect. Ant alone significantly decreased PARP cleavage as compared to controls. We conclude that the decrease in VEGF-A, its receptor Flk-1/KDR, and ANPT-1 produced by the administration of GnRH-I agonist is one of the mechanisms involved in ovarian cell apoptosis. This suggests an intraovarian role of an endogenous GnRH-like peptide in gonadotropin-induced follicular development.