ICI 216140
目录号 : GC43890
A GRP/bombesin receptor 2 antagonist
Cas No.:124001-41-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Bombesin is a peptide, originally isolated from the skin of the European fire-bellied toad, with pressor and sympathoexcitatory activity. Its three receptors are distributed throughout the central and peripheral nervous system and are involved in gastric acid secretion, emotional response, temperature control, learning, and memory. Neuromedin B and gastrin-releasing peptide (GRP) are mammalian homologs of bombesin. ICI 216140 is a GRP/bombesin receptor 2 antagonist (IC50 = 2 nM in vitro). At 2 mg/kg, it can reduce bombesin-stimulated pancreatic amylase secretion in rats. At 1 mM, it has been shown to attenuate bombesin-stimulated increases in blood pressure in rats.
| Cas No. | 124001-41-8 | SDF | |
| Canonical SMILES | CC(C)C(N[C@@H](CC1=CNC=N1)C(N[C@@H](CC2=CNC3=C2C=CC=C3)C(N[C@@H](C)C(N[C@@H](C(C)C)C(N[C@H](C)C(N[C@@H](CC4=CNC=N4)C(N[C@@H](CC(C)C)C(NC)=O)=O)=O)=O)=O)=O)=O)=O | ||
| 分子式 | C45H65N13O8 | 分子量 | 916.1 |
| 溶解度 | DMF: 2 mg/ml,DMSO: 2 mg/ml,PBS (pH 7.2): 10 mg/ml | 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 | 1.0916 mL | 5.4579 mL | 10.9158 mL |
| 5 mM | 0.2183 mL | 1.0916 mL | 2.1832 mL |
| 10 mM | 0.1092 mL | 0.5458 mL | 1.0916 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。
N-isobutyryl-His-Trp-Ala-Val-D-Ala-His-Leu-NHMe (ICI 216140) a potent in vivo antaconist analogue of bombesin/gastrin releasing peptide (BN/GRP) derived from the C-terminal sequence lacking the final methionine residue
Life Sci 1989;45(17):1521-7.PMID:2555638DOI:10.1016/0024-3205(89)90417-7.
The GRP receptor mediated growth response in Swiss 3T3 cells has been used to identify BN/GRP antagonists. Analysis of bombesin antagonism by substance P analogues and by truncated GRP analogues revealed that deletion of the C-terminal methionine residue was important for antagonism. Des-Met analogues showing potent antagonist activity in the in vitro 3T3 system (IC50 approximately 2nM) were synthesized. Further structural modification of these peptides led to the identification of (CH3)2CHCO-His-Trp-Ala-Val-D-Ala-His-Leu-NHCH3 (ICI 216140) which reduced bombesin-stimulated rat pancreatic amylase secretion to basal levels when administered subcutaneously at 2.0 mg per kg.
Effect of gastrointestinal hormones and synthetic analogues on the growth of pancreatic cancer
Int J Cancer 1995 Sep 27;63(1):69-75.PMID:7558455DOI:10.1002/ijc.2910630114.
The effects of hormones and synthetic analogues have been examined on the growth of 2 human pancreatic cancer cell lines, MiaPaCa2 a well-established cell line and PANI which was derived in our own laboratories from a tumour specimen. The hormones/growth factors included gastrin (G-17), epidermal growth factor (EGF) and bombesin, while the synthetic analogues used were a gastrin receptor antagonist (CR 1718), a somatostatin analogue (RC-160) and a bombesin receptor antagonist (ICI 216,140). Cell proliferation was assessed by the [75Se]selenomethionine uptake method which has been shown to correlate with cell counts. The effect of each hormone or growth factor on growth was expressed as a percentage of the untreated control. There were 5 replicates in each experiment, and each one was repeated at least 3 times. In vitro growth of both cell lines was unaffected by gastrin, bombesin or the respective antagonists (CR1718 and ICI 216140). The somatostatin analogue RC-160 also had no effect on basal growth. Significant growth stimulation of both MiaPaCa2 and PANI was seen with epidermal growth factor. We tested the hypothesis that somatostatin analogues may inhibit EGF-stimulated growth on both MiaPaCa2, a somatostatin receptor positive cell line, and on PANI which is negative for somatostatin receptors. RC-160 did not inhibit EGF-stimulated growth of either MiaPaCA2 or PANI. Both cell lines were established in vivo as xenografts in nude mice. The effect of RC-160 on tumour growth was measured. RC-160 inhibited the growth of MiaPaCa2, the somatostatin receptor-positive cell line, but not of PANI.
Pharmacological profiles of two bombesin analogues in cells transfected with human neuromedin B receptors
Eur J Pharmacol 1996 Jun 13;306(1-3):307-14.PMID:8813645DOI:10.1016/0014-2999(96)00223-3.
We examined the effect of two des-Met-bombesin analogues, [(CH3)2CHCO-His-Trp-Ala-Val-D-Ala-His-Leu-NHCH3] (ICI 216140) and [D-Phe6,des-Met14]bombesin(6-14) ethylamide (DPDM-bombesin ethylamide), on neuromedin B-induced Ca2+ and [3H]arachidonate release in BALB 3T3 cells transfected with human neuromedin B receptors. ICI 216140 and DPDM-bombesin ethylamide both stimulated Ca2+ mobilisation in a concentration-dependent manner but were less potent and efficacious than neuromedin B. BIM 23042 [D-Nal-Cys-Tyr-D-Trp-Lys-Val-Cys-Nal-NH2], a selective neuromedin B antagonist and [D-Arg1,D-Phe5,D-Trp7,9,Leu11]substance P, a broad-spectrum peptide receptor antagonist inhibited neuromedin B-, ICI 216140 and DPDM-bombesin ethylamide-induced Ca2+ release. Pretreatment of cells with either des-Met-bombesin analogue attenuated neuromedin B-induced Ca2+ elevations, suggesting similar agonist-sensitive Ca2+ pools. The pharmacological profiles revealed from the [3H]arachidonate assay were similar, although ICI 216140 was less potent and efficacious than DPDM-bombesin ethylamide. The data suggest that ICI 216140 and DPDM-bombesin ethylamide behave as agonists at the neuromedin B receptor, perhaps as a consequence of neuromedin B receptor overexpression.
Two bombesin analogues discriminate between neuromedin B- and bombesin-induced calcium flux in a lung cancer cell line
Peptides 1993 Nov-Dec;14(6):1231-5.PMID:8134305DOI:10.1016/0196-9781(93)90181-f.
We examined the profile of two bombesin (BN) antagonists, (CH3)2CHCO-His-Trp-Ala-Val-D-Ala-His-Leu-NHCH3] (ICI 216140) and [D-Phe6,des-Met14]BN(6-14)ethylamide (DPDM-BN EA), against neuromedin B-induced Ca2+ mobilization in the small cell lung cancer (SCLC) line NCI-H345. Neuromedin B (NMB), a BN-like peptide sharing sequence homology with ranatensin, elicited a concentration-dependent Ca2+ release (in part) from intracellular stores. Sequential addition of NMB attenuated Ca2+ mobilization. Desensitization occurred between BN and NMB; depletion of intracellular Ca2+ is a likely mechanism because thapsigargin stimulated Ca2+ release after a maximally desensitizing dose of NMB. ICI 216140 and DPDM-BN EA competitively inhibited BN-induced Ca2+ transients. In contrast, these compounds antagonized NMB-stimulated Ca2+ transients in a noncompetitive manner. The pharmacological profiles obtained support receptor heterogeneity for BN-like peptides on this SCLC line, underscoring the need for thorough examination of dose-response relationships when investigating effects of BN analogues on intact cells.