Vapreotide (RC160)
(Synonyms: 伐普肽,RC160; BMY 41606) 目录号 : GC34152
Vapreotide (RC160) 是一种神经激肽-1 (NK1) 受体拮抗剂，IC50 为 330 nM。
Cas No.:103222-11-3
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
Cell experiment: | The HEK293-NK1R cells and U373MG cells are incubated with or without Vapreotide (0, 5, 10, 20 μM) for 10 minutes and then incubated with or without SP for 3 hours. In some experiments, cells are first incubated with CYN for 10 minutes, and then Vapreotide is added and incubated for an additional 10 minutes, followed by stimulation with SP for 3 hours. Mock treated cells are used as controls[1]. |
References: [1]. Spitsin S et al. Analog of somatostatin vapreotide exhibits biological effects in vitro via interaction with neurokinin-1 receptor. Neuroimmunomodulation. 2013;20(5):247-55. | |
Vapreotide is a NK1R antagonist, with an IC50 of 330 nM.
Vapreotide attenuates the effect of SP on calcium release in a concentration-dependent manner. The concentration required for Vapreotide to completely inhibit the effect of SP is about 100 times higher than that required for the NK1R antagonist aprepitant. The effect of Vapreotide on cell proliferation is mediated primarily by SSTR2. In order to further establish the NK1R antagonist effect of Vapreotide, U373MG cells are pretreated with SSTR2 selective antagonist CYN followed by incubation with Vapreotide and SP stimulation. The results show that pretreatment with CYN does not reverse the inhibitory effect of Vapreotide on SP-stimulated IL-8 mRNA expression. Vapreotide reduces HIV-1 replication in MDM as indicated by limited HIV gag mRNA expression compared to control MDM. In addition, SP treatment (10 μM) reverses Vapreotide inhibition of HIV-1 replication in MDM. This observation indicates that the inhibition of HIV-1 replication by Vapreotide is most likely due to its interaction with NK1R[1].
[1]. Spitsin S et al. Analog of somatostatin vapreotide exhibits biological effects in vitro via interaction with neurokinin-1 receptor. Neuroimmunomodulation. 2013;20(5):247-55.
| Cas No. | 103222-11-3 | SDF | |
| 别名 | 伐普肽,RC160; BMY 41606 | ||
| Canonical SMILES | Phe-Cys-Tyr-Trp-Lys-Val-Cys-Trp-NH2 (Disulfide bridge: Cys2-Cys7) | ||
| 分子式 | C57H70N12O9S2 | 分子量 | 1131.37 |
| 溶解度 | Water : ≥ 60 mg/mL (53.03 mM) | 储存条件 | -20°C, protect from light |
| 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 | 0.8839 mL | 4.4194 mL | 8.8388 mL |
| 5 mM | 0.1768 mL | 0.8839 mL | 1.7678 mL |
| 10 mM | 0.0884 mL | 0.4419 mL | 0.8839 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。
Vapreotide labeled with Tc-99m for imaging tumors
Int J Oncol 1996 Sep;9(3):445-51.PMID:21541533DOI:10.3892/ijo.9.3.445.
Vapreotide (RC-160), an octapeptide analog of somatostatin, has a high affinity for somatostatin receptor subtypes SSTR2 and SSTR5. Vapreotide binds differently to the tumors of the breast, ovary, exocrine pancreas, prostate and colon, than octreotide another octapeptide analog of somatostatin. Vapreotide was labeled with Tc-99m, a radionuclide highly suitable for scintigraphic imaging. The labeling procedure was simple, produced >70% yields and could be applicable to label other peptides containing a cystine bridge. HPLC analysis showed that the tracer was stable when Tc-99m-RC-160 was challenged with 100 fold molar excess DTPA (diethylenetriaminepentaacetic acid), HSA (human serum albumin) or cysteine and incubated at 37 degrees C for 4 h. HPLC analysis of urine samples obtained from mice that received Tc-99m-RC-160 showed that the preparation was stable in vivo. Rat brain cortex membrane receptor displacement assays showed that the Kd values for Tc-99m-RC-160 (71x10(-9) M) and Tc-99m-octreotide (86x10(-9) M) (Sandostatin(R)) were in nM range, and were similar to that for I-125-RC-160 (46x10(-9) M). High binding affinity of Tc-99m-RC-160 for human breast tumor cells SKBR-3 was also observed. These results suggest that Tc-99m-RC-160 is worthy of evaluation as an agent for scintigraphic imaging of tumors rich in somatostatin receptor subtypes SSTR2 and SSTR5.
Response of patients with advanced prostatic cancer to administration of somatostatin analog RC-160 (Vapreotide) at the time of relapse
Prostate 2003 Aug 1;56(3):183-91.PMID:12772187DOI:10.1002/pros.10232.
Background: The aim of this study was to evaluate the effects of administration of the somatostatin analog RC-160 (Vapreotide) at the time of relapse in patients with androgen independent prostate cancer. Methods: Our study included 13 patients with biopsy-proven prostate cancer, stage D3. Eight patients had been treated with a depot formulation of the agonist D-Trp-6-LH-RH, with a median remission time of 68 (range 48-102 months). Five patients were initially treated by surgical orchiectomy, but relapsed after a median time of 33 months (range 17-91 months). A new remission period with a median duration of 10 months (range 2-29 months) was induced with Ketoconazole in the orchiectomy group. At the relapse time, all the patients received 1 mg of Vapreotide t.i.d., by subcutaneous route, in addition to D-Trp-6-LH-RH, or Ketoconazole in the orchiectomy group. Results: Eight of 13 patients demonstrated clinical improvement after 3 months of therapy with Vapreotide, six showing a decrease in serum prostate specific antigen (PSA) from 234.5 +/- 308.5 to 68.2 +/- 60.5 ng/ml (mean decline 71 +/- 8%; P < 0.05). Two additional patients presented a fall in serum prostatic acid phosphatase (PAP). Responding patients showed a decrease in the bone pain score from 2.62 +/- 0.48 to 0.37 +/- 0.69 and an increase in the Karnofsky performance status from 72.3 +/- 4.21 to 83.6 +/- 23.2 (P < 0.05). In accord with the ECOG criteria, two patients had a complete response; four had partial response, and two had a stable response. Four patients did not respond and one was not evaluable. Two patients died in remission, one at 16 months due to myocardial infarction and the other at 24 months due to pneumonia. Three patients relapsed at 5, 17, and 19 months respectively. Three patients who have been followed-up for more than 3 years continued in remission (79, 45, and 45 months) respectively. Vapreotide was well tolerated, only three patients having transitory mild diarrhea. Conclusions: Our results indicate that therapy with the somatostatin analog Vapreotide at the time of relapse can induce objective clinical responses in some patients with prostate cancer who are refractory to androgen ablation induced by LH-RH analogs or orchiectomy.
Technetium-99m somatostatin analogues: effect of labelling methods and peptide sequence
Eur J Nucl Med 1999 Aug;26(8):869-76.PMID:10436200DOI:10.1007/s002590050461.
In this paper the preclinical evaluation of the somatostatin analogue RC160 labelled with technetium-99m using bifunctional chelators (BFCs) based on the hydrazinonicotinamide (HYNIC) and N(3)S system is described and a comparison made with [Tyr(3)]-octreotide (TOC). Conjugates of both peptides with HYNIC, and of RC160 with benzoyl-MAG(3) and an N(3)S-adipate derivative were prepared and radiolabelling performed at high specific activities using tricine, tricine/nicotinic acid and ethylenediamine-N,N'-diacetic acid (EDDA) as co-ligands for HYNIC conjugates. All conjugates and (99m)Tc-labelled peptides showed preserved binding affinity for the somatostatin receptor (IC50, Kd<5 nM). The biodistribution was markedly dependent on the BFC and co-ligand used, with the amidothiol ligands showing a greater degree of hepatobiliary clearance, the HYNIC/tricine complex higher blood levels and the HYNIC/EDDA complex the highest level of renal excretion and lowest blood levels. All peptide conjugates showed receptor-mediated uptake in tumour xenografts, but tumour uptake was significantly lower for the (99m)Tc-RC160 derivatives compared with (99m)Tc-EDDA/HYNIC-[Tyr(3)]-octreotide (0.2%-3.5%ID/g vs 9.7%ID/g) and correlated well with the reduced internalisation rate for RC160 derivatives. Our results show that the selection of the labelling approach as well as the right choice of the peptide structure are crucial for labelling peptides with (99m)Tc to achieve complexes with favourable biodistribution. Despite the relatively low tumour uptake compared with (99m)Tc-EDDA/HYNIC-[Tyr(3)]-octreotide, (99m)Tc-RC160 could play a role in imaging tumours that do not bind octreotide derivatives.
Phase II study of RC-160 (Vapreotide), an octapeptide analogue of somatostatin, in the treatment of metastatic breast cancer
Br J Cancer 1999 Mar;79(9-10):1413-8.PMID:10188884DOI:10.1038/sj.bjc.6690226.
RC-160 (octastatin/Vapreotide) is a potent octapeptide analogue of somatostatin with growth inhibitory activity in experimental tumours in vitro and in vivo, including breast cancer. We evaluated the efficacy and tolerability of high-dose RC-160, 3 mg day(-1) on week 1 increased to 4.5 mg day(-1) for weeks 2-4 and subsequently 6 mg day(-1) until the end of treatment, administered by continuous subcutaneous infusion in the management of 14 women with previously treated metastatic breast cancer. The age range was 37-80 years (median 58.5 years) and performance status 0-2. The treatment was well tolerated with no dose reductions being required. No grade 3 or 4 toxicities were seen. Abscess formation developed at the infusion site in eight patients and erythema and discomfort was seen in a further three patients. A significant reduction in IGF-I levels occurred by day 7 and was maintained throughout the treatment. The lowest dose of RC-160 produced the maximal IGF-I response. Although there was no reduction in prolactin levels in patients whose baseline levels were normal, elevated prolactin levels found in three patients fell to within the normal range 7 days after commencing RC-160 treatment. A small but significant rise in fasting blood glucose levels was also recorded, the highest level on treatment being 7.6 mmol l(-1). No objective tumour responses were observed, all patients showing disease progression within 3 months of commencing treatment. These findings demonstrate that high-dose RC-160, administered as a continuous subcutaneous infusion, can reduce serum levels of the breast growth factors IGF-I and prolactin but is ineffective in the management of metastatic breast cancer. Encouraging preclinical anti-tumour activity and the favourable toxicity profile in patients suggest the merit of future studies combining RC-160 with anti-oestrogen, cytotoxic and anti-angiogenic agents.
[125I][Tyr3]octreotide labels human somatostatin sst2 and sst5 receptors
Eur J Pharmacol 1998 May 8;348(2-3):311-20.PMID:9652348DOI:10.1016/s0014-2999(98)00159-9.
Human somatostatin (somatotropin release inhibiting factor = SRIF) receptor subtypes sst2 and sst5 were stably expressed in Chinese hamster lung fibroblast (CCL39) cells. [125I][Tyr3]octreotide labelled with high affinity and in a saturable manner both sst2 (pKd = 9.89+/-0.02, Bmax = 210+/-10 fmol/mg, n = 3) and sst5 sites (pKd = 9.64+/-0.04, Bmax = 920+/-170 fmol/mg, n = 3). The pharmacological profile of sst2 sites established in CCL39 cells using SRIF and various peptide analogues was very similar to that described previously in CHO cells and in human cortex: SRIF14 = SRIF28 > or = seglitide > BIM 23014 = RC 160 > octreotide > CGP 23996 > or = L362,855 > BIM 23052 > L361,301 = cortistatin14 > BIM 23030 > BIM 23056 > cycloantagonist SA. However, peptides classically perceived as sst2 receptor selective (e.g., seglitide, octreotide, Vapreotide) showed also high affinity for human sst5 receptors labelled with [125I][Tyr3]octreotide: SRIF28 > seglitide > SRIF14 > L361,301 = octreotide > cortistatin14 = BIM 23014 = BIM 23052 > L362,855 = RC160 > CGP 23996 > BIM 23056 > cycloantagonist SA > BIM 23030. Further radioligand binding studies were performed with [Leu8,D-Trp22,125I-Tyr25]SRIF28 ([125I]LTT-SRIF28) and [125I]CGP 23996. At sst2 receptors, Bmax values determined with [125I][Tyr3]octreotide, [125I]LTT-SRIF28 and [125I]CGP 23996 were in the same range (180-370 fmol/mg). 5'-Guanylyl-imidodiphosphate (GppNHp) displaced all three radioligands to the same extent (85%) and the pharmacological profiles were superimposable. By contrast, at sst5 receptors Bmax values were very different: [125I][Tyr3]octreotide (920 fmol/mg), [125I]CGP 23996 (3530 fmol/mg) and [125I]LTT-SRIF28 (6950 fmol/mg). GppNHp affected [125I][Tyr3]octreotide more than [125I]CGP 23996 binding, whereas [125I]LTT-SRIF28 was much less affected. In addition, the affinity values determined in competition experiments at sst5 receptors, varied markedly; whereas SRIF14, cortistatin14 and SRIF28 showed 2-, 4- and 8-fold differences in affinity at sst5 receptors labelled with [125I][Tyr3]octreotide and [125I]LTT-SRIF28 compounds such as RC160, L363,301, L362,855, octreotide or CGP 23996 showed between 42- and 123-fold lower affinity when sst5 sites were labelled with [125I]LTT-SRIF28. The present data suggest caution to be used when comparing affinity profiles determined in binding studies using different radioligands. In addition, the present results suggest that effects produced by octreotide and related short chain SRIF analogues on hormone release, modulation of tumour growth and central effects may be mediated by either sst2 and/or sst5 receptors.