Verucopeptin
目录号 : GC61863
Verucopeptin 是一种有效的 HIF-1 (IC50=0.22 µM) 抑制剂，可以降低 HIF-1 靶基因的表达和 HIF-1α 的蛋白水平。通过直接靶向 v-ATPase ATP6V1G 亚基 (但不靶向 ATP1V1B2 或 ATP6V1D)，Verucopeptin 强烈抑制 v-ATPase 活性。Verucopeptin 对耐药性癌细胞表现出抗肿瘤活性，常用作癌症相关研究。
Cas No.:138067-14-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Verucopeptin is a potent HIF-1 (IC50=0.22 µM) inhibitor and decreases the expression of HIF-1 target genes and HIF-1α protein levels[1][2]. Verucopeptin strongly inhibits v-ATPase activity by directly targeting the v-ATPase ATP6V1G subunit but not ATP1V1B2 or ATP6V1D. Verucopeptin exhibits antitumor activity against multidrug resistance (MDR) cancers and can be used for cancer research[3].
ATP6V1G, a subunit of the vacuolar H+-ATPase (v-ATPase)[3].Verucopeptin (0-30 µM; 72 h) shows excellent antitumor activity against K562R cells, with an IC50 of 388 nM, although these cells exhibit resistance to some other chemotherapeutic agents, such as Taxol and vincristine at concentrations of 10 µM[3].Verucopeptin (0-1 µM) shows broad antiproliferative activity, with IC50 values of less than 100 nM against 66% of the cell lines evaluated among a total of 1,094 cancer cell lines. Moreover,Verucopeptin displays tissue specificity, such as leukemia, lymphoma, and melanoma, are classified in the lower IC50 groups, while the higher IC50 groups including other cancer types, such as non-small cell lung cancer[3].Verucopeptin (10 nM; 1 hour) pretreatment blocks VE-P labeling of ATP6V1G1 but not ATP1V1B2 or ATP6V1D in a competitive binding assay. Verucopeptin shows substantial inhibition of v-ATPase activity and suppresses lysosomal acidification in vitro, as does Baf A1, although to a lesser extent[3].Verucopeptin (0-500 nM; 1 hour) exhibits substantial inhibition of p-S6K as well as p-4EBP1 at concentrations of 10-200 nM. Additionally, Verucopeptin attenuates the phosphorylation of most of the tested mTORC1 downstream substrates, including p-4EBP1, pmTORS2448, p-mTORS2481, p-Rictor, p-ULK1, and p-Grb10, at concentrations ranging from 50 nM to 500 nM[3].Verucopeptin (0-335 nM; 24 hour) decreases the HIF-1 protein level in a dose-dependent manner but has no effects on c-Raf in HT1080 cells. However, the known hsp90 inhibitor Tanespimycin inhibits both HIF-1 and c-Raf expression in cells[2].
Verucopeptin (intravenous injection; 1 mg/kg; twice daily; 7 days) substantially represses tumor growth without significant body weight loss or gross signs of toxicity. HE staining indicated that Verucopeptin potently induces cell death and abrogates mTORC1 signaling by dephosphorylation of S6K and 4EBP1[3].
References:
[1]. Aya Yoshimura, et al.Structure Elucidation of Verucopeptin, a HIF-1 Inhibitory Polyketide-Hexapeptide Hybrid Metabolite from an Actinomycete. Org Lett. 2015 Nov 6;17(21):5364-7.
[2]. Nobuaki Takahashi, et al. Total synthesis of verucopeptin, an inhibitor of hypoxia-inducible factor 1 (HIF-1). Chem Commun (Camb). 2019 Oct 1;55(79):11956-11959.
[3]. Yuezhou Wang, et al. Pharmacological Targeting of Vacuolar H +-ATPase via Subunit V1G Combats Multidrug-Resistant Cancer. Cell Chem Biol. 2020 Jun 30;S2451-9456(20)30234-8.
| Cas No. | 138067-14-8 | SDF | |
| 分子式 | C43H73N7O13 | 分子量 | 896.08 |
| 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 | 1.116 mL | 5.5799 mL | 11.1597 mL |
| 5 mM | 0.2232 mL | 1.116 mL | 2.2319 mL |
| 10 mM | 0.1116 mL | 0.558 mL | 1.116 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。
Total synthesis of Verucopeptin, an inhibitor of hypoxia-inducible factor 1 (HIF-1)
Chem Commun (Camb) 2019 Oct 1;55(79):11956-11959.PMID:31531455DOI:10.1039/c9cc06169j.
Verucopeptin is an inhibitor of hypoxia-inducible factor 1 (HIF-1), which is a promising target for cancer chemotherapy. Here, we report the first total synthesis of Verucopeptin via condensation of the depsipeptide core and the polyketide side chain unit including three branched methyl groups after the synthesis of each segment.
Biosynthesis and Chemical Diversification of Verucopeptin Leads to Structural and Functional Versatility
Org Lett 2020 Jun 5;22(11):4366-4371.PMID:32459492DOI:10.1021/acs.orglett.0c01387.
A synthesis program for structurally complex macrocycles is very challenging. Herein, we propose a biosynthesis pathway of the pyranylated cyclodepsipeptide Verucopeptin to make enough supply and to diversify Verucopeptin by genetic manipulation and one-step semisynthesis. The synthesis relies on the intrinsic reactivity of the interchangeable hemiketal pyrane and opened keto along with adjacent alkene. Biological evaluation of verucopeptin-oriented analogs delivers a potent AMP-activated protein kinase (AMPK) agonist, antibacterial agent, and selective NFκB modulator.
Convergent synthesis of tetrahydropyranyl side chain of Verucopeptin, an antitumor antibiotic active against multidrug-resistant cancers
Chem Commun (Camb) 2022 Dec 6;58(97):13447-13450.PMID:36350039DOI:10.1039/d2cc04529j.
A concise synthesis of the tetrahydropyranyl side chain of Verucopeptin, an antitumor antibiotic cyclodepsipeptide efficacious against MDR cancers in vivo, is achieved using 12 steps in the longest linear sequence and 21 total steps, in which Julia-Kocienski olefination for the segments coupling, asymmetric hydroxylation as well as stereoselective synthesis of stable tetrahydropyran ring from a D-isoascorbic acid derivative are key steps. This convergent synthetic strategy enables the structural modification and mechanism study of Verucopeptin for its clinical applications.
Verucopeptin, a new antitumor antibiotic active against B16 melanoma. II. Structure determination
J Antibiot (Tokyo) 1993 Jun;46(6):928-35.PMID:8344874DOI:10.7164/antibiotics.46.928.
The structure of a new antibiotic Verucopeptin has been determined by the spectroscopic analyses and chemical degradation studies. It is a 19-membered cyclodepsipeptide which is structurally related to azinothricin and A83586C.
Structure Elucidation of Verucopeptin, a HIF-1 Inhibitory Polyketide-Hexapeptide Hybrid Metabolite from an Actinomycete
Org Lett 2015 Nov 6;17(21):5364-7.PMID:26484856DOI:10.1021/acs.orglett.5b02718.
The transcriptional factor, hypoxia inducible factor-1 (HIF-1), is a promising target for cancer chemotherapy. From an actinomycete, Verucopeptin (1) was identified as a HIF-1 signaling inhibitor. By a combination of chemical degradation and spectroscopic analyses, the absolute stereochemistry of metabolite 1 was determined to be 10R, 15S, 16S, 23S, 27S, 28R, 31S, 33S, 35R. Moreover, metabolite 1 was revealed to attenuate the HIF-1α and mTORC1 pathway, indicating that Verucopeptin (1) would be a potent lead compound for anticancer chemotherapy.