Leucinostatin A
(Synonyms: 白灰制菌素A,Antibiotic P168) 目录号 : GC44050
A fungal metabolite with diverse biological activities
Cas No.:76600-38-9
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
Leucinostatin A is a fungal metabolite originally isolated from P. lilacinus with diverse biological activities. It is active against P. oryzae, B. cinera, P. chrysogenum, X. oryzae, S. cerevisiae, and C. albicans fungi and B. subtilis, S. aureus, S. lutea, and M. phlei bacteria in a disc assay. Leucinostatin A (0.1-1 μg/ml) reduces T cell activation induced by phorbol 12-myristate 13-acetate or an anti-CD3 antibody in a concentration-dependent manner. It inhibits proliferation of DU145 prostate cancer cells co-cultured with PrSC stromal cells in vitro (IC50 = 0.045 μg/ml).
| Cas No. | 76600-38-9 | SDF | |
| 别名 | 白灰制菌素A,Antibiotic P168 | ||
| Canonical SMILES | CC(C)C[C@H](NC([C@H](CC(C)C)NC(C(C)(C)NC([C@H]([C@@H](C(C)C)O)NC([C@@H](NC([C@H]1N(C(/C=C/[C@@H](C)CC)=O)C[C@@H](C)C1)=O)C[C@H](C)C[C@H](O)CC(CC)=O)=O)=O)=O)=O)C(NC(C)(C)C(NC(C)(C)C(NCCC(N[C@@H](C)CN(C)C)=O)=O)=O)=O | ||
| 分子式 | C62H111N11O13 | 分子量 | 1218.6 |
| 溶解度 | DMF: soluble,DMSO: soluble,Ethanol: soluble,Methanol: 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。 |
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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 | 0.8206 mL | 4.1031 mL | 8.2061 mL |
| 5 mM | 0.1641 mL | 0.8206 mL | 1.6412 mL |
| 10 mM | 0.0821 mL | 0.4103 mL | 0.8206 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。
Catalytic Asymmetric Total Synthesis of Leucinostatin A
Chem Rec 2021 Jan;21(1):175-187.PMID:33107684DOI:10.1002/tcr.202000108.
This review describes our efforts toward achieving catalytic asymmetric total synthesis of Leucinostatin A, a compound that interferes with the tumor-stroma interaction. The synthesis utilizes four catalytic asymmetric reactions, including direct-type reactions exemplified by high atom-economy, and three C-C bond forming reactions. Thorough analysis of the NMR data, HPLC profiles, and biologic activity led us to unambiguously revise the absolute configuration regarding the 6-position of the AHMOD residue side chain from S (reported) to R. Other examples of previously reported important studies on the stereoselective synthesis of HyLeu and AHMOD are also described.
The nonapeptide Leucinostatin A acts as a weak ionophore and as an immunosuppressant on T lymphocytes
Biochim Biophys Acta 1994 Mar 31;1221(2):125-32.PMID:8148389DOI:10.1016/0167-4889(94)90004-3.
Earlier studies have disclosed that Leucinostatin A, a hydrophobic nonapeptide antibiotic, assumes an alpha-helical secondary structure in nonpolar environments. The present report demonstrates that the peptide acts as a weak ionophore facilitating the transport of mono-and divalent cations through the plasma membrane of T lymphocytes and through artificial membranes. Leucinostatin A does not change the thymidine uptake of both resting mouse thymocytes and peripheral blood lymphocytes but dose-dependently prevents the activation of T lymphocytes by tetradecanoyl-phorbol-acetate and by anti-T cell receptor antibody.
Leucinostatin A inhibits prostate cancer growth through reduction of insulin-like growth factor-I expression in prostate stromal cells
Int J Cancer 2010 Feb 15;126(4):810-8.PMID:19795463DOI:10.1002/ijc.24915.
Targeting stroma in tumor tissues is an attractive new strategy for cancer treatment. We developed in vitro coculture system, in which the growth of human prostate cancer DU-145 cells is stimulated by prostate stromal cells (PrSC) through insulin-like growth factor I (IGF-I). Using this system, we have been searching for small molecules that inhibit tumor growth through modulation of tumor-stromal cell interactions. As a result, we have found that leucinostatins and atpenins, natural antifungal antibiotics, inhibit the growth of DU-145 cells cocultured with PrSC more strongly than that of DU-145 cells alone. In this study we examined the antitumor effects of these small molecules in vitro and in vivo. When DU-145 cells were coinoculated with PrSC subcutaneously in nude mice, Leucinostatin A was found to significantly suppress the tumor growth more than atpenin B. The antitumor effect of Leucinostatin A in vivo was not obtained against the tumors of DU-145 cells alone. RT-PCR experiments revealed that Leucinostatin A specifically inhibited IGF-I expression in PrSC without effect on expressions of other IGF axis molecules. Leucinostatins and atpenins are known to abrogate mitochondrial functions. However, when we used mitochondrial DNA-depleted, pseudo-rho(0) cells, we found that one of leucinostain A actions certainly depended on mitochondrial function, but it actually inhibited the growth of DU-145 cells more strongly in coculture with pseudo-rho(0) PrSC and reduced IGF-I expression in pseudo-rho(0) PrSC. Taken together, our results suggested that Leucinostatin A inhibited prostate cancer cell growth through reduction of IGF-I expression in PrSC.
Catalytic Asymmetric Total Synthesis and Stereochemical Revision of Leucinostatin A: A Modulator of Tumor-Stroma Interaction
Chemistry 2017 Sep 4;23(49):11792-11796.PMID:28703358DOI:10.1002/chem.201703239.
Total synthesis of Leucinostatin A, a modulator of tumor-stroma interactions, using asymmetric catalyses, a nitroaldol reaction, thioamide-aldol reaction, Strecker-type reaction, and alcoholysis of 3-methylglutaric anhydride, is described. We demonstrated the applicability of the established catalytic asymmetric processes to the synthesis of molecules with a complex structure. Careful analysis of the NMR data, HPLC profiles, and biological activity revealed that the correct structure of Leucinostatin A is the epimeric form of the reported structure; the secondary alcohol within the AHMOD residue has an R configuration.
Leucinostatin-A loaded nanospheres: characterization and in vivo toxicity and efficacy evaluation
Int J Pharm 2004 May 4;275(1-2):61-72.PMID:15081138DOI:10.1016/j.ijpharm.2004.01.030.
Leucinostatin A (Leu-A) is a nonapeptide exerting a remarkable activity especially against Candida albicans and Cryptococcus neoformans; nevertheless, its employment is limited due its toxicity. Therefore, we recently developed liposomal formulations, as suitable delivery systems, in order to increase its therapeutic index. However, liposomes present disadvantages related to their long-term instability. For this reason poly(lactic-co-glycolic) nanospheres (NS) were chosen as alternative colloidal carriers for Leu-A delivery. NS were formulated by spontaneous emulsification solvent diffusion method. This study investigates the effects of different parameters on drug encapsulation efficiency and particle size as well. The best preparation obtained was also characterized for its in vitro release, in vivo acute toxicity (LD50), and effectiveness against C. albicans in mice. In vitro release was performed over 100 h and resulted sufficiently sustained with more than 93% of the peptide released. Acute toxicity showed that the LD50 was increased more than 18-fold and the study on systemic candidiasis models revealed high effectiveness of the NS in reducing either the growth of fungal colonies in infected mice liver or in the mortality index. In conclusion, we can propose that Leu-A loaded NS could represent a new promising therapeutic system against Candida infection.