Butyrolactone I
(Synonyms: 丁酸内酯I,Olomoucin) 目录号 : GC42997A Cdk1 inhibitor
Cas No.:87414-49-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Butyrolactone I is a secondary metabolite from A. terreus that acts as an ATP-competitive inhibitor of cyclin-dependent kinase 1 (Cdk1; IC50 = 20 μg/ml in PC-14 cells).1 It induces dose-dependent G2/M arrest, inhibits DNA synthesis, and decreases Cdk1 protein expression in vitro.1 Butyrolactone I has antitumor effects in non-small cell lung, small cell lung, and prostate cancer cell lines (mean IC50 = 50 μg/ml).[1],[2] It inhibits in vitro Cdk1 phosphorylation of tau and in vivo phosphorylation of transcription factor E2F-1.[3],[4] Additionally, exogenous application of butyrolactone I to A. terreus cultures increases biogenesis of the secondary metabolites lovastatin and conidiation in a quorum-sensing manner.[5]
Reference:
[1]. Nishio, K., Arioka, H., Kurokawa, H., et al. Antitumor effects of butyrolactone I, a selective cdc2 kinase inhibitor, on human lung cancer cell lines. Anticancer Res. 16(6B), 3387-3395 (1996).
[2]. Suzuki, M., Hosaka, Y., Matsushima, H., et al. Butyrolactone I induces cyclin B1 and causes G2/M arrest and skipping of mitosis in human prostate cell lines. Cancer Lett. 138(1-2), 121-130 (1999).
[3]. Hosoi, T., Uchiyama, M., Okumura, E., et al. Evidence for cdk5 as a major activity phosphorylating tau protein in porcine brain extract. J. Biochem. 117(4), 741-749 (1995).
[4]. Kitagawa, M., Higashi, H., Suzuki-Takahashi, I., et al. Phosphorylation of E2F-1 by cyclin A-cdk2. Oncogene 10(2), 229-236 (1995).
[5]. Palonen, E.K., Raina, S., Brandt, A., et al. Transcriptomic complexity of Aspergillus terreus velvet gene family under the influence of butyrolactone I. Microorganisms 14;5(1), (2017).
| Cas No. | 87414-49-1 | SDF | |
| 别名 | 丁酸内酯I,Olomoucin | ||
| 化学名 | (2R)-2,5-dihydro-4-hydroxy-2-[[4-hydroxy-3-(3-methyl-2-buten-1-yl)phenyl]methyl]-3-(4-hydroxyphenyl)-5-oxo-2-furancarboxylic acid, methyl ester | ||
| Canonical SMILES | O=C1O[C@@](CC2=CC(C/C=C(C)/C)=C(O)C=C2)(C(OC)=O)C(C3=CC=C(O)C=C3)=C1O | ||
| 分子式 | C24H24O7 | 分子量 | 424.5 |
| 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 | 2.3557 mL | 11.7786 mL | 23.5571 mL |
| 5 mM | 0.4711 mL | 2.3557 mL | 4.7114 mL |
| 10 mM | 0.2356 mL | 1.1779 mL | 2.3557 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。
Butyrolactone I attenuates inflammation in murine NASH by inhibiting the NF-κB signaling pathway
Biochem Biophys Res Commun 2022 Oct 20;626:167-174.PMID:35994826DOI:10.1016/j.bbrc.2022.07.050.
Nonalcoholic steatohepatitis (NASH) is the development of non-alcoholic fatty liver disease (NAFLD) and a key element in the exacerbation of NAFLD. Since there are currently no drugs approved by the U.S. Food and Drug Administration to treat this disease, the search for treatments that can be translated into clinical use is urgent. Butyrolactone I (BLI), isolated from Aspergillus terreus, is an active compound possessing multiple biological activities. However, the effects of BLI on NASH have never been reported. In this study, RAW264.7 cells stimulated by lipopolysaccharide (LPS) were applied to study the anti-inflammatory effect and the underlying mechanisms of BLI in vitro. Following this, mice fed with high-fat and -fructose diet (HFFD) were used to explore the alleviation of NASH by BLIin vivo. We found that BLI attenuated inflammation in LPS-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway and downregulating the expression of iNOS and COX-2. Moreover, results of experiments in vivo demonstrated that BLI reduced serum transaminase levels, decreased hepatic fat accumulation, inhibited inflammation, suppressed oxidative stress, and ameliorated liver fibrosis. For the first time, we investigated the role of BLI in the treatment of murine NASH. We found that BLI alleviates NASH partly by inhibiting the NF-κB pathway of signaling. Given its hepatoprotective effects and non-toxic properties, BLI can be a novel and effective drug for NASH patients.
Marine fungal metabolite Butyrolactone I prevents cognitive deficits by relieving inflammation and intestinal microbiota imbalance on aluminum trichloride-injured zebrafish
J Neuroinflammation 2022 Feb 7;19(1):39.PMID:35130930DOI:10.1186/s12974-022-02403-3.
Background: Mounting evidences indicate that oxidative stress, neuroinflammation, and dysregulation of gut microbiota are related to neurodegenerative disorders (NDs). Butyrolactone I (BTL-I), a marine fungal metabolite, was previously reported as an in vitro neuroprotectant and inflammation inhibitor. However, little is known regarding its in vivo effects, whereas zebrafish (Danio rerio) could be used as a convenient in vivo model of toxicology and central nervous system (CNS) diseases. Methods: Here, we employed in vivo and in silico methods to investigate the anti-NDs potential of BTL-I. Specifically, we established a cognitive deficit model in zebrafish by intraperitoneal (i.p.) injection of aluminum trichloride (AlCl3) (21 μg) and assessed their behaviors in the T-maze test. The proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) as well as acetylcholinesterase (AChE) activity or glutathione (GSH) levels were assayed 24 h after AlCl3 injection. The intestinal flora variation of the zebrafish was investigated by 16S rDNA high-throughput analysis. The marine fungal metabolite, Butyrolactone I (BTL-I), was used to modulate zebrafish cognitive deficits evoked by AlCl3 and evaluated about its effects on the above inflammatory, cholinergic, oxidative stress, and gut floral indicators. Furthermore, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) and drug-likeness properties of BTL-I were studied by the in silico tool ADMETlab. Results: BTL-I dose-dependently ameliorated AlCl3-induced cognitive deficits in zebrafish. While AlCl3 treatment elevated the levels of central and peripheral proinflammatory cytokines, increased AChE activity, and lowered GSH in the brains of zebrafish, these effects, except GSH reduction, were reversed by 25-100 mg/kg BTL-I administration. Besides, 16S rDNA high-throughput sequencing of the intestinal flora of zebrafish showed that AlCl3 decreased Gram-positive bacteria and increased proinflammatory Gram-negative bacteria, while BTL-I contributed to maintaining the predominance of beneficial Gram-positive bacteria. Moreover, the in silico analysis indicated that BTL-I exhibits acceptable drug-likeness and ADMET profiles. Conclusions: The present findings suggest that BTL-I is a potential therapeutic agent for preventing CNS deficits caused by inflammation, neurotoxicity, and gut flora imbalance.
Isolation and identification of phase I metabolites of Butyrolactone I in rats
Xenobiotica 2017 Mar;47(3):236-244.PMID:27604497DOI:10.3109/00498254.2016.1172280.
1. Butyrolactone I (BL-I), one of the major secondary metabolites of fungus Aspergillus terreus, is a selective cdc2 kinase inhibitor. In the present study, the metabolism of BL-I in male Wistar rats was investigated by characterizing metabolites excreted into feces. 2. Following an oral dose of 40 mg/kg BL-I, 10 phase I metabolites were isolated from the feces of rats, and their structures were identified on the basis of a range of spectroscopic data and ICD analysis. These metabolites were fully characterized as butyrolactone VI (M1), aspernolide E (M2), 7''S-hydroxy-9''-ene-butyrolactone I (M3), 7''R-hydroxy-9''-ene-butyrolactone I (M4), 7″S, 8″R-dihydroxy-aspernolide E (M5), 7″R, 8″S-dihydroxy-aspernolide E (M6), 7″R-acetyl-8″S-hydroxy-aspernolide E (M7), 7″S-acetyl-8″R-hydroxy-aspernolide E (M8), 7″R-methoxy-8″S-hydroxy-aspernolide E (M9), butyrolactone V (M10), respectively. It is the first time to describe the metabolites of BL-I in vivo, and metabolites M3 to M9 are new compounds. 3. BL-I and metabolites M2 to M10 were evaluated for their antimicrobial activity and in vitro antiproliferative activities. Only M-3 and M-4 showed inhibitory effect against staphylococcus aureus both with MIC of 125 μg/ml. BL-I and metabolites M-4 and M-5 exhibited potent cancer cell growth inhibitory activities against HL-60 (human leukemia) cell lines with the IC50 values of 13.2, 28.8 and 35.7 μM, respectively. 4. On the basis of metabolites profile, a possible metabolism pathway for BL-I in rats has been proposed. This is the first systematic study on the phase I metabolites of BL-I.
Butyrolactone I Quantification from Lovastatin Producing Aspergillus terreus Using Tandem Mass Spectrometry-Evidence of Signalling Functions
Microorganisms 2014 Jun 4;2(2):111-27.PMID:27682234DOI:10.3390/microorganisms2020111.
Aspergillus terreus is an industrially important filamentous fungus producing a wide spectrum of secondary metabolites, including lovastatin and itaconic acid. It also produces Butyrolactone I which has shown potential as an antitumour agent. Additionally, Butyrolactone I has been implicated to have a regulating role in the secondary metabolism and morphology of A. terreus. In this study, a quantitative time-course liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI-MS-MS) analysis of Butyrolactone I is reported for the first time in nine-day long submerged cultures of A. terreus. Butyrolactone I was fragmented in the mass analysis producing a reproducible fragmentation pattern of four main daughter ions (m/z 307, 331, 363 and 393) in all the samples tested. Supplementing the cultures with 100 nM Butyrolactone I caused a statistically significant increase (up to two-fold) in its production, regardless of the growth stage but was constitutive when Butyrolactone I was added at high cell density during the stationary phase. Furthermore, the extracellular Butyrolactone I concentration peaked at 48 h post inoculation, showing a similar profile as has been reported for bacterial quorum sensing molecules. Taken together, the results support the idea of Butyrolactone I as a quorum sensing molecule in A. terreus.
Deep-Sea-Derived Butyrolactone I Suppresses Ovalbumin-Induced Anaphylaxis by Regulating Mast Cell Function in a Murine Model
J Agric Food Chem 2018 Jun 6;66(22):5581-5592.PMID:29763312DOI:10.1021/acs.jafc.8b01674.
Deep-sea-derived Butyrolactone I (BTL-I), which was identified as a type of butanolide, was isolated from Aspergillus sp. Ovalbumin (OVA)-induced BALB/c anaphylaxis was established to explore the antifood allergic activity of BTL-I. As a result, BTL-I was able to alleviate OVA-induced allergy symptoms, reduce the levels of histamine and mouse mast cell proteinases, inhibit OVA-specific IgE, and decrease the population of mast cells in the spleen and mesenteric lymph nodes. BTL-I also significantly suppressed mast-dependent passive cutaneous anaphylaxis. Additionally, the maturation of bone marrow-derived mast cells (BMMCs) declined as BTL-I caused down-regulation of c-KIT receptors. Furthermore, molecular docking analyses revealed that BTL-I interacted with the inhibitory receptor, FcγRIIB. In conclusion, the reduction of mast cell function by deep-sea-derived BTL-I as well as its interactions with the inhibitory receptor, FcγRIIB, may contribute to BTL-I-related protection against food anaphylaxis.