Chaetocin
(Synonyms: 毛壳素) 目录号 : GC14936
Inhibitor of lys9-specific HMTs
Cas No.:28097-03-2
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
|
Cell lines |
SKOV-3, OVCAR-3, KGN and A2780 ovarian cancer (OC) cell line |
|
Preparation Method |
The OC cells were seeded in 96-well microplates (1×104 cells/well) and incubated at 37°C overnight. Following incubation with chaetocin (0.05, 0.1, 0.25, 0.5, 0.75, 1 and 2 µM) at 37°C for 24 h, |
|
Reaction Conditions |
0.05, 0.1, 0.25, 0.5, 0.75, 1 and 2 µM for 24 hours |
|
Applications |
Chaetocin significantly inhibited the viability of SKOV-3, OVCAR-3, KGN and A2780 cells in a dose-dependent manner, with half-maximal inhibitory concentrations of 0.30, 60.66, 81.86 and 100.60 nM, respectively. |
| Animal experiment [2]: | |
|
Animal models |
Female BALB/C nude mice |
|
Preparation Method |
Paired mice with equal tumor volume were divided into the chaetocin-treated group and the vehicle-treated group (n = 6 for each group), and then injected intraperitoneally (i.p.) daily with chaetocin (0.5 mg/kg) and the vehicle (DMSO), respectively. After 10 days of drug treatment, mice were sacrificed and the tumor were weighed. |
|
Dosage form |
Intraperitoneal injection, 0.5 mg/kg/day for 10 days |
|
Applications |
Significantly lower average tumor weight for chaetocin treatment group compared to control group |
|
References: [1]: Li Z, Huang L, Wei L, et al. Chaetocin induces caspase?dependent apoptosis in ovarian cancer cells via the generation of reactive oxygen species[J]. Oncology Letters, 2019, 18(2): 1915-1921. | |
Chaetocin was reported to be a nonspecific inhibitor of histone methyl transferase (HMT) such as SUV39H1, thereby affecting gene expression [1]. Chaetocin inhibited HMT SU(VAR)3-9 with an IC50 of 0.6 µM [2].
Chaetocin significantly reduces the proliferation, cloning potential, and migration ability of the glioblastoma cell line T98G [3]. Chaetocin abrogated the maintenance of stem cell characteristics and tumor growth of bladder cancer stem cells (BCSCs) by suppressing the KMT1A-GATA3-STAT3 circuit (inhibition ratio: 80.1%) [4]. Chaetocin inhibited ovarian cancer (OC) cell proliferation, induced G2/M phase cell cycle arrest, and induced apoptosis at the concentration of 2µM (24 hours) [5]. Chaetocin inhibited cell proliferation and reduced PI3K/AKT pathway and p-AKT in gastric cancer HGC-27 cell, at the concentration of 200µM (24 hours) [6].
Chaetocin inhibited tumor growth in HGC-27 cell injected Gastric cancer mice model, by 0.5 mg/kg/day every alternate day for 24 days [6]. Chaetocin inhibited tumor progression and reduced PCNA in U87MG cell injected glioma mice model, by 0.5 mg/kg/day every alternate day for 25 days [7].
References:
[1]. Cherblanc F L, Chapman K L, Brown R, et al. Chaetocin is a nonspecific inhibitor of histone lysine methyltransferases[J]. Nature chemical biology, 2013, 9(3): 136-137.
[2]. Greiner D, Bonaldi T, Eskeland R, et al. Identification of a specific inhibitor of the histone methyltransferase SU (VAR) 3-9[J]. Nature chemical biology, 2005, 1(3): 143-145.
[3]. Sepsa A, Levidou G, Gargalionis A, et al. Emerging role of linker histone variant H1x as a biomarker with prognostic value in astrocytic gliomas. A multivariate analysis including trimethylation of H3K9 and H4K20[J]. PLoS One, 2015, 10(1): e0115101.
[4]. Yang Z, Wang H, Zhang N, et al. Chaetocin Abrogates the Self-Renewal of Bladder Cancer Stem Cells via the Suppression of the KMT1A-GATA3-STAT3 Circuit[J]. Frontiers in cell and developmental biology, 2020, 8: 424.
[5]. Li Z, Huang L, Wei L, et al. Chaetocin induces caspase?dependent apoptosis in ovarian cancer cells via the generation of reactive oxygen species[J]. Oncology Letters, 2019, 18(2): 1915-1921.
[6]. Wen C, Wang H, Wu X, et al. ROS-mediated inactivation of the PI3K/AKT pathway is involved in the antigastric cancer effects of thioredoxin reductase-1 inhibitor chaetocin[J]. Cell death & disease, 2019, 10(11): 1-16.
[7]. Dixit D, Ghildiyal R, Anto N P, et al. Chaetocin-induced ROS-mediated apoptosis involves ATM-YAP1 axis and JNK-dependent inhibition of glucose metabolism[J]. Cell death & disease, 2014, 5(5): e1212-e1212.
据报道毛壳素是组蛋白甲基转移酶 (HMT)（例如 SUV39H1）的非特异性抑制剂，从而影响基因表达[1]。 Chaetocin 抑制 HMT SU(VAR)3-9，IC50 为 0.6 µM [2]。
Chaetocin 显着降低 HMT SU(VAR)3-9 的增殖、克隆潜力和迁移能力胶质母细胞瘤细胞系 T98G [3]. Chaetocin 通过抑制 KMT1A-GATA3-STAT3 回路（抑制率:80.1%），破坏了膀胱癌干细胞（BCSCs）干细胞特性的维持和肿瘤生长[4]。 Chaetocin 在浓度为 2µM（24 小时）[5] 时抑制卵巢癌 (OC) 细胞增殖，诱导 G2/M 期细胞周期停滞，并诱导细胞凋亡。 Chaetocin 在胃癌 HGC-27 细胞中抑制细胞增殖并降低 PI3K/AKT 通路和 p-AKT，浓度为 200µM（24 小时）[6]。
毛壳素在注射 HGC-27 细胞的胃癌小鼠模型中抑制肿瘤生长，每隔一天 0.5 mg/kg/天，持续 24 天[6]。 Chaetocin 在 U87MG 细胞注射神经胶质瘤小鼠模型中抑制肿瘤进展并减少 PCNA，每隔一天 0.5 mg/kg/天，持续 25 天[7]。
| Cas No. | 28097-03-2 | SDF | |
| 别名 | 毛壳素 | ||
| 化学名 | (3S,3'S,6R,6'R,14R,14'R,16S,16'S)-3,3'-bis(hydroxymethyl)-2,2'-dimethyl-2,2',3,3',6,6',7,7'-octahydro-1H,1'H-[14,14'-bi(3,11a-epidithiopyrazino[1',2':1,5]pyrrolo[2,3-b]indole)]-1,1',4,4'(15H,15'H)-tetraone | ||
| Canonical SMILES | O=C1[C@](CO)(SS2)N(C)C([C@]32N1[C@]4([H])[C@](C(C=CC=C5)=C5N4)([C@@]6(C(C=CC=C7)=C7N8)[C@@]8([H])N(C([C@](CO)(SS9)N%10C)=O)[C@]9(C6)C%10=O)C3)=O | ||
| 分子式 | C30H28N6O6S4 | 分子量 | 696.84 |
| 溶解度 | DMSO: 25 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.435 mL | 7.1752 mL | 14.3505 mL |
| 5 mM | 0.287 mL | 1.435 mL | 2.8701 mL |
| 10 mM | 0.1435 mL | 0.7175 mL | 1.435 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。
Chaetocin: A review of its anticancer potentials and mechanisms
Chaetocin is a natural metabolite product with various biological activities and pharmacological functions isolated from Chaetomium species fungi belonging to the thiodiketopyrazines. Numerous studies have demonstrated a wide range of antitumor activities of chaetocin in vitro and in vivo. Several studies have demonstrated that chaetocin suppresses the growth and proliferation of various tumour cells by regulating multiple signalling pathways related to tumour initiation and progression, inducing cancer cell apoptosis (intrinsic and extrinsic), enhancing autophagy, inducing cell cycle arrest, and inhibiting tumour angiogenesis, invasion, and migration. The antitumor effects and molecular mechanisms of chaetocin are reviewed and analysed in this paper, and the prospective applications of chaetocin in cancer prevention and therapy are also discussed. This review aimed to summarize the recent advances in the antitumor activity of chaetocin and to provide a rationale for further exploring the potential application of chaetocin in overcoming cancer in the future.
Chaetocin attenuates atherosclerosis progression and inhibits vascular smooth muscle cell phenotype switching
We aimed to explore the effect of chaetocin on atherosclerosis and its possible mechanism. In vitro, we observed that chaetocin treatment significantly inhibited the proliferation of VSMCs in concentration- and time-dependent manner. We also found that chaetocin suppressed the migration of VSMCs. Moreover, chaetocin treatment induced a contractile phenotype in VSMCs by increasing 汐-SMA and SM22汐 expression. In addition, chaetocin treatment attenuated the accumulation of H3K9me3 on VSMCs contractile gene promoters, which promoted the expression of 汐-SMA and SM22汐. In vivo, chaetocin treatment decreased the H3K9me3 expression, diminished atherosclerotic plaque formation, and increased plaque stability by decreasing necrotic core area and lipid accumulation and increasing collagen content and contractile VSMC phenotype. We demonstrated a new function of chaetocin in inhibiting atherosclerosis progression and increasing plaque stability partly by inhibiting pathological phenotypic switching of VSMCs. These newly identified roles of chaetocin might provide a novel therapeutic target in atherosclerosis.
Chaetocin induced chromatin condensation: effect on DNA repair signaling and survival
Purpose: The aim of the present study was to evaluate the effect of the histone lysine-methyltransferase (HKMT) inhibitor chaetocin on chromatin structure and its effect on ionizing radiation (IR) induced DNA damage response.
Methods: Concentration and time-dependent effects of chaetocin on chromatin clustering and its reversibility were analyzed by immunofluorescent assays in the non-small cell lung carcinoma (NSCLC) cell lines H460 and H1299Q4 and in human skin fibroblasts. In addition, IR induced damage response (污H2AX, 53BP1, and pATM foci formation) was studied by immunofluorescent assays. The effect on survival was determined by performing single-cell clonogenic assays.
Results: Chaetocin significantly increased the radiation sensitivity of H460 (F test on nonlinear regression, p < .0011) and of H1299 (p = .0201). In addition, treatment with 15 nM chaetocin also decreased the total radiation doses that control 50% of the plaque monolayers (TCD50) from 17.2 ㊣ 0.3 Gy to 7.3 ㊣ 0.4 Gy (p < .0001) in H1299 cells and from 11.6 ㊣ 0.1 Gy to 6.5 ㊣ 0.3 Gy (p < .0001). Phenotypically, chaetocin led to a time and concentration-dependent clustering of the chromatin in H1299 as well as in fibroblasts, but not in H460 cells. This phenotype of chaetocin induced chromatin clustering (CICC) was reversible and depended on the expression of the HKMTs SUV39H1 and G9a. Treatment with siRNA for SUV39h1 and G9a significantly reduced the CICC phenotype. Immunofluorescent assay results showed that the CICC phenotype was enriched for the heterochromatic marker proteins H3K9me3 and HP1汐. 污H2AX foci formation was not affected, neither in cells with normal nor with CICC phenotype. In contrast, repair signaling with 53BP1 and pATM foci formation was significantly reduced in the CICC phenotype.
Conclusions: Treatment with chaetocin increased the radiation sensitivity of cells in vitro and DNA damage response, especially of 53BP1 and ATM-dependent repair by affecting chromatin structure. The obtained results support the potential use of natural HKMT inhibitors such as chaetocin or other bioactive compounds in improving radiosensitivity of cancer cells.
ROS/JNK/C-Jun Pathway is Involved in Chaetocin Induced Colorectal Cancer Cells Apoptosis and Macrophage Phagocytosis Enhancement
There is an urgent need for novel agents for colorectal cancer (CRC) due to the increasing number of cases and drug-resistance related to current treatments. In this study, we aim to uncover the potential of chaetocin, a natural product, as a chemotherapeutic for CRC treatment. We showed that, regardless of 5-FU-resistance, chaetocin induced proliferation inhibition by causing G2/M phase arrest and caspase-dependent apoptosis in CRC cells. Mechanically, our results indicated that chaetocin could induce reactive oxygen species (ROS) accumulation and activate c-Jun N-terminal kinase (JNK)/c-Jun pathway in CRC cells. This was confirmed by which the JNK inhibitor SP600125 partially rescued CRC cells from chaetocin induced apoptosis and the ROS scavenger N-acetyl-L-cysteine (NAC) reversed both the chaetocin induced apoptosis and the JNK/c-Jun pathway activation. Additionally, this study indicated that chaetocin could down-regulate the expression of CD47 at both mRNA and protein levels, and enhance macrophages phagocytosis of CRC cells. Chaetocin also inhibited tumor growth in CRC xenograft models. In all, our study reveals that chaetocin induces CRC cell apoptosis, irrelevant to 5-FU sensitivity, by causing ROS accumulation and activating JNK/c-Jun, and enhances macrophages phagocytosis, which suggests chaetocin as a candidate for CRC chemotherapy.
Chaetocin Promotes Osteogenic Differentiation via Modulating Wnt/Beta-Catenin Signaling in Mesenchymal Stem Cells
Mesenchymal stemXin cells (MSCs) are a great cell source for bone regeneration. Although combining MSCs with growth factors and scaffolds provides a useful clinical strategy for bone tissue engineering, the efficiency of MSC osteogenic differentiation remains to be improved. Epigenetic modification is related to the differentiation ability of MSCs during osteogenic induction. In this study, we evaluate the effect of Chaetocin, an inhibitor of lysine-specific histone methyltransferases, on the differentiation of MSCs. We found that MSCs treated with Chaetocin demonstrated increased osteogenic ability and reduced adipogenic ability. The expression of osteogenic markers (Runx2 and OPN) was induced in MSCs by Chaetocin during osteogenic induction. Moveover, treatment of Chaetocin in MSCs improves Wnt/汕-catenin signaling pathways and its downstream targets. Finally, we showed increased bone formation of MSC and Wnt/汕-catenin signaling activity by treatment of Chaetocin using in vivo bone formation assays. Our data uncovered a critical role of Chaetocin in MSC osteogenic differentiation and provide new insights into bone tissue regeneration and repair.