Chlamydocin
目录号 : GC45717
An HDAC inhibitor
Cas No.:53342-16-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >70.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Chlamydocin is a histone deacetylase (HDAC) inhibitor that was originally isolated from D. chlamydosporia and has anticancer properties.1 It is selective for HDAC1 over HDAC6 (IC50 = 0.15 and 1,100 nM, respectively).2 Chlamydocin increases acetylation of histone H3 and histone H4 in A2780 cells when used at concentrations ranging from 1 to 1,000 nM.1 It inhibits growth of A2780, Malme-3M, MCF-7, HT-29, and HeLa cancer cells (IC50s = 0.36, 45, 5.3, 4.3, and 14 nM, respectively). Chlamydocin increases lifespan by 10% in a P185 mouse allograft model when administered at doses ranging from 20 to 160 mg/kg.3
|1. De Schepper, S., Bruwiere, H., Verhulst, T., et al. Inhibition of histone deacetylases by chlamydocin induces apoptosis and proteasome-mediated degradation of survivin. J. Pharmacol. Exp. Ther. 304(2), 881-888 (2003).|2. Furumai, R., Komatsu, Y., Nishino, N., et al. Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxin. Proc. Natl. Acad. Sci. U.S.A. 98(1), 87-92 (2001).|3. St•helin, H., and Trippmacher, A. Cytostatic activity of chlamydocin, a rapidly inactivated cyclic tetrapeptide. Eur. J. Cancer 10(12), 801-808 (1974).
| Cas No. | 53342-16-8 | SDF | |
| Canonical SMILES | O=C([C@H](CCCCCC([C@H]1OC1)=O)NC([C@]2([H])N3CCC2)=O)NC(C)(C)C(N[C@@H](CC4=CC=CC=C4)C3=O)=O | ||
| 分子式 | C28H38N4O6 | 分子量 | 526.6 |
| 溶解度 | 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 | 1.899 mL | 9.4949 mL | 18.9897 mL |
| 5 mM | 0.3798 mL | 1.899 mL | 3.7979 mL |
| 10 mM | 0.1899 mL | 0.9495 mL | 1.899 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。
Chlamydocin-hydroxamic acid analogues as histone deacetylase inhibitors
Bioorg Med Chem 2004 Nov 15;12(22):5777-84.PMID:15498654DOI:10.1016/j.bmc.2004.08.041.
Chlamydocin-hydroxamic acid analogues were designed and synthesized as histone deacetylase (HDAC) inhibitors based on the structure and HDAC inhibitory activity of Chlamydocin and trichostatin A. Chlamydocin is a cyclic tetrapeptide containing an epoxyketone moiety in the side chain that makes it an irreversible inhibitor of HDAC. We replaced the epoxyketone moiety of Chlamydocin with hydroxamic acid to design potent and reversible inhibitors of HDAC. In addition, a number of amino-cycloalkanecarboxylic acids (Acc) are introduced instead of the simple amino-isobutric acid (Aib) for a variety of the series of Chlamydocin analogues. The compounds synthesized were tested for HDAC inhibitory activity and the results showed that many of them are potent inhibitors of HDAC. The replacement of Aib residue of Chlamydocin with an aromatic amino acid enhances the in vivo and in vitro inhibitory activity. We have carried out circular dichroism and molecular modeling studies on chlamydocin-hydroxamic acid analogue and compared it with the solution structure of Chlamydocin.
Chlamydocin analogs bearing carbonyl group as possible ligand toward zinc atom in histone deacetylases
Bioorg Med Chem 2006 May 15;14(10):3438-46.PMID:16439135DOI:10.1016/j.bmc.2005.12.063.
A series of Chlamydocin analogs with various carbonyl functionalities were designed and synthesized as histone deacetylase (HDAC) inhibitors. Chlamydocin is a cyclic tetrapeptide containing an epoxyketone surrogate in the side chain which makes it irreversible inhibitor of HDACs, whereas apicidins are a class of cyclic tetrapeptides that contain an ethylketone moiety as zinc ligand. We replaced the epoxyketone moiety of Chlamydocin with several ketones and aldehyde to synthesize potent reversible and selective HDAC inhibitors. The inhibitory activity of the cyclic tetrapeptides against histone deacetylase enzymes were evaluated and the result showed most of them are potent inhibitors. Some of them have remarkable selectivity among the HDACs.
Inhibition of histone deacetylases by Chlamydocin induces apoptosis and proteasome-mediated degradation of survivin
J Pharmacol Exp Ther 2003 Feb;304(2):881-8.PMID:12538846DOI:10.1124/jpet.102.042903.
The naturally occurring cyclic tetrapeptide Chlamydocin is a very potent inhibitor of cell proliferation. Here we show that Chlamydocin is a highly potent histone deacetylase (HDAC) inhibitor, inhibiting HDAC activity in vitro with an IC(50) of 1.3 nM. Like other HDAC inhibitors, Chlamydocin induces the accumulation of hyperacetylated histones H3 and H4 in A2780 ovarian cancer cells, increases the expression of p21(cip1/waf1), and causes an accumulation of cells in G(2)/M phase of the cell cycle. In addition, Chlamydocin induces apoptosis by activating caspase-3, which in turn leads to the cleavage of p21(cip1/waf1) into a 15-kDa breakdown product and drives cells from growth arrest into apoptosis. Concomitant with the activation of caspase-3 and cleavage of p21(cip1/waf1), Chlamydocin decreases the protein level of survivin, a member of the inhibitor of apoptosis protein family that is selectively expressed in tumors. Although our data indicate a potential link between degradation of survivin and activation of the apoptotic pathway induced by HDAC inhibitors, stable overexpression of survivin does not suppress the activation of caspase-3 or cleavage of p21(cip1/waf1) induced by Chlamydocin treatment. The decrease of survivin protein level is mediated by degradation via proteasomes since it can be inhibited by specific proteasome inhibitors. Taken together, our results show that induction of apoptosis by Chlamydocin involves caspase-dependent cleavage of p21(cip1/waf1), which is strikingly associated with proteasome-mediated degradation of survivin.
Antitumoral cyclic peptide analogues of Chlamydocin
Peptides 1993 Nov-Dec;14(6):1091-3.PMID:8134289DOI:10.1016/0196-9781(93)90160-i.
A series of cyclic tetrapeptides bearing the bioactive alkylating group on an epsilon-amino-lysyl function have been examined for their antitumoral activity on L1210 and P388 murine leukemia cell lines. One analogue belonging to the Chlamydocin family and bearing a beta-chloroethylnitrosourea group was found to be potent at inhibiting L1210 cell proliferation and had a higher therapeutic index than the reference compound bis-beta-chloroethylnitrosourea (BCNU) on the in vivo P388-induced leukemia model.
Improved development of mouse somatic cell nuclear transfer embryos by Chlamydocin analogues, class I and IIa histone deacetylase inhibitors†
Biol Reprod 2021 Aug 3;105(2):543-553.PMID:33982061DOI:10.1093/biolre/ioab096.
In mammalian cloning by somatic cell nuclear transfer (SCNT), the treatment of reconstructed embryos with histone deacetylase (HDAC) inhibitors improves efficiency. So far, most of those used for SCNT are hydroxamic acid derivatives-such as trichostatin A-characterized by their broad inhibitory spectrum. Here, we examined whether mouse SCNT efficiency could be improved using Chlamydocin analogues, a family of newly designed agents that specifically inhibit class I and IIa HDACs. Development of SCNT-derived embryos in vitro and in vivo revealed that four out of five Chlamydocin analogues tested could promote the development of cloned embryos. The highest pup rates (7.1-7.2%) were obtained with Ky-9, similar to those achieved with trichostatin A (7.2-7.3%). Thus, inhibition of class I and/or IIa HDACs in SCNT-derived embryos is enough for significant improvements in full-term development. In mouse SCNT, the exposure of reconstructed oocytes to HDAC inhibitors is limited to 8-10 h because longer inhibition with class I inhibitors causes a two-cell developmental block. Therefore, we used Ky-29, with higher selectivity for class IIa than class I HDACs for longer treatment of SCNT-derived embryos. As expected, 24-h treatment with Ky-29 up to the two-cell stage did not induce a developmental block, but the pup rate was not improved. This suggests that the one-cell stage is a critical period for improving SCNT cloning using HDAC inhibitors. Thus, Chlamydocin analogues appear promising for understanding and improving the epigenetic status of mammalian SCNT-derived embryos through their specific inhibitory effects on HDACs.