Acetyloxycycloheximide
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| Category | Antibiotics |
| Catalog number | BBF-03445 |
| CAS | 2885-39-4 |
| Molecular Weight | 339.38 |
| Molecular Formula | C17H25NO6 |
| Purity | >98% |
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Description
Acetyloxycycloheximide is originally isolated from Streptomyces albulus ACTT 12757. When the concentration was 0.05-0.25 mg/kg, it could inhibit sarcoma 180 in mice, and its antifungal and antiyeast activities were very weak.
Specification
| Synonyms | E-73 acetate; Acetoxycycloheximide; Streptovitacin E 73; NSC 32743; Antibiotic E-73; 3-(2-(5-Acetoxy-3,5-dimethyl-2-oxocyclohexyl)-2-hydroxyethyl)glutarimide |
| IUPAC Name | [(1R,3S,5S)-3-[(1R)-2-(2,6-dioxopiperidin-4-yl)-1-hydroxyethyl]-1,5-dimethyl-4-oxocyclohexyl] acetate |
| Canonical SMILES | CC1CC(CC(C1=O)C(CC2CC(=O)NC(=O)C2)O)(C)OC(=O)C |
| InChI | InChI=1S/C17H25NO6/c1-9-7-17(3,24-10(2)19)8-12(16(9)23)13(20)4-11-5-14(21)18-15(22)6-11/h9,11-13,20H,4-8H2,1-3H3,(H,18,21,22)/t9-,12-,13+,17+/m0/s1 |
| InChI Key | UFDHNJJHPSGMFX-SQUSCZTCSA-N |
Properties
| Appearance | White Flaky or Acicular Crystals |
| Antibiotic Activity Spectrum | neoplastics (Tumor); fungi; yeast |
| Boiling Point | 529.4°C at 760 mmHg |
| Melting Point | 140-141°C |
| Density | 1.24 g/cm3 |
| Solubility | Soluble in Chloroform, Acetone |
Reference Reading
1. ERK and p38 MAP kinase are involved in downregulation of cell surface TNF receptor 1 induced by acetoxycycloheximide
Hirotsugu Ogura, Yoshinori Tsukumo, Hikaru Sugimoto, Masayuki Igarashi, Kazuo Nagai, Takao Kataoka Int Immunopharmacol. 2008 Jun;8(6):922-6. doi: 10.1016/j.intimp.2008.02.010. Epub 2008 Mar 18.
Tumor necrosis factor (TNF)-alpha activates the nuclear factor kappaB (NF-kappaB) signaling pathway. The protein synthesis inhibitor cycloheximide (CHX) and its structural derivative acetoxycycloheximide (Ac-CHX) have been recently shown to block the TNF-alpha-induced activation of NF-kappaB via ectodomain shedding of TNF receptor 1 (TNF-R1) in human lung carcinoma A549 cells. In this study, we show that ERK and p38 MAP kinase are involved in the downregulation of cell surface TNF-R1 upon exposure to Ac-CHX and the subsequent inhibition of TNF-alpha-induced NF-kappaB activation. Ac-CHX was capable of promoting the sustained activation of ERK, JNK, and p38 MAP kinase. Treatment with the MEK inhibitor U0126 and the p38 MAP kinase inhibitor SB203580, but not the JNK inhibitor SP600125, reversed the diminished expression of cell surface TNF-R1 as well as the blockade of TNF-alpha-induced IkappaBalpha degradation in Ac-CHX-treated cells. Our results indicate that Ac-CHX triggers the downregulation of cell surface TNF-R1 via the activation of ERK and p38 MAP kinase, thereby preventing activation of the NF-kappaB signaling pathway by TNF-alpha.
2. Acetoxycycloheximide (E-73) rapidly induces apoptosis mediated by the release of cytochrome c via activation of c-Jun N-terminal kinase
Kimiko Kadohara, Yoshinori Tsukumo, Hikaru Sugimoto, Masayuki Igarashi, Kazuo Nagai, Takao Kataoka Biochem Pharmacol. 2005 Feb 15;69(4):551-60. doi: 10.1016/j.bcp.2004.11.009. Epub 2004 Dec 28.
Cycloheximide (CHX) is an inhibitor of protein synthesis and commonly used to modulate death receptor-mediated apoptosis or to induce apoptosis in a number of normal and transformed cells. In this study we show that a close structural derivative of CHX, acetoxycycloheximide (E-73) induced rapid processing of procaspases and subsequent apoptosis with much higher efficacy than CHX in human leukemia Jurkat T cells. E-73 induced the release of cytochrome c from mitochondria even in the presence of the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethyl ketone. The Bcl-2 family protein Bcl-x(L) suppressed cytochrome c release as well as processing of procaspases-3, -8, and -9 in E-73-treated cells. In Jurkat T cells transfected with the caspase-8 modulator FLIP(L), E-73 still induced activation of procaspase-3 and subsequent apoptosis, suggesting that the caspase-8 activity is dispensable for apoptosis. In contrast to CHX, E-73 drastically induced activation of extracellular signal-regulated kinase, c-Jun N-terminal kinase (JNK), and p38 MAP kinase. Inhibitory profiles of small-molecular kinase inhibitors revealed that JNK activation was critical for induction of cytochrome c release in E-73-induced apoptosis. Thus, our present results demonstrate that E-73, unlike CHX, induces strong activation of the JNK pathway and triggers rapid apoptosis mediated by the release of cytochrome c.
3. Caspase-8 mediates mitochondrial release of pro-apoptotic proteins in a manner independent of its proteolytic activity in apoptosis induced by the protein synthesis inhibitor acetoxycycloheximide in human leukemia Jurkat cells
Kimiko Kadohara, Michiko Nagumo, Shun Asami, Yoshinori Tsukumo, Hikaru Sugimoto, Masayuki Igarashi, Kazuo Nagai, Takao Kataoka J Biol Chem. 2009 Feb 27;284(9):5478-87. doi: 10.1074/jbc.M808523200. Epub 2008 Dec 26.
The cysteine protease caspase-8 plays an essential role in apoptosis induced by death receptors. The protein synthesis inhibitor acetoxycycloheximide (Ac-CHX) has been previously shown to induce rapid apoptosis mediated by the release of cytochrome c in human leukemia Jurkat cells. In this study, the novel molecular mechanism that links caspase-8 to the mitochondrial release of pro-apoptotic proteins has been identified. Jurkat cells deficient in caspase-8 were more resistant to Ac-CHX than wild-type Jurkat cells and manifested decreased apoptosis induction and caspase activation as well as inefficient release of cytochrome c, Smac/DIABLO, and AIF into the cytosol. In contrast to Fas ligand stimulation, the general caspase inhibitor barely prevented the mitochondrial release of these pro-apoptotic proteins in Ac-CHX-treated cells, suggesting that caspase-8 activity is dispensable for triggering the mitochondrial pathway in Ac-CHX-induced apoptosis. Consistent with this notion, caspase-8-deficient Jurkat cells reconstituted with catalytically inactive caspase-8 became sensitive to Ac-CHX and exhibited apoptosis, caspase activation, the liberation of pro-apoptotic proteins into the cytosol, and Bak conformational change as efficiently as wild-type Jurkat cells. Unlike caspase-3, -6, -7, and -9, a small but significant portion of caspase-8 was found to localize in mitochondria before and after exposure to Ac-CHX. These results clearly demonstrate that caspase-8 is able to mediate the mitochondrial release of pro-apoptotic proteins in a manner independent of its proteolytic activity in Ac-CHX-induced apoptosis.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
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g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
