Ammocidin
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| Category | Enzyme inhibitors |
| Catalog number | BBF-00446 |
| CAS | |
| Molecular Weight | 1141.38 |
| Molecular Formula | C59H96O21 |
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Description
It is produced by the strain of Saccharothrix sp. AJ 9571. It can reduce the phosphorylation level of mitogen-activated protein kinase (MAPK)S6K. It induces apoptosis in Ras Ba/F3-V12 cells with an IC50 of 66 ng/mL, but not in IL-3 Ba/F3-V12 cells with 100 μg/mL.
Specification
| Synonyms | Ammocidin A |
| IUPAC Name | (3E,5Z,7E,11E,13E,15E)-20-[1-[5-[5-(4,5-dihydroxy-4,6-dimethyloxan-2-yl)oxy-4-hydroxy-6-methyloxan-2-yl]oxy-2,4-dihydroxy-3-methoxy-6-(3-methoxypropyl)-5-methyloxan-2-yl]ethyl]-17-hydroxy-5-methoxy-3,7,9,11,13,15,18-heptamethyl-10-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxy-1-oxacycloicosa-3,5,7,11,13,15-hexaen-2-one |
| Canonical SMILES | CC1CC(OC(=O)C(=CC(=CC(=CC(C(C(=CC(=CC(=CC1O)C)C)C)OC2C(C(C(C(O2)C)O)O)O)C)C)OC)C)C(C)C3(C(C(C(C(O3)CCCOC)(C)OC4CC(C(C(O4)C)OC5CC(C(C(O5)C)O)(C)O)O)O)OC)O |
| InChI | InChI=1S/C59H96O21/c1-29-20-30(2)24-41(60)32(4)26-43(76-55(67)35(7)25-40(71-15)23-31(3)22-34(6)50(33(5)21-29)78-56-49(64)48(63)47(62)37(9)75-56)36(8)59(69)54(72-16)53(66)58(13,44(79-59)18-17-19-70-14)80-45-27-42(61)51(38(10)73-45)77-46-28-57(12,68)52(65)39(11)74-46/h20-25,32,34,36-39,41-54,56,60-66,68-69H,17-19,26-28H2,1-16H3/b29-20+,30-24+,31-22+,33-21+,35-25+,40-23- |
| InChI Key | UFQXWTGALYJGHM-XOVDYNHBSA-N |
Properties
| Appearance | Colorless Powder |
| Melting Point | 154-156 °C |
| Solubility | Soluble in Methanol |
Reference Reading
1. 18O assisted analysis of a γ,δ-epoxyketone cyclization: synthesis of the C16-C28 fragment of ammocidin D
Stephen T Chau, Yoichi Hayakawa, Gary A Sulikowski Org Lett. 2011 Feb 18;13(4):756-9. doi: 10.1021/ol103003f. Epub 2011 Jan 19.
The C16-C28 fragment common to the cytotoxic macrolide ammocidin D has been prepared by a stereospecific 5-exo closure of a γ,δ-epoxyketone followed by a rearrangement to a pyran acetal. The reaction pathway was traced by (18)O labeling of the keto carbonyl and observation of (18)O induced (13)C shifts in the pyran acetal product. NMR data of the synthetic C16-C28 fragment compared favorably to the natural product providing support of the assigned stereochemistry.
2. Ammocidins B, C and D, new cytotoxic 20-membered macrolides from Saccharothrix sp. AJ9571
Ryo Murakami, Junko Shinozaki, Takayuki Kajiura, Ikuko Kozone, Motoki Takagi, Kazuo Shin-Ya, Haruo Seto, Yoichi Hayakawa J Antibiot (Tokyo). 2009 Mar;62(3):123-7. doi: 10.1038/ja.2008.23. Epub 2009 Jan 30.
Ammocidins B, C and D were isolated from the culture broth of Saccharothrix sp. AJ9571, an ammocidin A-producing strain. Their structures were determined by a detailed spectroscopic analysis and by a comparison of their NMR data with those of ammocidin A. Ammocidins A and B showed potent anti-proliferative activities against human cancer cell lines.
3. Apoptolidin family glycomacrolides target leukemia through inhibition of ATP synthase
Benjamin J Reisman, Hui Guo, Haley E Ramsey, Madison T Wright, Bradley I Reinfeld, P Brent Ferrell, Gary A Sulikowski, W Kimryn Rathmell, Michael R Savona, Lars Plate, John L Rubinstein, Brian O Bachmann Nat Chem Biol. 2022 Apr;18(4):360-367. doi: 10.1038/s41589-021-00900-9. Epub 2021 Dec 2.
Cancer cells have long been recognized to exhibit unique bioenergetic requirements. The apoptolidin family of glycomacrolides are distinguished by their selective cytotoxicity towards oncogene-transformed cells, yet their molecular mechanism remains uncertain. We used photoaffinity analogs of the apoptolidins to identify the F1 subcomplex of mitochondrial ATP synthase as the target of apoptolidin A. Cryogenic electron microscopy (cryo-EM) of apoptolidin and ammocidin-ATP synthase complexes revealed a novel shared mode of inhibition that was confirmed by deep mutational scanning of the binding interface to reveal resistance mutations which were confirmed using CRISPR-Cas9. Ammocidin A was found to suppress leukemia progression in vivo at doses that were tolerated with minimal toxicity. The combination of cellular, structural, mutagenesis, and in vivo evidence defines the mechanism of action of apoptolidin family glycomacrolides and establishes a path to address oxidative phosphorylation-dependent cancers.
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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
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
