FR-182877
* Please be kindly noted products are not for therapeutic use. We do not sell to patients.
| Category | Antibiotics |
| Catalog number | BBF-03553 |
| CAS | |
| Molecular Weight | 400.51 |
| Molecular Formula | C24H32O5 |
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Description
FR-182877 is produced by the strain of Streptomyces sp. No. 9885. It has a strong effect on rat ascites and solid tumors in vivo, and has no antibacterial activity.
Specification
| IUPAC Name | (1R,2S,4S,7S,8S,9S,10R,11S,12S,13R,17R,18S)-8,10-dihydroxy-1,5,9,18-tetramethyl-16,20-dioxahexacyclo[15.3.2.02,13.04,12.07,11.014,19]docosa-5,14(19)-dien-15-one |
| Canonical SMILES | CC1C(C2C=C(C3CC4C(C3C2C1O)C5=C6C(C(CCC4(O6)C)OC5=O)C)C)O |
| InChI | InChI=1S/C24H32O5/c1-9-7-13-17(21(26)11(3)20(13)25)16-12(9)8-14-18(16)19-22-10(2)15(28-23(19)27)5-6-24(14,4)29-22/h7,10-18,20-21,25-26H,5-6,8H2,1-4H3/t10-,11+,12+,13-,14-,15+,16+,17+,18-,20+,21-,24+/m0/s1 |
| InChI Key | WMRQHSFWMFGIFW-OUNSMTAHSA-N |
Properties
| Appearance | Colorless Powder |
| Antibiotic Activity Spectrum | neoplastics (Tumor) |
| Boiling Point | 585.1±50.0°C at 760 mmHg |
| Melting Point | 164-167°C |
| Density | 1.3±0.1 g/cm3 |
Reference Reading
1. Methods for studying microtubule binding site interactions: zampanolide as a covalent binding agent
Jessica J Field, Enrique Calvo, Peter T Northcote, John H Miller, Karl-Heinz Altmann, José Fernando Díaz Methods Cell Biol. 2013;115:303-25. doi: 10.1016/B978-0-12-407757-7.00019-0.
In this chapter, we describe the methods used to determine the binding site and binding profile of zampanolide, a novel microtubule-stabilizing agent (MSA) that binds covalently to tubulin. These methods can be applied to other novel MSAs in which the binding site and mechanism of binding are unknown. Using the described methods, we have shown that zampanolide binds to the taxoid site on β-tubulin, but unlike most other MSAs is able to covalently modify this site. The purpose of this chapter is to provide a step-by-step protocol for determining the binding site of a novel MSA.
2. Crystal Structure of the Cyclostreptin-Tubulin Adduct: Implications for Tubulin Activation by Taxane-Site Ligands
Francisco de Asís Balaguer, Tobias Mühlethaler, Juan Estévez-Gallego, Enrique Calvo, Juan Francisco Giménez-Abián, April L Risinger, Erik J Sorensen, Christopher D Vanderwal, Karl-Heinz Altmann, Susan L Mooberry, Michel O Steinmetz, María Ángela Oliva, Andrea E Prota, J Fernando Díaz Int J Mol Sci. 2019 Mar 20;20(6):1392. doi: 10.3390/ijms20061392.
It has been proposed that one of the mechanisms of taxane-site ligand-mediated tubulin activation is modulation of the structure of a switch element (the M-loop) from a disordered form in dimeric tubulin to a folded helical structure in microtubules. Here, we used covalent taxane-site ligands, including cyclostreptin, to gain further insight into this mechanism. The crystal structure of cyclostreptin-bound tubulin reveals covalent binding to βHis229, but no stabilization of the M-loop. The capacity of cyclostreptin to induce microtubule assembly compared to other covalent taxane-site agents demonstrates that the induction of tubulin assembly is not strictly dependent on M-loop stabilization. We further demonstrate that most covalent taxane-site ligands are able to partially overcome drug resistance mediated by βIII-tubulin (βIII) overexpression in HeLa cells, and compare their activities to pironetin, an interfacial covalent inhibitor of tubulin assembly that displays invariant growth inhibition in these cells. Our findings suggest a relationship between a diminished interaction of taxane-site ligands with βIII-tubulin and βIII tubulin-mediated drug resistance. This supports the idea that overexpression of βIII increases microtubule dynamicity by counteracting the enhanced microtubule stability promoted by covalent taxane-site binding ligands.
3. Taccalonolide binding to tubulin imparts microtubule stability and potent in vivo activity
A L Risinger, J Li, M J Bennett, C C Rohena, J Peng, D C Schriemer, S L Mooberry Cancer Res. 2013 Nov 15;73(22):6780-92. doi: 10.1158/0008-5472.CAN-13-1346. Epub 2013 Sep 18.
The taccalonolides are highly acetylated steroids that stabilize cellular microtubules and overcome multiple mechanisms of taxane resistance. Recently, two potent taccalonolides, AF and AJ, were identified that bind to tubulin directly and enhance microtubule polymerization. Extensive studies were conducted to characterize these new taccalonolides. AF and AJ caused aberrant mitotic spindles and bundling of interphase microtubules that differed from the effects of either paclitaxel or laulimalide. AJ also distinctly affected microtubule polymerization in that it enhanced the rate and extent of polymerization in the absence of any noticeable effect on microtubule nucleation. In addition, the resulting microtubules were found to be profoundly cold stable. These data, along with studies showing synergistic antiproliferative effects between AJ and either paclitaxel or laulimalide, suggest a distinct binding site. Direct binding studies demonstrated that AJ could not be displaced from microtubules by paclitaxel, laulimalide, or denaturing conditions, suggesting irreversible binding of AJ to microtubules. Mass spectrometry confirmed a covalent interaction of AJ with a peptide of β-tubulin containing the cyclostreptin-binding sites. Importantly, AJ imparts strong inter-protofilament stability in a manner different from other microtubule stabilizers that covalently bind to tubulin, consistent with the distinct effects of the taccalonolides as compared with other stabilizers. AF was found to be a potent and effective antitumor agent that caused tumor regression in the MDA-MB-231 breast cancer xenograft model. The antitumor efficacy of some taccalonolides, which stabilize microtubules in a manner different from other microtubule stabilizers, provides the impetus to explore the therapeutic potential of this site.
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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 ╳
