Reblastatin
* Please be kindly noted products are not for therapeutic use. We do not sell to patients.
| Category | Antibiotics |
| Catalog number | BBF-03725 |
| CAS | |
| Molecular Weight | 548.67 |
| Molecular Formula | C29H44N2O8 |
Online Inquiry
Description
Reblastatin is an Ansa antibiotic produced by Streptomyces hygroscopicus subsp. hygroscopicus SANK 61995 and is a reduction product of Geldanamycin. It is a cell cycle inhibitor that can inhibit cell proliferation. The IC50 for human mesenchymal lymphoma U-93 is 0.43 μg/mL, and the reference geldanamycin is 0.0011 μg/mL.
Specification
| Storage | Store at -20°C |
| IUPAC Name | (8S,9S,10E,13R,14S)-3,13,20-Trihydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-2-azabicyclo[16.3.1]docosa-1(22),2,4,10,18,20-hexaen-9-yl hydrogen carbonimidate |
| InChI | InChI=1S/C29H44N2O8/c1-16-11-20-14-21(15-22(32)27(20)38-7)31-28(34)17(2)9-8-10-23(36-5)26(39-29(30)35)19(4)13-18(3)25(33)24(12-16)37-6/h9,13-16,18,23-26,32-33H,8,10-12H2,1-7H3,(H2,30,35)(H,31,34)/b17-9+,19-13+/t16?,18?,23-,24-,25+,26-/m0/s1 |
| InChI Key | VFJOOSVDHSUNKR-KMVALDDASA-N |
Properties
| Antibiotic Activity Spectrum | neoplastics (Tumor) |
| Boiling Point | 720.5±70.0°C at 760 mmHg |
| Density | 1.2±0.1 g/cm3 |
Reference Reading
1. Synthesis, structure and anticancer activity of new geldanamycin amine analogs containing C(17)- or C(20)- flexible and rigid arms as well as closed or open ansa-bridges
Natalia Skrzypczak, Krystian Pyta, Piotr Ruszkowski, Maria Gdaniec, Franz Bartl, Piotr Przybylski Eur J Med Chem. 2020 Sep 15;202:112624. doi: 10.1016/j.ejmech.2020.112624. Epub 2020 Jul 3.
The nucleophilic attack of amines at C(17) or C(17)/C(20) positions of geldanamycin's (GDM) benzoquinone, via initial 1,4-Michael conjugate addition mechanism, yield new analogs with closed or open ansa-bridges (1-31), respectively. X-ray structures of analogs 22 and 24 reveals an unexpected arrangement of the ansa-bridge in solid (conformer B), that is located between those of conformers A, prevailing in solution (trans-lactam), and C, crucial at binding to Hsp90 (cis-lactam). The structure of a new-type conformer B allows to better understand the molecular recognition mechanism between the GDM analogs and the target Hsp90. Combined analysis of: anticancer test results (SKBR-3, SKOV-3, PC-3, U-87, A-549) and those performed in normal cells (HDF), KD values and docking modes at Hsp90 as well as clogP parameters, reveals that the rigid C(17)-arm (piperidyl, cyclohexyl) with a H-bond acceptor as carbonyl group together with a lipophilicity clogP~3 favor high potency of analogs, even up to IC50 ~0.08 μM, at improved selectivity (SIHDF > 30), when compared to GDM. The most active 25 show higher anticancer potency than 17-AAG (in SKOV-3 and A-549) as well as reblastatin (in SKBR-3 and SKOV-3). Opening of the ansa-bridge within GDM analogs, at the best case, decreases activity (IC50~2 μM) and toxicity in HDF cells (SIHDF~2-3), relative to GDM.
2. Heat Shock Proteins Revisited: Using a Mutasynthetically Generated Reblastatin Library to Compare the Inhibition of Human and Leishmania Hsp90s
Sona Mohammadi-Ostad-Kalayeh, Frank Stahl, Thomas Scheper, Klaus Kock, Christian Herrmann, Fernanda Aparecida Heleno Batista, Júlio César Borges, Florenz Sasse, Simone Eichner, Jekaterina Ongouta, Carsten Zeilinger, Andreas Kirschning Chembiochem. 2018 Mar 16;19(6):562-574. doi: 10.1002/cbic.201700616. Epub 2018 Feb 19.
Thirteen new reblastatin derivatives, with alkynyl, amino and fluoro substituents on the aromatic ring, were prepared by a chemo-biosynthetic approach using an AHBA(-) mutant strain of Streptomyces hygroscopicus, the geldanamycin producer. The inhibitory potencies of these mutaproducts and of an extended library of natural products and derivatives were probed with purified heat shock proteins (Hsps), obtained from Leishmania braziliensis (LbHsp90) as well as from human sources (HsHsp90). We determined the activities of potential inhibitors by means of a displacement assay in which fluorescence-labelled ATP competes for the ATP binding sites of Hsps in the presence of the inhibitor in question. The results were compared with those of cell-based assays and, in selected cases, of isothermal titration calorimetry (ITC) measurements. In essence, reblastatin derivatives are also able to bind effectively to the ATP-binding site of LbHsp90, and for selected derivatives, moderate differences in binding to LbHsp90 and HsHsp90 were encountered. This work demonstrates that parasitic heat shock proteins can be developed as potential pharmaceutical targets.
3. Reblastatins Inhibit Phenotypic Changes of Monocytes/Macrophages in a Milieu Rich in 27-Hydroxycholesterol
Jeongyoon Choi, Bo-Young Kim, Yonghae Son, Dongho Lee, Young-Soo Hong, Min Su Kim, Koanhoi Kim Immune Netw. 2020 Apr 23;20(2):e17. doi: 10.4110/in.2020.20.e17. eCollection 2020 Apr.
We investigated effects of reblastatins on phenotypic changes in monocytes/macrophages induced by 27-hydroxycholesterol (27OHChol). Treatment of THP-1 monocytic cells with reblastatin derivatives, such as 17-demethoxy-reblastatin (17-DR), 18-dehydroxyl-17-demethoxyreblastatin (WK88-1), 18-hydroxyl-17-demethoxyreblastatin (WK88-2), and 18-hydroxyl-17-demethoxy-4,5-dehydroreblastatin (WK88-3), resulted in blockage of CCL2, CCL3, and CCL4 expression at the transcription and protein levels, which, in turn, impaired migration of monocytes/macrophages and Jurkat T cells expressing CCR5, and almost complete inhibition of transcription of M1 marker cytokines, like CXCL10, CXCL11, and TNF-α. Reblastatins also downregulated surface CD14 as well as soluble CD14 along with inhibition of LPS response and matrix metalloprotease-9 expression. Surface levels of mature dendritic cell (mDC)-specific markers, including CD80, CD83, CD88, CD197, and MHC class I and II molecules, were remarkably down-regulated, and 27OHChol-induced decrease of endocytic activity was recovered following treatment with 17-DR, WK88-1, WK88-2, and WK88-3. However, 15-hydroxyl-17-demethoxyreblastatin (DHQ3) did not affect the molecular or functional changes in monocytic cells induced by 27OHChol. Furthermore, surface levels of CD105, CD137, and CD166 were also down-regulated by 17-DR, WK88-1, WK88-2, and WK88-3, but not by DHQ3. Collectively, results of the current study indicate that, except DHQ3, reblastatins regulate the conversion and differentiation of monocytic cells to an immunostimulatory phenotype and mDCs, respectively, which suggests possible applications of reblastatins for immunomodulation in a milieu rich in oxygenated cholesterol molecules.
Recommended Products
| BBF-01829 | Deoxynojirimycin | Inquiry |
| BBF-03755 | Actinomycin D | Inquiry |
| BBF-05862 | Epirubicin | Inquiry |
| BBF-01826 | Deoxymannojirimycin | Inquiry |
| BBF-00677 | 3-Amino-3-deoxy-D-glucose | Inquiry |
| BBF-02642 | Lactonamycin | Inquiry |
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 ╳
