Name: FR-901464
Brand: BOC Sciences
Price: 729 USD
Availability: MadeToOrder

Size

Price

Stock

Quantity

1 mg

$729

In stock

Synonyms

Fr901464; 2-Pentenamide, 4-(acetyloxy)-N-[(2R,3R,5S,6S)-6-[(2E,4E)-5-[(3R,4R,5R,7S)-4,7-dihydroxy-7-methyl-1,6-dioxaspiro[2.5]oct-5-yl]-3-methyl-2,4-pentadien-1-yl]tetrahydro-2,5-dimethyl-2H-pyran-3-yl]-, (2Z,4S)-; WB 2663B; Antibiotic WB 2663B; Antibiotic FR 901464

IUPAC Name

[(Z,2S)-5-[[(2R,3R,5S,6S)-6-[(2E,4E)-5-[(3R,4R,5R,7S)-4,7-dihydroxy-7-methyl-1,6-dioxaspiro[2.5]octan-5-yl]-3-methylpenta-2,4-dienyl]-2,5-dimethyloxan-3-yl]amino]-5-oxopent-3-en-2-yl] acetate

Canonical SMILES

CC1CC(C(OC1CC=C(C)C=CC2C(C3(CC(O2)(C)O)CO3)O)C)NC(=O)C=CC(C)OC(=O)C

InChI

InChI=1S/C27H41NO8/c1-16(8-11-23-25(31)27(15-33-27)14-26(6,32)36-23)7-10-22-17(2)13-21(19(4)35-22)28-24(30)12-9-18(3)34-20(5)29/h7-9,11-12,17-19,21-23,25,31-32H,10,13-15H2,1-6H3,(H,28,30)/b11-8+,12-9-,16-7+/t17-,18-,19+,21+,22-,23+,25+,26-,27+/m0/s1

InChIKey

PJKVJJDQXZARCA-QHYZBLTGSA-N

Density

1.21 g/cm3

Solubility

Soluble in methanol

Shipping

Room temperature, or blue ice upon request.

Storage

Store at -20°C

Boiling Point

702.7°C at 760 mmHg

In Vivo

FR901464 is a potent anticancer natural product that lowers the mRNA levels of oncogenes and tumor suppressor genes. The inhibitions of human breast cancer MCF-7 cell proliferation by synthetic FR901464 and meayamycin were studied, and the GI50 values for these compounds were determined to be 1.1 nM and 10 pM, respectively.

1. Structural basis of intron selection by U2 snRNP in the presence of covalent inhibitors

Patricia Gee, Vladimir Pena, Nicholas A Larsen, Andrew Cook, Anant Agrawal, Xiang Liu, Arun K Ghosh, Tuong-Vi Nguyen, Constantin Cretu, Melissa Jurica Nat Commun . 2021 Jul 23;12(1):4491. doi: 10.1038/s41467-021-24741-1.

Intron selection during the formation of prespliceosomes is a critical event in pre-mRNA splicing. Chemical modulation of intron selection has emerged as a route for cancer therapy. Splicing modulators alter the splicing patterns in cells by binding to the U2 snRNP (small nuclear ribonucleoprotein)-a complex chaperoning the selection of branch and 3' splice sites. Here we report crystal structures of the SF3B module of the U2 snRNP in complex with spliceostatin and sudemycin FR901464 analogs, and the cryo-electron microscopy structure of a cross-exon prespliceosome-like complex arrested with spliceostatin A. The structures reveal how modulators inactivate the branch site in a sequence-dependent manner and stall an E-to-A prespliceosome intermediate by covalent coupling to a nucleophilic zinc finger belonging to the SF3B subunit PHF5A. These findings support a mechanism of intron recognition by the U2 snRNP as a toehold-mediated strand invasion and advance an unanticipated drug targeting concept.

2. Enantioselective syntheses of FR901464 and spliceostatin A: potent inhibitors of spliceosome

Zhi-Hua Chen, Arun K Ghosh Org Lett . 2013 Oct 4;15(19):5088-91. doi: 10.1021/ol4024634.

Enantioselective syntheses of FR901464 and spliceostatin A, potent spliceosome inhibitors, are described. The synthesis of FR901464 has been accomplished in a convergent manner in 10 linear steps (20 total steps). The A-tetrahydropyran ring was constructed from (R)-isopropylidene glyceraldehyde. The functionalized tetrahydropyran B-ring was synthesized utilizing a Corey-Bakshi-Shibata reduction, an Achmatowicz reaction, and a stereoselective Michael addition as the key steps. Coupling of A- and B-ring fragments was accomplished via cross-metathesis.

3. Cytotoxic Spliceostatin Analogs from Pseudomonas sp

Lie-Feng Ma, Hong Zhao, Lin-Mei Shi, Zha-Jun Zhan, Bei Zhang Chem Biodivers . 2019 Sep;16(9):e1900266. doi: 10.1002/cbdv.201900266.

Two new spliceostatin analogs, designed as spliceostatins J and K (1 and 2), were isolated and identified from the culture of Pseudomonas sp., along with two known ones, FR901464 (3) and spliceostatin E (4). Their structures were elucidated by detailed interpretation of their spectroscopic data, especially 2D-NMR and HR-ESI-MS. Spliceostatin J (1) represented the first example of spliceostatins bearing an unusual hexahydrofuro[3,4-b]furan moiety. Biological assay showed all the isolated compounds except 1 displayed potent cytotoxic activities against two cancer cell lines (MDA-MB-231 and A-549). Structure-activity-relationship studies revealed that the tetrahydropyran ring in spliceostatin analogs was necessary for their bioactive retention.