WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H341588
CAS#: 146478-72-0
Description: FR901464 is a potent spliceosome inhibitor and a potential agent for colorectal cancer in combination therapy.
Hodoodo Cat#: H341588
Name: FR 901464
CAS#: 146478-72-0
Chemical Formula: C27H41NO8
Exact Mass: 507.28
Molecular Weight: 507.624
Elemental Analysis: C, 63.89; H, 8.14; N, 2.76; O, 25.21
Synonym: FR 901464; FR-901464; FR901464; WB 2663B.
IUPAC/Chemical Name: (2S,E)-5-(((2R,5S,6S)-6-((2E,4E)-5-((4R,5R,7S)-4,7-dihydroxy-7-methyl-1,6-dioxaspiro[2.5]octan-5-yl)-3-methylpenta-2,4-dien-1-yl)-2,5-dimethyltetrahydro-2H-pyran-3-yl)amino)-5-oxopent-3-en-2-yl acetate
InChi Key: PJKVJJDQXZARCA-AYSBKWRUSA-N
InChi Code: 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
SMILES Code: C[C@H]1CC([C@H](O[C@H]1C/C=C(\C)/C=C/[C@@H]2[C@H](C3(C[C@@](O2)(C)O)CO3)O)C)NC(=O)/C=C/[C@H](C)OC(=O)C
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | |
| In vitro activity: | |
| In vivo activity: |
The following data is based on the product molecular weight 507.62 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | |
| In vitro protocol: | |
| In vivo protocol: |
1: Cretu C, Gee P, Liu X, Agrawal A, Nguyen TV, Ghosh AK, Cook A, Jurica M, Larsen NA, Pena V. Structural basis of intron selection by U2 snRNP in the presence of covalent inhibitors. Nat Commun. 2021 Jul 23;12(1):4491. doi: 10.1038/s41467-021-24741-1. PMID: 34301950; PMCID: PMC8302644.
2: Zhao H, Zhang B, Ma LF, Shi LM, Zhan ZJ. Cytotoxic Spliceostatin Analogs from Pseudomonas sp. Chem Biodivers. 2019 Sep;16(9):e1900266. doi: 10.1002/cbdv.201900266. Epub 2019 Aug 8. PMID: 31298476.
3: Yamano T, Kubo S, Yano A, Kominato T, Tanaka S, Ikeda M, Tomita N. Splicing modulator FR901464 is a potential agent for colorectal cancer in combination therapy. Oncotarget. 2019 Jan 8;10(3):352-367. doi: 10.18632/oncotarget.26564. PMID: 30719229; PMCID: PMC6349454.
4: Zhao Y, Zhao J, Lu C, Zhang H, Qi H, Jiang S, Guo X, Wang J, Xiang W. Two new spliceostatin analogs from the strain Pseudomonas sp. HS-NF-1408. J Antibiot (Tokyo). 2018 Jul;71(7):667-671. doi: 10.1038/s41429-018-0052-0. Epub 2018 Apr 17. PMID: 29666478.
5: Yoshimoto R, Kaida D, Furuno M, Burroughs AM, Noma S, Suzuki H, Kawamura Y, Hayashizaki Y, Mayeda A, Yoshida M. Global analysis of pre-mRNA subcellular localization following splicing inhibition by spliceostatin A. RNA. 2017 Jan;23(1):47-57. doi: 10.1261/rna.058065.116. Epub 2016 Oct 17. PMID: 27754875; PMCID: PMC5159648.
6: Satoh T, Kaida D. Upregulation of p27 cyclin-dependent kinase inhibitor and a C-terminus truncated form of p27 contributes to G1 phase arrest. Sci Rep. 2016 Jun 10;6:27829. doi: 10.1038/srep27829. PMID: 27282251; PMCID: PMC4901259.
7: Liu X, Zhu H, Biswas S, Cheng YQ. Improved production of cytotoxic thailanstatins A and D through metabolic engineering of Burkholderia thailandensis MSMB43 and pilot scale fermentation. Synth Syst Biotechnol. 2016 Apr 1;1(1):34-38. doi: 10.1016/j.synbio.2016.02.002. PMID: 29062925; PMCID: PMC5640593.
8: Pham D, Koide K. Discoveries, target identifications, and biological applications of natural products that inhibit splicing factor 3B subunit 1. Nat Prod Rep. 2016 May 4;33(5):637-47. doi: 10.1039/c5np00110b. PMID: 26812544.
9: Eustáquio AS, Chang LP, Steele GL, O Donnell CJ, Koehn FE. Biosynthetic engineering and fermentation media development leads to gram-scale production of spliceostatin natural products in Burkholderia sp. Metab Eng. 2016 Jan;33:67-75. doi: 10.1016/j.ymben.2015.11.003. Epub 2015 Nov 24. PMID: 26620532.
10: He HY, Yuan H, Tang MC, Tang GL. An unusual dehydratase acting on glycerate and a ketoreducatse stereoselectively reducing α-ketone in polyketide starter unit biosynthesis. Angew Chem Int Ed Engl. 2014 Oct 13;53(42):11315-9. doi: 10.1002/anie.201406602. Epub 2014 Aug 27. PMID: 25160004.
11: Eustáquio AS, Janso JE, Ratnayake AS, O'Donnell CJ, Koehn FE. Spliceostatin hemiketal biosynthesis in Burkholderia spp. is catalyzed by an iron/α-ketoglutarate-dependent dioxygenase. Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):E3376-85. doi: 10.1073/pnas.1408300111. Epub 2014 Aug 5. PMID: 25097259; PMCID: PMC4143056.
12: Ghosh AK, Chen ZH, Effenberger KA, Jurica MS. Enantioselective total syntheses of FR901464 and spliceostatin A and evaluation of splicing activity of key derivatives. J Org Chem. 2014 Jun 20;79(12):5697-709. doi: 10.1021/jo500800k. Epub 2014 May 30. PMID: 24873648; PMCID: PMC4066912.
13: Convertini P, Shen M, Potter PM, Palacios G, Lagisetti C, de la Grange P, Horbinski C, Fondufe-Mittendorf YN, Webb TR, Stamm S. Sudemycin E influences alternative splicing and changes chromatin modifications. Nucleic Acids Res. 2014 Apr;42(8):4947-61. doi: 10.1093/nar/gku151. Epub 2014 Mar 11. PMID: 24623796; PMCID: PMC4005683.
14: He HY, Tang MC, Zhang F, Tang GL. Cis-Double bond formation by thioesterase and transfer by ketosynthase in FR901464 biosynthesis. J Am Chem Soc. 2014 Mar 26;136(12):4488-91. doi: 10.1021/ja500942y. Epub 2014 Mar 18. PMID: 24617828.
15: Ghosh AK, Chen ZH. Enantioselective syntheses of FR901464 and spliceostatin A: potent inhibitors of spliceosome. Org Lett. 2013 Oct 4;15(19):5088-91. doi: 10.1021/ol4024634. Epub 2013 Sep 19. PMID: 24050251; PMCID: PMC3827971.
16: Liu X, Biswas S, Tang GL, Cheng YQ. Isolation and characterization of spliceostatin B, a new analogue of FR901464, from Pseudomonas sp. No. 2663. J Antibiot (Tokyo). 2013 Sep;66(9):555-8. doi: 10.1038/ja.2013.38. Epub 2013 May 8. PMID: 23652603; PMCID: PMC4067007.
17: Liu X, Biswas S, Berg MG, Antapli CM, Xie F, Wang Q, Tang MC, Tang GL, Zhang L, Dreyfuss G, Cheng YQ. Genomics-guided discovery of thailanstatins A, B, and C As pre-mRNA splicing inhibitors and antiproliferative agents from Burkholderia thailandensis MSMB43. J Nat Prod. 2013 Apr 26;76(4):685-93. doi: 10.1021/np300913h. Epub 2013 Mar 21. PMID: 23517093; PMCID: PMC3696399.
18: Gao Y, Vogt A, Forsyth CJ, Koide K. Comparison of splicing factor 3b inhibitors in human cells. Chembiochem. 2013 Jan 2;14(1):49-52. doi: 10.1002/cbic.201200558. Epub 2012 Nov 22. PMID: 23172726.
19: Goronga T, Boyd VA, Lagisetti C, Jeffries C, Webb TR. Radiosynthesis of antitumor spliceosome modulators. Appl Radiat Isot. 2011 Sep;69(9):1231-4. doi: 10.1016/j.apradiso.2011.04.008. Epub 2011 Apr 16. PMID: 21531567; PMCID: PMC3105125.
20: Fan L, Lagisetti C, Edwards CC, Webb TR, Potter PM. Sudemycins, novel small molecule analogues of FR901464, induce alternative gene splicing. ACS Chem Biol. 2011 Jun 17;6(6):582-9. doi: 10.1021/cb100356k. Epub 2011 Mar 7. PMID: 21344922; PMCID: PMC3113647.
