Spliceostatin A - CAS 391611-36-2

Spliceostatin A - CAS 391611-36-2 Catalog number: BADC-00780

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Spliceostatin A is a potent inhibitor of in vitro and in vivo pre-mRNA splicing. It was shown to inhibit splicing and to interact with an essential component of the spliceosome, SF3b. Spliceostatin A is an inhibitor of RNA synthesis with excellent anticancer activity against a variety of human cancer cell lines. Spliceostatin A inhibits mitotic clone expansion and adipogenesis.

Category
ADCs Cytotoxin
Product Name
Spliceostatin A
CAS
391611-36-2
Catalog Number
BADC-00780
Molecular Formula
C28H43NO8
Molecular Weight
521.64
Spliceostatin A

Ordering Information

Catalog Number Size Price Quantity
BADC-00780 5 mg $2999
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Description
Spliceostatin A is a potent inhibitor of in vitro and in vivo pre-mRNA splicing. It was shown to inhibit splicing and to interact with an essential component of the spliceosome, SF3b. Spliceostatin A is an inhibitor of RNA synthesis with excellent anticancer activity against a variety of human cancer cell lines. Spliceostatin A inhibits mitotic clone expansion and adipogenesis.
Synonyms
(2S,3Z)-5-{[(2R,3R,5S,6S)-6-{(2E,4E)-5-[(3R,4R,5R,7S)-4-Hydroxy-7-methoxy-7-methyl-1,6-dioxaspiro[2.5]oct-5-yl]-3-methyl-2,4-pentadien-1-yl}-2,5-dimethyltetrahydro-2H-pyran-3-yl]amino}-5-oxo-3-penten-2-yl acetate; 2-Pentenamide, 4-(acetyloxy)-N-[(2R,3R,5S,6S)-tetrahydro-6-[(2E,4E)-5-[(3R,4R,5R,7S)-4-hydroxy-7-methoxy-7-methyl-1,6-dioxaspiro[2.5]oct-5-yl]-3-methyl-2,4-pentadien-1-yl]-2,5-dimethyl-2H-pyran-3-yl]-, (2Z,4S)-
IUPAC Name
[(Z,2S)-5-[[(2R,3R,5S,6S)-6-[(2E,4E)-5-[(3R,4R,5R,7S)-4-hydroxy-7-methoxy-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)OC)CO3)O)C)NC(=O)C=CC(C)OC(=O)C
InChI
InChI=1S/C28H43NO8/c1-17(9-12-24-26(32)28(16-34-28)15-27(6,33-7)37-24)8-11-23-18(2)14-22(20(4)36-23)29-25(31)13-10-19(3)35-21(5)30/h8-10,12-13,18-20,22-24,26,32H,11,14-16H2,1-7H3,(H,29,31)/b12-9+,13-10-,17-8+/t18-,19-,20+,22+,23-,24+,26+,27-,28+/m0/s1
InChIKey
XKSGIJNRMWHQIQ-CGPJBNNXSA-N
Density
1.17±0.1 g/cm3 (Predicted)
Solubility
Soluble in DMSO
Melting Point
65-70°C
In Vitro
Spliceostatin A are potent inhibitors of spliceosomes. These compounds have shown remarkable anticancer activity against multiple human cancer cell lines. With respect to the biological activity, the 1,2-deoxy-pyranose analogue of spliceostatin A suppressed AR-V7 expression at the nano level (IC50 = 3.3 nM). In addition, the in vivo toxicity test showed that the 1,2-deoxy-pyranose analogue was able to avoid severe toxicity compared to spliceostatin A.
Appearance
Solid Powder
Purity
≥95%
Shipping
Dry ice
Storage
- 80 °C
Boiling Point
683.2±55.0 °C at 760 mmHg
1. Spliceostatin A interaction with SF3B limits U1 snRNP availability and causes premature cleavage and polyadenylation
Rei Yoshimoto, Jagat K Chhipi-Shrestha, Tilman Schneider-Poetsch, Masaaki Furuno, A Maxwell Burroughs, Shohei Noma, Harukazu Suzuki, Yoshihide Hayashizaki, Akila Mayeda, Shinichi Nakagawa, Daisuke Kaida, Shintaro Iwasaki, Minoru Yoshida Cell Chem Biol. 2021 Sep 16;28(9):1356-1365.e4. doi: 10.1016/j.chembiol.2021.03.002. Epub 2021 Mar 29.
RNA splicing, a highly conserved process in eukaryotic gene expression, is seen as a promising target for anticancer agents. Splicing is associated with other RNA processing steps, such as transcription and nuclear export; however, our understanding of the interaction between splicing and other RNA regulatory mechanisms remains incomplete. Moreover, the impact of chemical splicing inhibition on long non-coding RNAs (lncRNAs) has been poorly understood. Here, we demonstrate that spliceostatin A (SSA), a chemical splicing modulator that binds to the SF3B subcomplex of the U2 small nuclear ribonucleoprotein particle (snRNP), limits U1 snRNP availability in splicing, resulting in premature cleavage and polyadenylation of MALAT1, a nuclear lncRNA, as well as protein-coding mRNAs. Therefore, truncated transcripts are exported into the cytoplasm and translated, resulting in aberrant protein products. Our work demonstrates that active recycling of the splicing machinery maintains homeostasis of RNA processing beyond intron excision.
2. Spliceostatin C, a component of a microbial bioherbicide, is a potent phytotoxin that inhibits the spliceosome
Joanna Bajsa-Hirschel, Zhiqiang Pan, Pankaj Pandey, Ratnakar N Asolkar, Amar G Chittiboyina, Louis Boddy, Marylou C Machingura, Stephen O Duke Front Plant Sci. 2023 Jan 12;13:1019938. doi: 10.3389/fpls.2022.1019938. eCollection 2022.
Spliceostatin C (SPC) is a component of a bioherbicide isolated from the soil bacterium Burkholderia rinojensis. The chemical structure of SPC closely resembles spliceostatin A (SPA) which was characterized as an anticancer agent and splicing inhibitor. SPC inhibited the growth of Arabidopsis thaliana seedlings with an IC50 value of 2.2 µM. The seedlings exposed to SPC displayed a significant response with decreased root length and number and inhibition of gravitropism. Reverse transcriptase semi-quantitative PCR (RT-sqPCR) analyses of 19 selected genes demonstrated the active impact of SPC on the quality and quantity of transcripts that underwent intron rearrangements as well as up or down expression upon exposure to SPC. Qualitative and quantitative proteomic profiles identified 66 proteins that were significantly affected by SPC treatment. Further proteomics data analysis revealed that spliceostatin C induces hormone-related responses in Arabidopsis seedlings. In silico binding studies showed that SPC binds to a pocket between the SF3B3 and PF5A of the spliceosome.
3. Spliceostatin A stabilizes CDKN1B mRNA through the 3' UTR
Daisuke Kaida, Kenta Shida Biochem Biophys Res Commun. 2022 Jun 11;608:39-44. doi: 10.1016/j.bbrc.2022.03.085. Epub 2022 Mar 29.
Pre-mRNA splicing is one of the most important mechanisms in gene expression in eukaryotes, and therefore splicing inhibition affects various cellular functions. We previously reported that the potent splicing inhibitor spliceostatin A (SSA) causes cell cycle arrest at G1 and G2/M phases. Upregulation of the p27 cyclin dependent kinase inhibitor, encoded by the CDKN1B gene, is one of the reasons for G1 phase arrest caused by SSA treatment. However, the molecular mechanism of p27 upregulation by SSA remains unknown. In this study, we found that SSA treatment caused stabilization of the p27 protein and increase of CDKN1B mRNA. SSA did not affect transcription of CDKN1B gene, but stabilized CDKN1B mRNA. Finally, we revealed that the 3' untranslated region of CDKN1B mRNA was involved in the stabilization. These results suggest that stabilization of CDKN1B mRNA is one of the reasons of upregulation of the p27 protein by SSA.
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Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

The dilution calculator equation

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

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