Name: Spliceostatin A
Brand: BOC Sciences
Price: 2999 USD
Availability: MadeToOrder

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)-; (2Z,4S)-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]-2-pentenamide

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

Solubility

Soluble in DMSO

Melting Point

65-70 °C

Appearance

White to off-white powder

Shipping

Dry ice

Storage

Store at -80 °C, dry and sealed storage

Boiling Point

683.2±55.0 °C at 760 mmHg

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.

Spliceostatin A is a potent natural product derivative and a highly cytotoxic ADC payload employed in antibody-drug conjugates for targeted cancer therapy. Its mechanism involves inhibition of the spliceosome by binding to the SF3b subunit, disrupting pre-mRNA splicing and leading to accumulation of unspliced transcripts. This interference with RNA processing induces cell cycle arrest and apoptosis in proliferating tumor cells. Spliceostatin A’s chemical structure allows covalent attachment to monoclonal antibodies through cleavable or non-cleavable linkers, enabling precise intracellular delivery in ADC applications while maintaining systemic stability.

Within antibody-drug conjugates, Spliceostatin A is conjugated to antibodies using linker chemistries designed for plasma stability and controlled intracellular payload release. The ADC remains inactive during circulation, minimizing off-target cytotoxicity. Following receptor-mediated internalization into antigen-expressing tumor cells, enzymatic or chemical cleavage liberates Spliceostatin A. Once released, it inhibits the SF3b complex, interferes with pre-mRNA splicing, and triggers apoptosis. This targeted delivery ensures cytotoxic activity is confined to tumor cells, enhancing specificity and reproducibility of tumor-targeted therapy.

Applications of Spliceostatin A include incorporation into ADCs targeting both solid tumors and hematologic malignancies with defined antigen expression. Its compatibility with diverse linker systems allows optimization of conjugation efficiency, intracellular release kinetics, and pharmacokinetic profiles. Preclinical studies demonstrate reproducible cytotoxicity in target-expressing tumor cells. Spliceostatin A supports the development of ADCs with defined spliceosome-inhibiting mechanisms, providing mechanistically precise apoptosis induction and tumor cell elimination, facilitating rational design of antibody-drug conjugates for targeted oncology applications.

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.

Catalog	Product Name	CAS	Inquiry
BADC-00781	Spliceostatin B
BADC-00782	Spliceostatin C

What is Spliceostatin A?

Spliceostatin A is a potent inhibitor of the spliceosome, acting as a cytotoxic payload in ADCs. It modulates RNA splicing, causing disruption of cell proliferation and induction of apoptosis in target cells.

28/10/2017

Dear BOC Sciences, how is Spliceostatin A used in ADCs?

Spliceostatin A is conjugated to antibodies to selectively deliver its spliceosome-inhibiting effects to tumor cells. This targeted approach enhances therapeutic activity and reduces off-target cytotoxicity.

20/9/2018

Dear BOC Sciences, which linkers are compatible with Spliceostatin A?

Spliceostatin A can be conjugated via cleavable linkers, including peptide and disulfide types, as well as non-cleavable linkers. Linker selection impacts drug release, ADC stability, and pharmacological profile.

3/3/2019

Dear Sir, may I ask if BOC Sciences provides Spliceostatin A ADC development?

BOC Sciences offers custom ADC services for Spliceostatin A, including payload conjugation, linker optimization, and analytical support, enabling precise design of ADC constructs for research purposes.

17/11/2022

Dear BOC Sciences, what precautions are required for handling Spliceostatin A?

Spliceostatin A is highly cytotoxic and must be handled with strict safety protocols, including PPE, controlled laboratory conditions, and adherence to biosafety guidelines to prevent exposure.

2/9/2019

— Dr. Jason Carter, Senior Scientist (USA)

Spliceostatin A from BOC Sciences arrived with high purity, enabling precise and reproducible experiments.

3/3/2019

— Dr. Christopher Reed, Senior Scientist (USA)

Spliceostatin A from BOC Sciences demonstrated excellent stability and high purity for our ADC conjugation experiments.

2/9/2019

— Ms. Lena Fischer, R&D Manager (Germany)

The batch of Spliceostatin A arrived with comprehensive QC documentation, supporting fast integration into our research.

17/11/2022

— Dr. William Hughes, Biotech Researcher (UK)

We achieved reproducible conjugation results using Spliceostatin A, reflecting the high quality of BOC Sciences’ supply.