Pladienolides, New Substances from Culture of Streptomyces platensis Mer‐11107. Part 2. Physico‐Chemical Properties and Structure Elucidation.

Sakai, Takashi; Asai, Naoki; Okuda, Akifumi; Kawamura, Naoto; Mizui, Yoshiharu

doi:10.1002/chin.200431194

Cited by 2 publications

(2 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several bacterial derived small molecules or their synthetic analogs have been used to inhibit the spliceosome assembly or the post-translational modifications of the core spliceosome components (Effenberger et al, 2017). Particularly, spliceostatins and pladienolides derived from Pseudomonas and Streptomyces, respectively, have shown to bind the SF3b component of U2 snRNP causing the inhibition of the spliceosome assembly and cell cycle arrest at G1 and G2/M phases (Nakajima et al, 1996;Sakai et al, 2002Sakai et al, , 2004. The binding of spliceostatin A to SF3b1 has been demonstrated to stimulate the production of unspliced p27 mRNA encoding the C-terminal truncated p27 * variant which causes cell cycle arrest at G1 phase by inhibiting CDK2 in HeLa cells (Kaida et al, 2007;Satoh and Kaida, 2016).…”

Section: Splicing-targeted Therapeutic Strategiesmentioning

confidence: 99%

The Role of RNA Splicing Factors in Cancer: Regulation of Viral and Human Gene Expression in Human Papillomavirus-Related Cervical Cancer

Cerasuolo

Buonaguro

Tornesello

2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The spliceosomal complex components, together with the heterogeneous nuclear ribonucleoproteins (hnRNPs) and serine/arginine-rich (SR) proteins, regulate the process of constitutive and alternative splicing, the latter leading to the production of mRNA isoforms coding multiple proteins from a single pre-mRNA molecule. The expression of splicing factors is frequently deregulated in different cancer types causing the generation of oncogenic proteins involved in cancer hallmarks. Cervical cancer is caused by persistent infection with oncogenic human papillomaviruses (HPVs) and constitutive expression of viral oncogenes. The aberrant activity of hnRNPs and SR proteins in cervical neoplasia has been shown to trigger the production of oncoproteins through the processing of pre-mRNA transcripts either derived from human genes or HPV genomes. Indeed, hnRNP and SR splicing factors have been shown to regulate the production of viral oncoprotein isoforms necessary for the completion of viral life cycle and for cell transformation. Target-therapy strategies against hnRNPs and SR proteins, causing simultaneous reduction of oncogenic factors and inhibition of HPV replication, are under development. In this review, we describe the current knowledge of the functional link between RNA splicing factors and deregulated cellular as well as viral RNA maturation in cervical cancer and the opportunity of new therapeutic strategies.

show abstract

Section: Splicing-targeted Therapeutic Strategiesmentioning

confidence: 99%

The Role of RNA Splicing Factors in Cancer: Regulation of Viral and Human Gene Expression in Human Papillomavirus-Related Cervical Cancer

Cerasuolo

Buonaguro

Tornesello

2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Data for ethyl (S)-2-(methoxymethoxy)propanoate 2 were consistent with those reported in the literature. 55 Ethyl-2-(Bis(2-(tert-butyl)phenoxy)phosphoryl)acetate (5). The preparation of ethyl 2-(bis(2-(tert-butyl)phenoxy)phosphoryl)acetate 5 followed the reported procedure.…”

Section: ■ Conclusionmentioning

confidence: 99%

Synthesis and Conformational Analysis of FR901464-Based RNA Splicing Modulators and Their Synergism in Drug-Resistant Cancers

Beard,

Bressin,

Markaj

et al. 2023

J. Med. Chem.

View full text Add to dashboard Cite

FR901464 is a cytotoxic natural product that binds splicing factor 3B subunit 1 (SF3B1) and PHD finger protein 5A (PHF5A), the components of the human spliceosome. The amide-containing tetrahydropyran ring binds SF3B1, and it remains unclear how the substituents on the ring contribute to the binding. Here, we synthesized meayamycin D, an analogue of FR901464, and three additional analogues to probe the conformation through methyl scanning. We discovered that the amide-containing tetrahydropyran ring assumes only one of the two possible chair conformations and that methylation of the nitrogen distorts the chair form, dramatically reducing cytotoxicity. Meayamycin D induced alternative splicing of MCL-1, showed strong synergism with venetoclax in drug-resistant lung cancer cells, and was cancer-specific over normal cells. Meayamycin D incorporates an alkyl ether and shows a long half-life in mouse plasma. The characteristics of meayamycin D may provide an approach to designing other bioactive L-shaped molecules.

show abstract

Pladienolides, New Substances from Culture of Streptomyces platensis Mer‐11107. Part 2. Physico‐Chemical Properties and Structure Elucidation.

Cited by 2 publications

References 1 publication

The Role of RNA Splicing Factors in Cancer: Regulation of Viral and Human Gene Expression in Human Papillomavirus-Related Cervical Cancer

The Role of RNA Splicing Factors in Cancer: Regulation of Viral and Human Gene Expression in Human Papillomavirus-Related Cervical Cancer

Synthesis and Conformational Analysis of FR901464-Based RNA Splicing Modulators and Their Synergism in Drug-Resistant Cancers

Contact Info

Product

Resources

About