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Review
. 2024 Jan;21(1):1-14.
doi: 10.1080/15476286.2024.2303558. Epub 2024 Feb 8.

Small molecule inhibition of RNA binding proteins in haematologic cancer

Amit K Jaiswal  1 , Michelle L Thaxton  1 , Georgia M Scherer  2 , Jacob P Sorrentino  2 , Neil K Garg  2 , Dinesh S Rao  1   3   4
Affiliations
Review

Small molecule inhibition of RNA binding proteins in haematologic cancer

Amit K Jaiswal et al. RNA Biol. 2024 Jan.

Abstract

In recent years, advances in biomedicine have revealed an important role for post-transcriptional mechanisms of gene expression regulation in pathologic conditions. In cancer in general and leukaemia specifically, RNA binding proteins have emerged as important regulator of RNA homoeostasis that are often dysregulated in the disease state. Having established the importance of these pathogenetic mechanisms, there have been a number of efforts to target RNA binding proteins using oligonucleotide-based strategies, as well as with small organic molecules. The field is at an exciting inflection point with the convergence of biomedical knowledge, small molecule screening strategies and improved chemical methods for synthesis and construction of sophisticated small molecules. Here, we review the mechanisms of post-transcriptional gene regulation, specifically in leukaemia, current small-molecule based efforts to target RNA binding proteins, and future prospects.

Keywords: Acute leukaemia; RNA binding proteins; RNA splicing; drug discovery; post-transcriptional gene regulation.

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Conflict of interest statement

D.S.R. serves on advisory boards and has consulted for AbbVie, Inc., a pharmaceutical company that markets drugs for hematologic malignancies. The other authors declare no potential competing interests.

Figures

Figure 1.
Figure 1.
Schematic of RNA homoeostasis. Gene expression initates with transcription of DNA into a pre-mRNA. Numerous steps of RNA processing occur, many in parallel with transcription. A separate pathway of microRNA (miRNA) processing occurs for primary transcripts that encode miRNAs. Please see text for further details. Schematic created at Biorender.com.
Figure 2.
Figure 2.
Small molecule inhibitors of pre-mRNA splicing. *Mechanism of action for inhibition not reported. Please see text for further details.
Figure 3.
Figure 3.
Inhibitors of RNA modification and nuclear export. *Mechanism of action for inhibition not reported. Please see text for further details.
Figure 4.
Figure 4.
Inhibitors of microRNA processing. *Mechanism of action for inhibition not reported. Please see text for further details.
Figure 5.
Figure 5.
Small molecules targeting regulators of mRNA stability. *Mechanism of action for inhibition not reported. Please see text for further details.
Figure 6.
Figure 6.
Inhibitors of protein translation and sequestration. *Mechanism of action for inhibition not reported. Please see text for further details.
See this image and copyright information in PMC

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