Intrinsically Disordered Proteins as Regulators of Transient Biological Processes and as Untapped Drug Targets
Abstract
:1. Introduction
2. Inhibitors of Intrinsically Disordered Proteins
2.1. Intrinsically Disordered Proteins (IDPs)
2.2. c-Myc and Max
2.3. P27
2.4. Ewing’s Sarcoma-Friend Leukemia Integration 1 (EWS-FLI1)
2.5. Nuclear Protein 1 (NUPR1)
2.6. Hypoxia-Inducible Factor-2α (HIF-2α)
2.7. BMAL1 and CLOCK
3. Liquid–Liquid Phase Separation
3.1. Liquid–Liquid Phase Separations
3.2. Tau
3.3. DEAD-Box Helicase 3 X-Linked DDX3X
3.4. Fused in Sarcoma
3.5. Transactive Response DNA-Binding Protein 43 kDa (TDP-43)
4. Summary and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compound | Structure | Target | Method 1 | Activity in Vitro | Activity in Cells | Refs |
---|---|---|---|---|---|---|
1 | c-Myc | YTH 2 | 21 μM | 15.1 μM | [64] | |
sAJM589 | c-Myc | PCA 3 | 1.8 μM 7 | 1.2 μM | [65] | |
sJ403 | p27 | NMR | 2.2 mM 8 | n/a | [66] | |
NSC635437 | EWS-FLI1 | SPR 4 | n/a | 20 μM | [67] | |
YK-4-279 | EWS-FLI1 | SPR 4 | 9.48 μM 8 | 0.9 μM | [67] | |
Trifluoperazine | NUPR1 | TSA 5 | 5.2 μM 8 | 26 % at 10 μM | [68] | |
ZZW-115 | NUPR1 | in silico | 2.1 μM 8 | 1.03 μM | [69] | |
THS-044 | HIF-2α | NMR | 2 μM 8 | n/a | [70] | |
CLK8 | CLOCK | in silico | n/a | 20 μM | [71] | |
2 | BMAL1 | FP 6 | ~1 μM 7 | n/a | [72] |
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Hosoya, Y.; Ohkanda, J. Intrinsically Disordered Proteins as Regulators of Transient Biological Processes and as Untapped Drug Targets. Molecules 2021, 26, 2118. https://doi.org/10.3390/molecules26082118
Hosoya Y, Ohkanda J. Intrinsically Disordered Proteins as Regulators of Transient Biological Processes and as Untapped Drug Targets. Molecules. 2021; 26(8):2118. https://doi.org/10.3390/molecules26082118
Chicago/Turabian StyleHosoya, Yusuke, and Junko Ohkanda. 2021. "Intrinsically Disordered Proteins as Regulators of Transient Biological Processes and as Untapped Drug Targets" Molecules 26, no. 8: 2118. https://doi.org/10.3390/molecules26082118