PROteolysis‐Targeting Chimeras (PROTACs) in leukemia: overview and future perspectives

MedComm, Journal Year: 2024, Volume and Issue: 5(6)

Published: June 1, 2024

Abstract Leukemia is a heterogeneous group of life‐threatening malignant disorders the hematopoietic system. Immunotherapy, radiotherapy, stem cell transplantation, targeted therapy, and chemotherapy are among approved leukemia treatments. Unfortunately, therapeutic resistance, side effects, relapses, long‐term sequelae occur in significant proportion patients severely compromise treatment efficacy. The development novel approaches to improve outcomes therefore an unmet need. Recently, drug discovery strategies, including protein degradation, have shown potential advance field personalized medicine for patients. Specifically, PROteolysis‐TArgeting Chimeras (PROTACs) revolutionary compounds that allow selective degradation by ubiquitin–proteasome Developed against wide range cancer targets, they show promising overcoming many drawbacks associated with conventional therapies. Following exponential growth antileukemic PROTACs, this article reviews PROTAC‐mediated leukemia‐associated targets. Chemical structures, vitro vivo activities, pharmacokinetics, pharmacodynamics, clinical trials PROTACs critically discussed. Furthermore, advantages, challenges, future perspectives covered, order understand these may as drugs treatment.

Language: Английский

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Human Beta Defensin-2 mRNA and Proteasome Subunit β Type 8 mRNA Analysis, Useful in Differentiating Skin Biopsies from Atopic Dermatitis and Psoriasis Vulgaris Patients

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9192 - 9192

Published: Aug. 24, 2024

(1): Atopic dermatitis and psoriasis vulgaris are chronic, inflammatory diseases. Clinical presentation usually leads to a proper diagnosis, but sometimes neither clinical examination nor histopathological evaluation can be conclusive. Therefore, we aimed build up novel diagnostic tool check it for accuracy. The main objective of our work was differentiate between healthy skin (C), atopic (AD) (PV) biopsies on the base involucrin (IVL) human β-defensin-2 (hBD-2) concentrations their mRNA, as well mRNA TPP2 PSMB8. (2): ELISA IVL hBD-2 proteins Real-time PCR relative expression for: (IVL mRNA), (hBD-2 PSMB8 (PSMB8 mRNA) (TPP2 isolated from taken AD PV patients volunteers were performed. (3): correlated with some parameters assessment disease severity. expression, exclusively, sufficient distinguish ones. (4): analysis most valuable in differentiating biopsies.

Language: Английский

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Targeting the ubiquitin proteasome system in cancer stem cells

Trends in Cell Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

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Current strategic trends in drug discovery: the present as prologue

Expert Opinion on Drug Discovery, Journal Year: 2023, Volume and Issue: 19(2), P. 147 - 159

Published: Nov. 7, 2023

Introduction Escalating costs and inherent uncertainties associated with drug discovery invite initiatives to improve its efficiency de-risk campaigns for inventing better therapeutics. One such initiative involves recognizing exploiting current approaches in therapeutics invention molecular mechanisms of action that hold promise designing targeting new chemical entities as drugs.

Language: Английский

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The Autocrine Motility Factor Receptor Delays the Pathological Progression of Alzheimer's Disease via Regulating the Ubiquitination-Mediated Degradation of APP

Published: Jan. 1, 2024

Language: Английский

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