Archives of Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: 763, P. 110223 - 110223
Published: Nov. 22, 2024
Language: Английский
Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)
Published: Nov. 26, 2024
Epigenetics governs a chromatin state regulatory system through five key mechanisms: DNA modification, histone RNA remodeling, and non-coding regulation. These mechanisms their associated enzymes convey genetic information independently of base sequences, playing essential roles in organismal development homeostasis. Conversely, disruptions epigenetic landscapes critically influence the pathogenesis various human diseases. This understanding has laid robust theoretical groundwork for developing drugs that target epigenetics-modifying pathological conditions. Over past two decades, growing array small molecule targeting such as methyltransferase, deacetylase, isocitrate dehydrogenase, enhancer zeste homolog 2, have been thoroughly investigated implemented therapeutic options, particularly oncology. Additionally, numerous epigenetics-targeted are undergoing clinical trials, offering promising prospects benefits. review delineates epigenetics physiological contexts underscores pioneering studies on discovery implementation drugs. include inhibitors, agonists, degraders, multitarget agents, aiming to identify practical challenges avenues future research. Ultimately, this aims deepen epigenetics-oriented strategies further application settings.
Language: Английский
Citations
20
Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(2), P. 258 - 258
Published: Feb. 14, 2025
Background: Antibody-drug conjugates (ADCs) represent a novel therapeutic class that combines an antibody against tumor-associated antigen (TAA), payload, and linker binds these two components. Serious adverse events (SAEs), particularly those of grade 3 (G3) or higher, frequently contribute to the abandonment ADCs during clinical development. Methods: In this study, we analyzed toxicity profiles all approved ADCs, aiming uncover correlations between their safety specific characteristics Results: our analysis, dose reductions, delays, treatment discontinuations, ≥G3 toxicities were not significantly different across payload types. Similarly, no association was found mechanism action toxicities, including anemia, neutropenia, febrile thrombocytopenia, diarrhea. By exploring observed by organ, identified most related action, like diarrhea in 10% patients treated with sacituzumab govitecan (the SN-38 is active metabolite irinotecan), very few presence TAA normal tissue (presence Nectin-4 skin rash 14% enfortumab vedotin). line this, major differences studies levels (trastuzumab deruxtecan Destiny Breast Studies HER2 expression levels). Conclusions: Our analysis reveals ADC are driven payload's effects on non-transformed tissues; however, detailed each component should be taken into consideration.
Language: Английский
Citations
1
Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14
Published: March 8, 2024
Lung cancer, ranking second globally in both incidence and high mortality among common malignant tumors, presents a significant challenge with frequent occurrences of drug resistance despite the continuous emergence novel therapeutic agents. This exacerbates disease progression, tumor recurrence, ultimately leads to poor prognosis. Beyond acquired due genetic mutations, mounting evidence suggests critical role epigenetic mechanisms this process. Numerous studies have indicated abnormal expression Histone Methyltransferases (HMTs) lung activation certain HMTs closely linked resistance. mediate tolerance cancer through pathways involving alterations cellular metabolism, upregulation stem cell-related genes, promotion epithelial-mesenchymal transition, enhanced migratory capabilities. The use HMT inhibitors also opens new avenues for treatment, targeting may contribute reversing comprehensive review delves into pivotal roles molecular offering fresh perspective on strategies. By thoroughly examining treatment approaches, it provides insights understanding supporting personalized fostering development, propelling therapy territories.
Language: Английский
Citations
5
Seminars in Cancer Biology, Journal Year: 2025, Volume and Issue: unknown
Published: March 1, 2025
Language: Английский
Citations
0
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 189270 - 189270
Published: Jan. 1, 2025
Language: Английский
Citations
0
Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111703 - 111703
Published: March 1, 2025
Language: Английский
Citations
0
RSC Advances, Journal Year: 2025, Volume and Issue: 15(11), P. 8443 - 8455
Published: Jan. 1, 2025
A series of novel s -triazine-isatin hybrids 7a–f were synthesized and characterized both experimentally computationally for their DNA binding interactions.
Language: Английский
Citations
0
Cancers, Journal Year: 2024, Volume and Issue: 16(12), P. 2175 - 2175
Published: June 8, 2024
G9a, also named EHMT2, is a histone 3 lysine 9 (H3K9) methyltransferase responsible for catalyzing H3K9 mono- and dimethylation (H3K9me1 H3K9me2). G9a contributes to various aspects of embryonic development tissue differentiation through epigenetic regulation. Furthermore, the aberrant expression frequently observed in tumors, particularly prostate cancer, where it cancer pathogenesis progression. This review highlights critical role multiple cancer-related processes, such as dysregulation, tumor suppressor gene silencing, lineage plasticity, hypoxia adaption, Despite increased research on there are still significant gaps, understanding its interactions within microenvironment broader effects. this discusses recent advancements inhibitors, including dual-target inhibitors that target along with other factors EZH2 HDAC. It aims bring together existing knowledge, identify gaps current research, suggest future directions treatment strategies.
Language: Английский
Citations
3
Future Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 16(15), P. 1561 - 1582
Published: July 31, 2024
Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, plays crucial role in tumor progression by regulating gene expression. EZH2 inhibitors have emerged as promising anti-tumor agents due to their potential cancer treatment strategies. However, single-target often face limitations such drug resistance and side effects. Dual-target inhibitors, exemplified EZH1/2 inhibitor HH-2853(28), offer enhanced efficacy reduced adverse This review highlights recent advancements dual targeting other proteins like BRD4, PARP1, EHMT2, emphasizing rational design, structure–activity relationships, safety profiles, suggesting clinical applications.
Language: Английский
Citations
2
Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)
Published: Nov. 30, 2024
Abstract Background Triple-negative breast cancer (TNBC) is currently the most aggressive subtype of cancer, characterized by high heterogeneity and strong invasiveness, lacks effective therapies. PRMT5, a type II protein arginine methyltransferase, upregulated in numerous cancers, including TNBC, plays critical role, marked it as an attractive therapeutic target. PROTAC (Proteolysis Targeting Chimeras) innovative drug development technology that utilizes ubiquitin-proteasome system (UPS) to degrade target proteins, which higher activity, enhanced safety, lower resistance, reduced toxicity, offering significant value for clinical translation. Methods This study develop potential degraders targeting PRMT5 vitro vivo. Results Through design, synthesis screening series targeted compounds, we identified YZ-836P compound exerted cytotoxic effects levels its key downstream KLF5 TNBC after 48 h. Its efficacy was significantly superior had been reported. induced G1 phase cell cycle arrest apoptosis cells. Additionally, demonstrated promoted ubiquitination degradation cereblon (CRBN)-dependent manner. Notably, exhibited pronounced inhibiting growth patient-derived organoids xenografts nude mice. Conclusions These findings position promising candidate advancing treatment modalities TNBC. Trial registration Ethics Committee Yunnan Cancer Hospital, KYCS2023-078. Registered 7 June 2023.
Language: Английский
Citations
2