BP-M345 as a Basis for the Discovery of New Diarylpentanoids with Promising Antimitotic Activity DOI Open Access
Joana Moreira, Patrícia Silva,

Eliseba Castro

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(3), С. 1691 - 1691

Опубликована: Янв. 30, 2024

Recently, the diarylpentanoid BP-M345 (5) has been identified as a potent in vitro growth inhibitor of cancer cells, with GI50 value between 0.17 and 0.45 µM, showing low toxicity non-tumor cells. promotes mitotic arrest by interfering spindle assembly, leading to apoptotic cell death. Following on from our previous work, we designed synthesized library analogs evaluated inhibitory activity three human lines within this order perform structure–activity relationship (SAR) studies obtain compounds improved antimitotic effects. Four (7, 9, 13, 16) were active, inhibition effects 7, 16 associated pronounced mitosis. These exhibited similar or even higher index than (5), compound 13 displaying highest activity, interference dynamics, inducing collapse and, consequently, prolonged arrest, culminating massive death apoptosis.

Язык: Английский

Herbal Therapies for Cancer Treatment: A Review of Phytotherapeutic Efficacy DOI Creative Commons
Andrej Jenča, David K. Mills,

Hadis Ghasemi

и другие.

Biologics, Год журнала: 2024, Номер Volume 18, С. 229 - 255

Опубликована: Сен. 1, 2024

Natural products have proven to be promising anti-cancer agents due their diverse chemical structures and bioactivity.This review examines central role in cancer treatment, focusing on mechanisms of action therapeutic benefits.Medicinal plants contain bioactive compounds, such as flavonoids, alkaloids, terpenoids polyphenols, which exhibit various anticancer properties.These compounds induce apoptosis, inhibit cell proliferation cycle progression, interfere with microtubule formation, act topoisomerase targets, angiogenesis, modulate key signaling pathways, improve the tumor microenvironment, reverse drug resistance activate immune cells.Herbal drugs offer advantages, particularly selective toxicity against cells, reducing adverse side effects associated conventional chemotherapy.Recent studies clinical trials highlight benefits herbal medicines alleviating effects, improving tolerance chemotherapy occurrence synergistic treatments.For example, medicine SH003 was found safe potentially effective treatment solid cancers, while Fucoidan showed anti-inflammatory properties that are beneficial for patients advanced cancer.The current research landscape is extensive.Numerous investigating efficacy, safety cancers lung, prostate, breast hepatocellular carcinoma.Promising developments include polypharmacological approach, combination therapies, immunomodulation improvement quality life.However, there still challenges development use natural drugs, need further into action, possible interactions optimal dosage.Standardizing extracts, bioavailability delivery, overcoming regulatory acceptance hurdles critical issues addressed.Nonetheless, warrant investigation development.Multidisciplinary collaboration essential advance therapy integrate these mainstream treatment.

Язык: Английский

Процитировано

20
Biomechanics in the tumor microenvironment: from biological functions to potential clinical applications DOI Creative Commons
Hao Peng,

Zheng Chao,

Zefeng Wang

и другие.

Experimental Hematology and Oncology, Год журнала: 2025, Номер 14(1)

Опубликована: Янв. 11, 2025

Abstract Immune checkpoint therapies have spearheaded drug innovation over the last decade, propelling cancer treatments toward a new era of precision therapies. Nonetheless, challenges low response rates and prevalent resistance underscore imperative for deeper understanding tumor microenvironment (TME) pursuit novel targets. Recent findings revealed profound impacts biomechanical forces within on immune surveillance progression in both murine models clinical settings. Furthermore, pharmacological or genetic manipulation mechanical checkpoints, such as PIEZO1, DDR1, YAP/TAZ, TRPV4, has shown remarkable potential activation eradication tumors. In this review, we delved into underlying mechanisms resulting intricate biological meaning TME, focusing mainly extracellular matrix, stiffness cells, synapses. We also summarized methodologies employed research translation derived from current evidence. This comprehensive review biomechanics will enhance functional role provide basic knowledge discovery therapeutic

Язык: Английский

Процитировано

3
Implications of nanotherapeutic advancements to leverage multi-drug resistant breast cancer: The state-of-the-art review DOI Creative Commons

Adhithya Aravindan,

Ashutosh Gupta, Sudheer Moorkoth

и другие.

Journal of Drug Delivery Science and Technology, Год журнала: 2024, Номер 100, С. 106007 - 106007

Опубликована: Авг. 5, 2024

Globally, cancer is regarded as a severe health issue. Among these breast (BC), the second most common kind in women after skin cancer. According to statistical data from NIH Cancer Institute, expected number of cases was around 3 lakh people, with 7.1 % fatality rate. The rise multidrug resistance (MDR) British Columbia issue it lowers effectiveness existing treatments. Traditional MDR treatment approaches BC have drawbacks, including toxicity, high cost, early discharge, restricted drug load before target, and poor effectiveness. Preventing has depended heavily on developing innovative therapy delivery methods utilizing nanomedicine new diagnosing treating BC. This review discusses its pathophysiology relation tumor kinetics. It focuses latest therapeutic over traditional like Surgery, Chemotherapy, Nanomedicine, Phototherapy, Immunotherapy, Gene therapy. also describes diagnostic techniques using MRI/PET, Mammography, Microwave Sensing, In-silico methods, Molecular techniques, AI-machine learning-based tools. discussed limitations nanoparticles article aims identify efficient ways diagnose treat prevent recurrence.

Язык: Английский

Процитировано

13
Discovery of novel thienopyridine indole derivatives as inhibitors of tubulin polymerization targeting the colchicine-binding site with potent anticancer activities DOI
Wen‐Bo Liu, Weiguang Yang,

Ji Wu

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2025, Номер 286, С. 117314 - 117314

Опубликована: Янв. 24, 2025

Язык: Английский

Процитировано

2
Structure-based discovery and rational design of microtubule-targeting agents DOI Creative Commons
Michel O. Steinmetz, A.E. Prota

Current Opinion in Structural Biology, Год журнала: 2024, Номер 87, С. 102845 - 102845

Опубликована: Май 27, 2024

Microtubule-targeting agents (MTAs) have demonstrated remarkable efficacy as antitumor, antifungal, antiparasitic, and herbicidal agents, finding applications in the clinical, veterinary, agrochemical industry. Recent advances tubulin microtubule structural biology provided powerful tools that pave way for rational design of innovative small-molecule MTAs future basic applied life science applications. In this mini-review, we present current status field, recent impact it had on discovery MTAs, exciting avenues MTA research.

Язык: Английский

Процитировано

7
Vaccine adjuvants for immunotherapy: type, mechanisms and clinical applications DOI Creative Commons
Nimeet Desai,

Sherrin Gotru,

Sagar Salave

и другие.

Frontiers in Biomaterials Science, Год журнала: 2025, Номер 4

Опубликована: Фев. 12, 2025

Immunotherapy has emerged as a powerful approach in treating various diseases, yet its success often hinges on the efficacy of adjuvants, agents that boost immune responses to therapeutic targets. Traditional adjuvants have offered foundational support but may fall short achieving specificity and potency required for advanced therapies. This review highlights new generation poised address these limitations. We explore range innovative agents, including non-inflammatory nucleic acid bacterial derivatives, synthetic molecules, which are redefining role immunotherapy. These emerging hold promise enhancing while tailoring therapies specific disease contexts, from cancer infectious diseases. By examining applications potential this aims provide comprehensive understanding how they can advance immunotherapy levels precision. Through development novel stands achieve more targeted sustained impacts, paving way improved outcomes patient care.

Язык: Английский

Процитировано

1
Identification of a ligand-binding site on tubulin mediating the tubulin–RB3 interaction DOI Creative Commons
Yong Li, Chufeng Zhang, Tang Dongmei

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(11)

Опубликована: Март 11, 2025

For decades, microtubules—composed of αβ-tubulin dimers—have been primary targets for cancer chemotherapy. While eight binding sites on the tubulin dimer have structurally characterized, this study reveals a ninth. We found that inhibitor Tumabulin-1 (TM1, BML284 derivative) binds simultaneously to well-known colchicine site and previously unknown site, designated as Tumabulin site. This resides at interface α1-tubulin, β1-tubulin, RB3 within tubulin–RB3–tubulintyrosine ligase complex. Remarkably, two TM1 molecules bind cooperatively relatively large pocket, interacting with all three proteins. Crucially, is dependent RB3; it absent when missing or key residue H71 mutated (H71Q). further designed synthesized Tumabulin-2 (TM2) selectively excluding TM2 acts molecular glue, strengthening interaction between consequently enhancing RB3’s tubulin-depolymerizing activity. In conclusion, our findings confirm existence ninth tubulin-binding offer promising foundation developing Tubulin–RB3 glues next generation anticancer therapeutics.

Язык: Английский

Процитировано

1
Advancements in antibody-drug conjugates as cancer therapeutics DOI Creative Commons

Jung Yin Fong,

Zhixin Phuna,

D. Chong

и другие.

Journal of the National Cancer Center, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

1
Synthesis, characterization of novel N‐(4‐cyano‐1,3‐oxazol‐5‐yl)sulfonamide derivatives and in vitro screening their activity against NCI‐60 cancer cell lines DOI
Oleksandr O. Severin, Stepan Pilyo, Maryna Kachaeva

и другие.

ChemMedChem, Год журнала: 2024, Номер 19(5)

Опубликована: Янв. 19, 2024

Abstract A novel series of N ‐(4‐cyano‐1,3‐oxazol‐5‐yl)sulfonamides have been synthesized and characterized by IR, 1 H NMR, 13 C NMR spectroscopy, elemental analysis chromato‐mass‐spectrometry. The anticancer activities all newly compounds were evaluated via a single high‐dose assay (10 μM) against 60 cancer cell lines the National Cancer Institute (USA) according to its screening protocol. Among them, 2 10 exhibited highest activity panel in one‐dose assay. Compounds showed inhibitory within GI 50 parameter five dose analyses. However, their cytostatic was only observed some lines, cytotoxic concentration outside maximum used, i. e., >100 μM. COMPARE that average graphs tested moderate positive correlation with L‐cysteine analog vinblastine (GI ) as well paclitaxel (TGI), which target microtubules. Therefore, disruption microtubule formation may be one mechanisms compounds, especially since among tubulin inhibitors antitumor activity, an oxazole motif are widely represented. promising for further functionalization obtain more active compounds.

Язык: Английский

Процитировано

6
Updates in pharmacotherapy for non-small cell lung cancer: a focus on emerging tubulin inhibitors DOI Creative Commons
Simone Nardin,

G. Sacco,

Agostina Lagodin D’Amato

и другие.

Expert Opinion on Pharmacotherapy, Год журнала: 2024, Номер 25(8), С. 1051 - 1069

Опубликована: Май 23, 2024

Introduction The treatment landscape of non-small cell lung cancer (NSCLC) has seen significant advancements in recent years, marked by a shift toward target agents and immune checkpoint inhibitors (ICIs). However, chemotherapy remains cornerstone treatment, alone or combination. Microtubule-targeting agents, such as taxanes vinca alkaloids, play crucial role clinical practice both early advanced settings NSCLC.

Язык: Английский

Процитировано

3