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CPUY201112, a novel synthetic small-molecule compound and inhibitor of heat shock protein Hsp90, induces p53-mediated apoptosis in MCF-7 cells.

Heat-shock protein 90 (Hsp90) is highly expressed in many tumor cells and is associated with the maintenance of malignant phenotypes. Targeting Hsp90 has had therapeutic success in both solid and hematological malignancies, which has inspired more studies to identify new Hsp90 inhibitors with improved clinical efficacy. Using a fragment-based approach and subsequent structural optimization guided by medicinal chemistry principles, we identified the novel compound CPUY201112 as a potent Hsp90 inhibitor. It binds to the ATP-binding pocket of Hsp90 with a kinetic dissociation (Kd) constant of 27

Targeted Hybrid Nanocarriers as Co-Delivery Systems for Enhanced Cancer Therapy.

Hybrid nanocarriers have realized a growing interest in drug delivery research because of the potential of being able to treat, manage or cure diseases that previously had limited therapy or cure. Cancer is currently considered the second leading cause of death globally. This makes cancer therapy a major focus in terms of the need for efficacious and safe drug formulations that can be used to reduce the rate of morbidity and mortality globally. The major challenge encountered over the years with cancer chemotherapy is the non-selectivity of anticancer drugs, leading to severe adverse effects i

Boron Chemicals in Drug Discovery and Development: Synthesis and Medicinal Perspective.

A standard goal of medicinal chemists has been to discover efficient and potent drug candidates with specific enzyme-inhibitor abilities. In this regard, boron-based bioactive compounds have provided amphiphilic properties to facilitate interaction with protein targets. Indeed, the spectrum of boron-based entities as drug candidates against many diseases has grown tremendously since the first clinically tested boron-based drug, Velcade. In this review, we collectively represent the current boron-containing drug candidates, boron-containing retinoids, benzoxaboroles, aminoboronic acid, carboran

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… Design, synthesis, and biological evaluation of (E)- and (Z)-styryl-2-acetoxyphenyl sulfides and sulfones as cyclooxygenase-2 inhibitors. Bioorg. Med. Chem. 2005;13:1715–1723. doi: 10.1016/j.bmc.2004.12.005. 102. Semenza G.L. Targeting HIF-1 for cancer therapy. Nat. Rev. …

From Bench to Bedside and Beyond: Therapeutic Scenario in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a heterogeneous group of clonal disorders characterized by abnormal proliferation of undifferentiated myeloid progenitors, impaired hematopoiesis, and variable response to therapy. To date, only about 30% of adult patients with AML become long-term survivors and relapse and/or disease refractoriness are the major cause of treatment failure. Thus, this is an urgent unmet clinical need and new drugs are envisaged in order to ameliorate disease survival outcomes. Here, we review the latest therapeutic approaches (investigational and approved agents) for AML treatme

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… Rigosertib (ON 01910.Na) developed by Onconova Therapeutics is a class of sulfones blocking RAS signaling by serving as a RAS mimetic which binds to the RAS-binding domain. …

Cyclic nucleotide phosphodiesterases as drug targets.

Cyclic nucleotides are synthesized by adenylyl and/or guanylyl cyclase, and downstream of this synthesis, the cyclic nucleotide phosphodiesterase families (PDEs) specifically hydrolyze cyclic nucleotides. PDEs control cyclic adenosine-3',5'monophosphate (cAMP) and cyclic guanosine-3',5'-monophosphate (cGMP) intracellular levels by mediating their quick return to the basal steady state levels. This often takes place in subcellular nanodomains. Thus, PDEs govern short-term protein phosphorylation, long-term protein expression, and even epigenetic mechanisms by modulating cyclic nucleotide levels

Doxorubicin-induced neurotoxicity differently affects the hippocampal formation subregions in adult mice.

Doxorubicin (DOX) is an anthracycline used to treat a wide range of tumours. Despite its effectiveness, it is associated with a long range of adverse effects, of which cognitive deficits stand out. The present study aimed to assess the neurologic adverse outcome pathways of two clinically relevant cumulative doses of DOX. Adult male CD-1 mice received biweekly intraperitoneal administrations for 3 weeks until reaching cumulative doses of 9 mg/kg (DOX9) or 18 mg/kg (DOX18). Animals were euthanized one week after the last administration, and biomarkers of oxidative stress and brain metabolism we

Comprehensive Review of Methodology to Detect Reactive Oxygen Species (ROS) in Mammalian Species and Establish Its Relationship with Antioxidants and Cancer.

Evidence suggests that reactive oxygen species (ROS) mediate tissue homeostasis, cellular signaling, differentiation, and survival. ROS and antioxidants exert both beneficial and harmful effects on cancer. ROS at different concentrations exhibit different functions. This creates necessity to understand the relation between ROS, antioxidants, and cancer, and methods for detection of ROS. This review highlights various sources and types of ROS, their tumorigenic and tumor prevention effects; types of antioxidants, their tumorigenic and tumor prevention effects; and abnormal ROS detoxification in

Molecular Approaches To Target GPCRs in Cancer Therapy

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Therapeutic drug monitoring for cytotoxic anticancer drugs: Principles and evidence-based practices.

Cytotoxic drugs are highly efficacious and also have low therapeutic index. A great degree of caution needs to be exercised in their usage. To optimize the efficacy these drugs need to be given at maximum tolerated dose which leads to significant amount of toxicity to the patient. The fine balance between efficacy and safety is the key to the success of cytotoxic chemotherapeutics. However, it is possibly more rewarding to obtain that balance for this class drugs as the frequency of drug related toxicities are higher compared to the other therapeutic class and are potentially life threatening

Chronic Kidney Disease: Strategies to Retard Progression.

Chronic kidney disease (CKD), defined as the presence of irreversible structural or functional kidney damages, increases the risk of poor outcomes due to its association with multiple complications, including altered mineral metabolism, anemia, metabolic acidosis, and increased cardiovascular events. The mainstay of treatments for CKD lies in the prevention of the development and progression of CKD as well as its complications. Due to the heterogeneous origins and the uncertainty in the pathogenesis of CKD, efficacious therapies for CKD remain challenging. In this review, we focus on the follo

The Mediterranean Diet, a Rich Source of Angiopreventive Compounds in Cancer.

Diet-based chemoprevention of cancer has emerged as an interesting approach to evade the disease or even target its early phases, reducing its incidence or slowing down tumor progression. In its basis in the essential role of angiogenesis for tumor growth and metastasis, angioprevention proposes the use of inhibitors of angiogenesis in cancer prevention. The anti-angiogenic potential exhibited by many natural compounds contained in many Mediterranean diet constituents makes this dietary pattern especially interesting as a source of chemopreventive agents, defined within the angioprevention str

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Microgel-Based 3D Bioprinting: A Convergent Strategy Integrating Material Design, Jamming Dynamics, and Biological Function.

Driven by rapid technological innovation and an increasing demand for personalized medicine, microgel-based bioprinting emerges as a versatile strategy for generating physiologically relevant tissue models and patient-specific constructs. By integrating microgel systems with 3D bioprinting, this approach enables the creation of complex, cell-laden architectures that closely recapitulate native tissue architecture and function. Pivotal to this potential are microgels that offer significant advantages over conventional hydrogel-based bioinks, including tunable rheological behavior, enhanced prin

FDA-Approved Drugs Containing Amide Functionality in the Last Five Years (2021-2025): Pharmaceutical Use, Trends and Synthetic Approaches.

The amide functional group remains a cornerstone of medicinal chemistry, serving as an indispensable scaffold in the design of modern therapeutics. This review presents an analysis of FDA-approved drugs (small molecules and peptides with MW ®), amides form the structural backbone of peptidomimetics, enabling high-affinity binding to a viral protease. In precision oncology, as seen with adagrasib (Krazati®), the amide acts as a critical, metabolically stable linker that positions a covalent warhead for selective inhibition of a mutant kinase. This analysis underscores that amide's unique combin

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… The molecule also contains sulfonic acid groups, which introduce strong polarity and a negative charge, significantly enhancing aqueous solubility. … While both are penicillanic acid sulfones (PAS), the structural difference lies in the addition of a methyl group to the triazole moiety of enmetazobactam. …

Уникальные диагностические и терапевтические функции порфиринов и фтальокянинов в области фотодинамической терапии, визуализации и термостимы.

Порфиринические молекулы играют уникальную тераностическую роль в лечении болезней; они используются для отображения, обнаружения и лечения различных форм заболевших тканей, в том числе в связи с возрастной маркулярной дегенерацией и рядом различных видов рака. В настоящее время основное внимание уделяется клинической съемке опухолей; целенаправленной доставке фотосенитеров и потенциалу фотоэнцедентов в мультимодальных биомедицинских наноплатформах. В настоящем Обзоре подчеркиваются роли порфириновых молекул в области съемки и пдта, а также исследования по совершенствованию их селективного пог

Safety and Tolerability of Letetresgene Autoleucel (GSK3377794): Pilot Studies in Patients with Advanced Non-Small Cell Lung Cancer.

PurposeThe study aims to evaluate the safety, tolerability, and antitumor response of letetresgene autoleucel (lete-cel), genetically modified autologous T cells expressing a T-cell receptor specific for New York esophageal squamous cell carcinoma 1 (NY-ESO-1)/LAGE-1a shared epitope, alone or in combination with pembrolizumab, in HLA-A*02-positive (HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06) patients with NY-ESO-1- and/or LAGE-1a-positive non-small cell lung cancer.Patients and methodsStudy 208749 was a single-arm study of lete-cel alone. Study 208471 was a multiarm study of lete-cel alone o

Improving Kidney Disease Care: One Giant Leap for Nephrology.

Nephrology is an ever-evolving field of medicine. The importance of such a discipline is related to the high clinical impact of kidney disease. In fact, abnormalities of kidney function and/or structure are common in the general population, reaching an overall prevalence of about 10%. More importantly, the onset of kidney damage is related to a strikingly high risk of cardiovascular events, mortality, and progression to kidney failure which, in turn, compromises quality and duration of life. Attempts to comprehend the pathogenesis and molecular mechanisms involved in kidney disease occurrence

Dendrimer-doxorubicin conjugates exhibit improved anticancer activity and reduce doxorubicin-induced cardiotoxicity in a murine hepatocellular carcinoma model.

Hepatocellular carcinoma (HCC) is the 2nd leading cause of cancer-related deaths every year globally. The most common form of treatment, hepatic arterial infusion (HAI), involves the direct injection of doxorubicin (DOX) into the hepatic artery. It is plagued with limited therapeutic efficacy and the occurrence of severe toxicities (e.g. cardiotoxicity). We aim to improve the therapeutic index of DOX delivered via HAI by loading the drug onto generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers targeted to hepatic cancer cells via N-acetylgalactosamine (NAcGal) ligands. DOX is attached to the

Vision of Life's Code: Molecular Probe Nanoarchitectonics for Deep RNA/DNA Illumination.

Visualization of RNA and DNA provides a window of opportunity for the early detection of multiple diseases and approaches to manipulate them before any pathological processes occur. However, current imaging systems often fail to meet these demands due to the need for multiple RNA and DNA chemical probes, which increases experimental complexity, reduces awareness of false positives, and limits imaging accuracy in complex biosystems. In this work, we identify the key challenges associated with using multiple probes for RNA and DNA imaging and analyze the mechanisms and performance of existing im

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… Exploring Photo-excited States of Aromatic Sulfones for Efficient Near-Infrared-Activated Photothermal Cancer Therapy Bull. Chem. Soc. Jpn. 2025 98 uoae137 10.1093/bulcsj/uoae137 Povie G. Segawa Y. Nishihara T. Miyauchi Y. Itami K. …

Роль кишечника микробиота-митохондрия в нейродегенерации: основополагающие механизмы и потенциальные методы лечения.

Появляющиеся данные свидетельствуют о том, что микробиота кишечника тесно связана с патологическими проявлениями множественных нейродегенеративных заболеваний через ось кишечника, которая относится к перекрестку между кишечником и центральной нервной системой. Еще важнее то, что митохондрия считается выдающимся посредником взаимодействия между кишечной микробиотой и мозгом. Кишечные микробы могут модифицировать функцию митохондриала в центральной нервной системе, чтобы повлиять на развитие нейродегенеративных заболеваний. Митохондрия необходима для удовлетворения значительных потребностей носи