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Bortezomib in the management of multiple myeloma.

Multiple myeloma (MM) is a B-cell malignancy characterized by clonal expansion of plasma cells within the bone marrow, the presence of a serum and/or urine monoclonal protein, lytic bone lesions, and anemia. On a cellular level, the disease is characterized by complex interactions between tumor cells and the surrounding bone marrow microenvironment. Understanding of the relationship between malignant plasma cells and the microenvironment has sparked ongoing efforts to develop targeted therapeutic agents for treatment of this disease. The successful development of the first-in-class small-molec

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… Bortezomib is a boronic acid dipeptide small molecule that reversibly inhibits the chymotrypsin-like activity of the 20S proteasome. …

Стратегии лечения множественной миеломы, основанные на наномедицине.

Множественная миелома (ММ) принадлежит к гематологическим маньякам, и общее число случаев заболевания MM растет во всем мире. В течение последних нескольких десятилетий повышенное внимание уделялось развитию и патогенезу MM. Существенные изменения произошли также в парадигме лечения MM, включая протеаозные ингибиторы, иммуномодуляторы и анти CD38 моноклонные антитела, которые значительно улучшили выживание пациентов. Уделение все большего внимания наномедицине обусловлено ее способностью улучшить лечение MM за счет уменьшения системных побочных эффектов и создания возможностей для более точног

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… In comparison, the investigation of free dexamethasone revealed its inactivity at an equivalent dose. 66 Bilgicer et al designed a BTZ prodrug liposome based on a boronic ester bond-linked lipid-BTZ, which can significantly inhibit proteasome activity and kill myeloma cells. 49 Kolemen et al summarized …

Ceftazidime-Avibactam Regimens for the Treatment of Bacteremic and Non-Bacteremic Episodes of Carbapenemase-Producing Enterobacterales Infections in Immunosuppressed Patients.

Ceftazidime-avibactam (CA) and CA plus aztreonam (ATM) are the preferred treatment options for KPC and MBL carbapenemase-producing Enterobacterales infections (CPEis). All episodes of monomicrobial CPEis in immunosuppressed patients (IPs) admitted from May 2019 to November 2024, who received definitive antibiotic therapy (AT) with CA or CA + ATM for at least 72 h, were prospectively included. Bacteremic episodes (BEs) and non-bacteremic episodes (NBEs) were compared. Logistic regressions adjusted by propensity score were used to identify variables associated with 30-day overall mortality. In t

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… Carbapenemase production was analyzed with the Blue-carba test and/or disk synergy tests with a carbapenem disk placed close to the boronic acid disk test for KPC, and the EDTA disk for identification of MBL. …

Three Drug Combinations in the Treatment of Fit Elderly Multiple Myeloma Patients.

The multiple myeloma (MM) non transplant eligible (NTE) population is growing in line with the aging of the population in Western countries. Historically, this population has been known for having a greater risk of treatment related toxicity, and therefore drug development was slow and rather oriented towards the improvement of safety profile than the optimization of disease control. However, NTE MM patients, at least for the fit/non frail patients in recent years, seemed to have benefited more from a less palliative care to improve the depth of response and then prolong survival. NTE MM being

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… In order to improve the PI + Rd regimen, increase the QoL and allow more continuous approach, another triplet attempt was developed with the use of ixazomib, IRd (ixazomib, a boronate acid oral-based PI lenalidomide-dexamethasone). …

Bortezomib (PS-341) treatment decreases inflammation and partially rescues the expression of the dystrophin-glycoprotein complex in GRMD dogs.

Golden retriever muscular dystrophy (GRMD) is a genetic myopathy corresponding to Duchenne muscular dystrophy (DMD) in humans. Muscle atrophy is known to be associated with degradation of the dystrophin-glycoprotein complex (DGC) via the ubiquitin-proteasome pathway. In the present study, we investigated the effect of bortezomib treatment on the muscle fibers of GRMD dogs. Five GRMD dogs were examined; two were treated (TD- Treated dogs) with the proteasome inhibitor bortezomib, and three were control dogs (CD). Dogs were treated with bortezomib using the same treatment regimen used for multip

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… Bortezomib (Velcade®) is a dipeptide boronic acid proteasome inhibitor that works by reversible inhibition of the chymotrypsin-like activity of the proteasome [15] , [16] . Previous reports have shown that proteasome inhibitors are able to block the activation of nuclear factor-κB (NFκB). …

Структурное и механистическое профилирование модулятуры Hurr1 vidofludimus позволяет проектировать лиганд на основе структуры.

В центре биомедицинских исследований находится фактор нейрозащиты, связанный с ядерным рецептором 1 (Nurr1, NR4A2) для его многообещающей нейрозащитной роли в болезни Паркинсона, болезни Альцгеймера и множественном склерозе. Его деятельность может контролироваться лигандами, предлагающими доступ к фармакологической модуляции Hurr1. Вместе с тем связующие эпитопы и механизмы молекулярной активации синтетических активаторов Hurr1 по-прежнему остаются труднодостижимыми, но имеют важное значение для продвижения к новым лекарствам лигандов Hurr1. Здесь мы охарактеризовали диссоциацию Hurr1 димера и

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… The designed ligand 1 was synthesized over two steps by reaction of aniline 2 with the anhydride 3 to the amide 4 and subsequent Suzuki coupling with boronic acid 5 with good overall yield (Fig.  4a ). …

Alpha-lipoic acid alters the antitumor effect of bortezomib in melanoma cells in vitro.

Bortezomib (BOZ) is a proteasome inhibitor chemotherapeutic agent utilized to treat multiple myeloma and recently offered to cure melanoma. Bortezomib-induced neuropathy is one of the dose-limiting side-effects, which can be treated with antioxidants (e.g. alpha-lipoic acid-ALA and Vitamin B1-vit B1). We hypothesized that these antioxidants may counteract the antitumor activity by disrupting the BOZ-induced pathways (e.g. proteasome inhibition or reactive oxygen species generation). The objectives were: (i) to verify the anti-proliferative effect of BOZ; (ii) to compare the influence of the an

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… BOZ is a low molecular weight, hydrophilic dipeptide-boronic acid derivative. It acts as a reversible inhibitor of the chymotrypsin-like protease activity of the proteasome 6 . …

Bone targeted nano-drug and nano-delivery.

There are currently no targeted delivery systems to satisfactorily treat bone-related disorders. Many clinical drugs consisting of small organic molecules have a short circulation half-life and do not effectively reach the diseased tissue site. This coupled with repeatedly high dose usage that leads to severe side effects. With the advance in nanotechnology, drugs contained within a nano-delivery device or drugs aggregated into nanoparticles (nano-drugs) have shown promises in targeted drug delivery. The ability to design nanoparticles to target bone has attracted many researchers to develop n

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… Dexp | Model | 278 Lipid nanoparticle | SiRNA_GNAS | Model | 279 Bone healing | ACP | ALN | Model | 280 Tissue engineering | PLGA–nHAP | Plasmid DNA | Model | 281 Osteoarticular tuberculosis | TC-PLGA-PEG | Rifapentine | Increased | 282 Osteomyelitis | PLA_CS | Etoricoxib | Model | 283 Silver-copper-boron …

Nanoparticle-Mediated Combination Therapy: Two-in-One Approach for Cancer.

Cancer represents a group of heterogeneous diseases characterized by uncontrolledgrowth and spread of abnormal cells, ultimately leading to death. Nanomedicine plays a significantrole in the development of nanodrugs, nanodevices, drug delivery systems and nanocarriers. Someof the major issues in the treatment of cancer are multidrug resistance (MDR), narrow therapeuticwindow and undesired side effects of available anticancer drugs and the limitations of anticancerdrugs. Several nanosystems being utilized for detection, diagnosis and treatment such as theranosticcarriers, liposomes, carbon nano

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… Xiong et al. (2015) designed carborane-conjugated amphiphilic copolymer NPs to deliver DOX for the combination of chemotherapy and boron neutron capture therapy, in which DOX-loaded carborane-conjugated PNPs are able to selectively deliver boron atoms and DOX to the tumor site simultaneously in vivo …

Promising Highly Targeted Therapies for Cholangiocarcinoma: A Review and Future Perspectives.

To overcome the poor prognosis of cholangiocarcinoma (CCA), highly targeted therapies, such as antibody-drug conjugates (ADCs), photodynamic therapy (PDT) with/without systemic chemotherapy, and experimental photoimmunotherapy (PIT), have been developed. Three preclinical trials have investigated the use of ADCs targeting specific antigens, namely HER2, MUC1, and glypican-1 (GPC1), for CCA. Trastuzumab emtansine demonstrated higher antiproliferative activity in CCA cells expressing higher levels of HER2. Similarly, "staphylococcal enterotoxin A-MUC1 antibody" and "anti-GPC1 antibody-monomethyl

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… and neck, gynaecological tumors brain, bladder tumors | 635 nm 375–400 nm | | | | | | 5-ALA-methylesther | Basal-cell carcinoma | 635 nm | | | | | | 5-ALA benzylesther | Gastrointestinal cancer | 635 nm | | | | | | 5-ALA hexylesther | Bladder tumors | 375–400 nm | | | | | | Boronated …

Dysregulation of sphingolipid metabolism contributes to bortezomib-induced neuropathic pain.

The development of chemotherapy-induced painful peripheral neuropathy is a major dose-limiting side effect of many chemotherapeutics, including bortezomib, but the mechanisms remain poorly understood. We now report that bortezomib causes the dysregulation of de novo sphingolipid metabolism in the spinal cord dorsal horn to increase the levels of sphingosine-1-phosphate (S1P) receptor 1 (S1PR1) ligands, S1P and dihydro-S1P. Accordingly, genetic and pharmacological disruption of S1PR1 with multiple S1PR1 antagonists, including FTY720, blocked and reversed neuropathic pain. Mice with astrocyte-sp

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… Introduction Bortezomib (Velcade) is a dipeptide boronic acid inhibitor of the 26S proteasome widely used in the treatment of multiple myeloma and mantle cell non-Hodgkin’s lymphoma ( Chen et al., 2011 ). …

Hesperidin Mitigates Cyclophosphamide-Induced Testicular Dysfunction via Altering the Hypothalamic Pituitary Gonadal Axis and Testicular Steroidogenesis, Inflammation, and Apoptosis in Male Rats.

Cyclophosphamide (CP) is a cytotoxic, cell cycle, non-specific, and antiproliferative drug. This study aimed to address the toxic effects of CP on male fertility and the possible ameliorative role of hesperidin (HSP). Thirty-two adult albino rats were randomly divided into four groups, namely, the negative control, HSP, CP-treated, and CP+HSP-treated groups. The CP-treated rats showed a significant reduction in the levels of serum LH, FSH, testosterone, prolactin, testicular glutathione peroxidase (GPx), and total antioxidant capacity (TAC) with an elevation in levels of malondialdehyde (MDA),

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… Cyclophosphamide induced oxidative stress, lipid per oxidation, apoptosis and histopathological changes in rats: Protective role of boron J. Trace Elem. Med. Biol. Organ Soc. Miner. Trace Elem. (GMS) 2020 62 126574 10.1016/j.jtemb.2020.126574 32516632 50. Torabi F. Malekzadeh Shafaroudi M. …

Bortezomib inhibits chikungunya virus replication by interfering with viral protein synthesis.

Chikungunya virus (CHIKV) is an alphavirus that causes a febrile illness accompanied by myalgia and arthralgia. Despite having re-emerged as a significant public health threat, there are no approved therapeutics or prophylactics for CHIKV infection. In this study, we explored the anti-CHIKV effects of proteasome inhibitors and their potential mechanism of antiviral action. A panel of proteasome inhibitors with different functional groups reduced CHIKV infectious titers in a dose-dependent manner. Bortezomib, which has been FDA-approved for multiple myeloma and mantle cell lymphoma, was further

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… Proteasome inhibitors tested belong to different compound classes, namely peptide aldehydes: MG132; peptide boronates: MLN-9708, MLN-2238 and delanzomib; peptide epoxyketones: carfilzomib, ONX-0914, epoxomicin and oprozomib; β-lactones: lactacystin; anthracycline derivatives: aclacinomycin A. *** P ≤ …

Small molecules in targeted cancer therapy: advances, challenges, and future perspectives.

Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments. Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration (FDA) in 2001, an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies. By December 2020, 89 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration (NMPA) of China. Despite great progress, small-mol

Mechanisms of resistance to antibody-drug conjugates in cancer therapy: molecular basis and therapeutic strategies.

Antibody-drug conjugates (ADCs) have emerged as a transformative class in oncology, integrating the target specificity of monoclonal antibodies with the potent cytotoxicity of small-molecule payloads. By harnessing tumor-specific antigen recognition, ADCs enable the selective delivery of chemotherapeutic agents, thereby enhancing therapeutic efficacy while reducing systemic toxicity. Their clinical success across both hematologic malignancies and solid tumors underscores their potential to redefine targeted cancer therapy. However, the clinical durability of ADCs is increasingly undermined by

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… When SN-38 is used in ADCs such as sacituzumab govitecan and labetuzumab govitecan, modification of the antibody with boronate linkers can restrict cytotoxic activity specifically to tumor cells [ 11 ] . …

Mesoporous Silica Nanoparticles as Drug Delivery Vehicles in Cancer.

Even though cancer treatment has improved over the recent decades, still more specific and effective treatment concepts are mandatory. Surgical removal is not always possible, metastases are challenging and chemo- and radiotherapy can not only have severe side-effects but also resistances may occur. To cope with these challenges more efficient therapies with fewer side-effects are required. One promising approach is the use of drug delivery vehicles. Here, mesoporous silica nanoparticles (MSN) are discussed as biodegradable drug carrier to improve efficacy and reduce side-effects. MSN excellen

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… First, β-cyclodextrin was conjugated to hollow MSN with a boronic-acid-catechol ester bond for sealing the pores which was degraded in the endosomes or lysosomes at pH 4.5 to 6.5. …

Axonal Transport Impairment in Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a dose-limiting side effect of several antineoplastic drugs which significantly reduces patients' quality of life. Although different molecular mechanisms have been investigated, CIPN pathobiology has not been clarified yet. It has largely been recognized that Dorsal Root Ganglia are the main targets of chemotherapy and that the longest nerves are the most damaged, together with fast axonal transport. Indeed, this bidirectional cargo-specific transport has a pivotal role in neuronal function and its impairment is involved in several neurodeg

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… Bortezomib Bortezomib, a boronic acid dipeptide, represents the first-in-class member of the proteasome inhibitors family, and it currently is the gold standard treatment for multiple myeloma [ 114 ]. …

Salvage therapy of multiple myeloma: the new generation drugs.

During the past decade, overall results of treatment of multiple myeloma (MM) have been improved and survival curves are now significantly better with respect to those obtained with historical treatment. These improvements are linked to a deeper knowledge of the biology of disease and to the introduction in clinical practice of drugs with different mechanism of action such as proteasome inhibitors and immunomodulatory drugs (IMiDs). However, MM remains in most cases an incurable disease. For patients who relapse after treatment with novel agents, the prognosis is dismal and new drugs and thera

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… Novel Proteasome Inhibitors Bortezomib is a dipeptide boronic analog that reversibly inhibits the chymotryptic activity of the 20S subunit of the proteasome [ 30 ]. …

Characterization of a rat model of bortezomib-induced painful neuropathy.

Background and purposeBortezomib (Velcade®) is a breakthrough treatment for multiple myeloma, significantly improving patient survival. However, its use is limited by painful neuropathy often resulting in dose reduction/cessation of first-line treatment due to lack of treatment. The aim of this study was to characterize a clinically relevant rat model of bortezomib-induced painful neuropathy, using established evoked measures and novel ethological techniques, to aid drug discovery.Experimental approachAdult male Sprague-Dawley rats were injected i.p. with 0.1 and 0.2 mg·kg-1 bortezomib, or its

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… Bortezomib is a boronic acid dipeptide which reversibly binds and inhibits the 20S catalytic subunit of the 26S proteasome (Adams, 2002 ). …

Update on treatment of follicular non-Hodgkin's lymphoma: focus on potential of bortezomib.

Follicular lymphoma is predominantly managed as a chronic disease, with intermittent chemo/immunotherapy reserved for symptomatic progression. It is considered incurable with conventional treatments, and current therapeutic options are associated with significant toxicities that are especially limiting in older patients. Bortezomib (PS-341; Velcade(®)), a first-in-class drug targeting the proteolytic core subunit of the 26S proteasome, has emerged as a therapeutic alternative in follicular lymphoma, with promising preclinical data and efficacy in patients with other hematological malignancies.

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… Specifically, bortezomib is a potent boronic acid inhibitor of the 20S proteolytic core subunit of the 26S proteasome. …