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FDA approved drugs with pharmacotherapeutic potential for SARS-CoV-2 (COVID-19) therapy.

In December 2019, a novel SARS-CoV-2 coronavirus emerged, causing an outbreak of life-threatening pneumonia in the Hubei province, China, and has now spread worldwide, causing a pandemic. The urgent need to control the disease, combined with the lack of specific and effective treatment modalities, call for the use of FDA-approved agents that have shown efficacy against similar pathogens. Chloroquine, remdesivir, lopinavir/ritonavir or ribavirin have all been successful in inhibiting SARS-CoV-2 in vitro. The initial results of a number of clinical trials involving various protocols of administr

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… The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. Antiviral Res. 2020;176:104742. doi: 10.1016/j.antiviral.2020.104742. Crosnier C., et al. Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum. …

Glycoprotein Non-Metastatic Protein B: An Emerging Biomarker for Lysosomal Dysfunction in Macrophages.

Several diseases are caused by inherited defects in lysosomes, the so-called lysosomal storage disorders (LSDs). In some of these LSDs, tissue macrophages transform into prominent storage cells, as is the case in Gaucher disease. Here, macrophages become the characteristic Gaucher cells filled with lysosomes laden with glucosylceramide, because of their impaired enzymatic degradation. Biomarkers of Gaucher cells were actively searched, particularly after the development of costly therapies based on enzyme supplementation and substrate reduction. Proteins selectively expressed by storage macrop

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… The novel monoclonal antibody 9F5 reveals expression of a fragment of GPNMB/osteoactivin processed by furin-like protease(s) in a subpopulation of microglia in neonatal rat brain. Glia. 2016;64:1938–1961. doi: 10.1002/glia.23034. 173. Huang J.-J., Ma W.-J., Yokoyama S. …

A review of feline infectious peritonitis virus infection.

Feline infectious peritonitis (FIP) is an infectious disease characterized by non-specific laboratory changes and clinical signs. Clinical symptoms include anorexia, jaundice, fever, and weight loss. Moreover, some lesions are found in the digestive and respiratory systems. FIP, whose virulence varies, cannot be distinguished using several diagnostic methods. Moreover, feline coronaviruses (FCoVs) can be classified into two serotypes based on differences in their amino acid sequences, spike (S) protein sequences, and antibody (Ab) neutralization. There are two pathotypes, namely those caused b

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… FCoV-I possesses two specific activation sites: S1/S2, which is cleaved by furin-like protease and S2’, which is cleaved by cathepsin B. FCoV-II contains only the S2’ site, which is cleaved by cathepsin B. …

Fate of hematopoietic stem cells determined by Notch1 signaling (Review).

Regulation of the fate of hematopoietic stem cells (HSCs), including silencing, self-renewal or differentiation into blood line cells, is crucial to maintain the homeostasis of the human blood system and prevent leukemia. Notch1, a key receptor in the Notch signaling pathway, plays an important regulatory role in these properties of HSCs, particularly in the maintenance of the stemness of HSCs. In recent decades, the ubiquitination modification of Notch1 has been gradually revealed, and also demonstrated to affect the proliferation and differentiation of HSCs. Therefore, a detailed elucidation

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… First, a single polypeptide precursor protein is cleaved in the Golgi by a furin-like convertase to produce a mature Notch receptor (S1) ( 21 ). …

Targeting the two-pore channel 2 in cancer progression and metastasis.

The importance of Ca2+ signaling, and particularly Ca2+ channels, in key events of cancer cell function such as proliferation, metastasis, autophagy and angiogenesis, has recently begun to be appreciated. Of particular note are two-pore channels (TPCs), a group of recently identified Ca2+-channels, located within the endolysosomal system. TPC2 has recently emerged as an intracellular ion channel of significant pathophysiological relevance, specifically in cancer, and interest in its role as an anti-cancer drug target has begun to be explored. Herein, an overview of the cancer-related functions

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… Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein . Proc Natl Acad Sci U S A . 2014 ; 111 : 15214 – 9 . 10.1073/pnas.1407087111 25288733 PMC4210292 37. Gunaratne GS Yang Y Li F Walseth TF Marchant JS. …

Advances and Hurdles in CAR T Cell Immune Therapy for Solid Tumors.

Chimeric antigen receptor (CAR) T cells in solid tumors have so far yielded limited results, in terms of therapeutic effects, as compared to the dramatic results observed for hematological malignancies. Many factors involve both the tumor cells and the microenvironment. The lack of specific target antigens and severe, potentially fatal, toxicities caused by on-target off-tumor toxicities constitute major hurdles. Furthermore, the tumor microenvironment is usually characterized by chronic inflammation, the presence of immunosuppressive molecules, and immune cells that can reduce CAR T cell effi

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… Processing of immunosuppressive pro-TGF-beta 1,2 by human glioblastoma cells involves cytoplasmic and secreted furin-like proteases J. Immunol. 2001 166 7238 7243 10.4049/jimmunol.166.12.7238 11390472 145. Bodmer S. Strommer K. Frei K. Siepl C. de Tribolet N. Heid I. Fontana A. …

Research advances in peptide‒drug conjugates.

Peptide‒drug conjugates (PDCs) are drug delivery systems consisting of a drug covalently coupled to a multifunctional peptide via a cleavable linker. As an emerging prodrug strategy, PDCs not only preserve the function and bioactivity of the peptides but also release the drugs responsively with the cleavable property of the linkers. Given the ability to significantly improve the circulation stability and targeting of drugs in vivo and reduce the toxic side effects of drugs, PDCs have already been extensively applied in drug delivery. Herein, we review the types and mechanisms of peptides, link

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… Furin-mediated intracellular self-assembly of olsalazine nanoparticles for enhanced magnetic resonance imaging and tumour therapy Nat Mater 18 2019 1376 1383 31636420 10.1038/s41563-019-0503-4 PMC6872935 27 Kamei N. Takeda-Morishita M. …

Diagnosis and treatment of type 1 diabetes at the dawn of the personalized medicine era.

Type 1 diabetes affects millions of people globally and requires careful management to avoid serious long-term complications, including heart and kidney disease, stroke, and loss of sight. The type 1 diabetes patient cohort is highly heterogeneous, with individuals presenting with disease at different stages and severities, arising from distinct etiologies, and overlaying varied genetic backgrounds. At present, the "one-size-fits-all" treatment for type 1 diabetes is exogenic insulin substitution therapy, but this approach fails to achieve optimal blood glucose control in many individuals. Wit

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… Another study showed the potential for combining ADSCs treatment with gene therapy by transducing ADSCs with a furin-cleavable insulin gene (INS-FUR), which led to enhanced insulin expression in the differentiated adipocytes, and alleviated hyperglycemia in diabetic mice [ 182 ]. …

BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.

The BCL-2 family of proteins plays a central role in the regulation of apoptosis, with BCL-2 and BCL-xL representing two of its most prominent antiapoptotic members. This review explores the molecular regulation of BCL-2 and BCL-xL genes, emphasizing the structural domains that define the functions of the broader BCL-2 family. Beyond their canonical roles in preventing mitochondrial outer membrane permeabilization, both proteins contribute significantly to cancer development. Their overexpression enhances invasiveness and tumor progression, supports angiogenesis, and critically modulates cellu

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… Moreover, BCL-2 expression in glioma cells increases Furin and transforming growth factor-β (TGF-β) expression which in turn leads to the upregulation of MMPs, promoting glioma cells invasiveness [ 174 ]. …

Structure and function of therapeutic antibodies approved by the US FDA in 2025.

In 2025, the 50th anniversary of the invention of hybridoma technology, the United States Food and Drug Administration (US FDA) approved a total of 44 new molecular entities (NMEs), of which 10 were therapeutic antibody-based molecules. Additionally, the US FDA approved 31 small molecules (of which one was a peptide), and 3 new nonantibody therapeutic proteins, but no new chimeric antigen receptor (CAR)-T-cell therapeutics. Of the new antibody-based biologics, two were antibody-drug conjugates, one was a T-cell engager-bispecific antibody, two were Fc-modified, half-life extended antibodies, a

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… Voyxact® (sibeprenlimab-szsi) for IgA nephropathy APRIL (A PRoliferation-Inducing Ligand) APRIL (aka CD256, TNFSF13, TALL2, TRDL1) is an unusual 26 kDa transmembrane protein that is cleaved intracellularly in the Golgi apparatus by furin and released extracellularly as a soluble ligand, where it trimerizes …

Tackling the cytokine storm in COVID-19, challenges and hopes.

The outbreak of Coronavirus disease 2019 (COVID-19) is the current world health concern, presenting a public health dilemma with ascending morbidity and mortality rates exceeding any previous viral spread, without a standard effective treatment yet. SARS-CoV-2 infection is distinguished with multiple epidemiological and pathological features, one of them being the elevated levels of cytokine release, which in turn trigger an aberrant uncontrolled response known as "cytokine storm". This phenomenon contributes to severe acute respiratory distress syndrome (ARDS), leading to pneumonia and respir

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… Dousa K.M., Malavade S.S., Furin J., et al. SARS-CoV-2 infection in a patient on chronic hydroxychloroquine therapy: implications for prophylaxis. IDCases. 2020;20 doi: 10.1016/j.idcr.2020.e00778. 113. Tang W., Cao Z., Han M., et al. …

Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway.

Transforming growth factor-beta (TGF-β) signaling regulates a wide range of biological processes. TGF-β plays an important role in tumorigenesis and contributes to the hallmarks of cancer, including tumor proliferation, invasion and metastasis, inflammation, angiogenesis, and escape of immune surveillance. There are several pharmacological approaches to block TGF-β signaling, such as monoclonal antibodies, vaccines, antisense oligonucleotides, and small molecule inhibitors. Galunisertib (LY2157299 monohydrate) is an oral small molecule inhibitor of the TGF-β receptor I kinase that specifically

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… . | NCT00063583 NCT00076102 NCT00287716 NCT01933334 NCT01366209 NCT00011076 NCT00754780 NCT00020631 NCT00053937 NCT02009293 NCT00332033 “bi-shRNAi(furin)/GMCSF DNA/autologous tumor cell” vaccine (FANG) | FANG™ vaccine | II | Melanoma, Ewing’s sarcoma, ovarian cancer, colorectal carcinoma | Gradalis Inc …

Novel therapies emerging in oncology to target the TGF-β pathway.

The TGF-β signaling pathway governs key cellular processes under physiologic conditions and is deregulated in many pathologies, including cancer. TGF-β is a multifunctional cytokine that acts in a cell- and context-dependent manner as a tumor promoter or tumor suppressor. As a tumor promoter, the TGF-β pathway enhances cell proliferation, migratory invasion, metastatic spread within the tumor microenvironment and suppresses immunosurveillance. Collectively, the pleiotropic nature of TGF-β signaling contributes to drug resistance, tumor escape and undermines clinical response to therapy. Based

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… autologous tumor cells harvested from the patient at the time of initial de-bulking surgery which are then transfected extracorporeally, with a plasmid encoding the gene for the immune-stimulatory cytokine GM-CSF, and a bifunctional short hairpin RNA (shRNA) which specifically knocks down expression of furin …

Therapeutic Vaccination in Head and Neck Squamous Cell Carcinoma-A Review.

Therapeutic vaccination is one of the most effective immunotherapeutic approaches, second only to immune checkpoint inhibitors (ICIs), which have already been approved for clinical use. Head and neck squamous cell carcinomas (HNSCCs) are heterogenous epithelial tumors of the upper aerodigestive tract, and a significant proportion of these tumors tend to exhibit unfavorable therapeutic responses to the existing treatment options. Comprehending the immunopathology of these tumors and choosing an appropriate immunotherapeutic maneuver seems to be a promising avenue for solving this problem. The c

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… A pilot study with Trojan vaccines, composed of HLA-I- and HLA-II-restricted MAGE-A3 or HPV-16 derived peptides, joined by furin-cleavable linkers and linked to a penetrin peptide sequence, showed the vaccine to have acceptable toxicity and good systemic immune responses against the HLA-II-restricted …

Progress of Cancer Nanotechnology as Diagnostics, Therapeutics, and Theranostics Nanomedicine: Preclinical Promise and Translational Challenges.

Early detection, right therapeutic intervention, and simultaneous effectiveness mapping are considered the critical factors in successful cancer therapy. Nevertheless, these factors experience the limitations of conventional cancer diagnostics and therapeutics delivery approaches. Along with providing the targeted therapeutics delivery, advances in nanomedicines have allowed the combination of therapy and diagnostics in a single system (called cancer theranostics). This paper discusses the progress in the pre-clinical and clinical development of therapeutics, diagnostics, and theranostics canc

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… For instance, gadolinium-containing monomers, which gather in cells through thiol-sensitive reduction of 1,2-aminothiol and 2-cyanobenzothiazole ligands with specific binding ability to furin and caspase-3 overexpressed on the tumor cells [ 55 ]. 2.2.1. …

Immunotherapies for pediatric cancer: current landscape and future perspectives.

The advent of immunotherapy has revolutionized how we manage and treat cancer. While the majority of immunotherapy-related studies performed to date have focused on adult malignancies, a handful of these therapies have also recently found success within the pediatric space. In this review, we examine the immunotherapeutic agents that have achieved the approval of the US Food and Drug Administration for treating childhood cancers, highlighting their development, mechanisms of action, and the lessons learned from the seminal clinical trials that ultimately led to their approval. We also shine a

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… Vigil immunotherapy is an autologous tumor cell product that is genetically engineered to express GM-CSF and shRNA for the protease furin, which normally activates TGFβ. …

Targeting Tumor Microenvironment for Cancer Therapy.

Cancer development is highly associated to the physiological state of the tumor microenvironment (TME). Despite the existing heterogeneity of tumors from the same or from different anatomical locations, common features can be found in the TME maturation of epithelial-derived tumors. Genetic alterations in tumor cells result in hyperplasia, uncontrolled growth, resistance to apoptosis, and metabolic shift towards anaerobic glycolysis (Warburg effect). These events create hypoxia, oxidative stress and acidosis within the TME triggering an adjustment of the extracellular matrix (ECM), a response

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… Vigil composition consists of patient autologous tumor cells extracorporeally transfected with the gene coding for GM-CSF and a short hairpin RNA targeting furin. …

Всемирный конгресс молекулярного воображения 2022.

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Organelle-oriented nanomedicines in tumor therapy: Targeting, escaping, or collaborating?

Precise tumor therapy is essential for improving treatment specificity, enhancing efficacy, and minimizing side effects. Targeting organelles is a key strategy for achieving this goal and is a frontier research area attracting a considerable amount of attention. The concept of organelle targeting has a significant effect on the structural design of the nanodrugs employed. Most notably, the intricate interactions among different organelles in a tumor cell essentially create a unified system. Unfortunately, this aspect might have been somewhat overlooked when existing organelle-targeting nanodru

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… (c) C 6 RVRRF 4 KY was self-assembled into furin-induced left-handed helical fibrils. (d) Left-handed helical fibrils were transported to the GA, where they self-assembled, disrupted membranes, and induced drug-resistant-free tumor cell death [ 237 ]. … (c) C 6 RVRRF 4 KY was self-assembled into furin-induced left-handed helical fibrils. (d) Left-handed helical fibrils were transported to the GA, where they self-assembled, disrupted membranes, and induced drug-resistant-free tumor cell death [ 237 ]. …

Vascular endothelial growth factor signaling in health and disease: from molecular mechanisms to therapeutic perspectives.

Vascular endothelial growth factor (VEGF) signaling is a critical regulator of vasculogenesis, angiogenesis, and lymphangiogenesis, processes that are vital for the development of vascular and lymphatic systems, tissue repair, and the maintenance of homeostasis. VEGF ligands and their receptors orchestrate endothelial cell proliferation, migration, and survival, playing a pivotal role in dynamic vascular remodeling. Dysregulated VEGF signaling drives diverse pathological conditions, including tumor angiogenesis, cardiovascular diseases, and ocular disorders. Excessive VEGF activity promotes tu

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… is a 419-amino acid protein with 30% sequence identity to VEGF-A and 27% to VEGF-B. 15 , 60 VEGF-C is initially synthesized as an inactive precursor sequestered in the ECM (Fig. 2c ) and undergoes sequential proteolytic cleavages to achieve full activation. 61 Proprotein convertases (PC) including furin …