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Molecular Diversity of Lupane Hybrids in Drug Design and Materials Science.

The need for new, more effective drugs to treat cancer, infectious diseases, various parasitic infestations, and metabolic disorders requires innovative approaches to the design of promising molecules. One of these areas is the creation of hybrid structures. Lupane triterpenoids are of significant interest for such research due to their high abundance in natural sources and their renewable nature, their molecular architecture, presence of several easily modifiable functional groups, enantiomeric purity, broad spectrum of biological activity, and low toxicity. Active research into the biologica

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… Figure 16 Lupeol-3-carbamates with antitumor activity. … Lupeol-3-carbamate derivatives: Synthesis and biological evaluation as potential antitumor agents. Molecules. 2024;29:3990–4007. doi: 10.3390/molecules29173990. 48. Asati V., Mahapatra D.K., Bharti S.K. …

Cardiovascular adverse events associated with BRAF versus BRAF/MEK inhibitor: Cross-sectional and longitudinal analysis using two large national registries.

BACKGROUND: Cardiovascular adverse events (CVAEs) associated with BRAF inhibitors alone versus combination BRAF/MEK inhibitors are not fully understood. METHODS: This study included all adult patients who received BRAF inhibitors (vemurafenib, dabrafenib, encorafenib) or combinations BRAF/MEK inhibitors (vemurafenib/cobimetinib; dabrafenib/trametinib; encorafenib/binimetinib). We utilized the cross-sectional FDA's Adverse Events Reporting System (FAERS) and longitudinal Truven Health Analytics/IBM MarketScan database from 2011 to 2018. Various CVAEs, including arterial hypertension, heart fai

Inhibition of adipocyte differentiation by HIV protease inhibitors.

Patients with AIDS who are receiving therapy with HIV protease inhibitors have been widely reported to be afflicted with a syndrome characterized by lipodystrophy (fat redistribution favoring the accumulation of abdominal and cervical adipose tissue), hyperlipidemia, and insulin resistance. HIV protease inhibitors have been suggested to have a direct role in modulating adipocyte differentiation. To address this hypothesis, several HIV protease inhibitors were studied for their ability to either augment or inhibit the differentiation of murine 3T3-L1 preadipocytes. Dose-responsive inhibition of

Hepatitis C therapy with direct antiviral agents in patients with advanced chronic kidney disease: real-world experience of the German Hepatitis C-Registry (Deutsches Hepatitis C-Register).

BACKGROUND: Direct-acting antiviral agents (DAAs) have revolutionized treatment of chronic hepatitis C in patients with normal glomerular filtration rate (GFR). However, patients with impaired kidney function have been excluded from several clinical trials. We, therefore, investigated the use, effectiveness, and tolerability of DAAs in patients with GFR less than 30 ml/min in the real-world setting. PATIENTS AND METHODS: An analysis was done within the German Hepatitis C-Registry on 5733 patients including 46 individuals with a baseline GFR less than 30 ml/min treated with sofosbuvir-based (6

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

Glucocorticoids-based prodrug design: Current strategies and research progress.

Attributing to their broad pharmacological effects encompassing anti-inflammation, antitoxin, and immunosuppression, glucocorticoids (GCs) are extensively utilized in the clinic for the treatment of diverse diseases such as lupus erythematosus, nephritis, arthritis, ulcerative colitis, asthma, keratitis, macular edema, and leukemia. However, long-term use often causes undesirable side effects, including metabolic disorders-induced Cushing's syndrome (buffalo back, full moon face, hyperglycemia, etc.), osteoporosis, aggravated infection, psychosis, glaucoma, and cataract. These notorious side e

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… Besides, these CatPhos linkers not only could solve the defect that carbamates cannot release drugs but also improve the poor stability of carbonate linkages in blood. … In general, different linkers were used to construct GCs-based ADCs in this section, including carbonate bonds, phosphate bonds, carbamates, cathepsin-responsive linkers, and protease-responsive linkers. …

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

Learn from antibody-drug conjugates: consideration in the future construction of peptide-drug conjugates for cancer therapy.

Cancer is one of the leading causes of death worldwide due to high heterogeneity. Although chemotherapy remains the mainstay of cancer therapy, non-selective toxicity and drug resistance of mono-chemotherapy incur broad criticisms. Subsequently, various combination strategies have been developed to improve clinical efficacy, also known as cocktail therapy. However, conventional "cocktail administration" is just passable, due to the potential toxicities to normal tissues and unsatisfactory synergistic effects, especially for the combined drugs with different pharmacokinetic properties. The drug

Modulation of the heart's electrical properties by the anticonvulsant drug retigabine.

Retigabine, currently used as antiepileptic drug, has a wide range of potential medical uses. Administration of the drug in patients can lead to QT interval prolongation in the electrocardiogram and to cardiac arrhythmias in rare cases. This suggests that the drug may perturb the electrical properties of the heart, and the underlying mechanisms were investigated here. Effects of retigabine on currents through human cardiac ion channels, heterologously expressed in tsA-201 cells, were studied in whole-cell patch-clamp experiments. In addition, the drug's impact on the cardiac action potential w

Efficacy and Safety of Ombitasvir, Paritaprevir, and Ritonavir in an Open-Label Study of Patients With Genotype 1b Chronic Hepatitis C Virus Infection With and Without Cirrhosis.

BACKGROUND & AIMS: Interferon-free treatment options are rapidly evolving for patients with chronic hepatitis C virus (HCV) genotype 1b (GT1b) infection with cirrhosis and for nonresponders to prior pegylated interferon and ribavirin therapy. We performed a phase 2b, open-label trial of the combination of ombitasvir (a NS5A replication complex inhibitor), paritaprevir, and ritonavir (an NS3/4A protease inhibitor)-an interferon- and ribavirin-free regimen-in difficult-to-treat patients, including prior null responders and patients with cirrhosis. METHODS: In an international study, 82 patients

Next-Generation Regimens: The Future of Hepatitis C Virus Therapy.

The treatment of chronic hepatitis C virus (HCV) has undergone a period of rapid evolution. The era of combination direct antivirals has led to high rates of sustained viral response (SVR), limited toxicities, and more broad applicability across patient demographics. Even current therapies have their limitations, however, including genotype specificity and variable durations of treatment depending on the presence or absence of cirrhosis. Developing a fixed-duration pangenotypic regimen that can broadly treat all stages of fibrosis with equal rates of SVR in all patients, irrespective of treatm

The Burden of Cancer, Government Strategic Policies, and Challenges in Pakistan: A Comprehensive Review.

Cancer is a severe condition characterized by uncontrolled cell division and increasing reported mortality and diagnostic cases. In 2040, an estimated 28.4 million cancer cases are expected to happen globally. In 2020, an estimated 19.3 million new cancer cases (18.1 million excluding non-melanoma skin cancer) had been diagnosed worldwide, with around 10.0 million cancer deaths. Breast cancer cases have increased by 2.26 million, lung cancer by 2.21 million, stomach by 1.089 million, liver by 0.96 million, and colon cancer by 1.93 million. Cancer is becoming more prevalent in Pakistan, with 19

Identification of potential inhibitors against SARS-CoV-2 by targeting proteins responsible for envelope formation and virion assembly using docking based virtual screening, and pharmacokinetics approaches.

WHO has declared the outbreak of COVID-19 as a public health emergency of international concern. The ever-growing new cases have called for an urgent emergency for specific anti-COVID-19 drugs. Three structural proteins (Membrane, Envelope and Nucleocapsid protein) play an essential role in the assembly and formation of the infectious virion particles. Thus, the present study was designed to identify potential drug candidates from the unique collection of 548 anti-viral compounds (natural and synthetic anti-viral), which target SARS-CoV-2 structural proteins. High-end molecular docking analysi

Regulation of microRNAs by natural agents: new strategies in cancer therapies.

MicroRNAs (miRNAs) are short noncoding RNA which regulate gene expression by messenger RNA (mRNA) degradation or translation repression. The plethora of published reports in recent years demonstrated that they play fundamental roles in many biological processes, such as carcinogenesis, angiogenesis, programmed cell death, cell proliferation, invasion, migration, and differentiation by acting as tumour suppressor or oncogene, and aberrations in their expressions have been linked to onset and progression of various cancers. Furthermore, each miRNA is capable of regulating the expression of many

A prospective study of daclatasvir and sofosbuvir in chronic HCV-infected kidney transplant recipients.

BACKGROUND: Only a few prospective trials exist regarding the use of novel direct-acting antiviral agents (DAAs) in kidney transplant recipients (KTR) with chronic hepatitis C virus (HCV) infection. METHODS: This prospective single-center trial evaluated treatment with daclatasvir (DCV) and sofosbuvir (SOF) over 12 weeks in 16 adult chronic HCV infected KTR and eGFR > 30 ml/min/1.73m2. Primary endpoint was sustained virological response 12 weeks after end of therapy (SVR12). Beside baseline liver biopsy, hepatic function and glucose metabolism were regularly assessed. RESULTS: Four of 16 stu

Emergent Nanotechnological Strategies for Systemic Chemotherapy against Melanoma.

Melanoma is an aggressive form of skin cancer, being one of the deadliest cancers in the world. The current treatment options involve surgery, radiotherapy, targeted therapy, immunotherapy and the use of chemotherapeutic agents. Although the last approach is the most used, the high toxicity and the lack of efficacy in advanced stages of the disease have demanded the search for novel bioactive molecules and/or efficient drug delivery systems. The current review aims to discuss the most recent advances on the elucidation of potential targets for melanoma treatment, such as aquaporin-3 and tyrosi

A review of potential suggested drugs for coronavirus disease (COVID-19) treatment.

The latest pandemic, coronavirus disease-2019 (COVID-19), is associated with high prevalence and easy transmission, which is expanding globally with no conventional treatment or vaccine. The new virus revealed 79% and 50% genomic similarities with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively. Accordingly, since the disease resists testing and adopting new therapeutics, repositioning pre-existing drugs may present a fast and attractive strategy with known safety, characteristics, and dosage used. However, they

Activation of the steroid and xenobiotic receptor (human pregnane X receptor) by nontaxane microtubule-stabilizing agents.

PURPOSE: Because induction of drug efflux transporters is one of the major underlying mechanisms of drug resistance in cancer chemotherapy, and human pregnane X receptor (hPXR) is one of the principal "xenobiotic" receptors whose activation induces transporter and drug-metabolizing enzyme gene transcription, it would be ideal to develop chemotherapy drugs that do not activate hPXR. This report describes studies undertaken to explore the characteristics of hPXR stimulation and mechanisms of drug-receptor interactions in vitro with new anti-tubulin drugs. EXPERIMENTAL DESIGN: In vitro transient

Общий синтез циклогельминтола I-IV свидетельствует о создании новой цистейно-селективной ковалентной реакционной группы.

Биосопоставимые кавалентные реактивные группы (КРГ) играют ключевую роль в ряде областей химической биологии и биологических наук, включая целевую ковалентную ингибиторную конструкцию и подготовку современных биологовых препаратов, таких, как антитела-наркотики. В этом исследовании мы представляем информацию о том, что небольшой хлорированный естественный продукт из поликетида циклогельминтиол II (CHM-II) действует в качестве нового типа CRG, предусматривающего как обратимую, так и необратимую реактивность. Мы разрабатываем первые синтезы из четырех простых циклогельминтолов, циклохелминтола I

Роль воспаления в нейродегенеративных болезнях: болезнь Паркинсона, болезнь Альцгеймера и множественный склероз.

Нейродегенеративные заболевания представляют собой группу заболеваний, которые, как правило, характеризуются постепенным повреждением и дегенерацией нейронов в центральной нервной системе. В эту группу входят болезнь Паркинсона, болезнь Альцгеймера и множественный склероз. В последние годы все больше фактов указывает на важную роль воспаления в патогенезе этих условий. Происхождение воспаления в мозге, которое часто вызывается провоспалительной активацией микроглий или астроцитов, может, следовательно, привести к хронической провокационной реакции, способствующей развитию нейродегенеративных п