Overexpression of protein tyrosine phosphatase 1B (PTP1B) disrupts signaling pathways and results in numerous human diseases. In particular, its involvement has been well documented in the pathogenesis of metabolic disorders (diabetes mellitus type I and type II, fatty liver disease, and obesity); neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease); major depressive disorder; calcific aortic valve disease; as well as several cancer types. Given this multitude of therapeutic applications, shortly after identification of PTP1B and its role, the pursuit to introduce safe and selective enzyme inhibitors began. Regrettably, efforts undertaken so far have proved unsuccessful, since all proposed PTP1B inhibitors failed, or are yet to complete, clinical trials. Intending to aid introduction of the new generation of PTP1B inhibitors, this work collects and organizes the current state of the art. In particular, this review intends to elucidate intricate relations between numerous diseases associated with the overexpression of PTP1B, as we believe that it is of the utmost significance to establish and follow a brand-new holistic approach in the treatment of interconnected conditions. With this in mind, this comprehensive review aims to validate the PTP1B enzyme as a promising molecular target, and to reinforce future research in this direction.

Polyamide noncoated device for adsorption-based microextraction (PANDA microextraction) is a brand new, easy to prepare, environmentally friendly, inexpensive, and efficient sample preparation method created entirely with the use of 3D printing. The proposed method is based on the extractive proprieties of the unmodified polyamide and carbon fiber blends and is compared with the highly selective thin-film microextraction (TFME). In addition, 3D printing was used to simplify the process of TFME. Prototype sample preparation devices were evaluated by the extraction of oral fluid spiked with 38 small molecules with diverse chemical natures, such as lipophilicity in the log P range of 0.2–7.2. The samples were analyzed by high-performance liquid chromatography coupled with tandem mass spectrometry. The results indicate that chemically and thermally resistant 3D printed supports can be successfully used as a cost-saving, environmentally friendly solution for the preparation of TFME devices, alternative to the conventional metal supports, with only marginal differences in the extraction yield (mean = 4.0%, median = 1.8%, range = 0.0–22.3%, n = 38). Even more remarkably, in some cases, the newly proposed PANDA microextraction method exceeded the reference TFME in terms of the extraction efficacy and offered excellent sample cleanup as favorable matrix effects were observed (mean = −8.5%, median = 7.5%, range = −34.7–20.0%, n = 20). This innovative approach paves the road to the simplified sample preparation with the use of emerging extractive 3D printing polymers.

Octadecyl (C₁₈) groups are arguably the most popular ligands used for preparation of solid phase microextraction (SPME) devices. However, conventional C₁₈-bonded silica particles are not fully compatible with the nearly 100% aqueous composition of typical biological samples (e.g., plasma, saliva, or urine). This study presents the first evaluation of thin-film SPME devices coated with special water-compatible C₁₈-bonded particles. Device performance was assessed by extracting a mixture of 30 model compounds that exhibited various chemical structures and properties, such as hydrophobicity. Additionally, nine unique compositions of desorption solvents were tested. Thin-film SPME devices coated with C₁₈-bonded silica particles with polar end-capping groups (10 µm) were compared with conventional trimethylsilane end-capped C₁₈-bonded silica particles of various sizes (5, 10, and 45 µm) and characteristics. Polar end-capped particles provided the best extraction efficacy and were characterized by the strongest correlations between the efficacy of the extraction process and the hydrophobicity of the analytes. The results suggest that the original features of octadecyl ligands are best preserved in aqueous conditions by polar end-capped particles, unlike with conventional trimethylsilane end-capped particles that are currently used to prepare SPME devices. The benefits associated with this improved type of coating encourage further implementation of microextractraction as greener alternative to the traditional sample preparation methods.

This work presents a rational synthesis of 14 innovative methyl salicylate based thiazole (MSBT) derivatives, designed as protein tyrosine phosphatase 1B (PTP1B) inhibitors with potent anticancer activity. Enzyme inhibition studies were performed for all compounds. In addition, molecular docking simulations and assessment of antiproliferative activity were performed for the most active of the lot. For antiproliferative studies, the cell lines of breast cancer (T47D) and non-small-cell lung carcinoma (A549), as well as healthy control of human skin fibroblasts (HSF), were used. As a result, 3 compounds were found to inhibit the PTP1B enzyme in submicromolar concentrations: 3j (IC₅₀ = 0.51 ± 0.15 µM), 3f. (IC₅₀ = 0.66 ± 0.38 µM) and 3d (IC₅₀ = 0.93 ± 0.51 µM), all surpassing the reference inhibitor as much as sixfold (IC₅₀ = 3.23 ± 0.85 µM). Moreover, compound 3j was found to be highly selective towards T47D cancer cells. The cellular mechanism of compound 3j action was associated with the inhibition of DNA replication via blocking the S phase of interphase and induction of apoptosis. Also, molecular docking simulations made for compound 3j revealed continuous interactions between the molecule and the catalytic site, as well as with all the loops involved in the catalytic activity of the protein. Therefore, the new group of MSBT derivatives offers great promise for safe and effective anticancer therapy.