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Introduction: The blockade of immune checkpoints, especially the PD-1/PD-L1 pathway with therapeutic antibodies, has shown success in treating cancers in recent years. Seven monoclonal antibodies (mAbs) targeting PD-1 or PD-L1 have been approved by FDA. However, mAbs exhibit several disadvantages as compared to small molecules such as poor permeation, high manufacturing costs, immunogenicity as well as lacking oral bioavailability. Recently, small-molecule inhibitors targeting PD-L1 have been disclosed with the ability to modulate the PD-1/PD-L1 pathway.
Areas Covered: The authors reviewed small molecules targeting PD-L1 that block the PD-1/PD-L1 protein-protein interaction for the treatment of various diseases.
Expert Opinion: Compared with mAbs, PD-1/PD-L1 small-molecule inhibitors show several advantages such as improved tissue penetration, low immunogenicity, well-understood formulation and lower manufacturing costs. They can serve as complementary or synergistically with mAbs for immune therapy. However, at this time most of the reported inhibitors are still inferior to therapeutic antibodies in their inhibitory activities due to smaller molecular weight. Therefore, better small molecules need to be developed to improve their potencies. Moreover, although several PD-L1 small-molecule inhibitors have shown excellent preclinical results, their safety and efficacy in the clinic still awaits further validation.
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http://dx.doi.org/10.1080/13543776.2022.2045276 | DOI Listing |
Adv Mater
December 2024
State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering, Nanjing Tech University, 30 Puzhu Road, Nanjing, 211816, P. R. China.
Crystalline membranes, represented by the metal-organic framework (MOF) with well-defined angstrom-sized apertures, have shown great potential for molecular separation. Nevertheless, it remains a challenge to separate small molecules with very similar molecular size differences due to angstrom-scale defects during membrane formation. Herein, a stepwise assembling strategy is reported for constructing MOF membranes with intrinsic angstrom-sized lattice aperture lattice to separate organic azeotropic mixtures separation.
View Article and Find Full Text PDFMed Oncol
December 2024
Venom and Biotherapeutics Molecules Laboratory, Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, 1316943551, Iran.
The immune system relies on a delicate balance between attacking harmful pathogens and preserving the body's own tissues, a balance maintained by immune checkpoints. These checkpoints play a critical role in preventing autoimmune diseases by restraining excessive immune responses while allowing the immune system to recognize and destroy abnormal cells, such as tumors. In recent years, immune checkpoint inhibitors (ICIs) have become central to cancer therapy, enabling the immune system to target and eliminate cancer cells that evade detection.
View Article and Find Full Text PDFAnal Chem
December 2024
School of Chemistry, University of Bristol, Bristol BS8 1TS, United Kingdom.
Aerosol droplets are unique microcompartments containing microscopic amounts of material and exhibiting surprising chemical reactivity. Although a diverse set of tools exists to characterize the chemical composition of individual submicron particles in air, comparatively fewer approaches can chemically analyze individual, airborne picolitre droplets. We describe a novel approach for mass spectrometric analysis of individual aqueous picolitre droplets (∼2-180 pL volume) containing down to ∼1 pg analyte mass per droplet.
View Article and Find Full Text PDFPharmacol Biochem Behav
December 2024
Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA; Rutgers Addiction Research Center, Brain Health Institute, Rutgers Health, Piscataway, NJ, USA; School of Psychology, Faculty of Science, University of Sydney, Sydney, NSW, Australia; Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia. Electronic address:
Medications to treat substance use disorders remain suboptimal or, in the case of stimulants and cannabis, non-existent. Many factors have contributed to this paucity, including the biological complexity of addiction, regulatory challenges, and a historical lack of enthusiasm among pharmaceutical companies to commit resources to this disease space. Despite these headwinds, the recent opioid crisis has highlighted the devastating consequences of SUDs for both individuals and society, stimulating urgent efforts to identify novel treatment approaches.
View Article and Find Full Text PDFThyroid
December 2024
Laboratory of Endocrinology and Receptor Biology, Bethesda, Maryland, USA.
Thyrotropin receptor (TSHR) and insulin-like growth factor 1 receptor (IGF-1R) have been shown to crosstalk in primary cultures of human thyrocytes (hThyros) and Graves' orbital fibroblasts. The phenomenon of TSHR/IGF-1R crosstalk has been largely studied in the pathogenesis of thyroid eye disease (TED) in human orbital fibroblasts. Here, we investigated the effects of inhibiting the IGF-1R-mediated contribution to crosstalk by linsitinib (Lins), a small-molecule IGF-1R kinase inhibitor, on TSH-induced regulation of thyroperoxidase (TPO) and thyroglobulin (TG) mRNAs and proteins in hThyros and on TPO and TG mRNAs and free thyroxine (fT4) levels in mice.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!