Current Topics in Medicinal Chemistry - Volume 19, Issue 1, 2019

Over the past decades, peptide as a therapeutic candidate has received increasing attention in drug discovery, especially for antimicrobial peptides (AMPs), anticancer peptides (ACPs) and antiinflammatory peptides (AIPs). It is considered that the peptides can regulate various complex diseases which are previously untouchable. In recent years, the critical problem of antimicrobial resistance drives the pharmaceutical industry to look for new therapeutic agents. Compared to organic small drugs, peptide- based therapy exhibits high specificity and minimal toxicity. Thus, peptides are widely recruited in the design and discovery of new potent drugs. Currently, large-scale screening of peptide activity with traditional approaches is costly, time-consuming and labor-intensive. Hence, in silico methods, mainly machine learning approaches, for their accuracy and effectiveness, have been introduced to predict the peptide activity. In this review, we document the recent progress in machine learning-based prediction of peptides which will be of great benefit to the discovery of potential active AMPs, ACPs and AIPs.

Malignant tumors are a major cause of death. The lack of methods that provide an early diagnosis and adequate treatment of cancers is the main obstacle to precision medicine. The C-X-C chemokine receptor 4 (CXCR4) is overexpressed in various tumors and plays a key role in tumor pathogenesis. Therefore, CXCR4-targeted molecular imaging can quickly and accurately detect and quantify CXCR4 abnormalities in real time. The expression level and activation status of CXCR4 are very important for screening susceptible populations and providing an accurate diagnosis and optimal treatment. In view of the fact that radionuclide-labeled peptides have become widely used for the diagnosis and treatment of tumors, this manuscript reviews the potential of different radionuclide-labeled peptide inhibitors for the targeted imaging of CXCR4- positive tumors and targeted treatment. The article also discusses the specificity and in vivo distribution of radionuclide-labeled peptide inhibitors, and translation of these inhibitors to the clinic.

Background: Prostate cancer (PCa) is the most common sex-related malignancy with high mortality in men worldwide. Prostate-specific membrane antigen (PSMA) is overexpressed on the surface of most prostate tumor cells and considered a valuable target for both diagnosis and therapy of prostate cancer. A series of radiolabeled agents have been developed based on the featured PSMA ligands in the previous decade and have demonstrated promising outcomes in clinical research of primary and recurrent PCa. Furthermore, the inspiring response and safety of lutetium-177-PSMA-617 (177Lu-PSMA-617) radiotherapy represent the potential for expanded therapeutic options for metastatic castration-resistant PCa. Retrospective cohort studies have revealed that radiolabeled PSMA agents are the mainstays of the current success, especially in detecting prostate cancer with metastasis and biochemical recurrence. Objective: This review is intended to present a comprehensive overview of the current literature on PSMA ligand-based agents for both radionuclide imaging and therapeutic approaches, with a focus on those that have been clinically adopted. Conclusion: PSMA-based diagnosis and therapy hold great promise for improving the clinical management of prostate cancer.

Traditional prostate cancer therapy and especially chemotherapy has faced many challenges. Low accumulation levels, rapid clearance or drug resistance at the tumor site have been central to why the effect of chemotherapy drugs has declined. Applications of nanotechnology to biomedicine have enabled the development of nanoparticle therapeutic carriers suited for the delivery of chemotherapeutics in cancer therapy. This review describes the current nature of nanoparticle therapeutic carriers for prostate cancer. It describes typical nanocarriers commonly used for the delivery of chemotherapy or for imaging examination. Targeting strategies and related influencing factors are investigated to find ways of enhancing treatment effects of nanoparticles. The overall purpose of this review is to further understanding and to offer recommendations on the design and development of therapeutic nanoparticles for prostate cancer.

Enzymatic dysregulation in tumor and intracellular microenvironments has made this property a tremendously promising responsive element for efficient diagnostics, carrier targeting, and drug release. When combined with nanotechnology, enzyme-responsive drug delivery systems (DDSs) have achieved substantial advancements. In the first part of this tutorial review, changes in tumor and intracellular microenvironmental factors, particularly the enzymatic index, are described. Subsequently, the peptide sequences of various enzyme-triggered nanomaterials are summarized for their uses in various drug delivery applications. Then, some other enzyme responsive nanostructures are discussed. Finally, the future opportunities and challenges are discussed. In brief, this review can provide inspiration and impetus for exploiting more promising internal enzyme stimuli-responsive nanoDDSs for targeted tumor diagnosis and treatment.