Mini Reviews in Medicinal Chemistry - Volume 24, Issue 4, 2024

Viruses cause a variety of diseases in the human body. Antiviral agents are used to prevent the production of disease-causing viruses. These agents obstruct and kill the virus's translation and replication. Because viruses share the metabolic processes of the majority of host cells, finding targeted medicines for the virus is difficult. In the ongoing search for better antiviral agents, the USFDA approved EVOTAZ, a new drug discovered for the treatment of Human Immunodeficiency Virus (HIV). It is a once-daily (OD) fixed-dose combination of Cobicistat, a cytochrome P450 (CYP) enzyme inhibitor, and Atazanavir, a protease inhibitor. The combination drug was created in such a way that it can inhibit both CYP enzymes and proteases at the same time, resulting in the virus's death. The drug is not effective in children under the age of 18; however, it is still being studied for various parameters. This review article focuses on EVOTAZ's preclinical and clinical aspects, as well as its efficacy and safety profiles.

Canopy FGF signaling regulator 2 (CNPY2) is a novel angiogenic growth factor. In recent years, increasing evidence highlights that CNPY2 has important functions in health and disease. Many new blood vessels need to be formed to meet the nutrient supply in the process of tumor growth. CNPY2 can participate in the development of tumors by promoting angiogenesis. CNPY2 also enhances neurite outgrowth in neurologic diseases and promotes cell proliferation and tissue repair, thereby improving cardiac function in cardiovascular diseases. Regrettably, there are few studies on CNPY2 in various diseases. At the same time, its biological function and molecular mechanism in the process and development of disease are still unclear. This paper reviews the recent studies on CNPY2 in cervical cancer, renal cell carcinoma, prostate cancer, colorectal cancer, lung cancer, gastric cancer, hepatocellular carcinoma, cerebral ischemia-reperfusion injury, spinal cord ischemia-reperfusion injury, Parkinson’s disease, ischemic heart disease, myocardial ischemiareperfusion injury, myocardial infarction, heart failure, and non-alcoholic fatty liver disease. The biological function and molecular mechanism of CNPY2 in these diseases have been summarized in this paper. Many drugs that play protective roles in tumors, cardiovascular diseases, non-alcoholic fatty liver disease, and neurologic diseases by targeting CNPY2, have also been summarized in this paper. In addition, the paper also details the biological functions and roles of canopy FGF signaling regulator 1 (CNPY1), canopy FGF signaling regulator 3 (CNPY3), canopy FGF signaling regulator 4 (CNPY4), and canopy FGF signaling regulator 5 (CNPY5). The mechanism and function of CNPY2 should be continued to study in order to accelerate disease prevention in the future.

Diabetes is a chronic, and metabolic disorder that has gained epidemic proportions in the past few decades creating a threat throughout the globe. It is characterized by increased glucose levels that may be due to immune-mediated disorders (T1DM), insulin resistance or inability to produce sufficient insulin by β-pancreatic cells (T2DM), gestational, or an increasingly sedentary lifestyle. The progression of the disease is marked by several pathological changes in the body like nephropathy, retinopathy, and various cardiovascular complications. Treatment options for T1DM are majorly focused on insulin replacement therapy. While T2DM is generally treated through oral hypoglycemics that include metformin, sulfonylureas, thiazolidinediones, meglitinides, incretins, SGLT-2 inhibitors, and amylin antagonists. Multidrug therapy is often recommended when patients are found incompliant with the first-line therapy. Despite the considerable therapeutic benefits of these oral hypoglycemics, there lie greater side effects (weight variation, upset stomach, skin rashes, and risk of hepatic disease), and limitations including short half-life, frequent dosing, and differential bioavailability which inspires the researchers to pursue novel drug targets and small molecules having promising clinical efficacy posing minimum side-effects. This review summarizes some of the current emerging novel approaches along with the conventional drug targets to treat type 2 diabetes.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks estrogen and progesterone receptors and does not overexpress the human epidermal growth factor receptor 2 (HER2). Previous treatment options for TNBC were limited to chemotherapy alone, resulting in a poor patient prognosis. In 2018, an estimated 2.1 million new cases of breast cancer were diagnosed globally, with the incidence increasing by 0.5% annually from 2014 to 2018. The exact prevalence of TNBC is difficult to determine because it is based on the absence of certain receptors and overexpression of HER2. Treatment options for TNBC include surgery, chemotherapy, radiation therapy, and targeted therapy. The available evidence suggests that combination immunotherapy using PD-1/PD-L1 inhibitors may be a promising treatment option for metastatic TNBC. In this review, we evaluated the efficacy and safety of different immunotherapies regimens for the treatment of TNBC. In many clinical trials, the overall response rate and survival were better in patients treated with these drug combinations than those treated with chemotherapy alone. Although definitive treatments are not within reach, efforts to gain a deeper understanding of combination immunotherapy have the potential to overcome the urge for safe and effective treatments.

In terms of female reproductive tract cancers, ovarian cancer remains the principal reason for mortality globally and is notably difficult to identify in its early stages. This fact highlights the critical need to establish prevention strategies for patients with ovarian cancer, look for new robust diagnostic and prognostic markers, and identify potential targets of response to treatment. MicroRNAs (miRNAs) are one of the novel treatment targets in cancer treatment. Thus, understanding the part of miRNAs in the pathogenesis and metastasis of ovarian cancer is at the center of researchers' attention. MiRNAs are suggested to play a role in modulating many essential cancer processes, like cell proliferation, apoptosis, differentiation, adhesion, epithelial-mesenchymal transition (EMT), and invasion. In two recent decades, natural polyphenols' anti-cancer features have been a focal point of research. Meanwhile, polyphenols are good research subjects for developing new cancer treatments. Polyphenols can modify miRNA expression and impact the function of transcription factors when used as dietary supplements. Multiple works have indicated the impact of polyphenols, including quercetin, genistein, curcumin, and resveratrol, on miRNA expression in vitro and in vivo. Here, we provide an in-depth description of four polyphenols used as dietary supplements: quercetin, genistein, curcumin, and resveratrol, and we summarize what is currently known about their regulatory abilities on influencing the miRNA functions in ovarian tumors to achieve therapeutic approaches.

The most abundant protein found in mammals is collagen, and there are around 28 different types of collagen found in the human body, but there are five types, namely, Type I, Type II, Type III, Type V, and Type X, most generally applied in supplements, and the five common types of collagen are available in various forms and form different sources, which result in various potential benefits. The epidermal growth factor is one of the main growth factor proteins in the skin, which has an important function in the production of collagen, hyaluronic acid, and elastin to keep the skin healthy and dense appearance. It is a single-chain polypeptide of 53 amino acids, which is a potent mitogen for a variety of cells in vivo and in vitro. It triggers cells to grow, produce, and divide proteins, such as collagen. It may increase collagen production in granulation tissue by stimulation of fibroblast proliferation. This review article aims to provide an overview of different collagens and epidermal growth factors from recently published studies and some important directions for future research. The key words search for Collagen, Epidermal growth, Polypeptides, Amino acids, Protein, and tissue engineering were performed using Google scholar, PubMed, and Scopus. Fibrillar collagens are collagen types I, II, III, V, XI, XXIV, XXVII, and non-fibrillar collagens are collagen types IV, VI, VII, VIII, IX, X, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXV, XXVI, XXVIII, and XXIX. Collagen I can be found in bone, skin, tendon, cornea and vascular ligature; collagen II can be discovered in cartilage, vitreous body and gristle; collagen III is the main ingredient of reticular fibers which is often found alongside type I, the location of collagen III is also in skin, uterus, intestine, and vessels. Collagen IV can be identified in capillaries, the epithelium-secreted layer of the basement membrane and forms basal lamina. It forms basal lamina, capillaries, and the epitheliumsecreted layer of the basement membrane, while Collagen V can be discovered in bones, skin, cornea, hair, placenta, and cell surfaces. In addition, collagen VI is found in bones, skin, gristle, cornea and vessels, while collagen VII can be found in skin, bladder, mucous membranes, amniotic fluid and umbilical cord. Lastly, collagen VIII is found in the skin, heart, kidney, brain, bones, gristle and vessels. Moreover, collagen X, XI and IX can be found in the gristle.