Wenlong Huang

Bio: Wenlong Huang is an academic researcher from China Pharmaceutical University. The author has contributed to research in topics: Multiple drug resistance & P-glycoprotein. The author has an hindex of 23, co-authored 155 publications receiving 2009 citations.

Interleukin-23: as a drug target for autoimmune inflammatory diseases.

Abstract: Interleukin-23 (IL-23) is a member of the IL-12 family of cytokines with pro-inflammatory properties. Its ability to potently enhance the expansion of T helper type 17 (Th17) cells indicates the responsibility for many of the inflammatory autoimmune responses. Emerging data demonstrate that IL-23 is a key participant in central regulation of the cellular mechanisms involved in inflammation. Both IL-23 and IL-17 form a new axis through Th17 cells, which has evolved in response to human diseases associated with immunoactivation and immunopathogeny, including bacterial or viral infections and chronic inflammation. Targeting of IL-23 or the IL-23 receptor or IL-23 axis is a potential therapeutic approach for autoimmune diseases including psoriasis, inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis. The current review focuses on the immunobiology of IL-23 and summarizes the most recent findings on the role of IL-23 in the pre-clinical and ongoing clinical studies.

Free fatty acid receptor agonists for the treatment of type 2 diabetes: drugs in preclinical to phase II clinical development

Abstract: Introduction: The alarming prevalence of type 2 diabetes mellitus (T2DM) stimulated the exploitation of new antidiabetic drugs with extended durability and enhanced safety. In this regard, the free fatty acid receptor 1 (FFA1) and FFA4 have emerged as attractive targets in the last decade. FFA1 has prominent advantages in promoting insulin and incretin secretion while FFA4 shows great potential in incretin secretion, insulin sensitization and anti-inflammatory effects.Area covered: Herein, the authors focus specifically on FFA1 and FFA4 agonists in clinical trials and preclinical development. LY2922470, P11187 and SHR0534 are currently active in clinical trials while the CNX-011-67, SAR1, DS-1558 and BMS-986118 are in preclinical phase. The information for this review is retrieved from Integrity, Scifinder, Espacenet and clinicaltrials.gov databases.Expert opinion: Current proof-of-concept in clinical trials suggests that FFA1 agonists have a significant improvement for T2DM without the risk of hy...

Free Fatty Acid Receptor 1 (FFAR1) as an Emerging Therapeutic Target for Type 2 Diabetes Mellitus: Recent Progress and Prevailing Challenges.

Abstract: The free fatty acid receptor 1 (FFAR1/GPR40) amplifies glucose-dependent insulin secretion; therefore, it has attracted widespread attention as a promising antidiabetic target. Current clinical proof of concept also indicates that FFAR1 agonists achieve the initially therapeutic endpoint for the treatment of type 2 diabetes mellitus (T2DM) without the hypoglycemic risk. Thus, many pharmaceutical companies and academic institutes are competing to develop FFAR1 agonists. However, several candidates have been discontinued in clinical trials, often without reporting the underlying reasons. Herein, we review the challenges and corresponding strategies chosen by different medicinal chemistry teams to improve the physicochemical properties, potency, pharmacokinetics, and safety profiles of FFAR1 agonists, with a brief introduction to the biology and pharmacology of related targets.

Design, Synthesis, and Biological Activity of Novel Dicoumarol Glucagon-like Peptide 1 Conjugates

Abstract: Twelve novel dicoumarol glucagon-like peptide 1 (GLP-1) conjugates were designed, synthesized, and tested for biological activity. All derivatives retained receptor activation efficacy, and exhibited improved albumin affinity and in vitro stability in rat plasma. The in vivo elimination half-lives of 13c and 13 l (22.07 and 18.78 h, respectively) were much longer than those of the GLP-1 receptor agonists exendin-4 (2.82 h) and liraglutide (12.53 h). The prolonged in vivo antidiabetic effects of 13c and 13 l on db/db mice were confirmed by the hypoglycemic efficacy test and the multiple intraperitoneal glucose tolerance test. Importantly, a once daily administration of 13c to db/db mice for 7 weeks provided long-term beneficial effects by lowering glycated hemoglobin (HbA1c) levels to 5.05%, which was lower than with liraglutide treatment (5.41%). These results suggest that 13c is a promising long-lasting GLP-1 mimetic that may be suitable for clinical use following further research.

Glucagon-like peptide 1 (GLP-1)

Abstract: Background The glucagon-like peptide-1 (GLP-1) is a multifaceted hormone with broad pharmacological potential. Among the numerous metabolic effects of GLP-1 are the glucose-dependent stimulation of insulin secretion, decrease of gastric emptying, inhibition of food intake, increase of natriuresis and diuresis, and modulation of rodent β-cell proliferation. GLP-1 also has cardio- and neuroprotective effects, decreases inflammation and apoptosis, and has implications for learning and memory, reward behavior, and palatability. Biochemically modified for enhanced potency and sustained action, GLP-1 receptor agonists are successfully in clinical use for the treatment of type-2 diabetes, and several GLP-1-based pharmacotherapies are in clinical evaluation for the treatment of obesity. Scope of review In this review, we provide a detailed overview on the multifaceted nature of GLP-1 and its pharmacology and discuss its therapeutic implications on various diseases. Major conclusions Since its discovery, GLP-1 has emerged as a pleiotropic hormone with a myriad of metabolic functions that go well beyond its classical identification as an incretin hormone. The numerous beneficial effects of GLP-1 render this hormone an interesting candidate for the development of pharmacotherapies to treat obesity, diabetes, and neurodegenerative disorders

Coumarin-Based Small-Molecule Fluorescent Chemosensors.

Abstract: Coumarins are a very large family of compounds containing the unique 2H-chromen-2-one motif, as it is known according to IUPAC nomenclature. Coumarin derivatives are widely found in nature, especially in plants and are constituents of several essential oils. Up to now, thousands of coumarin derivatives have been isolated from nature or produced by chemists. More recently, the coumarin platform has been widely adopted in the design of small-molecule fluorescent chemosensors because of its excellent biocompatibility, strong and stable fluorescence emission, and good structural flexibility. This scaffold has found wide applications in the development of fluorescent chemosensors in the fields of molecular recognition, molecular imaging, bioorganic chemistry, analytical chemistry, materials chemistry, as well as in the biology and medical science communities. This review focuses on the important progress of coumarin-based small-molecule fluorescent chemosensors during the period of 2012-2018. This comprehensive and critical review may facilitate the development of more powerful fluorescent chemosensors for broad and exciting applications in the future.

A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications.

Abstract: The analogs of nitrogen-based heterocycles occupy an exclusive position as a valuable source of therapeutic agents in medicinal chemistry. More than 75% of drugs approved by the FDA and currently available in the market are nitrogen-containing heterocyclic moieties. In the forthcoming decade, a much greater share of new nitrogen-based pharmaceuticals is anticipated. Many new nitrogen-based heterocycles have been designed. The number of novel N-heterocyclic moieties with significant physiological properties and promising applications in medicinal chemistry is ever-growing. In this review, we consolidate the recent advances on novel nitrogen-containing heterocycles and their distinct biological activities, reported over the past one year (2019 to early 2020). This review highlights the trends in the use of nitrogen-based moieties in drug design and the development of different potent and competent candidates against various diseases.

Antidepressant-Like Activity and Modulation of Brain Monoaminergic Transmission by Blockade of Anandamide Hydrolysis

Abstract: This Resource Is a peer-reviewed article by Gobi et al. published in the 2005-12-13 issue of the Proceedings of the National Academy of Sciences. The authors show, quoting from the Abstract: '[how] URB597, a selective inhibitor of the enzyme fatty-acid amide hydrolase, which catalyzes the intracellular hydrolysis of the endocannabinoid anandamide, exerts potent antidepressant-like effects in the mouse tail-suspension test and the rat forced-swim test... These actions are prevented by the CB1 antagonist rimonabant, are accompanied by increased brain anandamide levels... The findings support a role for anandamide in mood regulation and point to fatty-acid amide hydrolase as a previously uncharacterized target for antidepressant drugs.'