Pharmacology/Drug Development

Nemolizumab is a subcutaneously administered humanized anti-interleukin-31 (IL-31) receptor A (IL-31RA) monoclonal antibody that is being developed by Chugai Pharmaceutical Co. Ltd, Maruho Co. Ltd and Galderma Pharma S.A. for the treatment of skin diseases, including atopic dermatitis (AD), AD associated pruritus (ADaP), prurigo nodularis (PN), chronic kidney disease associated pruritus (CKDaP) and systemic sclerosis (SSc). IL-31 is a neuroimmune cytokine that induces itch, inflammation, keratinocyte differentiation and fibroblast activation in chronic pruritic skin diseases. Nemolizumab (Mitchga Syringes) was approved in Japan on 28 March 2022 for use in adults and children over the age of 13 years for the treatment of itch associated with AD (only when existing treatment is insufficiently effective). This article summarizes the milestones in the development of nemolizumab leading to this first approval.

Special populations (SPs) involve people who require additional consideration in clinical research. Effectiveness of treatment or occurrence of side effects may be different in SPs with respect to not-SPs.

There is some evidence that corticosteroids may have a beneficial effect in hand osteoarthritis. We examined the efficacy of corticosteroids on symptoms and structural outcomes in hand osteoarthritis.

Although nonsteroidal anti-inflammatory drugs (NSAIDs) are medicines that are widely used to relieve pain, reduce inflammation, and bring down high temperature, literature confirmed that they still have harmful side effects. Most of their side effects are in the digestive system due to the carboxylic group. As naproxen is one of the NSAIDs, in this work, we try to mask the carboxylic group in naproxen with a relatively safe functional group. So, herein, we report the synthesis of new naproxen-based hydrazones derivatives, namely, (E)-N'-1-(4-chlorophenyl)ethylidene)-2-(6-methoxynaphthalen-2-yl)propane hydrazide (4a) and (E)-N'-(4-hydroxybenzylidene)-2-(6-methoxynaphthalen-2-yl)propane hydrazide ethanol solvate (4b). The compounds were confirmed by X-ray diffraction studies. Hirshfeld surface analyses and energy frameworks of 4a and 4b have been carried out and blind molecular docking studies of them to the COX-2 enzyme were undertaken to obtain binding affinities for judging whether the compounds could act as anti-inflammatory agents. The compounds interact with the key residues: Arg120, Val349, Leu352, Tyr355, Val523, Ala527, Ser530, and Leu531 of the active enzyme pocket. Molecular dynamics studies predicted that the complexes of 4a and 4b with COX-2 are structurally stable and no major conformational changes were observed. Confirmation of the docking and simulation data was achieved by a binding free energies analysis that indicated the dominance of van der Waals energy. The compounds are drug-like molecules as they obey all prominent drug-like rules and have acceptable pharmacokinetic profiles. To investigate the relationship between their intrinsic electronic properties and their possible similarities to actual drugs, the gas-phase DFT optimizations and NBO analyses were also performed in this study.

Rheumatoid arthritis (RA) is an inflammatory type of arthritis that causes joint pain and damage. The inflammatory cell infiltration (e.g., M1 macrophages), the poor O supply at the joint, and the excess reactive oxygen species (ROS)-induced oxidative injury are the main causes of RA. We herein report a polydopamine (PDA)-coated CeO-dopped zeolitic imidazolate framework-8 (ZIF-8) nanocomposite CeO-ZIF-8@PDA (denoted as ) that can synergistically treat RA. Under near-infrared (NIR) light irradiation, PDA efficiently scavenges ROS and results in an increased temperature in the inflamed area because of its good light-to-heat conversion efficiency. The rise of temperature serves to obliterate hyper-proliferative inflammatory cells accumulated in the diseased area while vastly promoting the collapse of the acidic-responsive skeleton of ZIF-8 to release the encapsulated CeO. The released CeO exerts its catalase-like activity to relieve hypoxia by generating oxygen via the decomposition of HO highly expressed in the inflammatory sites. Thus, the constructed composite can treat RA through NIR-photothermal/ROS-scavenging/oxygen-enriched combinative therapy and show good regression of pro-inflammatory cytokines and hypoxia-inducible factor-1α (HIF-1α) in vitro and promising therapeutic effect on RA in rat models. The multimodal nano-platform reported herein is expected to shed light on the design of synergistic therapeutic nanomedicine for effective RA therapy.

Migraine attack is characterized by disabling pain and associated symptoms. Triptans represent the "gold standard" therapy, but cardiac subjects have significant limitations for this approach. New drug families are under consideration to expand therapeutic offerings, especially in the presence of contraindications or for non-responsive patients. This review aimed to analyze studies related to the category of "ditans," with a focus on lasmiditan, which is available for human use.

Psoriasis is considered an autoimmune, inflammatory disorder with a genetic basis. The underlying aetiology is yet unclear. Evidence suggests the congregation of immune cells and their secreted inflammatory cytokines, leukocytes, and other inflammation-promoting factors in large amounts within the epidermal layers of the skin, driving an inflammatory milieu. Although psoriasis is not a fatal condition, patients experience severe pain and suffering. It has a debilitating effect on the physiological and psychological state of the patient. Its distinguishing features are inflammation, formation of plaques on the skin and hyperproliferation of keratinocytes. Therapeutic strategies for treating psoriasis witnessed a radical improvement from traditional therapies to the approval of specific therapies like biologics and small molecules. The emerging evidence about new pharmacological targets and mechanisms in psoriasis has widened the scope for expanding therapeutic strategies. Our review discusses the existing treatments for plaque psoriasis and updates on therapies based on novel pharmacological targets in clinical development.