Recent Advances in Small Molecule Inhibitors for the Treatment of Osteoarthritis

Abstract

Osteoarthritis refers to a degenerative disease with joint pain as the main symptom, and it is caused by various factors, including fibrosis, chapping, ulcers, and loss of articular cartilage. Traditional treatments can only delay the progression of osteoarthritis, and patients may need joint replacement eventually. As a class of organic compound molecules weighing less than 1000 daltons, small molecule inhibitors can target proteins as the main components of most drugs clinically. Small molecule inhibitors for osteoarthritis are under constant research. In this regard, by reviewing relevant manuscripts, small molecule inhibitors targeting MMPs, ADAMTS, IL-1, TNF, WNT, NF-κB, and other proteins were reviewed. We summarized these small molecule inhibitors with different targets and discussed disease-modifying osteoarthritis drugs based on them. These small molecule inhibitors have good inhibitory effects on osteoarthritis, and this review will provide a reference for the treatment of osteoarthritis.

Curculigoside inhibits osteoarthritis <em>via</em> the regulation of NLRP3 pathway

“…The main cause of OA is cartilage abnormalities. 13 Previous study reveals that the degradation of extracellular matrix in articular cartilage induces the apoptosis of chondrocytes, which is regulated by ERK/NF-κB pathway. 14 Curculigoside, a key component of curculiginis rhizome, exhibits protective effects on arthritis via blocking NF-κB/NLRP3 signaling pathways.…”

Evaluating the potential of Vitamin D and curcumin to alleviate inflammation and mitigate the progression of osteoarthritis through their effects on human chondrocytes: A proof-of-concept investigation

“…Targeting the RANK/ RANKL pathway has been proposed as a potential therapeutic strategy for OA. Inhibition of RANKL using monoclonal antibodies or small molecule inhibitors has been shown to reduce subchondral bone resorption and cartilage degradation in animal models of OA [157]. Further to the above, TNF α induces the expression of RANKL in chondrocytes [158], which can activate RANK on the surface of the osteoclasts and promote bone resorption in the joints (Fig 13).…”

Comprehensive Review on the Virulence Factors and Therapeutic Strategies with the Aid of Artificial Intelligence against Mucormycosis

“…Three antifungal drugslipid formulations of amphotericin B, posaconazole, and isavuconazoleare currently used to treat mucormycosis, yet they pose reported toxicities and severe side effects . Managing mucormycosis is challenging due to the lack of effective antifungal drugs and the fungi’s inherent tendency to develop drug resistance and significant variability in susceptibility to available antifungals. , Despite newer antifungal agents, unchanged mortality rates reveal limited understanding of Mucorales’ pathophysiology and molecular pathways, hindering effective treatment development. − Targeted therapy, known for selectivity and efficacy, is revolutionary in treating cancer, chronic immunologic conditions, osteoarthritis, Alzheimer’s disease, and genetic disorders. − In 2022, the U.S. FDA approved 37 new medications21 small molecules and 15 biologicsunderscoring their ongoing impact . Researchers are making strides in drug discovery using AI/ML-based technologies which involve predicting ADMET, high-throughput virtual screening (in CADD), drug interactions, and using predicted protein models in small-molecule design, employing software like MolAICal for 3D protein target predictions and ML-based models for detecting antifungal resistance markers via genome sequencing along with MALDI-TOF MS data analysis. − …”