gsk-1016790a and Osteoarthritis

gsk-1016790a has been researched along with Osteoarthritis* in 1 studies

Other Studies

1 other study(ies) available for gsk-1016790a and Osteoarthritis

Article	Year
Discovery of Novel Transient Receptor Potential Vanilloid 4 (TRPV4) Agonists as Regulators of Chondrogenic Differentiation: Identification of Quinazolin-4(3 H)-ones and in Vivo Studies on a Surgically Induced Rat Model of Osteoarthritis. Journal of medicinal chemistry, 2019, 02-14, Volume: 62, Issue:3 Osteoarthritis (OA) is a degenerative disease characterized by joint destruction and loss of cartilage. There are many unmet needs in the treatment of OA and there are few promising candidates for disease-modifying OA drugs, particularly, anabolic agents. Here, we describe the identification of novel quinazolin-4(3 H)-one derivatives, which stimulate chondrocyte cartilage matrix production via TRPV4 and mitigate damaged articular cartilage. We successfully identified the water-soluble, highly potent quinazolin-4(3 H)-one derivative 36 and studied its intra-articular physicochemical profile to use in in vivo surgical OA model studies. Compound 36·HCl provided relief from OA damage in a rat medial meniscal tear (MT) model. Specifically, 36·HCl dose-dependently suppressed cartilage degradation and enhanced the messenger RNA expression of aggrecan and SOX9 in cartilage isolated from MT-operated rat knees compared with knees treated with vehicle. These results suggest that 36 induces anabolic changes in articular cartilage and consequently reduces OA progression. Topics: Aggrecans; Animals; Cartilage, Articular; Cell Differentiation; Chondrocytes; HEK293 Cells; Humans; Male; Menisci, Tibial; Mice; Molecular Structure; Osteoarthritis; Quinazolinones; Rats, Sprague-Dawley; RNA, Messenger; SOX9 Transcription Factor; Structure-Activity Relationship; TRPV Cation Channels	2019

Article

Year

Discovery of Novel Transient Receptor Potential Vanilloid 4 (TRPV4) Agonists as Regulators of Chondrogenic Differentiation: Identification of Quinazolin-4(3 H)-ones and in Vivo Studies on a Surgically Induced Rat Model of Osteoarthritis.

Journal of medicinal chemistry, 2019, 02-14, Volume: 62, Issue:3

Osteoarthritis (OA) is a degenerative disease characterized by joint destruction and loss of cartilage. There are many unmet needs in the treatment of OA and there are few promising candidates for disease-modifying OA drugs, particularly, anabolic agents. Here, we describe the identification of novel quinazolin-4(3 H)-one derivatives, which stimulate chondrocyte cartilage matrix production via TRPV4 and mitigate damaged articular cartilage. We successfully identified the water-soluble, highly potent quinazolin-4(3 H)-one derivative 36 and studied its intra-articular physicochemical profile to use in in vivo surgical OA model studies. Compound 36·HCl provided relief from OA damage in a rat medial meniscal tear (MT) model. Specifically, 36·HCl dose-dependently suppressed cartilage degradation and enhanced the messenger RNA expression of aggrecan and SOX9 in cartilage isolated from MT-operated rat knees compared with knees treated with vehicle. These results suggest that 36 induces anabolic changes in articular cartilage and consequently reduces OA progression.

Topics: Aggrecans; Animals; Cartilage, Articular; Cell Differentiation; Chondrocytes; HEK293 Cells; Humans; Male; Menisci, Tibial; Mice; Molecular Structure; Osteoarthritis; Quinazolinones; Rats, Sprague-Dawley; RNA, Messenger; SOX9 Transcription Factor; Structure-Activity Relationship; TRPV Cation Channels

2019