A Benzamide-Linked Small Molecule HS-Cf Inhibits TNF-α-Induced Interferon Regulatory Factor-1 in Porcine Chondrocytes: A Potential Disease-Modifying Drug for Osteoarthritis Therapeutics

Abstract

In a minilibrary containing 300 small molecules, we identified a benzamide-linked small molecule, HS-Cf, that through down-regulating TNF-α-induced IRF-1 activity suppressed chondrocyte activation and prevented cartilage destruction. HS-Cf might be a potential disease-modifying drug for OA therapeutics.

A Benzamide-linked Small Molecule NDMC101 Inhibits NFATc1 and NF-κB Activity: A Potential Osteoclastogenesis Inhibitor for Experimental Arthritis

“…By screening our benzamide-linked small molecules minilibrary, we identified NDMC101 as the potential candidate for osteoclastogenesis inhibitors. Also, our co-lab had demonstrated that related small molecule HS-Cf as a potential disease-modifying drug for osteoarthritis [13]. The present study examined the effects of benzamide-linked small molecule NDMC101, on osteoclast differentiation.…”

“…There has been continuing interest in the research of benzamide-linked small molecule and their systematic dissection largely on account of their biological activities [13]. In light of the structural similarity of these screening hits, we embarked on a focused SAR study to define the molecular basis for their NFATc1 and NF-κB activity inhibitory effects.…”

Metabolic syndrome and components exacerbate osteoarthritis symptoms of pain, depression and reduced knee function

“…However, in countries like China where access to health care is limited and not all patients can afford to pay for surgical interventions other less expensive treatment options are required (26). The treatment of metabolic disorders has been suggested as a possible avenue to retard the progression of osteoarthritic degeneration (27)(28)(29). Thus, identifying and further clarifying possible contributing factors in the pathogenesis and progression of symptomatic osteoarthritis is an ongoing requirement.…”

A New Application of Parallel Synthesis Strategy for Discovery of Amide-Linked Small Molecules as Potent Chondroprotective Agents in TNF-α-Stimulated Chondrocytes

“…In addition, the parallel synthesis approach has been widely used as a powerful method in the drug development [ 21 , 22 ]. Taking advantage of the concept of combinatorial chemistry, our previous studies have identified two potent amide-linked small molecules (HS-Cf and HS-Cm) from a mini-library chemical bank (containing more than 300 small molecules) by using TNF-α-induced inflammatory responses in chondrocytes as a screening tool ( Fig 1 ) [ 23 – 25 ]. In our previous study, HS-Cf (NDMC077) has been found to have the chondroprotective effect that could prevent TNF-α-induced cartilage destruction through downregulating the interferon regulatory factor-1 (IRF-1) signaling [ 25 ].…”