N,N Dimethylacetamide a drug excipient that acts as bromodomain ligand for osteoporosis treatment.
N,N-Dimethylacetamide (DMA) is a water-miscible solvent, FDA approved as excipient and therefore widely used as drug-delivery vehicle. As such, DMA should be devoid of any bioactivity. Here we report that DMA is epigenetically active since it binds bromodomains and inhibits osteoclastogenesis and inflammation. Moreover, DMA enhances bone regeneration in vivo. Therefore, our in vivo and in vitro data reveal DMA's potential as an anti-osteoporotic agent via the inhibition of osteoclast mediated bone resorption and enhanced bone regeneration. Our results highlight the potential therapeutic benefits of DMA and the need for reconsideration of previous reports where DMA was used as an 'inactive' drug-delivery vehicle.
Oral Biotechnology &Bioengineering, Center for Dental Medicine/MKG, University of Zürich, Switzerland.
Chafik
C
Ghayor
Oral Biotechnology &Bioengineering, Center for Dental Medicine/MKG, University of Zürich, Switzerland.|Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Switzerland.
Bebeka
B
Gjoksi
Department of Biochemistry, University of Zurich, Switzerland.
Jing
J
Dong
Oral Biotechnology &Bioengineering, Center for Dental Medicine/MKG, University of Zürich, Switzerland.|CABMM, Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland.
Barbara
B
Siegenthaler
Department of Biochemistry, University of Zurich, Switzerland.
Amedeo
A
Caflisch
Oral Biotechnology &Bioengineering, Center for Dental Medicine/MKG, University of Zürich, Switzerland.|Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Switzerland.|CABMM, Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland.
Franz E
FE
Weber
D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D018797:Cell Cycle Proteins; D002460:Cell Line; D005079:Excipients / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects; D011485:Protein Binding; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000378:metabolism*; D000092468:Bromodomain Containing Proteins
D000081:Acetamides; D000893:Anti-Inflammatory Agents; D050071:Bone Density Conservation Agents; D018797:Cell Cycle Proteins; D005079:Excipients; D009687:Nuclear Proteins; D014157:Transcription Factors; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins; C013959:dimethylacetamide