Novel non-natural small molecules DM350-P and DM300 outperform natural cannabinoids, steroid and immune suppressant positive controls in a mouse Colitis and rat Crohn’s model.
The data presented will highlight the significant impact of medicinal chemistry on cannabinoid pharmacology, demonstrating an innovative strategy for developing alternatives to biologics and steroids in the treatment of inflammatory bowel disease (IBD).
Despite the potential of natural cannabinoids such as cannabidiol (CBD) and cannabigerol (CBG), their low oral bioavailability requires high doses for clinical efficacy, leading to complications such as severe hepatic impairment. Demeetra identified key residues on natural cannabinoids that influence pharmacokinetic parameters and potency. Consequently, Structure Activity Relationships (SAR) analyses were conducted with a focus on these sites to develop novel compounds exhibiting enhanced properties.
Although the natural cannabinoid CBG proved either ineffective or toxic in a mouse model of TNBS-induced colitis and in an Indomethacin (NSAID)-induced Crohn’s Disease (CD) model in rats, both DM300 and DM350-P demonstrated significant efficacy in reducing inflammation and necrosis in the small bowel when administered orally. Furthermore, an oral pharmacokinetic study in rats revealed that these derivatives exhibited bioavailability up to 15 times higher than natural cannabinoids. Collectively, these data suggest that DM300 and DM350-P have the potential to prevent NSAID-induced gastrointestinal injury and treat inflammatory bowel disease (IBD), offering safer profiles than natural cannabinoids due to their improved bioavailability.
To our knowledge, cannabinoid derivatives have not been specifically developed for targeting IBD. These advancements will be presented at the 2025 Crohn’s & Colitis Congress®, on February 6–8, 2025, in San Francisco.
Title: Cannabinoid Medicinal Chemistry Has Vast Impact on Pharmacology in Mouse and Rat Models of Inflammatory Bowel Disease (IBD)
Presenting Author: Jack Crawford, CEO, Demeetra
Session Date and Time: Friday, Feb. 7, 2025, from 5–6:30 p.m. PST (UTC -8)
Presentation Location: Congress Exhibit Hall, Moscone Center
About Demeetra
Based in Lexington, KY, Demeetra's core focus is developing and optimizing gene editing technologies in commercially applicable systems. Our team of peer-review published scientific staff offers expert technical support, proprietary protocols, and extensive know-how. We transfer this knowledge to our partners and provide simple commercial licenses with freedom to operate. As a leader in gene editing technologies, we expanded research into hemp plant engineering, which led us to investigate the pharmacology and metabolism of natural cannabinoids. Through this research we discovered novel derivative development candidates, DM350-P and DM300, unveiling unforeseen commercial opportunities.