TM38837 / 7TM Pharma - LARVOL DELTA

Is Hepatic Cannabinoid 1 Receptor a Key Driver of Obesity? Implications of the Weight-Reducing Efficacy of the Hepatotropic Inverse Agonist TM38837. (PubMed, Obes Rev) - "This mechanism is activated prematurely in the cell cycle by lifestyle factors, which are known to cause oxidative stress in hepatocytes and are associated with the development of obesity. The consequence of such aberrant cannabinoid 1 receptor upregulation is sustained lipogenesis, leading to reduced cellular ATP levels, which drive increased food intake and contribute to other pathologies."

Journal • Genetic Disorders • Obesity

Efficacy in diet-induced obese mice of the hepatotropic, peripheral cannabinoid 1 receptor inverse agonist TM38837. (PubMed, Br J Pharmacol) - "Weight loss and metabolic benefits of TM38837 are likely not CNS-mediated but could be linked to enhanced liver exposure, which implicates intracellular CB1 receptors in hepatocytes as a possible driver of obesity and co-morbidities."

Journal • Preclinical • Genetic Disorders • Inflammation • Obesity • Psychiatry

Optimizing and characterizing 4-methyl substituted pyrazol-3-carboxamides leading to the peripheral cannabinoid 1 receptor inverse agonist TM38837. (PubMed, Bioorg Med Chem Lett) - "Several series of diverse pyrazole-3-carboxamides functionalized with 4-methylamides, 4-methylcarboxylic acids and 4-methyltetrazoles were prepared from the corresponding 4-cyanomethylpyrazoles and investigated as Cannabinoid receptor 1 (CB1) antagonists and inverse agonists with the aim of making compounds with less CNS (Central Nervous System) mediated side-effects compared to rimonabant. This opens opportunities to be explored in other indications such as nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH). Note that this is a first-time disclosure of the structure of TM38837 and other structures appearing in literature are not connected with this program."

Journal • Genetic Disorders • Hepatology • Inflammation • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Obesity

The Cannabinoid CB1 Antagonist TM38837 With Limited Penetrance to the Brain Shows Reduced Fear-Promoting Effects in Mice. (PubMed, Front Pharmacol) - "Taken together, TM38837 was at least one order of magnitude less effective in promoting fear responses than rimonabant. Given the equipotency of the two CB1 antagonists with regard to weight loss and metabolic syndrome-like symptoms in rodent obesity models, our results point to a critical dose range in which TM3887 might be beneficial for indications such as obesity and metabolic disorders with limited risk of fear-promoting effects."

Journal • Preclinical