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Metabolic Disease Therapies Based on DCL™

Background & Overview

Metabolic Disease Therapies Based on DCL™

Metabolic diseases are caused by problems in the physiological mechanism of human metabolism, which can affect various tissues and organs in the body, and even affect intelligence, growth and development and mental state. Clinically, metabolic diseases can be divided into six categories: protein metabolism disorder, glucose metabolism disorder, lipid metabolism disorder, water and electrolyte metabolism disorder, inorganic element metabolism disorder and other metabolic disorders. The most common ones include diabetes and hyperlipidemia. The pathogenesis of metabolic diseases is very complex, so patients may be accompanied by a variety of complications or comorbidities, which is also the difficulty in formulating drug treatment and diagnosis and treatment strategies.

Deuterated drugs for Metabolic Diseases

In pharmaceuticals, the incorporation of deuterium can both increase metabolic stability and reduce toxicity, affect enzymatic reactions, and also affect pure chemical processes such as epimerization. Several typical deuterated drugs are introduced below for the treatment of metabolic diseases.

Deuterated C-Aryl Glycoside

Diabetes has increasingly become a burden on the world's population. Type 1 diabetes is characterized by insufficient insulin production, while type 2 diabetes (DM2) is a complex disease in which interactions between environmental and genetic factors lead to the development of insulin resistance (IR) and beta cell dysfunction. C-arylglycoside SGLT2 inhibitors circumvent the glycosidase susceptibility problem by removing the glycoside anomeric oxygen, and are currently the mainstream drugs for the treatment of type 2 diabetes. Blocking metabolic hotspots by deuteration increases the metabolic stability of such inhibitors in vivo and prevents or reduces the possibility of formation of methine-quinone metabolites.

Fig.1 Deuteration strategy.Fig.1 Deuteration strategy.[1]

Deuterated Phenylpropionic Acid Derivatives

Free fatty acid receptor 1 (FFA1) has emerged as a promising antidiabetic target, and a series of FFA1 agonists have been developed at various stages as antidiabetic drugs. However, due to the susceptibility of phenylpropionic acid to β-oxidation, the pharmacokinetic (PK) profile of the drug candidate is poor. The introduction of two deuterium atoms at the α-position of phenylpropionic acid can effectively block the initial dehydrogenation reaction of β-oxidation, showing an excellent PK profile, especially in terms of half-life and plasma exposure.

Metabolic Disease Therapies Based on DCL™

Our DCL™ technology platform enables informed selection of molecules and deuterated sites to explore the metabolic fate and enzymology of a given compound. Our deuterated pool strategy has a rich range of deuterated substrates and relatively low cost, on the other hand, has mild and green experimental conditions. Therefore, the success rate of obtaining a patent for a deuterated drug can be increased.

For major metabolic diseases that seriously threaten people's life and health, BOC Sciences conducts research on the physiological and pathological mechanisms of metabolic regulation, the proposal, discovery and confirmation of deuterated compounds, and the research on the mechanism of drug action.

Development Process


  1. Xu G, et al. Design, synthesis, and biological evaluation of deuterated C-aryl glycoside as a potent and long-acting renal sodium-dependent glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes. Journal of Medicinal Chemistry. 2014, 57(4): 1236-1251.
  2. Li Z, et al. Design, synthesis, and biological evaluation of deuterated phenylpropionic acid derivatives as potent and long-acting free fatty acid receptor 1 agonists. Bioorganic Chemistry. 2018, 76: 303-313.

Customer Intellectual Property Protection

BOC Sciences has always regarded intellectual property as the most valuable asset of the company and its customers. We have signed non-disclosure agreements with customers and employees before the project starts, and provide synthetic route design and synthesis services in strict accordance with the terms of the non-disclosure agreement, striving to provide customers with target compounds in the shortest time possible.

About DCL™ Platform

BOC Sciences' DCL™ platform provides a deuterium strategy for both high-end custom markets and basic product needs. Our main business areas cover drug development, omics analysis, scientific research testing, and other markets, and strive to promote the development of biomedicine and scientific research.

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