UCP1 Activators Suppressing Adipocyte Inflammation for Next Generation Obesity Management

Background & Unmet Need

• Elevated adipose inflammation is a hallmark of obesity and is a key driver of insulin resistance, type 2 diabetes, and cardiovascular disease
• While GLP-1 receptor agonists have emerged as effective agents in promoting weight loss in obesity, patients demonstrate high discontinuation rates due to gastrointestinal side effects
• Moreover, these medications do not address the chronic inflammation and metabolic dysfunction that arise from adipose tissue remodeling in obesity
• Brown adipose tissue (BAT) is a key regulator of thermogenesis and metabolism in adults, not only elevating caloric dissipation but also exerting paracrine anti-inflammatory effects
• Uncoupling protein 1 (UCP1) plays a central role in promoting the browning of white adipocytes and presents a promising therapeutic target
• Unmet Need: Non-GLP-1 strategies for managing obesity and associated inflammatory comorbidities

Technology Overview

• The Technology: CDC1011, a small molecule HDAC inhibitor inducing UCP1, for promoting browning of white adipocytes in obesity-related metabolic disorders
• The Discovery: The inventors generated an in-house multicomponent reaction (MCR)-based chemical library (>21K compounds) and developed a proprietary high-throughput screening platform to identify UCP1 activators in human adipocytes
• Ten hit compounds were identified for further development, including lead compound CDC1011
• PoC Data: CDC1011 induces browning in pre- and mature white adipocytes, upregulating β3-adrenergic receptor (ADRB3), brown/beige markers, and mitochondrial electron transport chain subunits
• CDC1011’s functional effects include accelerated lipolysis, glucose uptake, metabolic flexibility, and a shift from proinflammatory to anti-inflammatory cytokine profiles

Technology Applications

• Management of obesity as a single agent or in combination with GLP-1 receptor agonists
• Management of insulin resistance and type 2 diabetes
• A next-generation metabolic solution for weight management in the general population

Technology Advantages

• Functions via a separate biological mechanism than GLP1 receptor agonists
• Addressees not only weight reduction but also biology underlying metabolic disorder and associated inflammatory comorbidities
• Reprograms white adipose tissue into metabolically active tissue

        Figure: Effect of CDC1011 on basal cAMP levels.