Unmet Need
Globally, in 2021, there were approximately 537 million cases of diabetes which resulted in about 6.7 million deaths and $966 billion of healthcare expenditure (IDF). About 95% of diabetes cases are type 2 diabetes (T2D), which is characterized by either impaired insulin production or insulin resistance, and primarily occurs in adults. There are numerous current therapeutic strategies for diabetes management, including biguanides, sulfonylureas, SGLT2 inhibitors, DPP-4 inhibitors incretin mimetics, and others. These drugs have different mechanisms of action which can be leveraged clinically in combination therapies (ADA). However, despite this, diabetes remains a leading cause of morbidity, mortality, and healthcare expenditure world-wide. Therefore, there is a strong need to develop new therapeutics, with novel mechanisms of action, that lower blood glucose levels and help reduce the disease burden of T2D.
Technology Overview
Johns Hopkins and Lieber Institute researchers have developed Inositol Hexakisphosphate Kinase (IP6K) inhibitors for the treatment of T2D. Work done in the lab of Dr. Solomon Snyder at Johns Hopkins and by others, has linked IP6K to insulin signaling, fat accumulation, glucose regulation, and other metabolic processes important to the pathogenesis of diabetes.1 Inhibition of IP6Ks has emerged as a novel pathway that can be targeted to protect against T2D. The compounds developed here by researchers at the Lieber Institute are a novel class of IP6K inhibitors that exhibit excellent potency and selectivity, and have a promising pharmacokinetic profile.
Stage of Development:
Pre-clinical at lead selection stage.
Publication:
Liao G, Ye W, Heitmann T, Ernst G, DePasquale M, Xu L, Wormald M, Hu X, Ferrer M, Harmel RK, Fiedler D, Barrow J, Wei H. Identification of Small-Molecule Inhibitors of Human Inositol Hexakisphosphate Kinases by High-Throughput Screening. ACS Pharmacol Transl Sci. 2021 Mar 3;4(2):780-789. doi: 10.1021/acsptsci.0c00218. PMID: 33860201; PMCID: PMC8033760.
