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The Evolution of SGLT2 Inhibitors: From Apple Tree Bark to Clinical Impacts Beyond Glycemic Control

Inhibition of SGLT2 with small molecules has emerged as one of the most successful strategies to date managing T2DM. Beyond glycemic control, SGLT2 inhibitors have demonstrated unexpected and transformative benefits in cardiovascular and renal diseases, among others. In this review, we explore the therapeutic hypothesis behind SGLT2 inhibition, the natural product origins of the drug class, key efficacy findings across large clinical trials, and…Read Article

Classics in Drug Discovery: A History of the Statins

13 years after the loss of patent exclusivity, atorvastatin (Lipitor®) remains the highest grossing small molecule in pharmaceutical history, redefining what a “blockbuster” drug can be. However, this commercial success was just the dramatic exclamation point to the statin story that encompassed Nobel prizes, blockbuster drugs, and 30+ years of target biology inquiry and drug discovery. This review will highlight the history of, and challenges a…Read Article

Two Divergent Approaches to Drugging IRF5

Targeting transcription factors for therapeutic intervention is a challenge in small molecule drug discovery. However excitement around IRF5, a key immune system regulator that is implicated in lupus and rheumatoid arthritis, has inspired renewed effort. This review highlights how two companies, HotSpot Therapeutics and Kymera Therapeutics, are tackling IRF5 with distinct strategies. Both approaches show promise by reducing inflammation and dise…Read Article

Simplifying Synthesis with Radical Cross-Coupling

In this Flash Talk, Phil Baran presents novel synthetic methodologies that harness the reactivity of radical intermediates to unlock more efficient and previously inaccessible synthetic routes. In this article, Phil provides answers to all questions from the seminar, including those that couldn’t be addressed during the live session. Phil highlights how his group rapidly constructs highly valuable, complex saturated heterocycles and discussed th…Read Article

Targeting 17β-HSD13: Emerging Patent Landscape in Fibrosis and NASH

17β-HSD13 is a member of a 15-enzyme family involved in the metabolism of steroid hormones, fatty acids, cholesterol, and bile acids. It is a promising target for NAFLD and NASH, supported by GWAS data showing that loss-of-function variants reduce liver enzyme levels and disease risk. Clinical validation came from Arrowhead’s ARO-HSD, an siRNA that lowered serum ALT. While the full function of 17β-HSD13 remains unclear, it acts on lipid substrat…Read Article

STAT6: A Challenging Target Gains Traction Utilizing Degraders for Th2-Driven Disease

STAT6, once deemed undruggable, is now being targeted through protein degradation. This article highlights recent developments including Kymera’s KT‑621, a cereblon-based STAT6 degrader, that entered Ph. 1 and has shown >95% knockdown of STAT6 as well as Th2 biomarker suppression. It also surfaces preclinical programs from Nurix and the University of Michigan. STAT6 degradation marks a shift in targeting transcription factors for immune and canc…Ann Arbor · Ann Arbor Read Article

Do LRRK2 Heterobifunctional Degraders Mitigate “On-Target” Toxicity?

LRRK2 kinase inhibitors promised to revolutionize Parkinson’s disease therapy—until preclinical lung toxicity, believed to be on-target, halted their progress. Heterobifunctional degraders now offer a fresh approach. By fully degrading the LRRK2 protein these molecules demonstrate enhanced efficacy. Additionally, initial results show the potential avoidance of the lung fibrosis seen with kinase inhibitors. This review provides a brief history of…Read Article

RNA-Targeting Splice Modulators Target Difficult to Treat CNS Disorders

Once thought undruggable, RNA is now fair game for small molecules. Since the approval of Risdiplam, the first FDA-approved RNA-targeting small molecule, there has been a wave of small molecule splice modulators in preclinical and clinical development. These small molecules act upstream of translation, modulating gene expression via RNA, with the potential to treat repeat expansion and splicing-driven diseases. This review focuses on diseases of…Read Article

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The Evolution of SGLT2 Inhibitors: From Apple Tree Bark to Clinical Impacts Beyond Glycemic Control

Classics in Drug Discovery: A History of the Statins

Two Divergent Approaches to Drugging IRF5

Simplifying Synthesis with Radical Cross-Coupling

Targeting 17β-HSD13: Emerging Patent Landscape in Fibrosis and NASH

STAT6: A Challenging Target Gains Traction Utilizing Degraders for Th2-Driven Disease

Do LRRK2 Heterobifunctional Degraders Mitigate “On-Target” Toxicity?

RNA-Targeting Splice Modulators Target Difficult to Treat CNS Disorders

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The Evolution of SGLT2 Inhibitors: From Apple Tree Bark to Clinical Impacts Beyond Glycemic Control

Classics in Drug Discovery: A History of the Statins

Two Divergent Approaches to Drugging IRF5

Simplifying Synthesis with Radical Cross-Coupling

Targeting 17β-HSD13: Emerging Patent Landscape in Fibrosis and NASH

STAT6: A Challenging Target Gains Traction Utilizing Degraders for Th2-Driven Disease

Do LRRK2 Heterobifunctional Degraders Mitigate “On-Target” Toxicity?

RNA-Targeting Splice Modulators Target Difficult to Treat CNS Disorders