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  Not Your Grandparents’ Drugs: How Approved Drugs Have Evolved Since the 70’s

  We recently explored how the lipophilicity (logP) of drugs has changed over time and found that, on average, drugs have become more lipophilic through the decades, primarily attributable to the industry’s move away from natural products. Despite this shift, it is clear from a broad qualitative comparison of structures from past decades to today that…

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  AI for All? How Pharma Partnerships Improve Software Solutions

  Artificial Intelligence (AI) is revolutionizing data processing, with applications to drug discovery ranging from automating cellular imaging to modeling protein folding. Although numerous startups are developing methods to apply AI-driven drug discovery to develop proprietary assets, a remaining challenge is making these powerful tools usable by drug discovery companies without deep in-house AI/ML expertise. Many…

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  The Molecular Glue Degrader Landscape in 2022

  Since the 2014 discoveries that thalidomide-like compounds “glue” together the cereblon (CRBN) unit of the ubiquitin E3 ligase complex and certain immune cell transcription factors, molecular glue degraders have been caught up in the targeted protein degradation zeitgeist that catapulted PROTACs, their bulkier bivalent counterparts, to the forefront of drug hunters’ attention. Interest in molecular…

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  Billion-Dollar Biotransformations: On the Metabolism of Ozanimod

  Today, ozanimod is a likely megablockbuster drug approved for ulcerative colitis and multiple sclerosis. But before it became the first S1P modulator approved in ulcerative colitis, it received a scary, headline-making “Refuse to File” letter from the FDA due to insufficient preclinical characterization of an active metabolite RP112273 (CC112273). Addressing the refusal to file letter…

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  Are Drugs Becoming More Lipophilic Over Time?

  Drug lipophilicity is a core property that contributes to drug solubility, permeability, metabolic disposition, and other key properties. Increasing lipophilicity can often lead to increased affinity in relevant biological assays due to the hydrophobic nature of many protein binding pockets,  but this may also increase promiscuity to off-targets. High drug lipophilicity can lead to  challenges…

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  Synthetic Access to Stable Atropisomers in Drug Discovery via Catalysis

  Drug candidates exhibiting atropisomerism are often considered challenging for development by pharmaceutical professionals from synthetic and regulatory perspectives. Molecules that exist as stable atropisomers can be acceptable for development, but are often difficult to synthesize in their isomerically pure form. Modern catalysis, chromatographic separation, and crystallographic resolution methods have made atropisomeric drugs more accessible on…