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…
Molecules of the Month – October 2022
Ten of the most interesting and instructive small molecule case studies that appeared in the literature in Oct. 2022 are shown below. Learn more about the molecules by navigating to the full reviews on the right which cover: why the molecules matter, how they were discovered, the key steps behind optimization, how the drugs work,…
Why Did Bristol Myers Squibb (BMS) Pay $4.1 Billion for Turning Point Therapeutics?
Turning Point Therapeutics ($TPTX) was recently acquired by BMS for a whopping $4.1 billion in cash. Turning Point’s most advanced molecule is repotrectinib, a potential best-in-class ROS1/TRK/ALK tyrosine kinase inhibitor in Ph. I/II studies for cancer. This article explores the science behind repotrectinib, one of our 2021 Molecules of the Month, what properties make it…
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…
Small Molecule PI3K Inhibition in Oncology: What’s Been Done and What’s to Come?
PI3 kinases are part of the PI3K/Akt/mTOR signaling pathway that is downstream of Receptor Tyrosine Kinases (RTKs), G-protein-coupled receptors (GPCR), and GTPases such as KRAS. Since their identification in the 1980s, and due to their central role in cancer, the therapeutic targeting of the phosphatidylinositol-3-kinase (PI3K), and more generally, the PI3K/Akt/mTOR axis has been an…
Small Molecules from AI/ML-Focused Companies Entering the Clinic (Part II)
Despite significant investment over the past decade, only a handful of companies are now bringing clinical candidates discovered with the assistance of AI/ML forward. Though there’s a looseness to what should count as an “AI-discovered drug,” here we highlight internally-generated drug programs from companies focused on leveraging AI/ML in drug discovery, who have explicitly stated…