Optimizing lead compounds to have drug candidate-like qualities is time-consuming and expensive. Oftentimes, critical drug discovery project questions, such as on-target pharmacology or toxicology, can be answered more efficiently with compounds that are "good enough," saving teams time and further resource investment. This article discusses [...]

There’s so many interesting new publications that don’t necessarily feature key molecules, but are helpful for drug hunters to know about. Here are some other interesting reviews, technology, and targets to watch from April and May: April 2022 Best Practices : Understanding PK-PD for Protein Degraders: A Review . Derek Bartlett and Adam [...]

Target-driven drug discovery evolves over time and is influenced by understanding of disease biology, technical innovation, and most of all, clinical data. Our new series reviews drug targets with significant recent clinical data or industry events that have influenced or changed recent perceptions of them. Here we look at 10 targeted agents [...]

In this article, we highlight the importance of p K a values in medicinal chemistry and drug discovery and provide a reference poster of p K a values of common amines’ conjugate bases. Since amines are often a part of marketed drugs, knowledge of their p K a s can provide guidance in the selection of basic moieties to match the desired [...]

In June 2022, the FDA approved vutrisiran (Amvuttra), a small interfering RNA (siRNA) for polyneuropathy of hereditary transthyretin-mediated (ATTR) amyloidosis in adults. This deep dive explores the drug in more detail, including the industry context, the clinical data, the target rationale, the mechanism of action, and the drug’s origins [...]

In the early 90’s, Wayne (Haifeng) Tang and Ray Zhao formed a friendship in high school in China. They were both stellar students in chemistry, and each was one of the country’s fraction of a percent to ace the notoriously difficult college entrance exams to land in China’s best universities. Wayne moved to the University of Science and [...]

We reviewed all of the biotech mergers and acquisitions in 2021 and did a deep dive on the list of biotech M&A transactions focused on drug discovery. In this series, we provide a high level overview of: The drug discovery biotech acquisitions by total consideration in 2021 The lead molecules in each acquisition and their structural [...]

A first-in-class intravenous kappa opioid receptor (KOR) agonist, an oral soluble guanylate cyclase (sGC) stimulator, a first-in-class subcutaneous complement C3 inhibitor, and an oral contraceptive comprising a synthetic progesterone (drospirenone) and a plant-based estrogen (estetrol) make up the final group of novel drugs from 2021 that we [...]

An oral, brain penetrant EGFR mutant inhibitor with exquisite selectivity, a drug that was originally developed from a brain cholesterol metabolite, and a muscarinic antagonist and β2 agonist that was developed using soft drug design are some examples of this month's MOTM. In the slide deck, you'll also find a drug utilizing an N-oxide motif and a drug optimized to overcome aldehyde oxidase metabolism. Check out the ten molecule minireviews in the slide deck which covers: Where are all of the Molecules of the Month in clinical development?

What's known about differentiation from previous mole...

This deep dive into 2021’s first-in-class large molecule drug approvals is the third in a series of focus articles on 2021’s novel large molecule drugs. See part one here , and part two here . For each of the 11 first-in-class large molecule drug approvals of 2021 (excluding vaccines), we’ll explore in more detail: how they work (MoA) key [...]

with Julien Lefranc We asked one of our reviewers, Julien Lefranc , about what inspires and excites him about drug discovery. Here, he tells us about an unexpected, moving connection with a cancer patient, and what drives him to work every day. About Julien Julien is a Principal Scientist at Merck KGaA in Darmstadt and is a member of the [...]

Context. Pevonedistat (Takeda) is a first-in-class intravenous or subcutaneous NEDD8-activating enzyme (NAE) inhibitor being developed for leukemia and advanced solid tumors. NAE is a pivotal regulator of the NEDD8 conjugation pathway which regulates the activity of the Cullin-RING ligases (CRLs), key proteins involved in the [...]

Context. “Compound 20” (Gedeon Richter) is an oral α5-GABA A receptor negative allosteric modulator (NAM) being developed for cognitive disorders . GABA receptor NAMs are known to exert effects opposite to the anxiolytic and anticonvulsant effects of positive allosteric modulators. However, NAM agents targeting α5-GABA A receptors, which have [...]

NVP-CLR457 (Novartis Institutes for BioMedical Research) is an oral, non-CNS-penetrating pan-class IA phosphoinositide 3-kinase (PI3K) inhibitor . Due to the key involvement of PI3K in the famed PI3K-Akt−mTOR pathway, whose deregulation has been observed in several cancers , it is no surprise that the last decade has seen over 600 [...]

Context. S udapyridine (WuXi AppTec) is an oral mycobacterial ATP synthase inhibitor being developed for tuberculosis (TB) . Despite the significant success achieved with the discovery of antibiotic drugs in the last several decades, drug resistance, particularly related to agents targeting organisms such as M. tuberculosis , remains a [...]

Context. TXA6101 (TAXIS Pharmaceuticals) is a filamentous temperature-sensitive mutant Z (FtsZ) protein inhibitor being developed for targeting gram-negative bacteria. Drug resistance continues to be a paramount challenge in antibiotic therapy and there is an ongoing need to explore and develop novel antibacterial drugs. FtsZ has long been [...]

Context. RLX-33 (Research Triangle Institute) is a nonpeptide relaxin-3/RXFP3 system antagonist . Evidence over the last 2 decades, since the discovery of relaxin‐3 in 2001 , suggests that the protein, through its receptor RXFP3, regulates responses to stress, anxiety-related and motivated behaviors, circadian rhythms, learning and memory [...]

Context. INCB13739 (Incyte) is an oral 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) antagonist . Inhibition of the tissue-specific generation of cortisol using agents that antagonize 11β-HSD1, the key metabolic enzyme involved in the conversion of inactive glucocorticoids to active ones, has been considered a desirable therapeutic strategy [...]