DILI is a leading cause of acute liver failure, accounting for half of these cases and often resulting in drug withdrawals. Understanding and managing DILI risk as a medicinal chemist involves exploring the intricate interplay among properties and structural features. In this article, we provide a medicinal chemist's perspective on the current understanding of DILI mechanisms, highlight cutting-edge assay developments for a holistic assessment, and discuss strategies for predicting DILI risks.

Drug Hunter has sifted through news articles, press releases, financial disclosures, SEC filings, and more to bring you a roundup of 2023’s biggest mergers and acquisitions (M&A) in the drug discovery world. Following our open-access industry overview, in the final installment of this four-part series we bring you the biologics-focused deals opening checkbooks in 2023.

Drug Hunter has sifted through news articles, press releases, financial disclosures, SEC filings, and more to bring you a roundup of 2023’s biggest mergers and acquisitions (M&A) in the drug discovery world. In part 3 of this 4-part series, we bring you the top-ranked small molecule-focused deals by value. Covering a range of targets and modalities, this article gives Drug Hunter members in-depth background and analysis of the hottest science opening checkbooks in 2023.

Drug Hunter has sifted through news articles, press releases, financial disclosures, SEC filings, and more to bring you a roundup of 2023’s biggest mergers and acquisitions (M&A) in the drug discovery world. Following our open-access industry overview, in part 2 of this 4-part series we bring you the small molecule-focused deals, ranked 11-20 by value. Covering a range of targets and modalities, this article gives Drug Hunter members in-depth background and analysis of the hottest science opening checkbooks in 2023.

Drug Hunter has sifted through news articles, press releases, financial disclosures, SEC filings and more to bring you a roundup of 2023's biggest mergers and acquisitions (M&A) in the drug discovery world. In this 4-part series we will give you an open-access overview of the M&A landscape, and then for Drug Hunter members in the coming weeks, we will be providing in-depth coverage and analysis of the small molecule-focused (parts 2 & 3) and biologics-based deals (part 4). This premium content includes background on the targets, chemical/biological matter and clinical data driving these deals.

In the aftermath of the thalidomide tragedy, the FDA advised excluding females in the childbearing age from early-stage clinical trials. However, this policy resulted in the prolonged underrepresentation of women in clinical research, limiting knowledge about how drugs affect genders differently. Recent policy changes, including the NIH's emphasis on considering sex as a biological variable, aim to reduce these disparities by promoting more diverse clinical trial participation. This article explores the current landscape of endometriosis therapies and how it relates to women’s healthcare.

There has been substantial interest in the development of screening methods capable of surveying a wider sample of chemical space and larger numbers of compounds. Over the past two decades, DEL technology has evolved into a broadly utilized and validated platform in drug discovery, yielding diverse hits for a wide range of biologically relevant targets. Read the full review for a historical and technical overview of DEL technology, including how libraries are prepared and screened, a comparison to other HTS methods, and examples of successful applications in drug discovery.

PRMT5 is an epigenetic “synthetic lethality” target that has attracted much attention among drug hunters. The first generation of PRMT5 inhibitors was limited by systemic toxicities resulting in a cooling of industry interest, until the recent identification of tumor-specific inhibitors. These second-generation compounds target the MTA:PRMT5 complex in MTAP-deleted cancers—15% of all tumors—leading to a revival of the target. Read on to find out which companies are prevailing in the search for a first-in-class PRMT5 inhibitor and how their clinical compounds differentiate.

Peptidic GLP-1R agonists have received significant media coverage over the past year for their astounding efficacy in several indications. While most of the recent fanfare has been related to their role in weight loss, GLP-1R agonists have been a mainstay of the type 2 diabetes treatment landscape for the past 2 decades. GLP-1R agonists have also recently shown efficacy in reducing heart disease risk and treating certain chronic kidney diseases. Here’s a recap of the March 14th, 2024, Flash Talk, from Oliver Philps.

If you are as excited as we are about this new era of non-opioid pain management and want to learn more, explore our series of articles that unravel the fascinating history of target validation of voltage-gated sodium channels, showcase the breakthroughs achieved so far, and look forward to what lies ahead for the industry.

The discovery that individuals with null mutations in the NaV1.7 exhibited pain insensitivity sparked interest in targeting NaV1.7 to potentially treat pain. Despite the potential of selectively inhibiting sodium channels like NaV1.7, NaV1.8, and NaV1.9 for pain management, developing selective inhibitors suitable for clinical use has proven challenging. This article complements our coverage of VX-548, NaV1.8 as a critical target in pain management, and our NaV1.8 compound roundup and provides a reminder of noteworthy preclinical and clinical NaV1.7 small molecule inhibitors as of April 2024.

NaV1.8, a member of the voltage-gated sodium channel (NaV) family, is predominantly expressed in peripheral sensory neurons. Based on rodent NaV1.8 knockout and knockdown studies and a 2012 report of gain-of-function mutations in humans, NaV1.8 has been linked to nociceptive, inflammatory, and neuropathic pain, including chronic neuropathic pain. This compound roundup provides a historical recap of both preclinical and clinical NaV1.8 inhibitors that shaped the landscape for the new era of pain management we are witnessing today.

NaV1.8 has become an industry focal point in the pursuit of pain therapeutics thanks to the success of Vertex’s selective inhibitor, VX-548, in Ph. III clinical trials for acute pain and Ph. II results in diabetic peripheral neuropathy. Unlike opioid receptor modulation, NaV1.8 inhibition does not carry the same addiction risks in part due to its lack of expression in the brain. Following our recent review of the leading NaV1.8 inhibitor VX-548, this article provides more details on the history of target validation for NaV1.8 in pain and why this could be the new frontier for pain management.

While KRAS(G12C) has been the most readily targeted form of KRAS thanks to its reactive cysteine residue, other mutations such as KRAS(G12D) make up the majority of KRAS-mutated cancers. In this roundup, we highlight 12 inhibitors, degraders, and other molecules that reflect progress in overcoming this challenge, including some of the first clinical candidates targeting non-KRAS(G12C)-mutant tumors, and why these molecules are notable.

The educational and professional resources on Drug Hunter are meant to help you with your job on a regular basis. Here are the ten most popular resource pages on Drug Hunter in 2023 - if you haven’t found and used these already, check them out!

The team reviews hundreds of compounds from thousands of papers, press releases, and other sources each month to select candidates for Molecules of the Month. Here we have compiled a table of >70 additional molecules that were of interest in November 2023 along with some highlights from some of our favorites below.

Several multi-million dollar acquisitions or license agreements took place in November 2023 for hot drug targets, with assets from selective PARP1 inhibitors to GLP1R agonists, and others. This recent news roundup highlights the notable acquisitions by pharma companies for rights to molecules in a range of different indications, with illustrative patent examples for undisclosed structures.

Whereas covalent drugs were once considered risky for indications other than cancer due to the potential for idiosyncratic drug-induced liver injury and other toxicities, concerns appear to have softened as an increasing number of non-oncology covalent inhibitor programs have achieved successful outcomes. Here we highlight several recent anecdotes in covalent inhibitor drug discovery that seem to reflect these changing attitudes, including billion-dollar acquisitions and approvals outside oncology, and a few modern examples that showcase the increasingly rich science in this area.

The team reviews hundreds of compounds from thousands of papers, press releases, and other sources each month to select candidates for Molecules of the Month. Here we have compiled a table of >70 additional molecules that were of interest in October 2023 but we did not have space for in MOTM. A few highlights are also discussed, including Novartis’s Werner helicase (WRN) inhibitor, APJ agonist AMG985 molecular glue degrader golcadomide, and more in the full article.

The Hippo pathway is a well-known regulator of tissue growth and organ size and gets its name from the Hippo kinase (Hpo in Drosophila, MST1/2 in humans), which when mutated leads to “hippopotamus”-like tissue overgrowth. Recently, industry interest in the pathway has increased thanks to several independent studies in 2023, and the field appears to be at an important inflection point for drug discovery. Here we review current efforts and therapeutic hypotheses for drugging the TEAD transcription factors in cancer, including clinical molecules, paralog-selective molecules, and TEAD degraders.

Peptidic GLP-1R agonists have received significant media coverage over the past year for their astounding efficacy in several indications. GLP-1R agonists now appear to be efficacious in reducing heart disease risk and in treating certain chronic kidney diseases, expanding their likely future use. This review by Oliver Philps provides an overview of GLP-1 agonists and where they fit in the treatment of diabetes, how the peptide drugs evolved over time to today’s weight loss medications, and what to expect next...

There continue to be opportunities for another KRAS(G12C) inhibitor to prove itself best-in-class.

This roundup highlights twelve KRAS(G12C) molecules to know, with links to recent case studies on Drug Hunter going in more detail.

The team reviews hundreds of compounds from thousands of papers, press releases, and other sources each month to select candidates for Molecules of the Month. Based on requests from readers to see more molecules, this article contains a table of >40 additional molecules that were of interest last month but not included in MOTM, with a few highlights including off-target toxicity seen in a KRAS(G12D) program and hits on challenging target classes.

In Wednesday’s Flash Talk webinar, we covered recent highlights in covalent drug discovery, with lots of great questions from the audience. The webinar and recording are available below to everyone thanks to our sponsor, Revvity Signals, and the slides are available for download to Premium members at the bottom.

Understanding how a small molecule ligand binds to its target is valuable in drug discovery, because it enables more efficient optimization through structure-based design, better mechanistic understanding of molecular pharmacology, and greater confidence in the therapeutic hypothesis from both safety and efficacy perspectives. Recently, Drug Hunter highlighted methods for target identification when the target is unknown.

Obtaining adequate drug exposure in the brain is key to treating CNS diseases effectively. Recently, Dennis Koester gave us a crash course in CNS drug discovery in a Drug Hunter Flash Talk. Here, he sums up some key points on how to find compounds that cross the blood-brain barrier.

The First Disclosures sessions at the 2023 ACS Fall Meeting in San Francisco, organized by Nikki Goodwin, presented a variety of new orally available small molecules. The standing room-only sessions were so highly attended that many attendees were unfortunately kicked out due to the fire code.

Targeted Protein Degradation (TPD) allows for elimination, rather than inhibition, of proteins by exploiting cells’ own protein clearance mechanisms. While traditional inhibitors can be very effective at preventing a protein from undertaking a particular function, blocking protein activity...

Macrocyclic molecules, containing 12 or more atoms in a ring system, are increasingly prevalent in drug discovery, with over 67 macrocyclic drugs approved so far and several notable examples of clinical success highlighted on Drug Hunter recently, including MK-0616 , repotrectinib , and pacritinib . By imparting conformational restraint and [...]

Here’s a common scenario - your team has just completed a phenotypic screening campaign, cleaned out the false positives through hit triage , and now you have modestly optimized validated leads with cell-based activity. The problem is, you have no idea how your compounds work, and whether they act on a target or set of targets that are worth [...]

The AACR 2023 first disclosures presented in the Chemistry in Cancer Research’s “New Drugs on the Horizon” sessions are always fascinating. This article contains the structures of all of the novel small molecule first disclosures presented at AACR in the session, along with notes on their significance, and another molecule disclosed in the [...]

Merck’s oral PCSK9 inhibitor is a surprisingly bioavailable and orally effective macrocyclic peptide with picomolar activity. It recently demonstrated significant LDL cholesterol reduction in Ph. IIb, paving the way for it to enter Ph. III later this year. Roche’s oral, SMN2-directed RNA splicing modifier and first molecule of its kind to be [...]

The First Disclosures section of the 2023 ACS Spring Meeting in Indianapolis, organized by GSK’s Nikki Goodwin , covers three novel small molecules and an ADC this year. The molecules include: MK-0616, Merck’s macrocyclic oral PCSK9 inhibitor (presented by Abbas Walji ) NX-2127, Nurix’s oral BTK degrader (presented by Jeff Wu ) BI 1015550 [...]

In 2022 there were 36 novel small molecule and large molecule drugs approved by the FDA, including 18 first-in-class drug approvals. This page contains posters and reviews of the science behind each molecule including the: 19 small molecule drug approvals (excluding atoms) 17 large molecule drug approvals (click to jump to poster) 9 first in [...]

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 [...]

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 [...]

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 [...]

There have been numerous reviews on the impact of AI/ML in drug discovery looking at broad numbers, but with the volume of companies in the space, few have spelled out exactly what these companies are working on to paint a picture of what the landscape of AI/ML in small molecule drug discovery actually looks like today. We concluded 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 [...]

In a recent webinar , we surveyed our audience and were surprised to see that a significant majority of attendees thought the application of artificial intelligence and machine learning (AI/ML) methods was the most exciting area for drug discovery, beyond even degraders or molecular glues. Machine learning methods have been increasingly [...]

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 [...]

We did a deep dive into the pharmaceutical industry’s 2022Q2/Q3 news, and there’s a ton of exciting updates to share. In this review, we highlight some emerging companies, technologies, and drug discovery modalities we thought drug hunters would find interesting, including: New strategies for covalent protein modification Different methods [...]

Our team conducted a review of all  the biotech acquisitions of 2021 and distilled it down to the acquisitions of drug discovery-focused biotechs. Navigate the 2021 M&A Series the top overall drug discovery M&A transactions by value (Part 1) the transactions with disclosed upfront payments (Part 2) the most valuable small molecule [...]

This article is Part VI of a review series covering all the initial public offerings for the biotech and pharmaceutical industries in 2021. Pt. I and Pt. II provided an overview of 2021 IPOs by therapy area, technology, and therapeutic class. Pt. III and Pt. IV provided a deep dive into the 2021 IPOs for oncology-focused companies, while P.t [...]

This year’s EFMC-ISMC conference in Nice, France, had a fantastic collection of talks. Among the highlights were the two First Disclosure sections, where companies shared the structures of their latest clinical candidates for the first time. Many thanks to Dr. Julien Lefranc , one of our featured reviewers , for sharing his notes on these [...]

This article explains what Phase II drug metabolism is, contains a poster summarizing common enzyme-mediated bioconjugation reactions, and provides interesting examples of Phase II transformations and their impact on drug pharmacology. "As any biotransformation scientist will know, metabolism is not a binary function, and drugs can be cleared [...]

We're here at ACS Chicago 2022, covering sections of particular interest to drug discovery scientists. Among the highlights are the First Disclosures sections, where companies are sharing structures of clinical candidates for the first time. We'll go more in-depth into the science from the conference soon - for now, here's a high-level [...]

How a Follow-on Drug Can Create Value After a First-in-Class Drug Novel drugs can make a big impact in two main ways—by being first-in-class (FIC) or by being best-in-class (BIC). A novel drug that produces its therapeutic effect by interacting with a new target or that is used to treat a new condition is considered first-in-class (FIC) [...]

This article is Part 5 of a review series covering all the initial public offerings for the biotech and pharmaceutical industries in 2021. Part 1 and Part 2 provided an overview of 2021 IPOs by therapy area, technology, and therapeutic class. Part 3 and Part 4 provided a deep dive into the 2021 IPOs for oncology-focused companies developing [...]

This short article and poster summary takes a deeper look into the 2021 IPOs for biotechnology-based therapeutics being developed by oncology-focused companies, including: Antibody-drug conjugates Monoclonal antibodies Protein-based therapeutics Cell and gene therapies Other biotechnology-based therapeutics This article is Part 4 of a review [...]

This article is Part 3 of a review series covering all of the initial public offerings for the biotech and pharmaceutical industries in 2021. Part 1 provided an overview of 2021 IPOs by therapy area, technology, and therapeutic class. Part 2 provided an overview of 2021 IPOs by therapeutic area. This short article takes a deeper look into the [...]

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 [...]

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 [...]

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 [...]

Our team conducted a review of all of the biotech mergers and acquisitions of 2021 and distilled it down to the acquisitions of drug discovery-focused biotechs here. There were 10 acquisitions of companies with large molecule drug assets in 2021. Here is a more in-depth look into all of the lead large molecules acquired in 2021, including a [...]

There were 16 acquisitions of companies with small molecule drug assets in 2021 and one merger. Here is a more in-depth look into all of the lead small molecules acquired in 2021, including a review of: The lead molecules in each acquisition and their structural representations where disclosed The mechanism of action, stage, and indication of [...]

This article is Part 2 of a review series covering all of the initial public offerings for the biotech and pharmaceutical industries in 2021. Part 1(link to article) provided an overview of 2021 IPOs by therapy area, technology, and therapeutic class. This short article takes a deeper look into the 2021 IPOs by technology and therapeutic [...]

We did a comprehensive review of all the initial public offerings for the biotech and pharmaceutical industry in 2021. This article is Part 1 in a review series about companies focused on drug discovery that IPO’d during this time. You can find recent years’ IPOs summarized here: 2020 Small Molecule IPOs 2020 Large Molecule IPOs 2019 Small [...]

It’s best to be first, but drugs that are approved later with the same mechanism of action can also create significant value for patients and society by being best-in-class (BIC), or what clinicians refer to as “gold standard.” Recently we highlighted key factors that can make a follow-on drug be considered a best-in-class drug. This article [...]

In this highlight, Dr. Dennis C. Koester reviews treatment options for HIV and explains how small molecule long-acting injectables (LAIs) are offering significant promise in both HIV treatment and prophylaxis. A Coming Paradigm Shift for HIV Treatment and Prophylaxis By Dennis C. Koester The surge of the coronavirus pandemic has made our [...]

We did a comprehensive review of industry news in 2022Q1 (there was.. a lot of stuff to cover). In this article, we highlight some emerging companies, technologies, and drug discovery modalities we thought drug hunters would find interesting, including: New platform companies focused on drug discovery Different approaches to glues and [...]

In this minireview, Dr. Romyr Dominique introduces three key concepts in fragment-based drug discovery and shares his favorite articles and resources on fragment-based drug discovery. Fragment-based drug discovery has emerged as a key tool for acquiring starting points for challenging targets like KRAS. By Dr. Romyr Dominique What is FBDD, or [...]

We did a comprehensive review of industry news in 2022Q1 (there was.. a lot of stuff to cover). This article highlights companies focused on drug discovery that IPO’d in the first quarter. The Drug Discovery IPO Market Slowdown As everyone knows, biotech’s been in a bear market since Feb. 2021 (with the entire $XBI index down more than 50% [...]

In this minireview, Drs. Jayme L. Dahlin and Michael A. Walters summarize the different mechanisms by which molecules can be AICs (assay interference compounds), a subset of which can be flagged as PAINS (pan-assay interference compounds) by a popular set of substructure filters. They bin these into non-technology-related interference [...]

What were the billion-dollar large molecules in 2021? This article and infographic, which is part 4 of a Premium series covering 2021 drug discovery M&A, covers: The ten largest drug discovery biotech acquisitions by total consideration in 2021 where the acquiree’s lead was a large molecule The lead molecules in each acquisition and their [...]

In this article, Dr. Thuy Tran , a CMC Project Leader at Servier, gives us a quick explanation of what an IND is, what a clinical hold is, and why clinical holds happen for drug discovery scientists. What is an IND? Health authorities require drug developers to provide and justify safety and efficacy information for new treatments in humans [...]

We reviewed all of the biotech mergers and acquisitions announced in 2021 and did a deep dive on the list of biotech M&A transactions focused on drug discovery. The infographic below, which is part 1 of a Premium series covering 2021 drug discovery M&A, covers: The top ten overall small or large molecule drug acquisitions of 2021 The lead [...]

Small-molecule drug candidates are increasingly falling “ beyond the rule of 5 ,” making oral administration more challenging. Optimizing a drug’s solid form can improve its solubility and bioavailability when further molecular modifications are prohibitive. This minireview covers solid form strategies for increasing the solubility and oral [...]

The ACS first disclosures from ACS Spring 2022 MEDI section included six molecules, summarized below. Together with industry veteran Jesse Keicher , we put these molecules in context, exploring what makes each molecule interesting to drug hunters beyond what was shared at the conference. The first disclosures were: AMG 650, Amgen’s kinesin [...]

This article explains what Phase I drug metabolism is, contains a poster summarizing common enzyme-mediated drug metabolism reactions, and provides interesting examples of phase I biotransformations and their impact on drug pharmacology. By Drake Anthony Russell , reviewed by Dr. Dian Su and Dr. Julia Shanu-Wilson. Thanks to Hypha Discovery [...]

This high-level overview of 2021’s novel large molecule drug approvals is the 2 nd in a series of focus articles on 2021’s new drugs (see the small molecules here ). You can find our deep-dive on 2021's large molecule drug approvals here . There were: [...]

We’ll be reviewing 2021’s novel FDA drug approvals in a series of articles, starting with this high-level overview of the small molecule drugs approved by the FDA in 2021. You can find Part 2 on First-in-Class Small Molecules here and the 2021 Large Molecules series here . Our deep dive on Small Molecule Oncology Approvals is also live [...]

In Aug. 2021, immuno-oncology company, Trillium Therapeutics, was acquired by Pfizer for $2.3 billion , adding Trillium’s two CD47-targeting biologics, TTI-621 and TTI-622, to Pfizer’s oncology pipeline. The acquisition followed Gilead’s $4.9B buyout of Forty Seven in early 2020, after clinical data was presented on Forty Seven’s lead, the [...]

The first disclosures of new drug candidates are always the highlight of medicinal chemistry conferences. Six novel drug candidates were recently disclosed by European companies at the European Federation for Medicinal Chemistry International Symposium on Medicinal Chemistry (EFMC-ISMC) Conference in [...]

Recently, our team at Drug Hunter compiled the lead programs and mechanisms of small molecule and large molecule biotechs that IPO’d in 2020. We asked featured reviewers from our community what stood out to them about the science of this group of companies, and here are some highlights that emerged from the discussion. Any thoughts and [...]

Looking at the pipelines of recent biotech IPOs is a great way to get a snapshot of new technologies and approaches to drug discovery or to see what’s coming in smaller indications. Complementing our recent highlight of large molecule-focused companies, below is a summary of 2020’s class of biotech IPOs focused on small molecule drug [...]

Browsing through the pipelines of recent biotech IPOs is great way to catch up on emerging targets, novel drug modalities, and science at the edge of development. Unlike conferences and publications which tend to be a lagging indicator of what’s going on in industry (with many publications only being released years after a program has ceased [...]

While biologic drugs currently dominate in immunology by sales , small molecule immunomodulators (SMIMs) are making a comeback fueled by better understanding of intracellular signaling pathways and new hit finding technologies. SMIMs can be grouped into two categories: those that engage large molecule (LM) targets in a new [...]

On Jun. 23 rd at 11AM PST, Dewakar Sangaraju and Dennis Hu gave a PBSS/CLSA webinar titled “Highlights from 2020’s FDA New Drug Approvals,” organized by Cyrus Khojasteh and Shichang Miao . One interesting fact about each approved small molecule drug was shared, along with statistics and specific case studies from the cohort of interest to the [...]

There were 15 novel large molecule drugs approved in 2020, an increase over the 12 large molecule drugs approved in 2019 . Here’s a visual list of the FDA’s 2020 large molecule drug approvals , with more scientific details and references below. There is no significance to the order in which molecules are presented. This summary is intended [...]

Assume a cow is an evenly distributed sphere... sometimes. I happened to take an animal physiology course in college because my girlfriend (now wife) needed it for her biology major and taking a class together about bird metabolism was my idea of a nice date.  I had no idea it would end up being one of the most useful courses in my career [...]

It's hard not to think about infectious diseases at the moment, but it's a great time to review the drug discovery literature. One area of drug discovery that has deep roots in infectious disease research is targeted covalent inhibition. Targeted covalent inhibitors form covalent bonds with discrete targets (as opposed to [...]

Of the 2019 biotech IPOs on the major US exchanges, there were 24 companies focused on developing non-small molecule drugs, about the same number as those developing small molecule drugs . Here’s a list of the companies (by market cap at IPO) along with a short summary of the key concepts for each company's main programs. *International [...]

Of the 2019 biotech IPOs on the major US exchanges, 25 companies are focused on discovering and developing small molecule drugs. Here's a list of the companies (by market cap at IPO, top to bottom) along with the main mechanisms of action of the lead molecules and other publicly disclosed targets. The largest company by market cap. at the [...]

This post briefly introduces chimeric molecules and companies working on them, contains a list of 10 recent “hot” papers in this field, and some predictions for where chimeras might head. It’s Chinese New Year time, which means a significant part of the global biopharma supply chain has ground to a halt, due to our colleagues and suppliers in [...]

or, How I Learned to Stop Worrying and Love My Own Definition. Recently I posted on “biologic drugs” which were approved in 2019 . All was well in my little scientific universe, until I received this in an email: “You recently reported "14 novel biologic drugs," referring to 'novel' biopharmaceuticals approved CDER. But, … You also include [...]

2019 was another big year for novel drug approvals (48 in total) though it wasn't the record year of 2018 (with 59). The overall explosion in biologic drugs / non-small molecule modalities continued with year with 14 novel biologic drugs, including 3 monoclonal antibodies, a recombinant fusion protein (Reblozyl), 3 ADCs, an siRNA drug [...]

2019 was another big year for drug discovery, with 29 FDA novel drug approvals for small molecules (including istradefylline which was first approved in Japan, but not including brilliant blue G, fluorodopa F18, Ga-68-DOTATOC, bremelanotide, afamelanotide, and ferric maltol, which could all be considered small molecules by some definitions) [...]

You’ve probably lived this story before: you’re working on your favorite kinase, YFK1, and are looking for selective inhibitors over YFK2.  The problem is, they’re virtually identical near the active site, save for a single residue sitting in the back pocket that your amazing structural biologist has identified.  The team [...]

Having a clinical drug-induced liver injury (DILI) signal is a surefire way to kill a drug candidate in non-serious indications like pain or chronic indications like diabetes, and will even give oncologists second thoughts as cancer patients are living longer. What can we do to prevent it? Plan A: Small Pill and No Greaseb ombs A widely [...]

Protein-ligand interactions are driven predominantly by strong hydrogen-bonding interactions, de-solvation energetics, and other entropic considerations including ligand lipophilicity. However, the combination of many weaker interactions can contribute to potency, and are often necessary to obtain selectivity when targets and anti-targets [...]

With the biochemistry magic available to the liver, it's a wonder that anything we consume is well-tolerated. Even carboxylic acids are structural alerts as they can be converted to bioreactive acyl glucoronides. The best we can do as drug hunters is minimize the risk of toxic metabolite formation and apply assays appropriately to select [...]

The global cancer immunotherapy pipeline continues to explode with nearly double the number of active targets in 2019 vs. only two years ago, comprising 3,876(!!) active drugs, with a subset undergoing >5000 active clinical trials. In 2016, I listened to Dan Chen, former Global Head of Cancer Immunotherapy Development at Genentech, comment on [...]

Of the record 59 FDA drug approvals from 2018, the majority were small molecules (64%). Keep at it, chemists! :) Oncology and infectious diseases were the areas with most small molecule approvals, followed by genetic/rare diseases. Some more statistics below. Last year the FDA approved a record 59 novel drugs , which included 38 small [...]

Modern hit-finding technologies are incredible. Dean Brown and Jonas Bostrom at AstraZeneca have a very nice review out summarizing the hit-finding strategies for 66 clinical candidates published from 2016-2017. Some highlights include a clinical candidate from DNA-encoded libraries at GSK, the discovery of an RNA-binding drug candidate by [...]