Momelotinib, an oral JAK1/2 inhibitor for myelofibrosis, is going to GSK as part of a $1.9 billion acquisition of Sierra Oncology. Anyone that’s ever worked on a kinase program probably looked at this structure and raised their eyebrows. $1.9 billion for another JAK2 inhibitor? It’s probably not super selective either, you might think… and [...]

A fat-tissue-targeting clinical candidate, a first-in-class Ph. III molecule that inhibits its target by covalently modifying the target’s substrate, and a fourth-generation glucokinase activator are some examples in Drug Hunter’s May 2022 edition of Molecules of the Month. In this month’s slide deck, you’ll find a molecule that had mitigated QTc prolongation over a prior molecule while hERG inhibition stayed constant, why reversible MAGL inhibition is being pursued, and much more, including: Industry context behind the molecules, target, and clinical applications

Biological rationale for dru...

It was great to see over 100 drug hunters at our first drug discovery webinar! You can find the video and slides at the bottom of this page. The scope of this talk grew to be a bit massive as we were planning it, so we decided to split it into two parts. This first part covered: Interesting tidbits from 2022 Q1's drug approvals Cool facets [...]

What were the billion-dollar small molecules in 2021? This article and infographic, which is part 3 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 small molecule The lead molecules in each acquisition and their [...]

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 [...]

This page contains Drug Hunter's practical PK calculators useful for day-to-day drug discovery, including a PK unit converter such as for uM to ng/mL unit conversion, an animal study requirement calculator for how much material to synthesize in preparation for animal studies, and a simple human equivalent dose estimator . Who doesn't find [...]

This article and infographic highlights the drug discovery biotech acquisitions of 2021 where the upfront payment was disclosed, along with the structures of lead molecules in each acquisition where disclosed, mechanism of action, development stage, and indication. You can find Part I here [...]

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 [...]

PRN1008 (rilzabrutinib, Sanofi) is an oral, reversible covalent Bruton’s tyrosine kinase (BTK) inhibitor in a Ph. III trial for immune thrombocytopenia. A simultaneously published inhibitor, PRN473, is in development as a topical treatment for atopic dermatitis. Following target discovery in 1993, and subsequent approval of the first [...]

INE963 (Novartis Institute for Tropical Diseases) is an oral, single dose, fast-acting blood-stage antimalarial candidate . The molecule was identified using a phenotypic high-throughput screening approach which has been successfully used to identify new antimalarial chemotypes . Phenotypic screens can be preferable to target-based [...]

MK-1454 (Merck) is an intratumoral stimulator of interferon (IFN) genes (STING) agonist that is being developed for treatment of advanced solid tumors and lymphomas. The molecule follows Aduro’s ADU-S100 , which was terminated after Ph. II due to a lack of substantial activity. Another chemotype of STING agonist, Eisai’s E7766 , has [...]

Context. “ Compound 24” (Amgen) is a kinesin-like protein 18A (KIF18A) inhibitor being developed for a subset of cancers with chromosomally unstable tumor cells . Their first-in-class, oral clinical candidate, AMG 650, was recently disclosed at ACS Spring 2022 and is in Ph. I for cancer. Both antimitotic drugs targeting microtubules and those [...]

“Compound 10” (AstraZeneca) is an oral CDK5-mediated PPARγ phosphorylation inhibitor and partial PPARγ agonist being developed as an antidiabetic drug . Although widely used PPARγ agonists such as rosiglitazone and pioglitazone are effective antidiabetics, they are limited by [...]

Context. Etavopivat (Forma Therapeutics) is an oral erythrocyte pyruvate kinase activator being developed for sickle cell disease and other hemoglobinopathies , previously reported in 2019 . Hydroxyurea had been the only approved drug for sickle cell disease until the “sickle cell drug boon” began in 2017 starting with approval of l-glutamine [...]

Context. BMS-986176/LX-9211 (BMS) is an oral, CNS-penetrable AAK1 kinase inhibitor being developed for treatment of neuropathic pain . There are six main classes of pain medications, NSAIDs, opioids, ion channel modulators, serotonergic, monoaminergic, and GABAnergic drugs that are broadly used for pain in general, but neuropathic pain due to [...]

Context. Branaplam (Novartis Institutes for Biomedical Research) is an oral brain-penetrant splicing modulator, originally developed as a small molecule splicing modulator for spinal muscular atrophy (SMA). It turns out to also lower huntingtin levels and is being developed (with Fast Track Designation ) for patients with Huntington’s Disease [...]

Context. MAK683 is an oral, allosteric and selective PRC2 inhibitor intended for PRC2-dependent cancers . PRC2 is an essential epigenetic regulator of gene expression and enhanced or diminished PRC2 function have been implicated in a number of cancers . Enhancer of zeste homolog 2 (EZH2), one of the four core components of PRC2 that directly [...]