Drug Hunter
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Drug Hunter is for drug discovery scientists who want to discover new ideas but don't have time to read everything. Our goal is to provide an inclusive platform that empowers, educates, and connects professional drug hunters, and celebrates the important work being done by the heroes in our industry.
Drug Hunter
16h ago
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 ..read more
Drug Hunter
16h ago
ORIC-533, a potential best-in-class oral inhibitor of CD73 from ORIC Pharmaceuticals, is currently in a Ph. Ib trial for relapsed/refractory multiple myeloma (MM). It inhibits the CD73-mediated conversion of AMP to adenosine which generates an immunosuppressive tumor microenvironment and has the potential to be a next-generation immunotherapy. The in-depth use of X-ray structures led the team to discover a novel set of phosphonate bioisosteres which acheived bioavailability in a polar scaffold. The structure and discovery of ORIC-533 were recently disclosed at the ACS Spring 2024 Meeting ..read more
Drug Hunter
3d ago
In March, Crinetics Pharmaceuticals revealed their discovery of CRN04894, a first-in-class nonpeptide melanocortin type 2 receptor (MC2R) antagonist which is currently being evaluated in several Ph. II trials. Additional molecules to make the top ten include a preclinical, brain-penetrant casein kinase 1 delta (CK1δ) inhibitor and a WT-sparing phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PI3Kα) H1047R inhibitor. Galapagos SASU and AbbVie disclosed the discovery story of their orally bioavailable cystic fibrosis transmembrane conductance regulator (CFTR) protein C2 co ..read more
Drug Hunter
6d ago
Minipigs have recently gained prominence as an alternative non-rodent in vivo model for pharmacokinetic (PK), efficacy, and toxicology studies supporting human dose predictions. This article provides an overview of the use of minipigs in small molecule preclinical drug discovery research, tracing their historical background and outlining practical considerations for selecting them in studies focusing on hepatic metabolism, oral bioavailability, CNS penetration, and toxicology. It highlights minipigs' unique advantages and makes a compelling case for their continued use in preclinical research ..read more
Drug Hunter
6d ago
The "New Drugs on the Horizon" sessions at the AACR Annual Meeting 2024 in San Diego revealed twelve innovative oncology agents and offered attendees a first look at their structures and preliminary data as they enter/progress in the clinic. In case you missed any of these exciting compounds – including selective CDK inhibitors, molecular glues, bifunctional degraders, a radiopharmaceutical, a bifunctional antibody, and an ADC – this article covers the structures and targets disclosed. A separate session disclosed the structure of a pan-RAS isoform inhibitor with remarkable clinical results ..read more
Drug Hunter
6d ago
Companies inked notable high-profile transactions in March 2024, including AbbVie's purchase of Landos Biopharma for $137.5M, AstraZeneca's $2.4B acquisition of Fusion Pharmaceuticals, and its subsequent deal to buy Amolyt for up to $1.05B. The FDA approved the first treatment for MASH. In parallel, expectations are high for the approval of Xcovery's ALK inhibitor, ensartinib. Praxis made headlines with PRAX-628, a next-generation oral NaV modulator, which showed anti-seizure efficacy in a Ph. IIa trial. Read below for more details on these and other drug discovery news stories from March 2024 ..read more
Drug Hunter
1w ago
Minipigs have recently gained prominence as an alternative non-rodent in vivo model for pharmacokinetic (PK), efficacy, and toxicology studies supporting human dose predictions. This article provides an overview of the use of minipigs in small molecule preclinical drug discovery research, tracing their historical background and outlining practical considerations for selecting them in studies focusing on hepatic metabolism, oral bioavailability, CNS penetration, and toxicology. It highlights minipigs' unique advantages and makes a compelling case for their continued use in preclinical research ..read more
Drug Hunter
1w ago
We asked the global drug discovery community to nominate and vote on their favorite molecule from 2023, and the results are in. The 2023 winner, with the most votes between ten molecules, is Merck’s oral macrocyclic peptide inhibitor of PCSK9, MK-0616, derived from mRNA display technology and shown to have clinical efficacy. Herein, we highlight what makes MK-0616 so impressive to the drug discovery community ..read more
Drug Hunter
1w ago
Merck’s macrocyclic PCSK9 protein-protein interaction (PPI) inhibitor, MK-0616, is a once-daily PCSK9-lowering and LDL-cholesterol-lowering small molecule that has recently demonstrated antibody-like efficacy as an oral agent in the clinic. The program highlights numerous technical achievements at the forefront of modern drug discovery, and will set a standard for modern “classics in drug discovery” for some time ..read more
Drug Hunter
2w ago
The accelerated approvals of Ras(OFF)-targeting KRAS G12C inhibitors sotorasib and adagrasib, decades in the making, marked the beginning of a new phase of KRAS drug discovery. While an increasing number of follow-on KRAS inhibitors are emerging with similar mechanisms of action, Revolution Medicines’ 2023 Molecule of the Year Nominee, RMC-6291, is representative of a completely novel approach that could become a strong addition to the clinical toolbox for KRAS, but also serves as proof-of-concept for a new class of small molecule therapeutics entirely ..read more