Deciphera’s DCC-3116 is an oral ULK1/2 inhibitor targeting the autophagy pathway, a key mechanism of tumor survival and resistance to targeted therapy. Currently in two open-label Ph. I/II trials as a monotherapy and in combination with RTK pathway inhibitors, the structure and discovery of this first-in-class compound were recently presented at the ACS Spring 2024 meeting ..read more

VVD-214/RO7589831 is an oral covalent, reversible, and allosteric inhibitor of WRN helicase discovered by the San Diego-based biotech Vividion Therapeutics and being developed by Roche for tumors marked by microsatellite instability and/or mismatch repair deficiency. Vividion has utilized its chemoproteomics platform to discover and develop novel treatment options for oncology targets. The structure and initial preclinical pharmacology data for VVD-214 were recently disclosed at the AACR Annual Meeting 2024 in San Diego. VVD-214 is currently being evaluated in a Ph. I trial ..read more

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 ..read more

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 ..read more

Drug Hunter offers industry professionals a faster way to find and absorb the latest research and insights in drug discovery. It is a curated collection of the most relevant and transferable scientific knowledge so you can spend less time weeding through the noise and more time turning molecules into medicines. But we also love hearing from you, the drug hunters in the field ..read more

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

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

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

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

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