Search Results

A Novel Class of Brain-Penetrant, Covalent Antiparasitic Drugs from Novartis Recently, Novartis disclosed a new class of brain-penetrant, covalent agents against kinetoplastid parasites in Science. Kinetoplastid parasites cause Chagas disease (T. cruzi), sleeping sickness (T. brucei), and leishmaniasis (Leishmania), but there are few effective treatment options, especially for infections in the brain (e.g. stage II…

And now for something completely different. The recent approvals of Ras(off)-targeting KRASG12C inhibitors sotorasib and adagrasib, decades in the making, mark the beginning of a new phase of KRAS drug discovery. Clinical data with both molecules suggest that there are opportunities for brain-penetrant KRAS inhibitors, a need for novel modalities to address drug resistance and…

An Active Prodrug, Triple Reuptake Inhibitor for Major Depressive Disorder  While SNRIs and selective serotonin reuptake inhibitors (SSRIs) have been hugely successful in treating major depressive disorder (MDD), many patients remain resistant to treatment or do not experience full symptom relief. The majority of current treatments for MDD increase levels of synaptic serotonin and/or norepinephrine…

An oral GLP-1R agonist competing with peptide injectables for diabetes and obesity. Peptidic GLP-1R agonists have received significant media coverage over the past year. Shortages of the semaglutide-based injectable diabetes medication Ozempic, which accounts for 40% of GLP-1R agonist US market share, have even emerged, driven by overwhelming demand for the weight loss formulation Wegovy,…

A potential best-in-class TRβ agonist prodrug for NASH demonstrates impressive efficacy and safety. Thyroid hormone receptor β (TRβ, THRβ or THR-β) agonists have seen a surge of interest in non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver disease (NAFLD), largely thanks to impressive Ph. III clinical data from resmetirom, a Breakthrough Therapy and 2022 Molecule of…

A diaziridine-based tumor-activated prodrug for AKR1C3-expressing cancers from a defunct Bay Area biotech. OBI-3424 (formerly TH-3424) is a tumor-activated prodrug in Ph. II that releases DNA-crosslinking diaziridine phosphamide (remniscent of thioTEPA) upon activation by the NAD(P)H-dependent aldoketoreductase, AKR1C3, which is differentially expressed in many cancers. The molecule was originated at Threshold Pharma in South San…